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Stanietzky N, Morani A, Surabhi V, Jensen C, Horvat N, Vikram R. Mucinous Rectal Adenocarcinoma-Challenges in Magnetic Resonance Imaging Interpretation. J Comput Assist Tomogr 2024; 48:683-692. [PMID: 38446711 DOI: 10.1097/rct.0000000000001599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2024]
Abstract
ABSTRACT Mucinous rectal cancer (MRC) is defined by the World Health Organization as an adenocarcinoma with greater than 50% mucin content. Classic teaching suggests that it carries a poorer prognosis than conventional rectal adenocarcinoma. This poorer prognosis is thought to be related to mucin dissecting through tissue planes at a higher rate, thus increasing the stage of disease at presentation. Developments in immunotherapy have bridged much of this prognostic gap in recent years. Magnetic resonance imaging is the leading modality in assessing the locoregional spread of rectal cancer. Mucinous rectal cancer carries unique imaging challenges when using this modality. Much of the difficulty lies in the inherent increased T2-weighted signal of mucin on magnetic resonance imaging. This creates difficulty in differentiating mucin from the adjacent background fat, making the detection of both the primary disease process as well as the locoregional spread challenging. Computed tomography scan can act as a valuable companion modality as mucin tends to be more apparent in the background fat. After therapy, diagnostic challenges remain. Mucin is frequently present, and distinguishing cellular from acellular mucin can be difficult. In this article, we will discuss each of these challenges and present examples of such situations and strategies that can be used to overcome them.
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Affiliation(s)
- Nir Stanietzky
- From the Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ajaykumar Morani
- From the Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Venkateswar Surabhi
- From the Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Corey Jensen
- From the Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Raghu Vikram
- From the Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
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Emile SH, Horesh N, Freund MR, Silva-Alvarenga E, Wexner SD. A Propensity Score-Matched Analysis of the Impact of Neoadjuvant Radiation Therapy on the Outcomes of Stage II and III Mucinous Rectal Carcinoma. Dis Colon Rectum 2024; 67:655-663. [PMID: 38231014 DOI: 10.1097/dcr.0000000000003081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
BACKGROUND Patients with mucinous rectal carcinoma tend to present in advanced stage with a poor prognosis. OBJECTIVE This study aimed to assess the effect of neoadjuvant radiation therapy on outcomes of patients with stage II and III mucinous rectal carcinomas using data from the National Cancer Database. DESIGN Retrospective analysis of prospective national databases. SETTING National Cancer Database between 2004 and 2019. PATIENTS Patients with mucinous rectal carcinoma. INTERVENTION Patients who did or did not receive neoadjuvant radiation therapy were matched using the nearest-neighbor propensity score method for age, clinical stage, neoadjuvant systemic treatment, and surgery type. MAIN OUTCOME MEASURES Main outcomes of the study were numbers of total harvested and positive lymph nodes, disease downstaging after neoadjuvant radiation, and overall survival. Other outcomes were hospital stay, short-term mortality, and readmission. RESULTS A total of 3062 patients (63.5% men) with stage II and III mucinous rectal carcinoma were included, 2378 of whom (77.7%) received neoadjuvant radiation therapy. After 2:1 propensity score matching, 143 patients in the no neoadjuvant group were matched to 286 patients in the neoadjuvant group. The mean overall survival was similar (77.3 vs 81.9 months; p = 0.316). Patients who received neoadjuvant radiation therapy were less often diagnosed with pathologic T3 and 4 disease (72.3% vs 81.3%, p = 0.013) and more often had pathologic stage 0 and 1 disease (16.4% vs 11.2%, p = 0.001), yet with a higher stage III disease (49.7% vs 37.1%, p = 0.001). Neoadjuvant radiation was associated with fewer examined lymph nodes (median: 14 vs 16, p = 0.036) and positive lymph nodes than patients who did not receive neoadjuvant radiation. Short-term mortality, readmission, hospital stay, and positive surgical margins were similar. LIMITATIONS Retrospective study and missing data on disease recurrence. CONCLUSIONS Patients with mucinous rectal carcinoma who received neoadjuvant radiation therapy had marginal downstaging of disease, fewer examined and fewer positive lymph nodes, and similar overall survival to patients who did not receive neoadjuvant radiation. See Video Abstract . UN ANLISIS EMPAREJADO POR PUNTUACIN DE PROPENSIN DEL IMPACTO DE LA RADIOTERAPIA NEOADYUVANTE EN LOS RESULTADOS DEL CARCINOMA MUCINOSO DE RECTO EN ESTADIO IIIII ANTECEDENTES:Los pacientes con carcinoma mucinoso de recto tienden a presentarse en estadio avanzado con mal pronóstico.OBJETIVO:Este estudio tuvo como objetivo evaluar el efecto de la radioterapia neoadyuvante en los resultados de pacientes con carcinomas mucinosos de recto en estadio II-III utilizando datos de la Base de Datos Nacional del Cáncer.DISEÑO:Análisis retrospectivo de bases de datos nacionales prospectivas.PACIENTES:Pacientes con carcinoma mucinoso de recto.AJUSTE:Base de datos nacional sobre el cáncer entre 2004 y 2019.INTERVENCIÓN:Los pacientes que recibieron o no radioterapia neoadyuvante fueron emparejados utilizando el método de puntuación de propensión del vecino más cercano por edad, estadio clínico, tratamiento sistémico neoadyuvante y tipo de cirugía.PRINCIPALES MEDIDAS DE VALORACIÓN:Los principales resultados del estudio fueron el número total de ganglios linfáticos extraídos y positivos, la reducción del estadio de la enfermedad después de la radiación neoadyuvante y la supervivencia general. Otros resultados fueron la estancia hospitalaria, la mortalidad a corto plazo y el reingreso.RESULTADOS:Se incluyeron 3.062 pacientes (63,5% hombres) con carcinoma mucinoso de recto estadio II-III, de los cuales 2.378 (77,7%) recibieron radioterapia neoadyuvante. Después de un emparejamiento por puntuación de propensión 2:1, 143 pacientes del grupo sin neoadyuvancia fueron emparejados con 286 del grupo neoadyuvante. La supervivencia global media fue similar (77,3 vs 81,9 meses; p = 0,316). A los pacientes que recibieron radiación neoadyuvante se les diagnosticó con menos frecuencia enfermedad pT3-4 (72,3% frente a 81,3%, p = 0,013) y con mayor frecuencia tenían enfermedad en estadio patológico 0-1 (16,4% frente a 11,2%, p = 0,001), aunque con una enfermedad en estadio III superior (49,7% vs 37,1%, p = 0,001). La radiación neoadyuvante se asoció con menos ganglios linfáticos examinados (mediana: 14 frente a 16, p = 0,036) y ganglios linfáticos positivos que los pacientes que no recibieron radiación neoadyuvante. La mortalidad a corto plazo, el reingreso, la estancia hospitalaria y los márgenes quirúrgicos positivos fueron similares.LIMITACIONES:Estudio retrospectivo y datos faltantes sobre recurrencia de la enfermedad.CONCLUSIONES:Los pacientes con carcinoma mucinoso de recto que recibieron radioterapia neoadyuvante tuvieron una reducción marginal de la enfermedad, menos ganglios linfáticos examinados y positivos, y una supervivencia general similar a la de los pacientes que no recibieron radiación neoadyuvante. (Traducción- Dr Ingrid Melo ).
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Affiliation(s)
- Sameh Hany Emile
- Department of Colorectal Surgery, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida
- Colorectal Surgery Unit, General Surgery Department, Mansoura University Hospitals, Mansoura, Egypt
| | - Nir Horesh
- Department of Colorectal Surgery, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida
- Department of Surgery and Transplantations, Sheba Medical Center, Ramat Gan, Israel, Tel Aviv University, Tel Aviv, Israel
| | - Michael R Freund
- Department of Colorectal Surgery, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida
- Department of General Surgery, Shaare Zedek Medical Center, the Hebrew University Faculty of Medicine, Jerusalem, Israel
| | - Emanuela Silva-Alvarenga
- Department of Colorectal Surgery, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida
| | - Steven D Wexner
- Department of Colorectal Surgery, Ellen Leifer Shulman and Steven Shulman Digestive Disease Center, Cleveland Clinic Florida, Weston, Florida
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Santini D, Danti G, Bicci E, Galluzzo A, Bettarini S, Busoni S, Innocenti T, Galli A, Miele V. Radiomic Features Are Predictive of Response in Rectal Cancer Undergoing Therapy. Diagnostics (Basel) 2023; 13:2573. [PMID: 37568936 PMCID: PMC10417449 DOI: 10.3390/diagnostics13152573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/14/2023] [Accepted: 07/19/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Rectal cancer is a major mortality cause in the United States (US), and its treatment is based on individual risk factors for recurrence in each patient. In patients with rectal cancer, accurate assessment of response to chemoradiotherapy has increased in importance as the variety of treatment options has grown. In this scenario, a controversial non-operative approach may be considered in some patients for whom complete tumor regression is believed to have occurred. The recommended treatment for locally advanced rectal cancer (LARC, T3-4 ± N+) is total mesorectal excision (TME) after neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) has become a standard technique for local staging of rectal cancer (tumor, lymph node, and circumferential resection margin [CRM] staging), in both the US and Europe, and it is getting widely used for restaging purposes. AIM In our study, we aimed to use an MRI radiomic model to identify features linked to the different responses of chemoradiotherapy of rectal cancer before surgery, and whether these features are helpful to understand the effectiveness of the treatments. METHODS We retrospectively evaluated adult patients diagnosed with LARC who were subjected to at least 2 MRI examinations in 10-12 weeks at our hospital, before and after nCRT. The MRI acquisition protocol for the 2 exams included T2 sequence and apparent diffusion coefficient (ADC) map. The patients were divided into 2 groups according to the treatment response: complete or good responders (Group 1) and incomplete or poor responders (Group 2). MRI images were segmented, and quantitative features were extracted and compared between the two groups. Features that showed significant differences (SF) were then included in a LASSO regression method to build a radiomic-based predictive model. RESULTS We included 38 patients (26 males and 12 females), who are classified from T2 and T4 stages in the rectal cancer TNM. After the nCRT, the patients were divided into Group 1 (13 patients), complete or good responders, and Group 2 (25 patients), incomplete or poor responders. Analysis at baseline generated the following significant features for the Mann-Whitney test (out of a total of 107) for each sequence. Also, the analysis at the end of the follow-up yielded a high number of significant features for the Mann-Whitney test (out of a total of 107) for each image. Features selected by the LASSO regression method for each image analyzed; ROC curves relative to each model are represented. CONCLUSION We developed an MRI-based radiomic model that is able to differentiate and predict between responders and non-responders who went through nCRT for rectal cancer. This approach might identify early lesions with high surgical potential from lesions potentially resolving after medical treatment.
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Affiliation(s)
- Diletta Santini
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Ginevra Danti
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Eleonora Bicci
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Antonio Galluzzo
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
| | - Silvia Bettarini
- Department of Health Physics, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Simone Busoni
- Department of Health Physics, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Tommaso Innocenti
- Clinical Gastroenterology Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Andrea Galli
- Clinical Gastroenterology Unit, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy
| | - Vittorio Miele
- Department of Radiology, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy; (D.S.)
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DeAngelis GA. Editorial Comment: Mucinous Degeneration on MRI After Neoadjuvant Therapy. AJR Am J Roentgenol 2023; 221:217. [PMID: 37095677 DOI: 10.2214/ajr.23.29359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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Miranda J, Pinto PVA, Kinochita F, Garcia CM, El Homsi M, Vilela de Oliveira C, Pandini RV, Nahas CSR, Nahas SC, Gollub MJ, Horvat N. Mucinous Degeneration on MRI After Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: Frequency and Association With Clinical Outcomes. AJR Am J Roentgenol 2023; 221:206-216. [PMID: 36919880 PMCID: PMC10777341 DOI: 10.2214/ajr.23.29002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.
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Affiliation(s)
- Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil
| | | | | | | | - Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY 10065
| | - Camila Vilela de Oliveira
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY 10065
| | | | | | - Sergio C Nahas
- Department of Surgery, University of Sao Paulo, Sao Paulo, Brazil
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY 10065
| | - Natally Horvat
- Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY 10065
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Chen C, Chen X, Jiang J. Long-term effect of neoadjuvant radiotherapy in patients with locally advanced rectal mucinous adenocarcinoma: a population-based study of 1514 patients. Sci Rep 2023; 13:11696. [PMID: 37474620 PMCID: PMC10359247 DOI: 10.1038/s41598-023-38846-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/16/2023] [Indexed: 07/22/2023] Open
Abstract
Rectal mucinous adenocarcinoma (RMAC) is a rare and aggressive form of rectal cancer. The effectiveness of neoadjuvant radiotherapy (NRT) for RMAC has not been well studied, and the survival benefit remains controversial. The purpose of this work was to determine the prognostic role of NRT in patients with RMAC by propensity-score matching (PSM). A retrospective cohort study using the Surveillance, Epidemiology, and End Results from 2004 to 2015 was performed. In the multivariate analysis before PSM, NRT provided better OS (HR 0.61, 95% CI 0.52-0.71, p < 0.001) and CSS (HR 0.68, 95% CI 0.56-0.82, p < 0.001). Multivariate analysis after PSM (n = 844) confirmed that patients receiving NRT survived longer than those without NRT (OS: HR 0.60, 95% CI 0.50-0.78, p < 0.001 and CSS: HR 0.68, 95% CI 0.54-0.84, p < 0.001). Subgroup analysis indicated that NRT had significantly improved OS and CSS in stage II RMAC and OS in stage III RMAC after adjusting for various confounding factors.
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Affiliation(s)
- Can Chen
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China
| | - Xi Chen
- Department of Dermatology, The First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province, China
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
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Chen M, Wang C, Liu H, Liang Z, Ye F, Luo S, Liu Z, Hu H, Lai S, Hou Y, Kang L, Huang L. The Deepest Extent of Acellular Mucin Pools in Resected Locally Advanced Rectal Cancer With Pathological Complete Response After Preoperative Chemoradiotherapy: A Hidden Killer? Am J Surg Pathol 2023; 47:812-818. [PMID: 37194966 DOI: 10.1097/pas.0000000000002055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
For patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR), the clinical significance of the distribution extent of acellular mucin pools (AMP) distribution remains unclear, so this study was conducted to address key unanswered questions. We performed a retrospective analysis of 317 patients with LARC with pCR after preoperative chemoradiotherapy and total mesorectal resection from January 2011 to June 2020. Based on AMP existence and the deepest tissue layer of distribution, patients were assigned new stages. The patient information was recorded, and the main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival (OS). A total of 83/317 (26.2%) patients exhibited AMP, and disease recurrence occurred in 46/317 (14.5%) patients. Over the 5-year median follow-up period, the patients with AMP showed 5-year DFS rates (75.9% vs. 88.9%, P =0.004) and 5-year OS rates (85.5% vs. 95.7%, P =0.002) statistically lower than those of patients without AMP. Disease recurrence was seen in 15/54 (27.8%) patients with AMP within the subserosa and/or the serosa, or adipose tissue. Univariate and multivariate analysis showed that the existence of AMP within the subserosa and/or the serosa, or adipose tissue was an independent risk factor for DFS [hazard ratio (HR): 2.344; 95% confidence interval (CI): 1.256-4.376; P =0.007] and OS [HR: 3.374; 95% CI: 1.438-7.917; P =0.005]. The new stages based on the deepest extent of AMP were related to worse DFS ( P =0.004) and OS ( P =0.003) rates among patients with pCR. In conclusion, the presence of AMP might reduce the prognosis of LARC patients with pCR after chemoradiotherapy, especially in patients with AMP in deeper tissue layers. Therefore, the influence of the deepest AMP extent might be worth considering in staging. Moreover, the revised staging of patients with pCR according to the deepest extent of AMP, which is unrelated to the clinical T stage, might facilitate postoperative management.
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Affiliation(s)
- Mian Chen
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chao Wang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huashan Liu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhenxing Liang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Fujin Ye
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuangling Luo
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huanxin Hu
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Sicong Lai
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yujie Hou
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Kang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Huang
- Department of Colorectal Surgery, General Surgery and Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
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Awiwi MO, Kaur H, Ernst R, Rauch GM, Morani AC, Stanietzky N, Palmquist SM, Salem UI. Restaging MRI of Rectal Adenocarcinoma after Neoadjuvant Chemoradiotherapy: Imaging Findings and Potential Pitfalls. Radiographics 2023; 43:e220135. [PMID: 36927125 DOI: 10.1148/rg.220135] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Rectal adenocarcinoma constitutes about one-third of all colorectal adenocarcinoma cases. Rectal MRI has become mandatory for evaluation of patients newly diagnosed with rectal cancer because it can help accurately stage the disease, impact the choice to give neoadjuvant therapy or proceed with up-front surgery, and even direct surgical dissection planes. Better understanding of neoadjuvant chemoradiotherapy effects on rectal tumors and recognition that up to 30% of patients can have a pathologic complete response have opened the door for the nonsurgical "watch-and-wait" management approach for rectal adenocarcinoma. Candidates for this organ-preserving approach should have no evidence of malignancy on all three components of response assessment after neoadjuvant therapy (ie, digital rectal examination, endoscopy, and rectal MRI). Hence, rectal MRI again has a major role in directing patient management and possibly sparing patients from unnecessary surgical morbidity. In this article, the authors discuss the indications for neoadjuvant therapy in management of patients with rectal adenocarcinoma, describe expected imaging appearances of rectal adenocarcinoma after completion of neoadjuvant therapy, and outline the MRI tumor regression grading system. Since pelvic sidewall lymph node dissection is associated with a high risk of permanent genitourinary dysfunction, it is performed for only selected patients who have radiologic evidence of sidewall lymph node involvement. Therefore, the authors review the relevant lymphatic compartments of the pelvis and describe lymph node criteria for determining locoregional nodal spread. Finally, the authors discuss limitations of rectal MRI, describe several potential interpretation pitfalls after neoadjuvant therapy, and emphasize how these pitfalls may be avoided. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.
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Affiliation(s)
- Muhammad O Awiwi
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Harmeet Kaur
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Randy Ernst
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Gaiane M Rauch
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Ajaykumar C Morani
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Nir Stanietzky
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Sarah M Palmquist
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
| | - Usama I Salem
- From the Division of Diagnostic Imaging, Department of Abdominal Imaging, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030
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Chen M, Zhang J, Hou Y, Liu H, Fan X, Luo S, Liu Z, Hu H, Lai S, Kang L, Huang L. Clinical significance of adjuvant chemotherapy for pathological complete response rectal cancer patients with acellular mucin pools after neoadjuvant chemoradiotherapy. Therap Adv Gastroenterol 2023; 16:17562848221117875. [PMID: 36755740 PMCID: PMC9900662 DOI: 10.1177/17562848221117875] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/07/2022] [Indexed: 02/10/2023] Open
Abstract
Background Approximately 15-30% of locally advanced rectal cancer (LARC) patients achieved pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision, but the clinical significance of adjuvant chemotherapy (ACT) for pCR patients remains unclear. Objectives To determine whether LARC pCR patients can benefit from the administration of ACT. Design Single center retrospective study. Methods This study retrospectively included 280 LARC patients who achieved pCR after CRT and surgery from 2011 to 2019. The information of patients was recorded. Main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival. Subgroup analysis was conducted on whether pCR patients with acellular mucin pools received ACT or not. Results A total of 74/280 (26.4%) patients were identified with acellular mucin pools. Disease recurrence occurred in 38/280 (13.6%) patients, and in the subgroup of patients with acellular mucin pools, 15/74 (20.3%) patients developed distant metastases. The existence of acellular mucin pools was associated with worse DFS (79.7% versus 88.8%, P = 0.037). Among pCR patients with acellular mucin pools, 9/25 (36.0%) of non-ACT patients occurred recurrence, and ACT was beneficial for improving DFS (hazard ratio: 0.245; 95% confidence interval: 0.084-0.719; P = 0.010). Conclusions The existence of acellular mucin pools may represent a sign of invasive tumor biology, which indicated a negative prognosis. ACT can improve the prognosis of patient with acellular mucin pools, so ACT should be considered for them.
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Affiliation(s)
| | | | | | - Huashan Liu
- Department of Colorectal Surgery, The Sixth
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong,
China,Guangdong Institute of Gastroenterology,
Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China
| | - Xinjuan Fan
- Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China,Department of Pathology, The Sixth Affiliated
Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Shuangling Luo
- Department of Colorectal Surgery, The Sixth
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong,
China,Guangdong Institute of Gastroenterology,
Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, The Sixth
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong,
China,Guangdong Institute of Gastroenterology,
Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China
| | - Huanxin Hu
- Department of Colorectal Surgery, The Sixth
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong,
China,Guangdong Institute of Gastroenterology,
Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China
| | - Sicong Lai
- Department of Colorectal Surgery, The Sixth
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong,
China,Guangdong Institute of Gastroenterology,
Guangzhou, Guangdong, China,Guangdong Provincial Key Laboratory of
Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun
Yat-sen University, Guangzhou, Guangdong, China
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10
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Horvat N, El Homsi M, Miranda J, Mazaheri Y, Gollub MJ, Paroder V. Rectal MRI Interpretation After Neoadjuvant Therapy. J Magn Reson Imaging 2023; 57:353-369. [PMID: 36073323 PMCID: PMC9851947 DOI: 10.1002/jmri.28426] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 08/23/2022] [Accepted: 08/25/2022] [Indexed: 02/01/2023] Open
Abstract
In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.
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Affiliation(s)
- Natally Horvat
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria El Homsi
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil
| | - Yousef Mazaheri
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Marc J. Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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11
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Chen M, Lin H, Zhang J, Pang X, Fan X, Luo S, Liu Z, Hu H, Lai S, Hou Y, Kang L, Huang L. Presence and clinical significance of acellular mucin pools in resected rectal cancer with pathological complete response after preoperative chemoradiotherapy. Histopathology 2022; 81:569-576. [DOI: 10.1111/his.14795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 07/25/2022] [Accepted: 08/06/2022] [Indexed: 11/26/2022]
Affiliation(s)
- Mian Chen
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Hongcheng Lin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Jianwei Zhang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Xiaolin Pang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Radiation Oncology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Xinjuan Fan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Shuangling Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Zhanzhen Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Huanxin Hu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Sicong Lai
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Yujie Hou
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Liang Kang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
| | - Liang Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
- Guangdong Institute of Gastroenterology 510655 Guangzhou Guangdong China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat‐sen University 510655 Guangzhou Guangdong China
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12
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Acellular mucin in lymph nodes isolated from treatment-naïve colorectal cancer resections: a clinicopathologic analysis of 16 cases. Virchows Arch 2022; 481:63-72. [PMID: 35513610 PMCID: PMC9979094 DOI: 10.1007/s00428-022-03332-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 04/15/2022] [Accepted: 04/27/2022] [Indexed: 10/18/2022]
Abstract
Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.
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13
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Fernandes MC, Gollub MJ, Brown G. The importance of MRI for rectal cancer evaluation. Surg Oncol 2022; 43:101739. [PMID: 35339339 PMCID: PMC9464708 DOI: 10.1016/j.suronc.2022.101739] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 02/20/2022] [Indexed: 12/19/2022]
Abstract
Magnetic resonance imaging (MRI) has gained increasing importance in the management of rectal cancer over the last two decades. The role of MRI in patients with rectal cancer has expanded beyond the tumor-node-metastasis (TNM) system in both staging and restaging scenarios and has contributed to identifying "high" and "low" risk features that can be used to tailor and personalize patient treatment; for instance, selecting the patients for neoadjuvant chemoradiation (NCRT) before the total mesorectal excision (TME) surgery based on risk of recurrence. Among those features, the status of the circumferential resection margin (CRM), extramural vascular invasion (EMVI), and tumor deposits (TD) have stood out. Moreover, MRI also has played a role in surgical planning, especially when the tumor is located in the low rectum, when the relationship between tumor and the anal canal is important to choose the best surgical approach, and in cases of locally advanced or recurrent tumors invading adjacent pelvic organs that may require more complex surgeries such as pelvic exenteration. As approaches using organ preservation emerge, including transanal local excision and "watch-and-wait", MRI may help in the patient selection for those treatments, follow up, and detection of tumor regrowth. Additionally, potential MRI-based prognostic and predictive biomarkers, such as quantitative and semi-quantitative metrics derived from functional sequences like diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE), and radiomics, are under investigation. This review provides an overview of the current role of MRI in rectal cancer in staging and restaging and highlights the main areas under investigation and future perspectives.
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14
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Koëter T, Stijns RCH, van Koeverden S, Hugen N, van der Heijden JAG, Nederend J, van Zwam PH, Nagtegaal ID, Verheij M, Rutten HJT, de Wilt JHW. Poor response at restaging MRI and high incomplete resection rates of locally advanced mucinous rectal cancer after chemoradiation therapy. Colorectal Dis 2021; 23:2341-2347. [PMID: 34051043 PMCID: PMC8519080 DOI: 10.1111/codi.15760] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 04/09/2021] [Accepted: 05/19/2021] [Indexed: 02/08/2023]
Abstract
AIM Mucinous carcinoma is a histological subtype of rectal cancer and has been associated with a poor response to neoadjuvant chemoradiotherapy (CRT). The primary aim of this study was to analyse the response on MRI of mucinous locally advanced rectal cancer (LARC) after CRT compared to regular adenocarcinoma. METHOD Patients with LARC (defined as cT4 and/or cN2), who underwent CRT followed by restaging MRI and surgery in two tertiary referral hospitals were retrospectively included in the study. Pre- and post-treatment MRI was reviewed by an experienced abdominal radiologist. RESULTS A total of 102 patients, of whom 29 were diagnosed with mucinous carcinoma, were included for analysis. At restaging MRI, adenocarcinoma patients demonstrated significantly less clinical involvement of the mesorectal fascia (37% vs. 62%, P = 0.003) while this was not demonstrated in mucinous carcinoma patients (86% vs. 97%, P = 0.16). Significant downstaging after CRT in adenocarcinoma patients (P = 0.01) was seen while, in mucinous carcinoma patients, no downstaging after CRT (P = 0.89) was seen. Pathology revealed significantly higher rates of an involved circumferential resection margin in mucinous carcinoma versus adenocarcinoma patients (27.6% vs. 1.4%; P < 0.001). After multivariate regression analysis, mucinous carcinoma remained an independent prognostic factor for local recurrence (hazard ratio 3.6; 95% CI 1.1-12.4), although no differences in overall or disease-free survival were observed. CONCLUSION Mucinous rectal carcinoma is associated with a poor clinical response at restaging MRI after CRT, leading to relatively higher rates of involved circumferential resection margins at pathology. In this cohort, mucinous carcinoma seems to be a prognostic factor for increased risk of local recurrence, without an effect on overall survival.
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Affiliation(s)
- Tijmen Koëter
- Department of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | - Rutger C. H. Stijns
- Department of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | - Sebastiaan van Koeverden
- Department of Radiology and Nuclear MedicineRadboud University Medical CentreNijmegenThe Netherlands
| | - Niek Hugen
- Department of SurgeryRadboud University Medical CentreNijmegenThe Netherlands
| | | | - Joost Nederend
- Department of RadiologyCatharina HospitalEindhovenThe Netherlands
| | - Peter H. van Zwam
- Department of PathologyPAMM Laboratory for Pathology and Medical MicrobiologyEindhovenThe Netherlands
| | - Iris D. Nagtegaal
- Department of PathologyRadboud University Medical CentreNijmegenThe Netherlands
| | - Marcel Verheij
- Department of Radiation OncologyRadboud University Medical CentreNijmegenThe Netherlands
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15
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Suarez-Weiss KE, Jhaveri KS, Harisinghani MG. MRI Evaluation of Rectal Cancer Following Preoperative Chemoradiotherapy. Semin Roentgenol 2020; 56:177-185. [PMID: 33858644 DOI: 10.1053/j.ro.2020.07.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
| | - Kartik S Jhaveri
- Division of Diagnostic Radiology, University of Toronto University Health Network, Mt. Sinai and WCH, Toronto, Canada
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16
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Serrablo A, Paliogiannis P, Paradisi C, Hörndler C, Sarría L, Tejedor L, Serrablo L, Azoulay D. Radio-Pathological Correlations in Patients with Liver Metastases for Colorectal Cancer. Dig Surg 2020; 37:383-389. [PMID: 32224622 DOI: 10.1159/000506105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 01/22/2020] [Indexed: 12/10/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the most frequent gastrointestinal cancer. The liver is the organ most commonly affected by CRC metastases. Synchronous CRC liver metastases (CRCLM) are present in 15-25% at diagnosis, and metastases are confined to the liver in 70-80% of these cases. The aim of the present study was to investigate the existence of significant correlations between the pathological features and computed tomography scan morpho-densitometric findings. SUMMARY A retrospective study of prospectively collected data has been performed; all patients underwent curative-intent hepatic resection from January 2004 to December 2012 and had histologically confirmed CRCLM. Key Messages: Thirty-four (57%) patients were males; the mean age was 64.4 (±10.2) years. Statistically significant differences have been found with the percentages of intra-tumoral fibrosis (p = 0.038) and necrosis (p = 0.007); the values of fibrosis are higher in the absence of a peri-lesional ring, while those of necrosis are higher in the presence of a peri-lesional ring.There was a correlation between the histopathological response to treatments and the global attenuation levels observed in the computed tomography scan of CRCLM. Furthermore, the presence of a radiologically evidenced peripheral ring was associated with the amount of viable tumor cells in the periphery of the tumor, and with responses predominated by necrosis. More studies are needed to clarify the radiological and histological correlation and to be able to better select patients who are going to undergo surgery.
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Affiliation(s)
- Alejandro Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain,
| | - Panagiotis Paliogiannis
- Experimental Pathology and Oncology, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Carlos Paradisi
- Radiology Department, Clinic University Hospital, Zaragoza, Spain
| | - Carlos Hörndler
- Pathological Department, Miguel Servet University Hospital, Zaragoza, Spain
| | - Luis Sarría
- Radiology Department, Miguel Servet University Hospital, Zaragoza, Spain
| | - Luis Tejedor
- General Surgery Department Puerta Europa Hospital, Algeciras, Spain
| | | | - Daniel Azoulay
- The Center of Liver Diseases, Sheba Medical Center, Tel Aviv, Israel
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17
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Kalisz KR, Enzerra MD, Paspulati RM. MRI Evaluation of the Response of Rectal Cancer to Neoadjuvant Chemoradiation Therapy. Radiographics 2020; 39:538-556. [PMID: 30844347 DOI: 10.1148/rg.2019180075] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
MRI plays a critical role in the staging and restaging of rectal cancer. Although newly diagnosed early-stage rectal cancers may immediately be amenable to surgical resection, patients with advanced disease first undergo neoadjuvant therapy that consists of a combination of chemotherapy and radiation therapy. Evaluation of rectal cancer after neoadjuvant therapy is best performed with MRI, given its superior soft-tissue contrast and its ability to allow multiplanar imaging and functional evaluation. In this setting, MRI allows accurate evaluation of primary tumor staging, which is determined on the basis of the depth of invasion within and through the rectal wall and the involvement of adjacent organs. MRI can also be used to evaluate posttreatment morphologic components within the tumors, including fibrosis and mucinous changes that have been shown to correlate with the response to treatment. Additional features such as the circumferential resection margin and extramural vascular invasion-factors shown to affect prognosis and local recurrence-are also assessed before and after therapy. Functional assessment with diffusion-weighted MRI and perfusion MRI plays a role in predicting tumor aggressiveness and the likelihood of response to treatment, as well as the extent of residual tumor after therapy. Lymph node staging is also performed at MRI, with assessment of not only lymph node size but also the internal architecture and signal intensity characteristics. ©RSNA, 2019 See discussion on this article by Wasnik and Al-Hawary .
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Affiliation(s)
- Kevin R Kalisz
- From the Department of Radiology, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106
| | - Michael D Enzerra
- From the Department of Radiology, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106
| | - Raj M Paspulati
- From the Department of Radiology, University Hospitals Cleveland Medical Center, 11100 Euclid Ave, Cleveland, OH 44106
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18
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How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement. Cancer Treat Rev 2020; 84:101964. [PMID: 32000055 DOI: 10.1016/j.ctrv.2020.101964] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 02/06/2023]
Abstract
Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.
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19
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Hope TA, Gollub MJ, Arya S, Bates DDB, Ganeshan D, Harisinghani M, Jhaveri KS, Kassam Z, Kim DH, Korngold E, Lalwani N, Moreno CC, Nougaret S, Paroder V, Paspulati RM, Golia Pernicka JS, Petkovska I, Pickhardt PJ, Rauch GM, Rosenthal MH, Sheedy SP, Horvat N. Rectal cancer lexicon: consensus statement from the society of abdominal radiology rectal & anal cancer disease-focused panel. Abdom Radiol (NY) 2019; 44:3508-3517. [PMID: 31388697 PMCID: PMC6824987 DOI: 10.1007/s00261-019-02170-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Standardized terminology is critical to providing consistent reports to referring clinicians. This lexicon aims to provide a reference for terminology frequently used in rectal cancer and reflects the consensus of the Society of Abdominal Radiology Disease Focused Panel in Rectal cancer. This lexicon divided the terms into the following categories: primary tumor staging, nodal staging, treatment response, anal canal anatomy, general anatomy, and treatments.
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Affiliation(s)
- Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 505 Parnassus Avenue, M-391, San Francisco, CA, 94143, USA.
- Department of Radiology, San Francisco VA Medical Center, San Francisco, CA, USA.
- UCSF Helen, Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
| | - Marc J Gollub
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | - David D B Bates
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | | | | | - Kartik S Jhaveri
- University of Toronto University Health Network, Toronto, ON, Canada
| | - Zahra Kassam
- Schulich School of Medicine, Western University, London, ON, Canada
| | - David H Kim
- School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | | | - Neeraj Lalwani
- Department of Radiology, Section of Abdominal Imaging, Wake Forest University and Baptist Medical Center, Winston-Salem, NC, USA
| | | | - Stephanie Nougaret
- Montpellier Cancer Research Institute, Montpellier, France
- Department of Radiology, Montpellier Cancer Institute, INSERM, U1194, University of Montpellier, Montpellier, France
| | - Viktoriya Paroder
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Raj M Paspulati
- Department of Radiology, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
| | | | - Iva Petkovska
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Perry J Pickhardt
- School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | - Gaiane M Rauch
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael H Rosenthal
- Harvard Medical School, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | - Natally Horvat
- Department of Radiology, Hospital Sirio-Libanes, São Paulo, São Paulo, Brazil
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20
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Horvat N, Hope TA, Pickhardt PJ, Petkovska I. Mucinous rectal cancer: concepts and imaging challenges. Abdom Radiol (NY) 2019; 44:3569-3580. [PMID: 30993392 DOI: 10.1007/s00261-019-02019-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Rectal adenocarcinoma with mucinous components is an uncommon type of rectal cancer with two distinct histologic subtypes: mucinous adenocarcinoma and signet-ring cell carcinoma. Mucin can also be identified as pattern of response after neoadjuvant treatment. On imaging modalities, mucin typically demonstrates high signal intensity on T2-weighted images, low attenuation on computed tomography, and may be negative on 18-fluorodeoxyglucose positron emission tomography. After neoadjuvant CRT, cellular and acellular mucin share similar imaging features, and differentiating them is currently the main challenge faced by radiologists. Radiologists should be aware of pros, cons, and limitations of each imaging modality in the primary staging and restaging to avoid misinterpretation of the radiological findings.
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Affiliation(s)
- Natally Horvat
- Department of Radiology, Hospital Sirio-Libanes, São Paulo, SP, Brazil
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Perry J Pickhardt
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Iva Petkovska
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 29, New York, NY, 10065, USA.
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21
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Mucin Pools Following Neoadjuvant Chemoradiotherapy for Rectal Cancer: A Marker of Response or Epiphenomenon? Am J Surg Pathol 2019; 44:280-287. [PMID: 31567193 DOI: 10.1097/pas.0000000000001373] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.
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22
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Reynolds IS, McNamara DA, Kay EW, O'Neill B, Deasy J, Burke JP. The significance of mucin pools following neoadjuvant chemoradiotherapy for locally advanced rectal cancer. J Surg Oncol 2018; 118:1129-1134. [PMID: 30261095 DOI: 10.1002/jso.25247] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 09/01/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Neoadjuvant chemo-radiotherapy is utilized for locally advanced rectal cancer to optimize local control. A subset of patients form mucin pools following radiotherapy but the association between mucin pools and pathological and oncological outcomes following curative proctectomy for rectal cancer remains unknown. OBJECTIVE The aim of this study was to determine the significance of mucin pool formation after neoadjuvant chemoradiotherapy for rectal cancer. METHODS This is a retrospective analysis of a prospectively maintained rectal cancer database. Patients who underwent curative proctectomy for rectal cancer following long course chemoradiotherapy between January 2007 and December 2016 were eligible for inclusion. RESULTS A total of 297 patients were eligible for inclusion; of these 36 (12.1%) had mucin pools on final histopathology. Tumors with mucin pools were less likely to be ypT3/T4 (25.0 vs 51.0%, P = 0.003), were more likely to have a good response (83.3 vs 53.6%, P < 0.001) and more likely to have a pathologic complete response (41.7 vs 19.2%, P = 0.006) to radiotherapy. The presence of mucin pools was associated with less distant recurrence ( P < 0.05) and improved overall survival ( P = 0.02). CONCLUSIONS The presence of mucin pools following neoadjuvant chemoradiotherapy for rectal cancer represents a surrogate marker of response to treatment and downstaging and is associated with improved survival.
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Affiliation(s)
- Ian S Reynolds
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland.,Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Deborah A McNamara
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland.,Department of Surgery, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Elaine W Kay
- Department of Pathology, Beaumont Hospital, Dublin, Ireland
| | - Brian O'Neill
- Department of Radiation Oncology, Beaumont Hospital, Dublin, Ireland
| | - Joseph Deasy
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
| | - John P Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin, Ireland
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23
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Sakuyama N, Kojima M, Kawano S, Matsuda Y, Mino-Kenudson M, Ochiai A, Ito M. Area of residual tumor is a robust prognostic marker for patients with rectal cancer undergoing preoperative therapy. Cancer Sci 2018; 109:871-878. [PMID: 29388280 PMCID: PMC5834774 DOI: 10.1111/cas.13521] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 01/11/2018] [Accepted: 01/13/2018] [Indexed: 12/17/2022] Open
Abstract
The aim of this study was to elucidate differences in the histological features of rectal cancer between patients treated with preoperative chemoradiotherapy and those treated with preoperative chemotherapy. Area of residual tumor (ART) was also evaluated for its utility as a potential prognostic marker between them. Sixty‐eight patients with rectal cancer who underwent sphincter‐saving surgery were enrolled in this study. Of these, 39 patients received preoperative chemoradiotherapy (CRT group) and 29 patients received preoperative (neoadjuvant) chemotherapy (NAC group). Area of residual tumor was determined by using morphometric software. Tumors in the two groups were compared for differences in their histological features and clinical outcomes. Tumors in the CRT and NAC groups varied greatly with regard to their histological features after preoperative therapy. Tumors in the CRT group showed more marked fibrosis than those in the NAC group. The total ART were significantly smaller in tumors in the CRT group than those in the NAC group. However, in circumferential resection margin‐negative pathologic stage 0‐III cases, clinical outcomes were not statistically different between the CRT and NAC groups. Both ART and pathologic TNM classification were associated with clinical outcome in preoperative CRT and NAC groups, but Dworak regression grade and fibrotic change were not. Tumors in those undergoing preoperative CRT and NAC were shown to differ significantly in their histological features. Area of residual tumor‐based assessment may provide useful prognostic information, regardless of preoperative therapy.
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Affiliation(s)
- Naoki Sakuyama
- Department of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Motohiro Kojima
- Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Shingo Kawano
- Department of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Yoko Matsuda
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Atsushi Ochiai
- Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Masaaki Ito
- Department of Colorectal and Pelvic Surgery, National Cancer Center Hospital East, Chiba, Japan
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24
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Lefevre JH, Mineur L, Kotti S, Rullier E, Rouanet P, de Chaisemartin C, Meunier B, Mehrdad J, Cotte E, Desrame J, Karoui M, Benoist S, Kirzin S, Berger A, Panis Y, Piessen G, Saudemont A, Prudhomme M, Peschaud F, Dubois A, Loriau J, Tuech JJ, Meurette G, Lupinacci R, Goasgen N, Parc Y, Simon T, Tiret E. Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol 2017; 34:3773-3780. [PMID: 27432930 DOI: 10.1200/jco.2016.67.6049] [Citation(s) in RCA: 312] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes [8.5%]). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum [I] 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.
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Affiliation(s)
- Jérémie H Lefevre
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Laurent Mineur
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Salma Kotti
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Eric Rullier
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Philippe Rouanet
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Cécile de Chaisemartin
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Bernard Meunier
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Jafari Mehrdad
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Eddy Cotte
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Jérome Desrame
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Mehdi Karoui
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Stéphane Benoist
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Sylvain Kirzin
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Anne Berger
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Yves Panis
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Guillaume Piessen
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Alain Saudemont
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Michel Prudhomme
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Frédérique Peschaud
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Anne Dubois
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Jérome Loriau
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Jean-Jacques Tuech
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Guillaume Meurette
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Renato Lupinacci
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Nicolas Goasgen
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Yann Parc
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Tabassome Simon
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
| | - Emmanuel Tiret
- Jérémie H. Lefevre, Salma Kotti, Yann Parc, Tabassome Simon, and Emmanuel Tiret, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Sorbonne Universités; Mehdi Karoui, Centre Hospitalier Universitaire (CHU) Pitié-Salpétrière; Anne Berger, CHU Hôpital Européen Georges-Pompidou; Jérome Loriau, Hôpital Saint-Joseph; Renato Lupinacci, Hôpital Croix Saint-Simon; Nicolas Goasgen, Hôpital des Diaconesses-Croix Saint-Simon, Paris; Laurent Mineur, Sainte-Camille Institut, Avignon; Eric Rullier, CHU Saint-André, Bordeaux; Philippe Rouanet, Val d'Aurelle Institut, Montpellier; Cécile de Chaisemartin, Paoli-Calmettes Institut, Marseille CHU, Marseille; Bernard Meunier, CHU Rennes, Rennes; Jafari Mehrdad, Oscar Lambret Center; Guillaume Piessen and Alain Saudemont, Centre Hospitalier Régional Universitaire, Lille; Eddy Cotte, CHU Lyon-Sud, Pierre-Bénite; Jérome Desrame, Jean Mermoz Institut, Lyon; Stéphane Benoist, CHU Bicètre, Le Kremlin-Bicêtre; Sylvain Kirzin, CHU Purpan, Toulouse; Yves Panis, Hôpital Beaujon, Université Paris VII, Clichy; Michel Prudhomme, CHU Carémeau, Nîmes; Frédérique Peschaud, CHU Ambroise-Paré, Boulogne-Billancourt; Anne Dubois, CHU Estaing, Clermont-Ferrand; Jean-Jacques Tuech, CHU, Rouen; and Guillaume Meurette, CHU Hôtel-Dieu, Nantes, France
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Li LH, Chen ZF, Wang XF, Liu X, Jiang WZ, Zhuo SM, Jiang LW, Guan GX, Chen JX. Monitoring neoadjuvant therapy responses in rectal cancer using multimodal nonlinear optical microscopy. Oncotarget 2017; 8:107323-107333. [PMID: 29291032 PMCID: PMC5739817 DOI: 10.18632/oncotarget.22366] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Accepted: 08/27/2017] [Indexed: 02/07/2023] Open
Abstract
Most patients with rectal cancer have a better prognosis after receiving neoadjuvant therapy because of its remarkable curative effect. However, no device delivers real-time histopathologic information on treatment response to help clinicians tailor individual therapeutic strategies. We assessed the potential of multimodal nonlinear optical microscopy to monitor therapeutic responses, including tumoral and stromal responses. We found that two-photon excited fluorescence imaging can, without labeling, identify colloid response, inflammatory cell infiltration, vascular proliferation, and tumor regression. It can also directly detect rare residual tumor cells, which may be helpful for distinguishing tumor shrinkage from tumor fragmentation. In addition, second harmonic generation imaging shows the ability to monitor three types of fibrotic responses: mature, intermediate, and immature. We also determined nonlinear spectra, collagen density, and collagen orientation indexes to quantitatively analyze the histopathologic changes induced by neoadjuvant therapy in rectal cancer. Our work demonstrates that nonlinear optical microscopy has the potential to become a label-free, real-time, in vivo medical imaging technique and provides the groundwork for further exploration into the application of nonlinear optical microscopy in a clinical setting.
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Affiliation(s)
- Lian-Huang Li
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China
| | - Zhi-Fen Chen
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Xing-Fu Wang
- Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xing Liu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Wei-Zhong Jiang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Shuang-Mu Zhuo
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China
| | - Li-Wei Jiang
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China
| | - Guo-Xian Guan
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jian-Xin Chen
- Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, Fujian, China
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Park SH, Lim JS, Lee J, Kim HY, Koom WS, Hur H, Park MS, Kim MJ, Kim H. Rectal Mucinous Adenocarcinoma: MR Imaging Assessment of Response to Concurrent Chemotherapy and Radiation Therapy—A Hypothesis-generating Study. Radiology 2017; 285:124-133. [DOI: 10.1148/radiol.2017162657] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Seung Hyun Park
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Joon Seok Lim
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Jinae Lee
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Ha Yan Kim
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Woong Sub Koom
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Hyuk Hur
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Mi-Suk Park
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Myeong-Jin Kim
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Honsoul Kim
- From the Department of Radiology and Research Institute of Radiological Science (S.H.P., J.S.L., M.S.P., M.J.K., H.K.); Biostatistics Collaboration Unit (J.L., H.Y.K.); Department of Radiation Oncology (W.S.K.); and Department of Surgery, Division of Colon and Rectal Surgery (H.H.); Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
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Applicability of American Joint Committee on Cancer and College of American Pathologists Regression Grading System in Rectal Cancer. Dis Colon Rectum 2017; 60:815-826. [PMID: 28682967 DOI: 10.1097/dcr.0000000000000806] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Different tumor grading systems have been proposed to predict the association between tumor response and clinical outcome after preoperative chemoradiotherapy in patients with rectal cancer. The American Joint Committee on Cancer and College of American Pathologists regression grading system was recommended as the standard tumor regression grading system for rectal adenocarcinoma. OBJECTIVE This study evaluated the clinical applicability of the American Joint Committee on Cancer and College of American Pathologists regression grading system in neoadjuvant-treated patients with rectal cancer. DESIGN This is a retrospective cohort study based on clinical data from a prospectively maintained colorectal cancer database. SETTINGS This study was performed at a single tertiary referral center. PATIENTS A total of 144 patients with primary locally advanced mid-to-low rectal adenocarcinoma who underwent preoperative long-course chemoradiotherapy and total mesorectal excision between 2003 and 2012 were included. MAIN OUTCOMES MEASURES The primary outcome measures were the 5-year overall survival rate, the relapse-free survival rate, the cancer-specific survival rate, and cumulative recurrence rates. RESULTS Of the 144 patients, 16 (11%) were diagnosed as American Joint Committee on Cancer and College of American Pathologists regression grade 0, 43 patients (30%) as grade 1, 61 patients (42%) as grade 2, and 25 patients (17%) as grade 3.After a median follow-up time of 83 months (range, 3 to 147 mo), 5-year survival estimates for grades 0, 1, 2, and 3, were 93%, 77%, 81%, and 54% for overall survival (p = 0.006); 93%, 82%, 75%, and 55% for relapse-free survival (p = 0.03); and 100%, 86%, 89%, and 63% for cancer-specific survival (p = 0.006). The multivariate Cox regression analyses confirmed the American Joint Committee on Cancer and College of American Pathologists regression grading system as a prognostic factor for overall (p = 0.04), relapse-free (p = 0.02), and cancer-specific survival (p = 0.04). LIMITATIONS This was a retrospective study. CONCLUSIONS Our study findings confirm the clinical relevance and applicability of the American Joint Committee on Cancer and College of American Pathologists regression grade system as a predictive factor for patients with rectal cancer. See Video Abstract at http://links.lww.com/DCR/A320.
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van Wyk H, Going J, Horgan P, McMillan DC. The role of perineural invasion in predicting survival in patients with primary operable colorectal cancer: A systematic review. Crit Rev Oncol Hematol 2017; 112:11-20. [DOI: 10.1016/j.critrevonc.2017.02.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 11/28/2016] [Accepted: 02/06/2017] [Indexed: 12/18/2022] Open
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Sun YW, Chi P, Lin HM, Lu XR, Huang Y, Xu ZB, Huang SH, Wang XJ. Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous Adenocarcinoma: A Propensity Score-Matched Study. Gastroenterol Res Pract 2017; 2017:5715219. [PMID: 28400820 PMCID: PMC5376407 DOI: 10.1155/2017/5715219] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 11/11/2016] [Accepted: 11/15/2016] [Indexed: 01/04/2023] Open
Abstract
Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.
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Affiliation(s)
- Yan-wu Sun
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Pan Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Hui-ming Lin
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Xing-rong Lu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Ying Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Zong-bin Xu
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Sheng-hui Huang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
| | - Xiao-jie Wang
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, China
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Sakuyama N, Kojima M, Kawano S, Akimoto T, Saito N, Ito M, Ochiai A. Histological differences between preoperative chemoradiotherapy and chemotherapy for rectal cancer: a clinicopathological study. Pathol Int 2017; 66:273-80. [PMID: 27112135 DOI: 10.1111/pin.12409] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 02/18/2016] [Accepted: 03/03/2016] [Indexed: 12/13/2022]
Abstract
Pathological studies on the different histological effects between neoadjuvant chemotherapy (NAC) and preoperative chemoradiation therapy (preoperative CRT) have not been performed. The purpose of this study is to elucidate the histological differences in tissue received from NAC and preoperative CRT for rectal cancer to evaluate whether a pathological assessment method used after CRT can be applied for NAC. One hundred and thirty-eight patients were enrolled in this study; 88 patients underwent their operations after preoperative CRT or NAC, and 50 patients underwent surgery only. Residual tumor area was measured using morphometry software and we compared the stromal component of myofibroblasts, immune cells, and vasculature to elucidate the difference of therapeutic effect between them. The grade of reduction after preoperative CRT was more prominent than that seen in NAC. Also, ypT downstaging was more prominent in preoperative CRT than in NAC, and ypN downstaging was more frequent in NAC than in preoperative CRT. Preoperative CRT showed more marked myofibroblasts and fewer immune cells than did NAC, which indicates different effects on the cancer microenvironment. Our histological results suggest different effects between NAC and preoperative CRT on tumor tissue. The best assessment method available for a variable therapeutic protocol should be further investigated.
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Affiliation(s)
- Naoki Sakuyama
- Division of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan.,Juntendo University Graduate School of Medicine, Advanced Clinical Research of Cancer, Tokyo, Japan
| | - Motohiro Kojima
- Division of Pathology, National Cancer Center Hospital East, Chiba, Japan
| | - Shingo Kawano
- Division of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan.,Juntendo University Graduate School of Medicine, Advanced Clinical Research of Cancer, Tokyo, Japan
| | - Tetsuo Akimoto
- Juntendo University Graduate School of Medicine, Advanced Clinical Research of Cancer, Tokyo, Japan
| | - Norio Saito
- Division of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Masaaki Ito
- Division of Colorectal Surgery, National Cancer Center Hospital East, Chiba, Japan
| | - Atsushi Ochiai
- Division of Pathology, National Cancer Center Hospital East, Chiba, Japan
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Perineural Invasion is a Strong Prognostic Factor in Colorectal Cancer: A Systematic Review. Am J Surg Pathol 2016; 40:103-12. [PMID: 26426380 DOI: 10.1097/pas.0000000000000518] [Citation(s) in RCA: 161] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Perineural invasion (PNI) is a possible route for metastatic spread in various cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis, but systematic analyses are lacking. This study systematically reviews the frequency and impact of PNI in CRC. A literature search was performed using PubMed database from inception to January 1, 2014. Data were analyzed using Review Manager 5.3. A quality assessment was performed on the basis of modified REMARK criteria. Endpoints were local recurrence (LR), 5-year disease-free survival (5yDFS), 5-year cancer-specific survival (5yCSS), and 5-year overall survival (5yOS). Meta-analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). In this meta-analysis, 58 articles with 22,900 patients were included. PNI was present in 18.2% of tumors. PNI is correlated with increased LR (RR 3.22, 95% CI, 2.33-4.44) and decreased 5yDFS (RR 2.35, 95% CI, 1.66-3.31), 5yCSS (RR 3.61, 95% CI, 2.76-4.72), and 5yOS (RR 2.09, 95% CI, 1.68-2.61). In multivariate analysis PNI remains an independent prognostic factor for 5yDFS, 5yCSS, and 5yOS (HR 2.35, 95% CI, 1.97-3.08; HR 1.91, 95% CI, 1.50-2.42; and HR 1.85, 95% CI, 1.63-2.12, respectively). We confirmed the strong impact of PNI for LR and survival in CRC. The prognostic value of PNI is similar to that of well-established prognostic factors as depth of invasion, differentiation grade, lymph node metastases, and lymphatic and extramural vascular invasion. Therefore, PNI should be one of the factors in the standardized reporting of CRC and might be considered a high-risk feature.
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Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long-term results from a single-center experience. TUMORI JOURNAL 2016; 2016:316-22. [PMID: 27002948 DOI: 10.5301/tj.5000481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2016] [Indexed: 11/20/2022]
Abstract
PURPOSE To evaluate the influence of radiation dose on tumor regression grade (TRG) and sphincter preservation rate in a series of cT3N0-1 rectal cancer patients treated with neoadjuvant chemoradiotherapy (CT-RT) with or without a sequential radiation boost. MATERIALS AND METHODS Between May 2002 and September 2013, 116 cases were eligible for retrospective evaluation. Radiotherapy was delivered for a total dose of 45 Gy (no boost arm) or 50.4 Gy (boost arm). TRG was evaluated with the Dworak scale. RESULTS Median follow-up was 62 months (range, 12-138 months). The 5-year overall survival and local control rates were 72% and 93%, respectively. Fifty-five patients (47%) were treated with a sequential radiation boost and 61 (53%) without a boost. Eighty patients (72%) presented T3N0 disease and 32 (28%) T3N1 disease. Concomitant capecitabine was administered in 92 cases (79%) and intravenous 5-fluorouracil in 24 cases (21%). Sphincter preservation was performed in 82% of patients in the boost arm and 66% in the no-boost arm. A higher TRG was related to a longer interval between neoadjuvant treatment and surgery (p<0.001). The probability of a TRG ≥2 was 2.5 times higher in the boost arm. A gain in local control, estimated at 4% during the first 3 years after CT-RT, favored the boost arm. CONCLUSIONS The long-term results from our single-center experience confirm literature data on the role of a sequential boost in tumor response after neoadjuvant CT-RT in a series of cT3N0-1 rectal cancer patients.
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Kang CM, Lim SB, Hong SM, Yu CS, Hong YS, Kim TW, Park JH, Kim JH, Kim JC. Prevalence and clinical significance of cellular and acellular mucin in patients with locally advanced mucinous rectal cancer who underwent preoperative chemoradiotherapy followed by radical surgery. Colorectal Dis 2016; 18:O10-6. [PMID: 26530997 DOI: 10.1111/codi.13169] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 08/15/2015] [Indexed: 02/08/2023]
Abstract
AIM The frequent presence of acellular mucin in specimens showing pathological complete response to preoperative chemoradiotherapy (CRT) and the poor response to preoperative CRT in mucinous rectal cancer have been reported. However, the prevalence and prognostic significance of cellular and acellular mucin have not been evaluated in resected specimens from patients with mucinous rectal cancer who undergo preoperative CRT. METHOD We retrospectively evaluated the clinicopathological features and prognostic significance of mucin in resected specimens from 59 consecutive patients with mucinous rectal cancer who underwent long-course CRT followed by resection between January 2000 and December 2009. Patients were categorized according to the presence of mucin, as identified by pathological analysis. The clinicopathological findings and oncological results were compared. RESULTS Mucin was identified in 25 of 59 patients with mucinous rectal cancer (42.4%). Mucin was more frequent in men (hazard ratio = 23.94, 95% confidence interval = 1.875-305.504, P = 0.015) and in specimens showing a good tumour response grade (hazard ratio = 64.26, 95% confidence interval = 6.940-595.045, P < 0.001). With a median follow-up of 67.7 (range 8.6-133.2) months, the 5-year overall survival (60.7% without mucin vs 51.4% with mucin, P = 0.898) and disease-free survival (59.9% without mucin vs 56.9% with mucin, P = 0.813) did not differ between the groups. CONCLUSION The presence of mucin in rectal cancer with mucinous differentiation after preoperative CRT and resection is associated with male gender and a good tumour response grade, without significant impact on oncological outcome.
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Affiliation(s)
- C M Kang
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - S-B Lim
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - S-M Hong
- Department of Pathology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - C S Yu
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Y S Hong
- Department of Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - T W Kim
- Department of Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - J-H Park
- Department of Radiation Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - J H Kim
- Department of Radiation Oncology, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - J C Kim
- Department of Colon and Rectal Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
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Clinical significance of cellular and acellular mucin pools in rectal carcinoma following preoperative chemoradiotherapy. Clin Transl Oncol 2015; 18:714-21. [PMID: 26474872 DOI: 10.1007/s12094-015-1422-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 09/26/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND OBJECTIVES The standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by surgery. Pathological findings remain the most significant prognostic factor. The presence of mucin pools and their prognostic significance is a controversial issue. The aim of this study was to analyze the incidence of cellular and acellular mucin pools and their clinical significance. METHODS Four-hundred and forty-six consecutive prospectively collected specimens from patients with LARC treated with long-course preoperative CRT and surgery were analyzed. Kaplan-Meier analysis was performed. RESULTS Mucin pools were present in 182 specimens (40.8 %); 66 (14.7 %) were acellular, and viable tumor cells were identified in 116 (26 %). The complete pathological response rate was 13.5 % (60 of 446). With a median follow-up of 79.0 months, the 5- and 10-year disease-free survivals for patients with acellular and cellular mucin pools were 81.5, 78.1, 63.7 and 61.2 %, respectively (p ≤ 0.026). The presence of cells in the colloid response to treatment was associated with a 17.8 and 16.9 % decrease in 5- and 10-year disease survival vs. acellular colloid response. CONCLUSIONS Our results suggest that cellular mucin pools are an indicator of an aggressive phenotype and harbingers of a worse prognosis.
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Abstract
The majority of colorectal cancers (CRCs) are classified as adenocarcinoma not otherwise specified (AC). Mucinous carcinoma (MC) is a distinct form of CRC and is found in 10-15% of patients with CRC. MC differs from AC in terms of both clinical and histopathological characteristics, and has long been associated with an inferior response to treatment compared with AC. The debate concerning the prognostic implications of MC in patients with CRC is ongoing and MC is still considered an unfavourable and unfamiliar subtype of the disease. Nevertheless, in the past few years epidemiological and clinical studies have shed new light on the treatment and management of patients with MC. Use of a multidisciplinary approach, including input from surgeons, pathologists, oncologists and radiologists, is beginning to lead to more-tailored approaches to patient management, on an individualized basis. In this Review, the authors provide insight into advances that have been made in the care of patients with MC. The prognostic implications for patients with colon or rectal MC are described separately; moreover, the predictive implications of MC regarding responses to commonly used therapies for CRC, such as chemotherapy, radiotherapy and chemoradiotherapy, and the potential for, and severity of, metastasis are also described.
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Yang Y, Huang X, Sun J, Gao P, Song Y, Chen X, Zhao J, Wang Z. Prognostic value of perineural invasion in colorectal cancer: a meta-analysis. J Gastrointest Surg 2015; 19:1113-22. [PMID: 25663635 DOI: 10.1007/s11605-015-2761-z] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 01/21/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND The prognostic value of perineural invasion (PNI) in colorectal cancer (CRC) does not reach a consensus. METHODS A comprehensive literature search for relevant reports published up to October 2014 was performed using the electronic databases: PubMed, Embase, and Web of Science. The pooled hazard ratio (HR) with 95 % confidence intervals (CI) was used to estimate the prognostic effects. RESULT Thirty-eight studies comprising 12,661 CRC patients were analyzed. Our results showed that PNI is significantly associated with poor prognosis in OS (overall survival) (HR = 2.07, 95 % CI = 1.87-2.29, P < 0.01) and DFS (disease-free survival) (HR = 2.23, 95 % CI = 1.79-2.78, P < 0.01). There was no significant prognostic difference in DFS between stage II CRC patients with PNI(+) and stage III patients (HR = 1.67, 95 % CI = 0.53-5.25, P = 0.38). Further subgroup analysis revealed that the significance of the association between PNI and worse prognosis in CRC patients is not affected by many factors, including geographic setting, PNI positive rate, treatment, TNM stage, tumor site, and quality of the study. CONCLUSIONS The meta-analysis indicates that PNI is a poor prognostic factor in CRC patients. The postoperative survival of stage II CRC patients with PNI(+) is probably more similar to that of stage III patients. Currently available adjuvant therapy should be considered in stage II CRC patients with PNI(+).
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Affiliation(s)
- Yuchong Yang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City, 110001, People's Republic of China
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Li L, Chen Z, Wang X, Zhuo S, Li H, Jiang W, Guan G, Chen J. Assessment of colloid response by nonlinear optical microscopy after preoperative radiochemotherapy for rectal carcinoma. JOURNAL OF BIOMEDICAL OPTICS 2015; 20:051009. [PMID: 25436512 DOI: 10.1117/1.jbo.20.5.051009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/23/2014] [Accepted: 10/27/2014] [Indexed: 06/04/2023]
Abstract
Colloid response is a type of tumor response that occurs after preoperative radiochemotherapy for rectal carcinoma. Given its important influence on survival, the colloid response should be considered when estimating histopathological reactions. Here, multiphoton microscopy (MPM) was applied to evaluate the colloid response ex vivo. This study demonstrated that MPM has the capability to visualize the colloid response in the absence of labels and can, in particular, identify rare residual carcinomatous cells in mucin pools. These results highlight the potential of this nonlinear optical technique as a diagnostic tool for tumor response after neoadjuvant treatment.
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Affiliation(s)
- Lianhuang Li
- Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007, China
| | - Zhifen Chen
- Fujian Medical University, The Affiliated Union Hospital, Department of Colorectal Surgery, Fuzhou 350001, China
| | - Xingfu Wang
- Fujian Medical University, The First Affiliated Hospital, Department of Pathology, Fuzhou 350001, China
| | - Shuangmu Zhuo
- Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007, China
| | - Hongsheng Li
- Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007, China
| | - Weizhong Jiang
- Fujian Medical University, The Affiliated Union Hospital, Department of Colorectal Surgery, Fuzhou 350001, China
| | - Guoxian Guan
- Fujian Medical University, The Affiliated Union Hospital, Department of Colorectal Surgery, Fuzhou 350001, China
| | - Jianxin Chen
- Institute of Laser and Optoelectronics Technology, Fujian Provincial Key Laboratory for Photonics Technology, Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Normal University, Fuzhou 350007, China
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Perineal transanal approach: a new standard for laparoscopic sphincter-saving resection in low rectal cancer, a randomized trial. Ann Surg 2015; 260:993-9. [PMID: 24950270 DOI: 10.1097/sla.0000000000000766] [Citation(s) in RCA: 127] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Laparoscopic sphincter preservation for low rectal cancer is challenging because of the high risk of positive circumferential resection margin. We hypothesized that perineal dissection of the distal rectum may improve quality of surgery, compared with the conventional abdominal dissection. METHODS Between 2008 and 2012, 100 patients with low rectal cancer (< 6 cm from the anal verge) suitable for sphincter preservation were randomized between perineal and abdominal low rectal dissection. Surgery included laparoscopic mobilization of the left colon with high rectal dissection. Distal rectal dissection was performed laparoscopically in the abdominal group and transanally in the perineal group. The primary endpoint was quality of surgery (circumferential resection margin, mesorectum grade, and lymph nodes). Secondary end points were morbidity and conversion. RESULTS The rate of positive circumferential resection margin decreased significantly after perineal compared with abdominal low rectal dissection, 4% versus 18% (P = 0.025). The mesorectum grade and the number of lymph nodes analyzed did not differ between the 2 groups. There was no difference in surgical morbidity (12% vs 14%; P = 0.766) and conversion (4% vs 10%; P = 0.436) between perineal and abdominal rectal dissection. Multivariate analysis showed that abdominal rectal dissection was the only independent factor of positive circumferential resection margin (odds ratio = 5.25; 95% confidence interval: 1.03-26.70; P = 0.046). CONCLUSIONS Perineal rectal dissection reduces the risk of positive circumferential resection margin, as compared with the conventional abdominal dissection in low rectal cancer. This suggests the perineal rectal dissection as a new standard in laparoscopic sphincter-saving resection for low rectal cancer.
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Hugen N, van de Velde CJ, Bosch SL, Fütterer JJ, Elferink MA, Marijnen CA, Rutten HJ, de Wilt JH, Nagtegaal ID. Modern Treatment of Rectal Cancer Closes the Gap Between Common Adenocarcinoma and Mucinous Carcinoma. Ann Surg Oncol 2015; 22:2669-76. [PMID: 25564178 DOI: 10.1245/s10434-014-4339-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Mucinous carcinoma (MC) is a distinct form of rectal cancer (RC) comprising 10 % of all cases and has been associated with an impaired prognosis compared with non-mucinous adenocarcinoma (AC). The benefit of today's modern treatment for MC patients is unknown but a prospective randomized trial to answer this does not seem feasible. This study provides an analysis of the modern treatment of rectal MC and efficacy of preoperative therapies for MC patients. METHODS Data from three large (trial) cohorts were used. Data from the Netherlands Cancer Registry (NCR) were used to analyze the prognosis of RC patients over time (N = 38,035). To study the benefit of preoperative short-term radiotherapy, patients from the total mesorectal excision (TME) trial (N = 1,530) were selected, and the benefit from preoperative chemoradiotherapy was analyzed with data on 540 locally advanced RC (LARC) patients from two hospitals. RESULTS Data from the NCR confirmed that 5-year overall survival for MC was significantly worse from 1989 to 1998, but no longer different from AC from 1999 onwards. MC patients had a higher rate of positive circumferential resection margin than AC patients (TME trial 27.2 vs. 16.5 %, p = 0.006; LARC cohort 34.5 vs. 9.8 %, p < 0.0001), but there was no difference in outcome between MC and AC patients after preoperative short-term radiotherapy or chemoradiotherapy. CONCLUSIONS Modern treatment of RC has benefited MC patients, leading to equal survival for MC and AC patients. Enhancements in the fields of imaging and quality of surgery have improved outcome and preoperative therapies should be recommended for both histological subtypes.
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Affiliation(s)
- Niek Hugen
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands,
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40
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Bhatti ABH, Akbar A, Khattak S, Kazmi AS, Jamshed A, Syed AA. Impact of acellular mucin pools on survival in patients with complete pathological response to neoadjuvant treatment in rectal cancer. Int J Surg 2014; 12:1123-1126. [PMID: 25072703 DOI: 10.1016/j.ijsu.2014.07.267] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2014] [Accepted: 07/22/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Rarely, patients with pathological complete response (PCR) after neoadjuvant chemoradiotherapy demonstrate acellular mucin pools. The prognostic significance of this finding is controversial. The objective of this study was to determine impact of acellular mucin pools on disease free and overall survival in patients with complete pathological response to neoadjuvant chemoradiotherapy in rectal cancer. METHODS One hundred and seventy two patients received neoadjuvant chemoradiotherapy for rectal cancer and underwent surgery. Patients were divided into two groups based on presence of acellular mucin pools. Locoregional failures, distant failures and deaths were compared. Expected 5 year disease free and overall survival was calculated. RESULTS Median follow-up was 36(4-94) months. Complete pathological response was identified in 35(20.3%) patients. Of these, 12(34.2%) had acellular mucin pools in resected specimen. Majority of mucin negative tumors were moderately differentiated (78% vs 25%) (P = 0.005). Median overall survival for mucin positive and mucin negative tumors was 4(1.3-5.7) and 3.3(0.1-6.3) years respectively. Expected 5 year disease free and overall survival for mucin positive and mucin negative tumors was 73% and 89% (P = 0.1) and 75% and 87% (P = 0.4). CONCLUSION Acellular mucin pools in rectal cancer following a PCR to neoadjuvant treatment do not impact survival.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan.
| | - Ali Akbar
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Shahid Khattak
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Ather Saeed Kazmi
- Department of Medical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Aarif Jamshed
- Department of Radiation Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Aamir Ali Syed
- Department of Surgical Oncology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
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Swellengrebel HAM, Bosch SL, Cats A, Vincent AD, Dewit LGH, Verwaal VJ, Nagtegaal ID, Marijnen CAM. Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: a near pathologic complete response does not translate into good clinical outcome. Radiother Oncol 2014; 112:44-51. [PMID: 25018000 DOI: 10.1016/j.radonc.2014.05.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Revised: 04/02/2014] [Accepted: 05/04/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum. AIM The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients. METHODS Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6-8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators. RESULTS The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators. CONCLUSION The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that "watch-and-wait" in LARC patients should be applied with care.
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Affiliation(s)
- Hendrik A M Swellengrebel
- Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Steven L Bosch
- Department of Pathology, Radboud University Nijmegen Medical Centre, The Netherlands
| | - Annemieke Cats
- Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Andrew D Vincent
- Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Luc G H Dewit
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Vic J Verwaal
- Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Nijmegen Medical Centre, The Netherlands
| | - Corrie A M Marijnen
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Clinical Oncology, Leiden University Medical Centre, The Netherlands.
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Hwang MR, Park JW, Park S, Yoon H, Kim DY, Chang HJ, Kim SY, Park SC, Choi HS, Oh JH, Jeong SY. Prognostic impact of circumferential resection margin in rectal cancer treated with preoperative chemoradiotherapy. Ann Surg Oncol 2014; 21:1345-51. [PMID: 24468928 DOI: 10.1245/s10434-014-3484-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND The circumferential resection margin (CRM) is a strong prognostic factor in rectal cancer. The purpose of this study was to investigate the relationship between CRM distance and recurrence in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy (CRT). METHODS We analyzed data for 561 patients who underwent preoperative CRT and curative surgery for locally advanced rectal cancer between August 2001 and December 2008. CRM was divided into four groups: group 1, CRM > 2 mm; group 2, 1.1-2.0 mm; group 3, 0.1-1.0 mm; and group 4, 0 mm. We assessed the associations of CRM with local recurrence and disease-free survival. RESULTS Groups 1, 2, 3, and 4 comprised 487, 36, 20, and 18 patients, respectively. The local recurrence rate was highest and the disease-free survival rate was lowest in group 4, followed by groups 3, 2, and 1. Survival was similar between groups 2 and 1. Local recurrence rates were lower in groups 3, 2, and 1 than in group 4 [hazard ratio (HR) 0.28, 95 % confidence interval (CI) 0.09-0.91, P = 0.035; HR 0.11, 95 % CI 0.03-0.46, P = 0.002; HR 0.18, 95 % CI 0.08-0.42, P < 0.0001, respectively]. Disease-free survival rates were higher in groups 3, 2, and 1 than in group 4 (HR 0.32, 95 % CI 0.13-0.75, P = 0.009; HR 0.24, 95 % CI 0.10-0.54, P = 0.001; HR 0.26, 95 % CI 0.14-0.48, P < 0.0001, respectively). CONCLUSIONS After preoperative CRT, CRM distance provides useful information for risk stratification in the recurrence of rectal cancer.
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Affiliation(s)
- Mi Ri Hwang
- Center for Colorectal Cancer, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do, Korea
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Yu SKT, Chand M, Tait DM, Brown G. Magnetic resonance imaging defined mucinous rectal carcinoma is an independent imaging biomarker for poor prognosis and poor response to preoperative chemoradiotherapy. Eur J Cancer 2014; 50:920-7. [PMID: 24440086 DOI: 10.1016/j.ejca.2013.12.007] [Citation(s) in RCA: 80] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 12/05/2013] [Accepted: 12/09/2013] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Mucinous adenocarcinomas represent a potentially poor prognostic subgroup identifiable by imaging. We compared outcomes between magnetic resonance imaging (MRI) detected rectal mucinous carcinoma and adenocarcinomas. The diagnostic performance of MRI compared with initial biopsy in detecting mucinous adenocarcinoma was also assessed. METHODS The proportion of patients downstaged in the mrMucinous and adenocarcinoma groups was compared. Cox proportional hazard models were used to test independence of mucinous status and baseline MRI and clinical variables on survival. Differences in survival for mucinous versus non-mucinous tumours were tested for significance using the Mantel-Cox log rank test. RESULTS 60/330 (18%) patients were correctly diagnosed with mucinous rectal cancer based on pre treatment MRI compared with 15/330 (5%) on initial biopsy (diagnostic odds ratio=4.67, p<0.05). All 60 (100%) patients undergoing surgery for mrMucinous tumours were confirmed as such on final histopathology. Significantly fewer mrMucinous tumours showed ypT downstaging when compared with non-mucinous tumours (14/60 (23%) versus 111/270 (40%), p=0.01). Three-year survival outcomes for patients for MRI detected mucinous tumours were significantly worse: disease free survival (DFS) was 48% versus 71%, p=0.006 and OS was 69% versus 79% p=0.04. MRI Mucin was an independent variable for poor DFS (hazard ratios (HR)) 0.58 95% Confidence interval (CI) 0.38-0.89). CONCLUSIONS MRI diagnosis of mucinous adenocarcinoma is diagnostically superior to preoperative biopsy and occurs in up to 20% of rectal cancer patients. It is an independent imaging biomarker for response to preoperative chemoradiotherapy (CRT) and prognosis. MRI documentation of mucinous status will enable future pursuit of treatment strategies in this poor prognostic subgroup.
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Affiliation(s)
- Stanley K T Yu
- Radiotherapy Department, Royal Marsden NHS Foundation Trust, Sutton/London, United Kingdom
| | - Manish Chand
- Colorectal Research Fellow, Department of Colorectal Surgery, Croydon University Hospital, Croydon CR7 7YE, United Kingdom; Radiology Department, Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Diana M Tait
- Radiotherapy Department, Royal Marsden NHS Foundation Trust, Sutton/London, United Kingdom
| | - Gina Brown
- Radiology Department, Royal Marsden NHS Foundation Trust, London, United Kingdom.
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Maggiori L, Bretagnol F, Aslam MI, Guedj N, Zappa M, Ferron M, Panis Y. Does pathologic response of rectal cancer influence postoperative morbidity after neoadjuvant radiochemotherapy and total mesorectal excision? Surgery 2013; 155:468-75. [PMID: 24439750 DOI: 10.1016/j.surg.2013.10.020] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Accepted: 10/17/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND A pathologic complete response (pCR) can be observed in up to 25% of patients after preoperative chemoradiotherapy for rectal cancer and is associated with an improved long-term prognosis. However, few data are available regarding the effect of pCR on postoperative morbidity. This study aimed to assess the impact of the pCR on postoperative outcomes after laparoscopic total mesorectal excision (TME). METHODS A prospectively maintained database (2006-2011) was reviewed for all consecutive patients (n = 143) undergoing laparoscopic TME for mid or low rectal cancer after neoadjuvant chemoradiotherapy. Postoperative data were compared for pCR-group and non-pCR-group. A pCR was defined as the absence of gross and microscopic tumor in the specimen, irrespective of the nodal status (ypT0). RESULTS Thirty-three patients (23%) had a pCR. Median operating time was greatly shorter in the pCR-group (230 minutes, 180-360), compared with the non-pCR-group (240 minutes, 130-420, P = .02). Lymph node involvement was noted for 12% of the patients in the pCR-group and 33% of the patients in the non-pCR-group (P = .91). Clavien Dindo grade 3 and 4 complications (6% vs 22%, P = .04), infection related morbidity (47% vs 76%, P = .04), and clinical anastomotic leakage rates (9% vs 29%, P = .02) were lesser in the pCR group compared with the non-pCR group. Mean duration of hospital stay was lesser in the pCR-group (9 vs 12 days, P = .01). CONCLUSION This study showed that Clavien Dindo grade 3 and 4 complications, including anastomosis leakage, and infection related complications rates were lesser in patients with pathologic complete response after RCT and laparoscopic TME for rectal cancer.
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Affiliation(s)
- Léon Maggiori
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Frédéric Bretagnol
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Muhammad I Aslam
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France; Department of Cancer Studies and Molecular Medicine, University of Leicester, University Hospitals of Leicester NHS Trust, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, UK
| | - Nathalie Guedj
- Department of Pathology, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Magaly Zappa
- Department of Radiology, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Marianne Ferron
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France
| | - Yves Panis
- Department of Colorectal Surgery, Pôle des Maladies de l'Appareil Digestif (PMAD), Beaujon Hospital (AP-HP), 100 boulevard du Général Leclerc, 92118 Clichy, France.
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Prevalence and clinical significance of acellular mucin in locally advanced rectal cancer patients showing pathologic complete response to preoperative chemoradiotherapy. Am J Surg Pathol 2013; 37:47-52. [PMID: 23060350 DOI: 10.1097/pas.0b013e3182657186] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Occasionally, patients with locally advanced rectal adenocarcinoma who receive preoperative chemoradiotherapy (CRT) show acellular mucin in resection specimens that had shown pathologic complete response (pCR), but the clinical and prognostic significance of this finding has been controversial. This study analyzed data from 217 consecutive patients showing pCR to preoperative CRT followed by resection to evaluate the clinicopathologic features and prognostic significance of acellular mucin. Patients were categorized according to the presence of acellular mucin, as identified by pathologic analysis. The clinicopathologic findings and oncologic results were compared. Acellular mucins were identified in 35 (16.1%) of 217 pCR patients. Acellular mucins were found predominantly in male patients (20.8% vs. 9.8%, P=0.039) and in those with mucinous/signet ring cell differentiation (66.7% vs. 15.1%, P=0.008). The presence of acellular mucin was more frequent in patients with a shorter (<42 d) CRT-operation interval (22.6% vs. 10.3%, P=0.017). With a mean follow-up of 41 months (range, 2 to 119 mo), the 3-year overall survival (96.8% with mucin vs. 95.9% without mucin, P=0.314) and the 3-year disease-free survival (97.0% with mucin vs. 93.0% without mucin, P=0.131) did not differ between the groups. The presence of acellular mucin in rectal cancer patients showing pCR to preoperative CRT is associated with male sex and mucinous differentiation and does not have a significant impact on oncologic outcomes. Acellular mucins are also associated with the CRT-operation interval as a phenomenon of time-dependent response to CRT.
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Predictive factors of positive circumferential resection margin after radiochemotherapy for rectal cancer: The French randomised trial ACCORD12/0405 PRODIGE 2. Eur J Cancer 2013; 49:82-9. [DOI: 10.1016/j.ejca.2012.06.028] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Revised: 05/08/2012] [Accepted: 06/23/2012] [Indexed: 02/03/2023]
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47
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Shia J, Klimstra DS, Bagci P, Basturk O, Adsay NV. TNM staging of colorectal carcinoma: issues and caveats. Semin Diagn Pathol 2012; 29:142-53. [PMID: 23062421 DOI: 10.1053/j.semdp.2012.02.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The TNM staging system of the American Joint Committee on Cancer and the Union for International Cancer Control provides the most reliable guidelines for the prognostication and treatment of colorectal carcinoma. However, issues and caveats exist in the application of this system, mostly relating to the definition of the staging parameters and the pathologic interpretation of the gross and microscopic findings of the resected specimens. This article highlights some of the major issues in both areas. First, it assesses the definition of selected staging parameters, including pTis, pT4a versus pT4b, tumor deposits/N1c, ypT/ypN, and the TNM for rectal versus anal carcinoma. Second, it discusses major problematic areas in the pathologic interpretation of "pseudoinvasion" versus true invasion, deep pT2 versus superficial pT3, serosal involvement, radial margin, total mesorectal excision specimens, and postneoadjuvant chemoradiation rectal resections. The article also provides a brief discussion about some of the major adjunct histopathologic prognostic factors, such as medullary-type histology and tumor differentiation.
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Affiliation(s)
- Jinru Shia
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
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48
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MRI after treatment of locally advanced rectal cancer: how to report tumor response--the MERCURY experience. AJR Am J Roentgenol 2012; 199:W486-95. [PMID: 22997398 DOI: 10.2214/ajr.11.8210] [Citation(s) in RCA: 145] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The Magnetic Resonance Imaging and Rectal Cancer European Equivalence (MERCURY) Study validated the use of MRI for posttreatment staging and its correlation with survival outcomes. As a consequence, reassessment of MRI scans after preoperative therapy has implications for surgical planning, the timing of surgery, sphincter preservation, deferral of surgery for good responders, and development of further preoperative treatments for radiologically identified poor responders. CONCLUSION In this article we report a validated systematic approach to the interpretation of MR images of patients with rectal cancer after chemoradiation.
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49
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Tumor invasion of muscular vessels predicts poor prognosis in patients with pancreatic ductal adenocarcinoma who have received neoadjuvant therapy and pancreaticoduodenectomy. Am J Surg Pathol 2012; 36:552-9. [PMID: 22301496 DOI: 10.1097/pas.0b013e318240c1c0] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Lymphovascular invasion (LVI) is a prognostic factor in many types of human malignancies, including pancreatic ductal adenocarcinoma (PDAC). However, the prognostic significance of LVI in patients with PDAC who have received neoadjuvant therapy and pancreaticoduodenectomy is unclear. In this study, we analyzed LVI in 212 patients who had received neoadjuvant chemoradiation and subsequent pancreaticoduodenectomy at our institution between January 1999 and December 2007. LVI was present in 61.8% (131/212) of the patients. Of the 131 patients who were positive for LVI, 67 (31.6%) had tumor invasion into lymphovascular spaces without muscle layer (nonmuscular lymphovascular spaces), and 64 (30.2%) had tumor invasion into muscular vessels. Tumor invasion into muscular vessels correlated with higher frequencies of positive resection margin, lymph node metastasis, and locoregional/distant recurrence. Patients with tumor invasion into muscular vessels had significantly shorter disease-free survival and overall survival than did patients who had no LVI or who had tumor invasion of nonmuscular lymphovascular spaces (P<0.01). Tumor invasion into muscular vessels is an independent prognostic factor in patients with PDAC who have received neoadjuvant therapies. Our results showed that tumor invasion into muscular vessels plays an important role in the progression of PDAC and in predicting prognosis in this group of patients.
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50
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Poultsides GA, Bao F, Servais EL, Hernandez-Boussard T, DeMatteo RP, Allen PJ, Fong Y, Kemeny NE, Saltz LB, Klimstra DS, Jarnagin WR, Shia J, D'Angelica MI. Pathologic response to preoperative chemotherapy in colorectal liver metastases: fibrosis, not necrosis, predicts outcome. Ann Surg Oncol 2012; 19:2797-804. [PMID: 22476753 DOI: 10.1245/s10434-012-2335-1] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2011] [Indexed: 01/25/2023]
Abstract
BACKGROUND Pathologic response to preoperative chemotherapy for colorectal liver metastases (CLM) is associated with survival after hepatectomy. Histologically, dominant response patterns include fibrosis, necrosis and/or acellular mucin, but some of these changes can appear without previous chemotherapy and their individual correlation with outcome is unknown. METHODS Pathology slides from patients who underwent CLM resection (irrespective of preoperative chemotherapy status) were rereviewed by a blinded pathologist. Pathologic response was recorded as the summation of percentage necrosis, fibrosis and acellular mucin. Associations between pathologic response, its components, preoperative chemotherapy, and survival were analyzed. RESULTS Pathology slides were rereviewed in 366 patients undergoing CLM resection from 2003 to 2007. Preoperative chemotherapy was administered in 249 (68 %) patients, who, when compared to no preoperative chemotherapy patients, had higher rates of overall pathologic response (57 vs. 46 %, P < .01), fibrosis (21 vs. 12 %, P < .01) and acellular mucin (6 vs. 3 %, P = .05) but similar rates of necrosis (30 vs. 31 %, P = .30). In patients receiving preoperative chemotherapy, overall pathologic response ≥ 75 % (5 year, 83 vs. 47 %, P < .01) and fibrosis ≥ 40 % (5 year, 87 vs. 51 %, P < .01) independently correlated with disease-specific survival after hepatectomy. Preoperative hepatic artery infusion chemotherapy (P = .04) and bevacizumab (P = .05) were marginally associated with overall pathologic response and fibrosis, respectively. CONCLUSIONS Fibrosis is the predominant chemotherapy-related pathologic alteration driving the association of treatment response with survival after CLM resection. Necrosis in CLM is not related to chemotherapy or outcome.
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Affiliation(s)
- George A Poultsides
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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