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Araruna GF, Ribeiro HSC, Torres SM, Diniz AL, Godoy AL, Farias IC, Costa WL, Coimbra FJF. Impact of Minimally Invasive Surgery on Early and Late Outcomes of Patients With Gastric Cancer Treated Using Neoadjuvant Chemotherapy. J Surg Oncol 2024. [PMID: 39295557 DOI: 10.1002/jso.27904] [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: 04/01/2024] [Revised: 08/28/2024] [Accepted: 09/04/2024] [Indexed: 09/21/2024]
Abstract
BACKGROUND Gastric cancer is the fifth most common neoplasm and the third leading cause of cancer-related death worldwide. Neoadjuvant chemotherapy is recommended for Stages II-III resectable tumors, but the comparative effectiveness of minimally invasive surgery (MIS) versus open gastrectomy (OG) post-neoadjuvant therapy has not been adequately investigated. METHODS A retrospective cohort analysis was performed on patients with clinical Stage II and III gastric adenocarcinoma who underwent neoadjuvant chemotherapy followed by either MIS or OG between 2007 and 2020. Propensity score matching was utilized to compare the clinical and surgical outcomes, morbidity, and mortality, and the influence of MIS on 3-year survival rates was evaluated. RESULTS After matching, no statistical differences in clinical aspects were noted between the two groups. MIS was associated with increased D2 lymphadenectomy, curative intent, and complete neoadjuvant therapy. Furthermore, this therapeutic approach resulted in reduced transfusion rates and shorter hospital stays. Nonetheless, no significant differences were observed in global, clinical, or surgical complications or mortality between the two groups. Weight loss emerged as a significant risk factor for complications, but MIS did not independently affect survival rates. Extended resection and higher American Society of Anesthesiology scores were independent predictors of reduced survival. CONCLUSION MIS after neoadjuvant chemotherapy for gastric cancer appears to be a viable option, with oncological outcomes comparable to those of OG, less blood loss, and shorter hospital stays. Although MIS did not independently affect long-term survival, it offered potential benefits in terms of postoperative recovery and morbidity. Further studies are needed to validate these findings, especially across diverse populations.
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Affiliation(s)
| | - Heber S C Ribeiro
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - Silvio M Torres
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - Alessandro L Diniz
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - André L Godoy
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - Igor C Farias
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
| | - Wilson L Costa
- Department of Medicine, Epidemiology, and Population Sciences, Dan L Duncan Comprehensive, Cancer Center, Baylor College of Medicine, Houston, Texas, USA
| | - Felipe J F Coimbra
- Department of Abdominal Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil
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Kano Y, Ichikawa H, Aizawa M, Muneoka Y, Usui K, Hanyu T, Ishikawa T, Yabusaki H, Kobayashi K, Kuwabara S, Makino S, Kawachi Y, Miura K, Tajima Y, Shimada Y, Sakata J, Wakai T. Macroscopic type is implicated in the prognostic impact of initial chemotherapy on peritoneal lavage cytology-positive gastric cancer with no other noncurative factors. Int J Clin Oncol 2024; 29:790-800. [PMID: 38512543 DOI: 10.1007/s10147-024-02496-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 02/19/2024] [Indexed: 03/23/2024]
Abstract
BACKGROUND Initial chemotherapy (Initial-C) followed by surgery is a promising treatment strategy for peritoneal lavage cytology-positive gastric cancer (CY1 GC) with no other noncurative factors. The aim of this study was to investigate the survival advantage of Initial-C compared to initial surgery (Initial-S) for this disease according to the macroscopic type, which was associated with prognosis and the efficacy of chemotherapy in GC. METHODS One hundred eighty-nine patients who were diagnosed with CY1 GC with no other noncurative factors at four institutions from January 2007 to December 2018 were enrolled. The patients were divided into a macroscopic type 4 group (N = 48) and a non-type 4 group (N = 141). The influence of initial treatment on overall survival (OS) in each group was evaluated. RESULTS In the type 4 group, the 5-year OS rates of Initial-C (N = 35) and Initial-S (N = 13) were 11.6% and 0%, respectively (P = 0.801). The multivariate analysis could not show the survival advantage of Initial-C. In the non-type 4 group, the 5-year OS rates of Initial-C (N = 41) and Initial-S (N = 100) were 48.4% and 29.0%, respectively (P = 0.020). The multivariate analysis revealed that Initial-C was independently associated with prolonged OS (hazard ratio, 0.591; 95% confidence interval, 0.375-0.933: P = 0.023). CONCLUSIONS Initial-C improves the prognosis of non-type 4 CY1 GC with no other noncurative factors. On the other hand, further development of effective chemotherapeutic regimens and innovative treatment strategies are required for type 4 CY1 GC.
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Affiliation(s)
- Yosuke Kano
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Hiroshi Ichikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
| | - Masaki Aizawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2‑15‑3 Kawagishi‑cho, Chuo‑ku, Niigata, 951‑8566, Japan
| | - Yusuke Muneoka
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Kenji Usui
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Takashi Ishikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Hiroshi Yabusaki
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, 2‑15‑3 Kawagishi‑cho, Chuo‑ku, Niigata, 951‑8566, Japan
| | - Kazuaki Kobayashi
- Department of Digestive Surgery, Niigata City General Hospital, 463‑7 Shumoku, Chuo‑ku, Niigata, 950‑1197, Japan
| | - Shirou Kuwabara
- Department of Digestive Surgery, Niigata City General Hospital, 463‑7 Shumoku, Chuo‑ku, Niigata, 950‑1197, Japan
| | - Shigeto Makino
- Department of Surgery, Nagaoka Chuo General Hospital, 2041 Kawasaki‑cho, Nagaoka, Niigata, 940‑0861, Japan
| | - Yasuyuki Kawachi
- Department of Surgery, Nagaoka Chuo General Hospital, 2041 Kawasaki‑cho, Nagaoka, Niigata, 940‑0861, Japan
| | - Kohei Miura
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Yosuke Tajima
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Yoshifumi Shimada
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Jun Sakata
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan
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ARHGAP-RhoA signaling provokes homotypic adhesion-triggered cell death of metastasized diffuse-type gastric cancer. Oncogene 2022; 41:4779-4794. [PMID: 36127398 DOI: 10.1038/s41388-022-02469-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 11/09/2022]
Abstract
Genetic alteration of Rho GTPase-activating proteins (ARHGAP) and GTPase RhoA is a hallmark of diffuse-type gastric cancer and elucidating its biological significance is critical to comprehensively understanding this malignancy. Here, we report that gene fusions of ARHGAP6/ARHGAP26 are frequent genetic events in peritoneally-metastasized gastric and pancreatic cancer. From the malignant ascites of patients, we established gastric cancer cell lines that spontaneously gain hotspot RHOA mutations or four different ARHGAP6/ARHGAP26 fusions. These alterations critically downregulate RhoA-ROCK-MLC2 signaling, which elicits cell death. Omics and functional analyses revealed that the downstream signaling initiates actin stress fibers and reinforces intercellular junctions via several types of catenin. E-cadherin-centered homotypic adhesion followed by lysosomal membrane permeabilization is a pivotal mechanism in cell death. These findings support the tumor-suppressive nature of ARHGAP-RhoA signaling and might indicate a new avenue of drug discovery against this refractory cancer.
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Cieśla S, Lisiecki R, Ławnicka A, Kudliński B, Ostrowska P, Davì A, Veroux M, Murawa D. Clinical Significance of Peritoneal Fluid Examination for Free Cancer Cells in Patients Qualified for Surgery for Gastric Cancer. Front Surg 2021; 8:685868. [PMID: 34235174 PMCID: PMC8255366 DOI: 10.3389/fsurg.2021.685868] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Accepted: 05/24/2021] [Indexed: 12/27/2022] Open
Abstract
Background: Peritoneal lavage cytology in patients with gastric cancer may correlate with an unfavorable prognosis. This study evaluated the presence of free cancer cells in the peritoneal lavage of a population of patients with gastric cancer and its correlation with the outcome of surgical treatment. Methods: One hundred patients diagnosed with gastric or gastrointestinal junction adenocarcinoma underwent surgery. In all patients, a cytological and immunohistochemical analysis of peritoneal lavage was performed. Based on the presence of free cancer cells (fcc) at the cytological and immunohistochemical examination of peritoneal lavage, patients undergoing surgery for gastric cancer were divided into two groups: fcc (+) and fcc (–). Results: A total of 100 patients, 37 women, and 63 men with a median age of 65 years were included in the study. In the entire study group, 16 (16%) patients were positive for the presence of free cancer cells (fcc +) at peritoneal lavage examination. However, in the group of patients who underwent gastrectomy, fcc (+) was found in 10 out of 77 (13%) patients. The presence of cancer cells in peritoneal lavage was a strong predictive factor in an unfavorable outcome after surgery, and 1-year and 2-year patient survival was 34 and 0% in fcc (+) patients and 79 and 59% in fcc (–), respectively. Moreover, the presence of free cancer cells was associated with a five-fold increased risk of death within 2 years after surgery. When analyzing the group of patients undergoing R0/R1 surgery, this difference was even more significant (p < 0.0001). Conclusions: The presence of free cancer cells in peritoneal lavage may significantly affect the outcome of patients with gastric cancer. Radical surgery in patients with free cancer cells in the peritoneal lavage did not result in a survival advantage. Identification of free cancer cells could help for a better stratification of gastric cancer patients, identifying those patients who could better benefit from a radical surgical treatment, finally improving long-term survival.
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Affiliation(s)
- Sławomir Cieśla
- General and Oncological Surgery Clinic of the K. Marcinkowski University Hospital in Zielona Góra, Zielona Góra, Poland
| | - Radosław Lisiecki
- Department of General and Oncological Surgery of the Medical Centre in Pleszew, Pleszew, Poland
| | - Agnieszka Ławnicka
- General and Oncological Surgery Clinic of the K. Marcinkowski University Hospital in Zielona Góra, Zielona Góra, Poland
| | - Bartosz Kudliński
- Department of Anaesthesiology, Intensive Care and Emergency Medicine at Collegium Medicum of the University of Zielona Góra, Zielona Góra, Poland
| | - Paulina Ostrowska
- Department of Oncology of the Medical Centre in Pleszew, Pleszew, Poland
| | - Alberto Davì
- Vascular and Endovascular Surgery Unit, Cuneo, Italy
| | - Massimiliano Veroux
- General Surgery Unit, Department of Medical and Surgical Sciences and Advanced Technologies University Hospital of Catania, Catania, Italy
| | - Dawid Murawa
- General and Oncological Surgery Clinic of the K. Marcinkowski University Hospital in Zielona Góra, Zielona Góra, Poland.,Department of Surgery and Oncology, Faculty of Medicine and Health Sciences of the University of Zielona Góra, Zielona Góra, Poland
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Strandby RB, Svendsen LB, Ambrus R, Rostved AA, Hasselby JP, Achiam MP. The Incidence of Free Peritoneal Tumor Cells before and after Neoadjuvant Chemotherapy in Gastroesophageal Junction Cancer. J Cytol 2019; 37:40-45. [PMID: 31942097 PMCID: PMC6947737 DOI: 10.4103/joc.joc_164_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 03/01/2019] [Accepted: 10/24/2019] [Indexed: 01/07/2023] Open
Abstract
Context The utility of peritoneal washing cytology in patients with gastroesophageal junction cancer has not been thoroughly evaluated. Aims The study aimed to determine the incidence of free peritoneal tumor cells by peritoneal washing cytology before and after neoadjuvant chemotherapy using conventional cytopathological methods and immunohistochemical staining for the analysis of peritoneal washings. Settings and Design A prospective study conducted at a single tertiary referral hospital. Materials and Methods Patients with gastroesophageal junction cancer and without suspicion of intra- or extraabdominal metastases before the staging laparoscopy were prospectively and consecutively enrolled. Peritoneal washing cytology was performed at staging laparoscopy (primary cytology) and after neoadjuvant chemotherapy during robot-assisted or open resection (secondary cytology). Peritoneal fluid samples were analyzed by conventional cytology and an immunohistochemical panel. Results Overall, 81 patients met the primary inclusion criteria. During primary cytology, positive cytology without overt metastases (C1M0) was detected in three patients (3.8%) while five patients (6.3%) had overt intra-abdominal metastases but negative cytology (C0M1). None of the patients with C1M0 underwent surgery due to extra-abdominal (n = 1) or intra-abdominal metastases (n = 2), and the overall survival was 4, 7, and 14 months. During secondary cytology, no patients with free peritoneal tumor cells were identified, but seven patients were classified as C0M1 (10.9%). Conclusions The incidence of C1M0 was 3.8% and 0% before and after neoadjuvant chemotherapy, respectively in patients with gastroesophageal junction cancer. Free peritoneal tumor cells were not identified in several patients with intra-abdominal metastases suggesting that peritoneal washing cytology with conventional cytology and immunohistochemical staining lack sensitivity.
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Affiliation(s)
- Rune B Strandby
- Department of Surgical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Lars B Svendsen
- Department of Surgical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Rikard Ambrus
- Department of Surgical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Andreas A Rostved
- Department of Surgical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Jane P Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
| | - Michael P Achiam
- Department of Surgical Gastroenterology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark
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Fukagawa T. Role of staging laparoscopy for gastric cancer patients. Ann Gastroenterol Surg 2019; 3:496-505. [PMID: 31549009 PMCID: PMC6749947 DOI: 10.1002/ags3.12283] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2019] [Revised: 07/26/2019] [Accepted: 07/29/2019] [Indexed: 12/16/2022] Open
Abstract
Staging laparoscopy (SL) is frequently carried out in patients with advanced gastric cancer. However, some clinical questions are being debated and consensus must be obtained. With this aim, a literature search of PubMed/MEDLINE was carried out using the keywords "gastric cancer," "SL," and "diagnostic laparoscopy". Articles published online up to February 2019 were analyzed, focusing on the following questions. (i) What is an adequate indication for SL? (ii) How do you carry out SL? (iii) Does SL provide accurate information about peritoneal dissemination? (iv) Is the yield of SL different by tumor location? (v) Is SL a safe procedure? (vi) Is "repeat SL" needed? (vii) Does SL provide oncological benefit? Results provided the following responses: (i) In Western countries, clinically resectable advanced tumor is an indication for SL. Terms to be introduced for adequate indication include "location," "type 4 (linitis feature)," "large tumor," "equivocal computed tomography (CT] findings," and "lymph node swelling". (ii) Exploration of the entire peritoneal cavity is preferable. (iii) Detection rate of peritoneal disease is 43%-52% in Japanese institutions and 7.8%-40% in other countries. False-negative findings during SL were 0%-17%, and 10%-13% when limited to cytology. (iv) Yield of SL was higher in gastric cancer compared with esophagogastric junctional tumor. (v) SL-related complications were estimated to occur in 0.4%. (vi) Repeat SL is important after treatment. (vii) If the efficacy of neoadjuvant chemotherapy for patients with P0CY1 is established, SL can provide oncological benefit. SL can be carried out safely and effectively. Considering the prevalence of neoadjuvant treatment, the role of SL will become more important.
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Affiliation(s)
- Takeo Fukagawa
- Department of SurgerySchool of MedicineTeikyo UniversityTokyoJapan
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Endo S, Ikenaga M, Ohta K, Ueda M, Tsuda Y, Kato R, Itakura H, Matsuyama J, Nishikawa K, Yamada T. Prognostic factors for cytology-positive gastric cancer. Surg Today 2019; 49:56-64. [PMID: 30167924 DOI: 10.1007/s00595-018-1704-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 07/19/2018] [Indexed: 12/27/2022]
Abstract
PURPOSE Positive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed. METHODS The participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses. RESULTS The operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2-3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2-3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses. CONCLUSIONS The prognoses of CY1 gastric cancer patients with cN2-3 or PNI < 40 were poor, even after gastrectomy.
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Affiliation(s)
- Shunji Endo
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Masakazu Ikenaga
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Katsuya Ohta
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Masami Ueda
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Yujiro Tsuda
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Ryo Kato
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Hiroaki Itakura
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan
| | - Jin Matsuyama
- Department of Surgery, Yao Municipal Hospital, Osaka, Japan
| | - Kazuhiro Nishikawa
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Terumasa Yamada
- Department of Gastroenterological Surgery, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan.
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Kodera Y. Surgery with curative intent for stage IV gastric cancer: Is it a reality of illusion? Ann Gastroenterol Surg 2018; 2:339-347. [PMID: 30238074 PMCID: PMC6139716 DOI: 10.1002/ags3.12191] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 06/13/2018] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer with metastases outside of the regional lymph nodes is deemed oncologically unresectable. Nevertheless, some metastatic lesions are technically resectable by applying established surgical techniques such as para-aortic lymphadenectomy and hepatectomy. At the time of compilation of the Japanese gastric cancer treatment guidelines version 4, systematic reviews were conducted to see whether it is feasible to make any recommendation to dissect both the primary and metastatic lesions with intent to cure, possibly as part of multimodality treatment. Long-term survivors were found among carefully selected groups of patients both in prospective and retrospective studies. In addition, there is a growing list of publications reporting encouraging outcomes of gastrectomy conducted after exceptionally good response to chemotherapy, usually among patients who underwent R0 resection. This type of surgery is often referred to as conversion surgery. It is sometimes difficult to define a clear borderline between curative surgery scheduled after neoadjuvant chemotherapy and the conversion surgery. This review summarizes what we knew after the literature reviews conducted at the time of compiling the Japanese guidelines and in addition reflects some new findings obtained thereafter through clinical trials and retrospective studies. Metastases were divided into three categories based on the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each of these categories, there were findings that could provide hope for patients with metastatic disease. These findings implied that the surgical technique that we already use could become more useful upon further developments in antineoplastic agents and drug delivery.
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Affiliation(s)
- Yasuhiro Kodera
- Department of Gastroenterological SurgeryNagoya University Graduate School of MedicineNagoyaAichiJapan
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Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol 2018; 44:1805-1810. [PMID: 30087071 DOI: 10.1016/j.ejso.2018.06.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/23/2018] [Accepted: 06/27/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.
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Jamel S, Markar SR, Malietzis G, Acharya A, Athanasiou T, Hanna GB. Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis. Gastric Cancer 2018; 21:10-18. [PMID: 28779261 PMCID: PMC5741790 DOI: 10.1007/s10120-017-0749-y] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/16/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis. METHODS An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease. RESULTS Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77-4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31-0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56-0.73; P < 0.0001). CONCLUSION This study suggests that patients with initial positive cytology may have a good prognosis following neoadjuvant treatment if the cytology results change to negative after treatment.
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Affiliation(s)
- Sara Jamel
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
| | - Sheraz R. Markar
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
| | - George Malietzis
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
| | - Amish Acharya
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
| | - Thanos Athanasiou
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
| | - George B. Hanna
- Department of Surgery and Cancer, Imperial College London, 10th Floor QEQM Building, St Mary’s Hospital, South Wharf Road, London, W2 1NY UK
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12
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Yarema R. Gastric cancer with high risk of intraperitoneal progression: clinical course and current treatments. CURRENT ISSUES IN PHARMACY AND MEDICAL SCIENCES 2017; 30:190-194. [DOI: 10.1515/cipms-2017-0036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2023] Open
Abstract
Abstract
Locally advanced gastric cancer with a high risk of intraperitoneal progression is characterized by poor prognosis. After radical surgery, most patients die during the first two years post-operation as a result of disease progression. The prevailing type of progression and the leading cause of death in patients with gastric cancer is implantation metastasis.
The main risk factors for peritoneal carcinomatosis in such patients include: gastric tumor invasion into serosa, the presence of tumor cells in peritoneal washings, the largeness of the tumor as accompanied by extensive serous lesions, infiltrative type of tumor growth, histological variants of gastric cancer prone to implantation metastasis and metastatic lesions in regional lymph nodes. Systemic chemotherapy does not provide effective eradication of subclinical peritoneal carcinomatosis in patients with locally advanced gastric cancer.
The vast majority of patients who suffer from locally advanced gastric cancer and run a high risk of implantation metastasis are characterized by subclinical peritoneal dissemination at primary diagnosis, which means a rapidly fatal prognosis for such patients. In recent years, however, the paradigm of treatment of locally advanced gastric cancer has changed: a combination of surgery and adjuvant hyperthermic intraperitoneal chemotherapy is used increasingly, and presents an alternative to the previously accepted surgery only approach. It is also likely to increase the survival rate.
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Affiliation(s)
- Roman Yarema
- Department of Oncology and Medical Radiology , Danylo Halytsky Lviv National Medical University , Pekarska 69, 79010 , Lviv , Ukraine
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13
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Wu F, Shi C, Wu R, Huang Z, Chen Q. Peritoneal recurrence in gastric cancer following curative resection can be predicted by postoperative but not preoperative biomarkers: a single-institution study of 320 cases. Oncotarget 2017; 8:78120-78132. [PMID: 29100454 PMCID: PMC5652843 DOI: 10.18632/oncotarget.17696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 02/28/2017] [Indexed: 12/11/2022] Open
Abstract
To determine the risk factors for peritoneal recurrence in gastric cancer patients after curative resection, we included 320 patients with stage I-III primary gastric cancer between January 2008 and June 2012. Data on each patient's surgical and pathological information, preoperative and postoperative tumor markers were collected and analyzed retrospectively. The risk factors for peritoneal recurrence were investigated by univariate and multivariate analysis. In patients with peritoneal recurrence, advanced T or N stage, low differentiation, vascular/lymphatic invasion, perineural invasion, and elevated postoperative CEA/CA19-9 were more common than in patients without peritoneal recurrence. Patients with peritoneal recurrence showed a worse overall survival (OS) compared to those without peritoneal recurrence. In addition, patients with peritoneal recurrence within the first year had a worse OS compared to those with recurrence after 1 year. The univariate and multivariate analyses revealed that elevated number of metastatic lymph nodes and elevated postoperative CEA and CA19-9 were three independent risk factors for peritoneal recurrence in gastric cancer patients. For patients with N3 stage and high postoperative CEA and CA19-9, we found an initial steep slope within approximately 1 year and a subsequent gentle slope in the risk curve. Combined receiver operating characteristic curve analysis using the three independent risk factors for peritoneal recurrence yielded an area under the curve value of 0.73 with 73.7% sensitivity and 64.2% specificity. Therefore, the risk factors may be associated with peritoneal recurrence after curative resection in selected gastric cancer patients.
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Affiliation(s)
- Fan Wu
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China
| | - Chunmei Shi
- Fujian Medical University Union Hospital, Fuzhou, Fujian Province, PR, China.,Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian Province, PR, China
| | - Riping Wu
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Union Hospital, Fuzhou, Fujian Province, PR, China
| | - Zhiqing Huang
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian Province, PR, China
| | - Qiang Chen
- The Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian Province, PR, China.,Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian Province, PR, China
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14
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Ushiku H, Yamashita K, Ema A, Minatani N, Kikuchi M, Kojo K, Yokoi K, Tanaka T, Nishizawa N, Ishii S, Hosoda K, Moriya H, Mieno H, Katada N, Kikuchi S, Katoh H, Watanabe M. DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer. Gastric Cancer 2017; 20:784-792. [PMID: 28243814 DOI: 10.1007/s10120-017-0697-6] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Accepted: 01/20/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease. METHODS One hundred and two GC patients were investigated for peritoneal fluid cytology test (CY), and detection level of the promoter DNA methylation of CDO1 gene was assessed by quantitative methylation specific PCR (Q-MSP) in the sediments (DNA CY). RESULTS (1) CY1 was pathologically confirmed in 8 cases, while DNA CY1 was detected in 18 cases. All 8 CY1 were DNA CY1. (2) DNA CY1 was recognized in 14.3, 25.0, 20.0, and 42.9%, in macroscopic Type II, small type III, large type III, and type IV, respectively, while it was not recognized in Type 0/I/V. (3) DNA CY1 was prognostic relevance in gastric cancer (p = 0.0004), and its significance was robust among Type III/IV gastric cancer (p = 0.006 for overall survival and p = 0.0006 for peritoneal recurrence free survival). (4) The peritoneal recurrence was hardly seen in GC patients with potent perioperative chemotherapy among those with DNA CY1. CONCLUSIONS DNA CY1 detected by Q-MSP for CDO1 gene promoter DNA methylation has a great potential to detect minimal residual disease of the peritoneum in GC clinics as a novel DNA marker.
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Affiliation(s)
- Hideki Ushiku
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Keishi Yamashita
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Akira Ema
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Naoko Minatani
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Mariko Kikuchi
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Ken Kojo
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Keigo Yokoi
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Toshimichi Tanaka
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Nobuyuki Nishizawa
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Satoru Ishii
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Kei Hosoda
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Hiromitsu Moriya
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Hiroaki Mieno
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Natsuya Katada
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Shiro Kikuchi
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Hiroshi Katoh
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan
| | - Masahiko Watanabe
- Department of Surgery, Kitasato University School of Medicine, Kitasato 1-15-1, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.
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15
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Prognostic significance, diagnosis and treatment in patients with gastric cancer and positive peritoneal washings. A review of the literature. Rep Pract Oncol Radiother 2017; 22:434-440. [PMID: 28883764 DOI: 10.1016/j.rpor.2017.08.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Revised: 03/17/2017] [Accepted: 08/03/2017] [Indexed: 12/17/2022] Open
Abstract
Peritoneal dissemination is a common consequence of a relapse following a radical surgical treatment of gastric cancer. The development of the disease in the peritoneum depends not only on its stage, but also on free cancer cells exfoliated from the tumor mass or from involved lymph nodes, and which are capable of being implanted in the peritoneum. According to the latest TNM (7 edition; 2010) classification, patients with free cancer cells in the peritoneal washings qualify for stage IV of the disease. Patients in whom free cancer cells were found during the operation - have a recurrence of gastric cancer - mainly in the peritoneum, and the majority of them die within two years of the diagnosis. To properly assess the prognosis, it is vital to determine the stage of cancer by additionally assessing the washings for the presence of free cancer cells before taking a therapeutic decision. This also allows identifying those patients who require different medical procedures to obtain the best treatment results possible. Medical literature describes various methods of examining peritoneal washings aimed at detecting free cancer cells. The methods apply different cancer cell detection rates, sensitivity and specificity in prediction of a peritoneal relapse. Oncological Departments performing the evaluation of the washings employ non-standard methods of treatment in this group of patients and the results presented are promising.
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16
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17
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Tanaka T, Suda K, Satoh S, Kawamura Y, Inaba K, Ishida Y, Uyama I. Effectiveness of laparoscopic stomach-partitioning gastrojejunostomy for patients with gastric outlet obstruction caused by advanced gastric cancer. Surg Endosc 2017; 31:359-367. [PMID: 27287913 DOI: 10.1007/s00464-016-4980-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/09/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Distal advanced gastric cancer (AGC) occasionally causes gastric outlet obstruction (GOO). We developed a laparoscopic stomach-partitioning gastrojejunostomy (LSPGJ) to restore the ability of food intake. METHODS This was a retrospective study performed at a single institution. Of consecutive 78 patients with GOO caused by AGC between 2006 and 2012, 43 patients who underwent LSPGJ were enrolled. The procedure was performed in an antiperistaltic Billroth II fashion, and the afferent loop was elevated and fixed along the staple line of the proximal partitioned stomach. Then, patients for whom R0 resection was planned received chemotherapy prior to laparoscopic gastrectomy. The primary end point was food intake at the time of discharge, which was evaluated using the GOO scoring system (GOOSS). Short- and long-term outcomes were assessed as secondary end points. Overall survival was estimated and compared between the groups who received neoadjuvant chemotherapy followed by surgery (NAC group), definitive chemotherapy followed by curative resection (Conversion group), and best supportive care (BSC group). RESULTS The median operative time was 92 min, blood loss did not exceed 30 g in any patient, and postoperative complications (Clavien-Dindo grade ≥2) were only seen in four patients (9.3 %). The median time to food intake was 3 days, and GOOSS scores were significantly improved in 41 patients (95.3 %). Chemotherapy was administered to 38 patients (88.4 %), of whom 11 later underwent radical resection, and 4 of 11 patients underwent conversion surgery following definitive chemotherapy. Median survival times were significantly superior in the NAC (n = 7; 46.8 months) and Conversion (n = 4; 35.9 months) groups than in the BSC group (n = 26; 12.2 months); however, the difference was not significant between the Conversion and NAC groups. CONCLUSIONS LSPGJ is a feasible and safe minimally invasive induction surgery for patients with GOO from surgical and oncological perspectives.
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Affiliation(s)
- Tsuyoshi Tanaka
- Division of Upper GI, Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
| | - Koichi Suda
- Division of Upper GI, Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.
| | - Seiji Satoh
- Department of Surgery, Himeji Medical Center, Himeji, Japan
| | | | - Kazuki Inaba
- Division of Upper GI, Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
| | - Yoshinori Ishida
- Division of Upper GI, Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
| | - Ichiro Uyama
- Division of Upper GI, Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
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18
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Tustumi F, Bernardo WM, Roncon Dias A, Kodama Pertille Ramos MF, Cecconello I, Zilberstein B, Ribeiro-Júnior U. Detection value of free cancer cells in peritoneal washing in gastric cancer: a systematic review and meta-analysis. Clinics (Sao Paulo) 2016; 71:733-745. [PMID: 28076519 PMCID: PMC5175297 DOI: 10.6061/clinics/2016(12)10] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2016] [Revised: 08/29/2016] [Accepted: 09/09/2016] [Indexed: 02/05/2023] Open
Abstract
Intraperitoneal free cancer cells in gastric adenocarcinoma are associated with a poor outcome. However, the true prognostic value of intraperitoneal free cancer cells is still unclear, leading to a lack of consensus in the management of gastric cancer. The aim of the present study is to perform a systematic review and meta-analysis to analyze intraperitoneal free cancer cells-positive patients with regard to tumor oncologic stage, recurrence, grade of cellular differentiation, and survival rates and to analyze the clinical significance of intraperitoneal free cancer cells with regard to prognosis. Databases were searched up to January 2016 for prognostic factors associated with intraperitoneal free cancer cells, including oncologic stage, depth of neoplasm invasion, lymph nodal spread, differentiation grade of the tumor, and recurrence and survival rates. A total of 100 studies were identified. Meta-analysis revealed a clear association between intraperitoneal free cancer cells and a poor prognosis. intraperitoneal free cancer cells -positive patients had higher rates of nodal spread (risk difference: 0.29; p<0.01), serosal invasion (risk difference: 0.43; p<0.01), recurrence (after 60 months of follow-up, risk difference: 0.44; p<0.01), and mortality (after 60 months of follow-up, risk difference: 0.34; p<0.01). Intraperitoneal free cancer cells are associated with a poor outcome in gastric cancer. This surrogate biomarker should be used to guide therapy both prior to and after surgery.
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Affiliation(s)
- Francisco Tustumi
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil
| | | | - Andre Roncon Dias
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil
| | | | - Ivan Cecconello
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil
| | - Bruno Zilberstein
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil
| | - Ulysses Ribeiro-Júnior
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil
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19
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Prognostic role of gastrectomy in patients with gastric cancer with positive peritoneal cytology. Int Surg 2016; 99:830-4. [PMID: 25437595 DOI: 10.9738/intsurg-d-14-00119.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
This retrospective study identified the optimal treatment strategy for patients with gastric cancer with positive peritoneal cytology. We analyzed clinicopathologic and survival data for 54 patients who had undergone gastrectomy and/or chemotherapy for treatment of gastric cancer with positive peritoneal cytology with (n = 40) or without (n = 14) metastatic disease. The median overall survival did not differ significantly between patients with gastric cancer with positive peritoneal cytology with and without metastatic disease (19 versus 13 months, respectively). Among 14 clinicopathologic variables, the lack of gastrectomy was the only significant independent unfavorable factor for survival (odds ratio, 1.64; 95% confidence interval, 1.04-2.57; P = 0.03). The median overall survival significantly differed among patients who had undergone gastrectomy plus chemotherapy, chemotherapy alone, and gastrectomy alone (25, 10, and 17 months, respectively; P < 0.01). Gastrectomy may be optimal for patients with (gastric cancer with positive peritoneal cytology), considering its favorable prognostic effect with respect to perioperative chemotherapy.
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20
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Feingold PL, Kwong MLM, Sabesan A, Sorber R, Rudloff U. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer and other less common disease histologies: is it time? J Gastrointest Oncol 2016; 7:87-98. [PMID: 26941987 DOI: 10.3978/j.issn.2078-6891.2015.098] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is the fourth most commonly diagnosed cancer worldwide, and once spread to the peritoneum, has a 5-year survival of less than 5%. Recent years have demonstrated advances in the use of cytoreductive surgery (CRS) in combination with heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis due to various malignancies. The frequent desmoplastic stroma and poor vascularization impeding drug delivery particularly in the diffuse form of gastric cancer is thought to provide a sound rationale for a regionalized treatment approach in this disease. Here, we seek to review the available data to define the role of CRS and HIPEC in gastric cancer metastatic to the peritoneal surface, and furthermore, analyze the use of CRS and HIPEC in malignancies less commonly treated with the regionalized perfusion approach.
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Affiliation(s)
- Paul L Feingold
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Mei Li M Kwong
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Arvind Sabesan
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Rebecca Sorber
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Udo Rudloff
- Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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21
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Pecqueux M, Fritzmann J, Adamu M, Thorlund K, Kahlert C, ReiΔfelder C, Weitz J, Rahbari NN. Free intraperitoneal tumor cells and outcome in gastric cancer patients: a systematic review and meta-analysis. Oncotarget 2015; 6:35564-78. [PMID: 26384352 PMCID: PMC4742125 DOI: 10.18632/oncotarget.5595] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2015] [Accepted: 08/22/2015] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Despite continuously improving therapies, gastric cancer still shows poor survival in locally advanced stages with local recurrence rates of up to 50% and peritoneal recurrence rates of 17% after curative surgery. We performed a systematic review with meta-analyses to clarify whether positive intraperitoneal cytology (IPC) indicates a high risk of disease recurrence and poor overall survival in gastric cancer. METHODS Multiple databases were searched in December 2014 to identify studies on the prognostic significance of positive intraperitoneal cytology in gastric cancer, including: Medline, Biosis, Science Citation Index, Embase, CCMed and publisher databases. Hazard ratios (HR) and associated 95% confidence intervals (CI) were extracted from the identified studies. A meta-analysis was performed using a random-effects model on overall survival, disease-free survival and peritoneal recurrence free survival. RESULTS A total of 64 studies with a cumulative sample size of 12,883 patients were included. Cytology, quantitative real time polymerase chain reaction (PCR) or both were performed in 35; 21 and 8 studies, respectively. Meta analyses revealed free intraperitoneal tumor cells (FITC) to be associated with poor overall survival in univariate (HR 3.27; 95% CI 2.82 - 3.78]) and multivariate (HR 2.45; 95% CI 2.04 - 2.94) analysis and poor peritoneal recurrence free survival in univariate (4.15; 95% CI 3.10 - 5.57) and multivariate (3.09; 95% CI 2.02 - 4.71) analysis. Subgroup analysis showed this effect to be independent of the detection method, Western or Asian origin or the time of publication. CONCLUSIONS FITC oder positive peritoneal cytology is associated with poor survival and increased peritoneal recurrence in gastric cancer.
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Affiliation(s)
- Mathieu Pecqueux
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Johannes Fritzmann
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Mariam Adamu
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Kristian Thorlund
- Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario, Canada
| | - Christoph Kahlert
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Christoph ReiΔfelder
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Jürgen Weitz
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
| | - Nuh N. Rahbari
- Department for Visceral, Thoracic and Vascular Surgery, University of Dresden, Dresden, Germany
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22
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Kang Y, Li S, Ge Q, Liu X, Yang Z, Xue Y, Wang F. Extent of Serosal Changes Predicts Peritoneal Recurrence and Poor Prognosis After Curative Surgery for Gastric Cancer. Medicine (Baltimore) 2015; 94:e1750. [PMID: 26496292 PMCID: PMC4620790 DOI: 10.1097/md.0000000000001750] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
To investigate whether the width of gastric serosal lesions in advanced gastric cancer patients have a predictive value for peritoneal recurrence and the 5-year survival rate.A total of 1109 patients with advanced noncardia primary gastric adenocarcinoma, who underwent curative gastrectomy between January 1997 and December 2007, were included. Data about tumor size, longitudinal tumor location, resection type, serum albumin concentration, lymphatic/venous invasion, lymph node metastasis status, lesion size, histological and Borrmann type of tumor, as well as the recurrence rate and width of the gastric serosal lesions were collected and analyzed.The peritoneal recurrence rate in patients with gastric serosal lesions ≤3 cm was lower than in patients with gastric serosal lesions >3 cm. Multivariate analyses of the 5-year survival rate variables for all patients revealed significant correlations with serum albumin concentrations (HR 1.382, P = 0.002, 95% CI 1.123-1.701), width of serosa changes (HR 1.377, P = 0.020, 95% CI 1.053-1.802), depth of invasion (HR 1.529, P < 0.001, 95% CI 1.288-1.814), and lymph node metastasis (HR 1.551, P < 0.001, 95% CI 1.420-1.694), whereas for recurrent patients only serum albumin concentrations (HR 2.000, P < 0.001, 95% CI 1.425-2.805), width of serosa changes (HR 1.867, P = 0.002, 95% CI 1.248-2.793), and lymph node metastasis (HR 1.521, P < 0.001, 95% CI 1.249-1.852) correlated with the 5-year survival rate.Gastric serosal lesions >3 cm may indicate a high risk for peritoneal recurrence and serve as additional indicators for preventive postoperative adjuvant chemotherapies in patients with advanced gastric cancer.
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Affiliation(s)
- Yue Kang
- From the Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University (YK, SL, XL, FW); Department of Internal Medicine, Orthopedic Hospital of Harbin (QG); Intensive Care Unit, The Second Affiliated Hospital of Harbin Medical University (ZY); and Department of Gastroenterologic Surgery, The Tumor Hospital of Harbin Medical University, Harbin, China (YX)
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23
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Yamashita K, Ushiku H, Katada N, Hosoda K, Moriya H, Mieno H, Kikuchi S, Hoshi K, Watanabe M. Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival with advanced gastric cancer with positive cytology test. Eur J Surg Oncol 2015; 41:1324-32. [PMID: 26251341 DOI: 10.1016/j.ejso.2015.05.021] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 05/09/2015] [Accepted: 05/31/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Peritoneal lavage cytology cancer-positive (CY1) is a critical prognostic factor and is taken as representing stage IV in gastric cancer. There is no consensus treatment strategy for CY1-gastric cancer, and the detailed clinicopathological features remain obscure. PATIENTS AND METHODS Among 790 gastric cancer patients between 2005 and 2009, 52 cases of CY1 were identified (6.6%). A multivariate prognostic model was applied to the univariate prognostic factors to identify independent prognostic factors and factors associated with long-term survival in CY1-gastric cancer. RESULTS (1) Five-year overall survival (OS) was 17.6% in CY1-gastric cancer as compared with 93.9% in CYX and 77.7% in CY0 (77.7%), where tumors with pT2 or beyond were included in 11% of CYX, 73% of CY0, and 98% of CY1 cases. (2) On univariate analysis, factors associated with a negative prognosis were the presence of peritoneal dissemination (p = 0.029) and high preoperative serum albumin (p = 0.011) in CY1-gastric cancer. The multivariate Cox proportional hazards and logistic regression model using propensity score identified preoperative albumin as a critical independent prognostic indicator. (3) Long-term survivors were identified and, were often characterized by long-term postoperative adjuvant treatment. CONCLUSION Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival in patients with advanced gastric cancer with positive cytology test. Long-term postoperative adjuvant therapy might improve survival of patients with CY1.
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Affiliation(s)
- K Yamashita
- Department of Surgery, Kitasato University School of Medicine, Japan.
| | - H Ushiku
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - N Katada
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - K Hosoda
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - H Moriya
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - H Mieno
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - S Kikuchi
- Department of Surgery, Kitasato University School of Medicine, Japan
| | - K Hoshi
- Department of Hygiene, Kitasato University School of Medicine, Japan
| | - M Watanabe
- Department of Surgery, Kitasato University School of Medicine, Japan
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24
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Fujita T, Chiwaki F, Takahashi RU, Aoyagi K, Yanagihara K, Nishimura T, Tamaoki M, Komatsu M, Komatsuzaki R, Matsusaki K, Ichikawa H, Sakamoto H, Yamada Y, Fukagawa T, Katai H, Konno H, Ochiya T, Yoshida T, Sasaki H. Identification and Characterization of CXCR4-Positive Gastric Cancer Stem Cells. PLoS One 2015; 10:e0130808. [PMID: 26110809 PMCID: PMC4481351 DOI: 10.1371/journal.pone.0130808] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 05/25/2015] [Indexed: 12/18/2022] Open
Abstract
Diffuse-type solid tumors are often composed of a high proportion of rarely proliferating (i.e., dormant) cancer cells, strongly indicating the involvement of cancer stem cells (CSCs) Although diffuse-type gastric cancer (GC) patients have a poor prognosis due to high-frequent development of peritoneal dissemination (PD), it is limited knowledge that the PD-associated CSCs and efficacy of CSC-targeting therapy in diffuse-type GC. In this study, we established highly metastatic GC cell lines by in vivo selection designed for the enrichment of PD-associated GC cells. By microarray analysis, we found C-X-C chemokine receptor type 4 (CXCR4) can be a novel marker for highly metastatic CSCs, since CXCR4-positive cells can grow anchorage-independently, initiate tumors in mice, be resistant to cytotoxic drug, and produce differentiated daughter cells. In clinical samples, these CXCR4-positive cells were found from not only late metastasis stage (accumulated ascites) but also earlier stage (peritoneal washings). Moreover, treatment with transforming growth factor-β enhanced the anti-cancer effect of docetaxel via induction of cell differentiation/asymmetric cell division of the CXCR4-positive gastric CSCs even in a dormant state. Therefore, differentiation inducers hold promise for obtaining the maximum therapeutic outcome from currently available anti-cancer drugs through re-cycling of CSCs.
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Affiliation(s)
- Takeshi Fujita
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
- Second Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Fumiko Chiwaki
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Ryou-u Takahashi
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Kazuhiko Aoyagi
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Kazuyoshi Yanagihara
- Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Chiba, Japan
| | - Takao Nishimura
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Masashi Tamaoki
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Masayuki Komatsu
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | - Rie Komatsuzaki
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
| | | | - Hitoshi Ichikawa
- Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan
- Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan
| | - Hiromi Sakamoto
- Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan
| | - Yasuhide Yamada
- Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Takeo Fukagawa
- Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hitoshi Katai
- Gastric Surgery Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroyuki Konno
- Second Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Teruhiko Yoshida
- Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan
| | - Hiroki Sasaki
- Department of Translational Oncology, National Cancer Center Research Institute, Tokyo, Japan
- * E-mail:
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25
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Kano Y, Kosugi SI, Ishikawa T, Otani T, Muneoka Y, Sato Y, Hanyu T, Hirashima K, Bamba T, Wakai T. Prognostic significance of peritoneal lavage cytology at three cavities in patients with gastric cancer. Surgery 2015; 158:1581-9. [PMID: 25958064 DOI: 10.1016/j.surg.2015.04.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 03/15/2015] [Accepted: 04/05/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND We sought to determine the prognostic significance of intraoperative peritoneal lavage cytology (CY) at 3 different abdominal cavities and establish the optimal treatment for gastric cancer patients with positive peritoneal cytology (CY1). METHODS A total of 1,039 patients with primary gastric adenocarcinoma who underwent CY at 3 cavities (Douglas' pouch, left subphrenic cavity, and right subhepatic cavity) were enrolled; 116 (11%) patients had at least one positive cavity. We retrospectively analyzed the clinicopathologic characteristics and survival of these 116 patients with CY1. RESULTS Seventeen (15%) of the patients had negative cytology at Douglas' pouch but positive cytology at one or both of the other cavities. The 116 patients' overall 2-year survival rate was 22.9%, with the median survival time of 11 months. The overall 2-year survival rates for the patients with positive cytology at 1, 2, and 3 cavities were 41.9%, 35.8%, and 15%, with median survival times of 17, 18, and 9 months, respectively (P < .01). A multivariate analysis revealed that macroscopic type 4 tumor, R2 resection, lymph node metastasis, and postoperative chemotherapy were independent prognostic factors. Among the CY1 patients with type 4 tumors, there was no substantial difference in survival between the patients who underwent R1 or R2 resection, although the statistical power of this subgroup analysis was low. CONCLUSION CY at 3 cavities might be a useful method to decrease the false-negative rate. Palliative gastrectomy for CY1 patients with type 4 tumors is still controversial.
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Affiliation(s)
- Yosuke Kano
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Shin-ichi Kosugi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
| | - Takashi Ishikawa
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takahiro Otani
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yusuke Muneoka
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yu Sato
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takaaki Hanyu
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kotaro Hirashima
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takeo Bamba
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Cabalag CS, Chan STF, Kaneko Y, Duong CP. A systematic review and meta-analysis of gastric cancer treatment in patients with positive peritoneal cytology. Gastric Cancer 2015; 18:11-22. [PMID: 24890254 DOI: 10.1007/s10120-014-0388-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 05/02/2014] [Indexed: 02/07/2023]
Abstract
Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48; 95% CI 0.32-0.70; p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 9 % CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with 4.6% for IPC group). However, these promising results need to be validated in larger prospective randomized trials.
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Affiliation(s)
- Carlos Suhady Cabalag
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, 7 St. Andrews Place, East Melbourne, VIC, 3002, Australia,
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27
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Kagawa S, Shigeyasu K, Ishida M, Watanabe M, Tazawa H, Nagasaka T, Shirakawa Y, Fujiwara T. Molecular diagnosis and therapy for occult peritoneal metastasis in gastric cancer patients. World J Gastroenterol 2014; 20:17796-17803. [PMID: 25548478 PMCID: PMC4273130 DOI: 10.3748/wjg.v20.i47.17796] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 06/07/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
To apply an individualized oncological approach to gastric cancer patients, the accurate diagnosis of disease entities is required. Peritoneal metastasis is the most frequent mode of metastasis in gastric cancer, and the tumor-node-metastasis classification includes cytological detection of intraperitoneal cancer cells as part of the staging process, denoting metastatic disease. The accuracy of cytological diagnosis leaves room for improvement; therefore, highly sensitive molecular diagnostics, such as an enzyme immunoassay, reverse transcription polymerase chain reaction, and virus-guided imaging, have been developed to detect minute cancer cells in the peritoneal cavity. Molecular targeting therapy has also been spun off from basic research in the past decade. Although conventional cytology is still the mainstay, novel approaches could serve as practical complementary diagnostics to cytology in near future.
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28
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Tokumitsu Y, Yoshino S, Iida M, Yoshimura K, Ueno T, Hazama S, Oka M. Intraoperative dissemination during gastrectomy for gastric cancer associated with serosal invasion. Surg Today 2014; 45:746-51. [DOI: 10.1007/s00595-014-1005-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 07/11/2014] [Indexed: 12/13/2022]
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Cardona K, Zhou Q, Gönen M, Shah MA, Strong VE, Brennan MF, Coit DG. Role of repeat staging laparoscopy in locoregionally advanced gastric or gastroesophageal cancer after neoadjuvant therapy. Ann Surg Oncol 2012; 20:548-54. [PMID: 22941159 DOI: 10.1245/s10434-012-2598-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2012] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Staging laparoscopy (SL) can identify occult, subradiographic metastatic (M1) disease in patients with gastric or gastroesophageal (G/GEJ) cancer who are unlikely to benefit from gastrectomy. The purpose of this study is to determine the yield of repeat SL following neoadjuvant therapy for G/GEJ adenocarcinoma after initial negative pretreatment SL. METHODS Retrospective review of a prospective database identified patients with locoregionally advanced (T3-4Nany or TanyN+) G/GEJ adenocarcinoma who underwent pretreatment SL. The yield of repeat SL following neoadjuvant therapy was determined. RESULTS From 1994 to 2010, 276 patients with locoregionally advanced G/GEJ adenocarcinoma were identified, of whom 244 proceeded to operation after neoadjuvant therapy, at a median time of 105 days. One hundred sixty-four patients (67 %) underwent repeat SL, and 80 patients (33 %) proceeded directly to laparotomy. Occult M1 disease was identified in 12 (7.3 %) and 6 (7.5 %) patients, respectively. In the repeat SL cohort, M1 disease was identified at laparoscopy in nine patients (5.5 %). M1 disease not identified by laparoscopy was discovered at laparotomy in three patients (1.8 %). The median follow-up for the study population was 31 months. For patients with M1 disease, median overall survival was 15 months, versus 41 months for patients resected without M1 disease (p < 0.0001). CONCLUSIONS Occult, subradiographic M1 disease develops in approximately 7 % of patients following neoadjuvant therapy for locoregionally advanced G/GEJ adenocarcinoma. These patients have poor prognosis, and repeat SL can be a valuable tool in selecting patients with locoregionally advanced G/GEJ tumors for potentially curative resection after neoadjuvant therapy.
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Affiliation(s)
- Kenneth Cardona
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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30
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Abstract
There has been much speculation regarding differences in outcome for patients who have gastric cancer in the Eastern versus Western world. Among other factors, these differences have contributed to a unique cohort of patients and experience in the Western staging/evaluation of gastric cancer and in the application of minimally invasive approaches for treatment. This review summarizes the current state of laparoscopic approaches for the staging and treatment of gastric adenocarcinoma for patients presenting in Western countries, with their associated unique presentation, comorbidities, and outcomes.
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Affiliation(s)
- Vivian E Strong
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, 1275 York Avenue, H-1217, New York, NY 10065, USA.
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31
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Satoh S, Okabe H, Teramukai S, Hasegawa S, Ozaki N, Ueda S, Tsuji A, Sakabayashi S, Fukushima M, Sakai Y. Phase II trial of combined treatment consisting of preoperative S-1 plus cisplatin followed by gastrectomy and postoperative S-1 for stage IV gastric cancer. Gastric Cancer 2012; 15:61-9. [PMID: 21667134 DOI: 10.1007/s10120-011-0066-9] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 05/17/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND To improve the poor prognosis in patients with stage IV (StIV) gastric cancer (GC), we conducted a multicenter phase II study of preoperative S-1 plus cisplatin followed by gastrectomy and postoperative S-1 for StIV GC (the protocol is registered at the clinical trial site of the National Cancer Institute; KYUH-UHA-GC03-01, NCT00088816). METHODS Eligibility criteria included histologically proven StIVGC. Patients received S-1 (80 mg/m(2)/day, days 1-21) plus cisplatin (60 mg/m(2) on day 8) for 2 courses. After preoperative chemotherapy (CTx), radical gastrectomy was performed. Postoperative S-1 (80 mg/m(2)/day, days 1-14) was administered every 3 weeks for 1 year. RESULTS Fifty-one patients were enrolled and all patients were followed for more than 2 years. The 2-year overall survival and progression-free survival rates were 43.1% (95% confidence interval [CI] 29.4-56.1%) and 33.3% (95% CI 20.9-46.2%), respectively. Preoperative chemotherapy was accomplished in 44 patients (86.3%). These 44 patients underwent surgery and R0 resection was achieved in 26. The rate of R0 resection for GC with a single StIV factor (n = 24) was 79.2% and that for GC with multiple StIV factors (n = 27) was 25.9%. All patients with cancer cells in peritoneal washings (cytology [Cy] 1) alone (n = 12) became Cy0 after preoperative chemotherapy. Postoperative chemotherapy was completed in 11 patients, including 8 with Cy1 alone. No treatment-related death was recorded. Recurrences were observed in 14 patients after R0 resection. The most frequent recurrence site was the peritoneum. Patients who underwent R0 resection and those with Cy1 alone had a better survival. CONCLUSIONS This perioperative treatment was safe and feasible for StIVGC but failed to show a survival benefit. In patients with StIVGC with Cy1 alone this treatment resulted in a better prognosis.
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Affiliation(s)
- Seiji Satoh
- Kyoto University Surgical Oncology Group, Kyoto, Japan.
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32
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Imano M, Imamoto H, Itoh T, Satou T, Peng YF, Yasuda A, Kato H, Shiraishi O, Shinkai M, Yasuda T, Takeyama Y, Okuno K, Shiozaki H. Safety of intraperitoneal administration of paclitaxel after gastrectomy with en-bloc D2 lymph node dissection. J Surg Oncol 2011; 105:43-7. [PMID: 21837682 DOI: 10.1002/jso.22065] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Accepted: 07/20/2011] [Indexed: 01/26/2023]
Abstract
BACKGROUND The aim of this study was to examine the safety, pharmacokinetics, and cytological efficacy against free intraperitoneal cancer cells of intraperitoneal chemotherapy (IPC) with paclitaxel after gastrectomy with en-bloc D2 lymph node dissection (GD2) in cases of gastric cancer with peritoneal carcinomatosis (PC) and/or positive cytological findings in peritoneal washings (CFPW). METHODS Twenty-one patients with gastric cancer with PC and/or positive CFPW who underwent GD2 were treated with early, post-operative, intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complication were measured using the common toxicity criteria of the National Cancer Institute, version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatography assay. RESULTS Grade 3 anemia occurred in two patients (9.5%) and neutropenia was observed in three patients (14.3%). No grade 4 toxicity was observed. A grade 2 operative complication was a superficial surgical site infection (4.8%) that was treated with antibiotics. Cytologically, no viable cancer cells were observed in the intra-abdominal fluid 24 hr after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve (AUC) ratio was 596.9:1. CONCLUSION IPC with paclitaxel after GD2 is a safe and cytologically effective treatment modality for free intraperitoneal cancer cells. However, additional data are required to determine the effect on survival.
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Affiliation(s)
- Motohiro Imano
- Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
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Kwon SJ. Evaluation of the 7th UICC TNM Staging System of Gastric Cancer. J Gastric Cancer 2011; 11:78-85. [PMID: 22076207 PMCID: PMC3204489 DOI: 10.5230/jgc.2011.11.2.78] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2011] [Accepted: 04/30/2011] [Indexed: 02/06/2023] Open
Abstract
Since January of 2010, the seventh edition of UICC tumor node metastasis (TNM) Classification, which has recently been revised, has been applied to almost all cases of malignant tumors. Compared to previous editions, the merits and demerits of the current revisions were analyzed. Many revisions have been made for criteria for the classification of lymph nodes. In particular, all the cases in whom the number of lymph nodes is more than 7 were classified as N3 without being differentiated. Therefore, the coverage of the N3 was broad. Owing to this, there was no consistency in predicting the prognosis of the N3 group. By determining the positive cases to a distant metastasis as TNM stage IV, the discrepancy in the TNM stage IV compared to the sixth edition was resolved. In regard to the classification system for an esophagogastric (EG) junction carcinoma, it was declared that cases of an invasion to the EG junction should follow the classification system for esophageal cancer. A review of clinical cases reported from Asian patients suggests that it would be more appropriate to follow the previous editions of the classification system for gastric cancer. In addition, in the classification of the TNM stages in the overall cases, the discrepancy in the prognosis between the different stages and the consistency in the prognosis between the same TNM stages were achieved to a lesser extent as compared to that previously. Accordingly, further revisions are needed to develop a purposive classification method where the prognosis can be predicted specifically to each variable and the mode of the overall classification can be simplified.
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Affiliation(s)
- Sung Joon Kwon
- Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
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Mezhir JJ, Shah MA, Jacks LM, Brennan MF, Coit DG, Strong VE. Positive peritoneal cytology in patients with gastric cancer: natural history and outcome of 291 patients. Indian J Surg Oncol 2011; 2:16-23. [PMID: 22696066 PMCID: PMC3373003 DOI: 10.1007/s13193-011-0074-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2010] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort. METHODS Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS). RESULTS From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+, DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt + disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt + patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003). CONCLUSIONS Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt + disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.
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Affiliation(s)
- James J. Mezhir
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | - Manish A. Shah
- Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | - Lindsay M. Jacks
- Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | - Murray F. Brennan
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | - Daniel G. Coit
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY USA
| | - Vivian E. Strong
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY USA
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35
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Mezhir JJ, Shah MA, Jacks LM, Brennan MF, Coit DG, Strong VE. Positive peritoneal cytology in patients with gastric cancer: natural history and outcome of 291 patients. Ann Surg Oncol 2010; 17:3173-80. [PMID: 20585870 DOI: 10.1245/s10434-010-1183-0] [Citation(s) in RCA: 126] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2010] [Indexed: 12/18/2022]
Abstract
BACKGROUND Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort. METHODS Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS). RESULTS From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+ , DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt+ disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt+ patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003). CONCLUSIONS Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt+ disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.
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Affiliation(s)
- James J Mezhir
- Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
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36
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Nakagohri T, Yoneyama Y, Kinoshita T, Konishi M, Inoue K, Takahashi S. Prognostic significance of peritoneal washing cytology in patients with potentially resectable gastric cancer. Br J Surg 2009; 99:397-403. [PMID: 19102421 DOI: 10.1002/bjs.7812] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/20/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS The prognostic value of cytological examination of intraoperative washings in potentially resectable gastric cancer is controversial. METHODOLOGY Between February 1993 and August 2001, clinicopathological features and surgical outcome of 26 consecutive patients with gastric cancer with positive cytological findings of peritoneal washings without peritoneal dissemination were retrospectively analyzed. RESULTS The overall 1, 2, 3-year survival rates for 26 patients were 69%, 35%, and 0%, respectively. The median survival was 17.5 months. The median survival of patients with curative resection (n=16) and non-curative resection (n=10) was 19 months and 12.5 months, respectively. There was no significant difference in survival between curative resection and non-curative resection (p=0.10). Recurrent disease frequently occurred as peritoneal dissemination (69%). No patient survived for more than 34 months. CONCLUSIONS Aggressive surgical resections do not provide any survival benefit for gastric cancer with positive cytological findings of peritoneal washings even in the absence of peritoneal dissemination.
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Affiliation(s)
- Toshio Nakagohri
- Department of Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa 277-8577, Japan.
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