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Sakon R, Hayashi T, Ogawa R, Nishino M, Ishizu K, Wada T, Yamagata Y, Daiko H, Yoshikawa T. Is Primary Surgery Followed by S-1 Applicable Even for Type 4 or Large Type 3 Gastric Cancer With Positive Peritoneal Lavage Cytology? World J Surg 2025; 49:727-733. [PMID: 39938946 DOI: 10.1002/wjs.12487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/19/2024] [Accepted: 12/29/2024] [Indexed: 02/14/2025]
Abstract
BACKGROUND The recommended treatment for gastric cancer with positive peritoneal cytology (CY1) is primary surgery and S-1 chemotherapy, with 5-year overall survival rates of 24.6%-30.2% reported in previous studies. However, it is unclear whether this strategy is applicable in cases of Type 4 or large Type 3 tumors, which have malignant characteristics and are considered to have different chemosensitivities. METHODS The present study examined the survival of patients who were diagnosed with gastric cancer with CY1, without any other macroscopic distant metastasis, who underwent primary gastrectomy with D2 or more lymph node resection, achieved curative resection except for CY1-positive, and received S-1 postoperative chemotherapy between 2000 and 2017. Patients were divided into the S group (Type 4 or large Type 3 GC) and C group (common GC types). RESULTS Among the 352 patients who underwent gastrectomy with CY1, 40 patients were analyzed as the S group and 28 patients as the C group in this study. Both groups were similar in age and ASA-PS, but the S group had more female patients and larger tumors. The median duration of S-1 chemotherapy was 273 days in the S group and 358.5 days in the C group, with similar 1-year continuation rates. The median overall survival of these patients was 24.1 months in the S group and 45.6 months in the C group, with a 5-year survival rate of 23.7% in the S group and 22.0% in the C group. There was no significant difference. Recurrence occurred in 35 patients in the S group and 20 in the C group, with peritoneal metastasis as the most common recurrence site in both groups. CONCLUSIONS Primary surgery and S-1 chemotherapy could be considered a viable treatment option, even for Type 4 or large Type 3 gastric cancer with CY1.
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Affiliation(s)
- Ryota Sakon
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan
| | - Tsutomu Hayashi
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Rei Ogawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Masashi Nishino
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Kenichi Ishizu
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Takeyuki Wada
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Yukinori Yamagata
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Hiroyuki Daiko
- Course of Advanced Clinical Research of Cancer, Juntendo University Graduate School of Medicine, Bunkyo-ku, Japan
- Department of Esophageal Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tsukiji Chuo-Ku, Japan
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Bąk M, Wojciech M, Pielech A, Holka S, Zawadzki M, Murawa D. The Advancement Stage of Gastric Cancer and the Levels of CEA and Ca19-9 in Serum and Peritoneal Lavage. Biomedicines 2024; 12:2584. [PMID: 39595150 PMCID: PMC11592263 DOI: 10.3390/biomedicines12112584] [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: 09/26/2024] [Revised: 10/30/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND This study aimed to analyze the relationship between the levels of tumor markers-specifically, carcinoembryonic antigen (CEA) and Ca19-9 antigen-determined in both serum (sCEA and sCa19-9) and intraoperative peritoneal washings (pCEA and pCa19-9) and the advanced stage of gastric cancer (including the occurrence of cancer cells in cytology from abdominal fluid). METHODS This study included 47 patients with histopathologically confirmed gastric cancer or gastroesophageal junction cancer who underwent surgical treatment. The material for the cytological examination and assessment of CEA and Ca19-9 concentrations in peritoneal fluid was collected intraoperatively. Later, blood was drawn to assess the CEA and Ca19-9 concentrations in blood serum. RESULTS There was a statistical correlation between a positive cytology result or the presence of peritoneal carcinomatosis and a positive result for the tumor markers obtained from abdominal washings. This correlation was not observed with marker levels obtained from blood serum. The pCEA marker was highly sensitive (93.3%) and specific (93.8%) for detecting cancer cells. The pCa19-9 marker was less effective in detecting cancer but matched pCEA in identifying the absence of cancer. No differences were observed in sCEA and sCA19-9 levels between patients who underwent neoadjuvant chemotherapy and those who did not receive this treatment. However, statistical analysis showed that this relationship did not apply to pCEA and pCa19-9 levels. CONCLUSIONS Intraoperative determinations of tumor marker levels in peritoneal washings may be a predictive factor for a poor prognosis in patients with gastric cancer.
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Affiliation(s)
- Michał Bąk
- General and Oncological Surgery, The Karol Marcinkowski University Hospital in Zielona Góra, 65-046 Zielona Góra, Poland
- Department of Surgery and Oncology, University of Zielona Góra, 65-417 Zielona Góra, Poland
| | - Magdalena Wojciech
- Institute of Mathematics, University of Zielona Góra, 65-417 Zielona Góra, Poland
| | - Adrianna Pielech
- General and Oncological Surgery, The Karol Marcinkowski University Hospital in Zielona Góra, 65-046 Zielona Góra, Poland
| | - Sylwia Holka
- Department of Pathomorphology, The Karol Marcinkowski University Hospital in Zielona Góra, 65-046 Zielona Góra, Poland
| | - Marek Zawadzki
- Faculty of Medicine, Wroclaw University of Science and Technology, 50-370 Wrocław, Poland
| | - Dawid Murawa
- General and Oncological Surgery, The Karol Marcinkowski University Hospital in Zielona Góra, 65-046 Zielona Góra, Poland
- Department of Surgery and Oncology, University of Zielona Góra, 65-417 Zielona Góra, Poland
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Mizuno K, Isaka M, Terada Y, Konno H, Mizuno T, Tone K, Kawata T, Nakajima T, Funai K, Ohde Y. Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer. Gen Thorac Cardiovasc Surg 2024; 72:127-133. [PMID: 37395938 DOI: 10.1007/s11748-023-01954-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 06/17/2023] [Indexed: 07/04/2023]
Abstract
OBJECTIVE Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. METHODS A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. RESULTS The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. CONCLUSIONS Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.
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Affiliation(s)
- Kiyomichi Mizuno
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
- First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Mitsuhiro Isaka
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan.
| | - Yukihiro Terada
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Hayato Konno
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Tetsuya Mizuno
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Kiyoshi Tone
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Takuya Kawata
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Takashi Nakajima
- Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
| | - Kazuhito Funai
- First Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Yasuhisa Ohde
- Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, Japan
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Bausys A, Ümarik T, Dobrzhanskyi O, Luksta M, Kondratskyi Y, Reinsoo A, Vassiljev M, Bausys B, Bickaite K, Rauduvyte K, Luksaite-Lukste R, Bausys R, Strupas K. Neoadjuvant Chemotherapy Followed by Gastrectomy for Cytology-Positive Gastric Cancer without Any Other Non-Curative Factors in a Western Setting: An International Eastern European Cohort Study. Cancers (Basel) 2023; 15:5794. [PMID: 38136339 PMCID: PMC10741658 DOI: 10.3390/cancers15245794] [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: 10/18/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16-25) and 19 (95% CI: 11-20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03-0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.
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Affiliation(s)
- Augustinas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Toomas Ümarik
- Upper Gastrointestinal Tract Surgery Department, North Estonia Medical Centre, 13419 Tallinn, Estonia; (T.Ü.)
| | - Oleksii Dobrzhanskyi
- Upper Gastrointestinal Tumors Department, National Cancer Institute, 03022 Kyiv, Ukraine; (O.D.)
| | - Martynas Luksta
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Yourii Kondratskyi
- Upper Gastrointestinal Tumors Department, National Cancer Institute, 03022 Kyiv, Ukraine; (O.D.)
| | - Arvo Reinsoo
- Upper Gastrointestinal Tract Surgery Department, North Estonia Medical Centre, 13419 Tallinn, Estonia; (T.Ü.)
| | - Mihhail Vassiljev
- Pathology Department, North Estonia Medical Centre, 13419 Tallinn, Estonia
| | - Bernardas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Klaudija Bickaite
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Kornelija Rauduvyte
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Raminta Luksaite-Lukste
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
| | - Rimantas Bausys
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Department of Abdominal Surgery and Oncology, National Cancer Institute, 08406 Vilnius, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
- Centre for Visceral Medicine and Translational Research, Faculty of Medicine, Institute of Clinical Medicine, Vilnius University, 03101 Vilnius, Lithuania
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Liu P, Ding P, Wu H, Wu J, Yang P, Tian Y, Guo H, Zhao Q. Prediction of occult peritoneal metastases or positive cytology using CT in gastric cancer. Eur Radiol 2023; 33:9275-9285. [PMID: 37414883 DOI: 10.1007/s00330-023-09854-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 04/17/2023] [Accepted: 04/19/2023] [Indexed: 07/08/2023]
Abstract
OBJECTIVE Accurate prediction of preoperative occult peritoneal metastasis (OPM) is critical to selecting appropriate therapeutic regimen for gastric cancer (GC). Considering the clinical practicability, we develop and validate a visible nomogram that integrates the CT images and clinicopathological parameters for the individual preoperative prediction of OPM in GC. METHODS This retrospective study included 520 patients who underwent staged laparoscopic exploration or peritoneal lavage cytology (PLC) examination. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of OPM risk. The performance of the model was detected by using ROC, accuracy, and C-index. The bootstrap resampling method was considered internal validation of the model. The Delong test was used to evaluate the difference in AUC between the two models. RESULTS Grade 2 mural stratification, tumor thickness, and the Lauren classification diffuse were significant predictors of OPM (p < 0.05). The nomogram of these three factors (compared with the original model) showed a higher predictive effect (p < 0.001). The area under the curve (AUC) of the model was 0.830 (95% CI 0.788-0.873), and the internally validated AUC of 1000 bootstrap samples was 0.826 (95% CI 0.756-0.870). The sensitivity, specificity, and accuracy were 76.0%, 78.8%, and 78.3%, respectively. CONCLUSIONS CT phenotype-based nomogram demonstrates favorable discrimination and calibration, and it can be conveniently used for preoperative individual risk rating of OPM in GC. CLINICAL RELEVANCE STATEMENT In this study, the preoperative OPM prediction model based on CT images (mural stratification, tumor thickness) combined with pathological parameters (the Lauren classification) showed excellent predictive ability in GC, and it is also suitable for clinicians to use rather than limited to professional radiologists. KEY POINTS • Nomogram based on CT image analysis can effectively predict occult peritoneal metastasis in gastric cancer (training area under the curve (AUC) = 0.830 and bootstrap AUC = 0.826). • Nomogram model combined with CT features performed better than the original model (established using only clinicopathological parameters) in differentiating occult peritoneal metastasis of gastric cancer.
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Affiliation(s)
- Pengpeng Liu
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Ping'an Ding
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Haotian Wu
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Jiaxiang Wu
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Peigang Yang
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Yuan Tian
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Honghai Guo
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China
| | - Qun Zhao
- The Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
- Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric Cancer, Shijiazhuang, China.
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Liu L, Zheng L, Liu S, Zhang M, Zhang S, Jiang Z, Qin C, Wang D. Prognostic Analysis of Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Advanced Gastric Cancer: a Propensity Score-Matched Analysis. J Gastrointest Surg 2023; 27:2297-2307. [PMID: 37715013 DOI: 10.1007/s11605-023-05823-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 08/18/2023] [Indexed: 09/17/2023]
Abstract
PURPOSE To investigate the efficacy of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). METHODS We included 198 patients treated from December 2016 to January 2019; of these patients, the 132 who had clinical T4 gastric cancer were divided into a hyperthermic intraperitoneal chemotherapy group (HIPEC group) and a radical gastrectomy and D2 lymph node dissection group (control group). Because this study was retrospective, we used propensity score matching (PSM) to reduce selectivity bias; we then assessed risk factors for recurrence and compared prognosis in terms of survival in the gastrectomy and prophylactic HIPEC groups. RESULTS Prophylactic HIPEC reduced the risk of postoperative peritoneal metastasis (PM: 27.5% vs. 10.5%, P = 0.015) and did not increase the risk of postoperative complications, but there was no significant difference in the effect on hepatic metastases or other distant metastases. Risk factors for recurrence included pT4 staging and positive lymph node metastases. Both disease-free survival (DFS: HR 0.592; 95% CI 0.354-0.990; P = 0.042) and peritoneal recurrence-free survival (PFS: HR 0.314; 95% CI 0.127-0.774; P = 0.008) were better in the prophylactic HIPEC group than in the gastrectomy-only group. In addition, there was no difference in the prognosis of patients between the two groups of raltitrexed (RT) and paclitaxel (PTX) for perfusion dosing. CONCLUSION Our study showed that prophylactic HIPEC could prevent postoperative PM in patients with AGC and did not increase the incidence of postoperative complications. However, it was not found to be effective in the prevention of other metastases, such as hepatic metastases.
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Affiliation(s)
- Lei Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Longbo Zheng
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Shanglong Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Maoshen Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Simeng Zhang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Zinian Jiang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Chen Qin
- Department of Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, 266042, China.
| | - Dongsheng Wang
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
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Chen X, Wu Z, He Y, Hao Z, Wang Q, Zhou K, Zhou W, Wang P, Shan F, Li Z, Ji J, Fan Y, Li Z, Yue S. Accurate and Rapid Detection of Peritoneal Metastasis from Gastric Cancer by AI-Assisted Stimulated Raman Molecular Cytology. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023:e2300961. [PMID: 37114845 PMCID: PMC10375130 DOI: 10.1002/advs.202300961] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Revised: 04/04/2023] [Indexed: 06/19/2023]
Abstract
Peritoneal metastasis (PM) is the mostcommon form of distant metastasis and one of the leading causes of death in gastriccancer (GC). For locally advanced GC, clinical guidelines recommend peritoneal lavage cytology for intraoperative PM detection. Unfortunately, current peritoneal lavage cytology is limited by low sensitivity (<60%). Here the authors established the stimulated Raman molecular cytology (SRMC), a chemical microscopy-based intelligent cytology. The authors firstly imaged 53 951 exfoliated cells in ascites obtained from 80 GC patients (27 PM positive, 53 PM negative). Then, the authors revealed 12 single cell features of morphology and composition that are significantly different between PM positive and negative specimens, including cellular area, lipid protein ratio, etc. Importantly, the authors developed a single cell phenotyping algorithm to further transform the above raw features to feature matrix. Such matrix is crucial to identify the significant marker cell cluster, the divergence of which is finally used to differentiate the PM positive and negative. Compared with histopathology, the gold standard of PM detection, their SRMC method could reach 81.5% sensitivity, 84.9% specificity, and the AUC of 0.85, within 20 minutes for each patient. Together, their SRMC method shows great potential for accurate and rapid detection of PM from GC.
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Affiliation(s)
- Xun Chen
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
- School of Engineering Medicine, Beihang University, 100191, Beijing, China
| | - Zhouqiao Wu
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Yexuan He
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
| | - Zhe Hao
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
| | - Qi Wang
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Keji Zhou
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
| | - Wanhui Zhou
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
| | - Pu Wang
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
| | - Fei Shan
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Jiafu Ji
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Yubo Fan
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
- School of Engineering Medicine, Beihang University, 100191, Beijing, China
| | - Ziyu Li
- Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, 100142, Beijing, China
| | - Shuhua Yue
- Key Laboratory of Biomechanics and Mechanobiology, Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, 100191, Beijing, China
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Surgical Options for Peritoneal Surface Metastases from Digestive Malignancies-A Comprehensive Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020255. [PMID: 36837456 PMCID: PMC9960111 DOI: 10.3390/medicina59020255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023]
Abstract
The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.
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Zhou Y, Qi M, Zhou YX, Fang SQ. Application of intraperitoneal hyperthermic perfusion chemotherapy in gastric cancer. Shijie Huaren Xiaohua Zazhi 2023; 31:1-7. [DOI: 10.11569/wcjd.v31.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Gastric cancer is one of the most common malignant tumors in China. Intraperitoneal hyperthermic perfusion chemotherapy is a comprehensive therapy that combines intraperitoneal perfusion, hyperthermia, and chemotherapy. It has a good curative effect in peritoneal metastasis of gastric cancer. In recent years, with the continuous progress of technology and the deepening of research, the scope of application of intraperitoneal hyperthermic perfusion chemotherapy is more extensive. In this paper, we discuss intraperitoneal hyperthermic perfusion chemotherapy with regard to its application in gastric cancer, commonly used drugs, safety, and prospects.
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Affiliation(s)
- Yue Zhou
- Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese medicine, Shanghai 200437, China
| | - Mei Qi
- Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese medicine, Shanghai 200437, China
| | - Yu-Xuan Zhou
- Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese medicine, Shanghai 200437, China
| | - Sheng-Quan Fang
- Department of Gastroenterology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese medicine, Shanghai 200437, China
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10
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Foster JM, Zhang C, Rehman S, Sharma P, Alexander HR. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA Cancer J Clin 2023; 73:49-71. [PMID: 35969103 DOI: 10.3322/caac.21749] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 01/17/2023] Open
Abstract
Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.
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Affiliation(s)
- Jason M Foster
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Chunmeng Zhang
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shahyan Rehman
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey
| | - Prateek Sharma
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
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Chung YH, Volckaert BA, Steinmetz NF. Metastatic Colon Cancer Treatment Using S100A9-Targeted Cowpea Mosaic Virus Nanoparticles. Biomacromolecules 2022; 23:5127-5136. [PMID: 36375170 PMCID: PMC9772157 DOI: 10.1021/acs.biomac.2c00873] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Peritoneal metastases (PMs) occur due to the metastasis of gynecological and gastrointestinal cancers such as ovarian, colon, pancreatic, or gastric tumors. PM outgrowth is often fatal, and patients with PMs have a median survival of 6 months. Cowpea mosaic virus (CPMV) has been shown, when injected intratumorally, to act as an immunomodulator reversing the immunosuppressive tumor microenvironment, therefore turning cold tumors hot and priming systemic antitumor immunity. However, not all tumors are injectable, and PMs especially will require targeted treatments to direct CPMV toward the disseminated tumor nodules. Toward this goal, we designed and tested a CPMV nanoparticle targeted to S100A9, a key immune mediator for many cancer types indicated in cancer growth, invasiveness, and metastasis. Here, we chose to use an intraperitoneal (IP) colon cancer model, and analysis of IP gavage fluid demonstrates that S100A9 is upregulated following IP challenge. S100A9-targeted CPMV particles displaying peptide ligands specific for S100A9 homed to IP-disseminated tumors, and treatment led to improved survival and decreased tumor burden. Targeting CPMV to S100A9 improves preclinical outcomes and harbors the potential of utilizing CPMV for the treatment of IP-disseminated diseases.
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Affiliation(s)
- Young Hun Chung
- Department of Bioengineering and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0021, United States
| | - Britney A. Volckaert
- Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093-0021, United States
| | - Nicole F. Steinmetz
- Corresponding Author: Nicole F. Steinmetz – Department of Bioengineering, Moores Cancer Center, Department of NanoEngineering, Department of Radiology, Institute for Materials Discovery and Design, Center for Nano-Immuno Engineering, and Center for Engineering in Cancer, University of California, San Diego, La Jolla, California 92093-0021, United States;
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Abstract
BACKGROUND Lavage cytology is a method to detect cancer cells released within the abdominal cavity. It has been widely utilized, in particular, for gastric cancer. However, its clinical significance has not yet been determined in colorectal cancer. OBJECTIVE This study aimed to investigate the frequency of lavage cytology positivity and its influence on the prognosis of patients with colorectal cancer. DESIGN This is a single-institution retrospective observational study. SETTING This study was conducted at a comprehensive cancer center. PATIENTS We retrospectively analyzed 3135 colorectal cancer cases from 2007 to 2013 at our institution. Intraoperative peritoneal washing cytology was performed just after the start of the operation. Fluids were centrifuged for 5 minutes at 2500 rotations per minute, cell pellets were smeared on microscope glass slides, and Papanicolaou staining was performed. MAIN OUTCOME MEASURES The primary outcome was the 5-year overall survival rate. The secondary outcome was the 5-year recurrence rate. RESULTS Lavage cytology positivity was detected in 19 (2.0%) and 86 (16.9%) cases of stage III and IV colorectal cancer; however, no positive cases were found in stage I and II colorectal cancer. Lavage cytology positivity was an independent prognostic factor in stage III and IV colorectal cancer in the multivariate analysis (5-year mortality HR 3.59 [1.69-7.64] in stage III, 2.23 [1.15-4.31] in stage IV). The prognosis of the 5-year survival rate was significantly worse in the lavage cytology-positive group in stages III and IV. In terms of recurrence, the results of the lavage cytology-positive group in stage III were similar to those of the lavage cytology-positive/negative group in stage IV (73.7%, 70.0%, and 75.0%). LIMITATIONS This study was limited by its retrospective study design. CONCLUSIONS Lavage cytology positivity is an independent prognostic and regulatory factor of stage IV colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B770.INCIDENCIA Y VALOR PRONÓSTICO EN LA CITOLOGÍA DEL LAVADO PERITONEAL EN CÁNCER COLORECTALANTECEDENTES:La citología del lavado peritoneal es un método para detectar células cancerosas liberadas dentro de la cavidad abdominal. Se ha utilizado ampliamente, en particular para el cáncer gástrico. Sin embargo, aún no se ha determinado su importancia clínica en el cáncer colorrectal.OBJETIVO:Este estudio tuvo como objetivo investigar la frecuencia de positividad de la citología del lavado y su influencia en el pronóstico de los pacientes con cáncer colorrectal.DISEÑO:Este fue un estudio observacional retrospectivo de una sola institución.DISENTORNO CLÍNICO:El estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Analizamos retrospectivamente 3.135 casos de cáncer colorrectal desde 2007 hasta 2013 en nuestra institución. La citología de lavado peritoneal intraoperatorio se realizó inmediatamente después del inicio de la operación. Los fluidos se centrifugaron durante 5 min a 2.500 rpm, los sedimentos celulares se extendieron sobre portaobjetos de vidrio de microscopio y se realizó la tinción con Papanicolaou.DISPRINCIPALES MEDIDAS DE VALORACIÓN:El primer resultado fueron las tasas de supervivencia general a 5 años. El segundo resultado las tasas de recurrencia a los 5 años.RESULTADOS:Se detectó positividad en la citología de lavado en 19 (2,0%) y 86 (16,9%) casos de cáncer colorrectal en estadio III y IV, respectivamente; sin embargo, no se encontraron casos positivos en el cáncer colorrectal en estadio I y II. La positividad de la citología de lavado fue un factor pronóstico independiente en el cáncer colorrectal en estadio III y IV en el análisis multivariado [cociente de riesgo de mortalidad a 5 años 3,59 (1,69-7,64), en estadio III, 2,23 (1,15-4,31), en estadio IV]. El pronóstico de la tasa de supervivencia a 5 años fue significativamente peor en el grupo con citología de lavado positiva en los estadios III y IV. En cuanto a la recurrencia, los resultados del grupo de lavado con citología positiva en el estadio III fueron similares a los del grupo de lavado con citología positiva / negativa en el estadio IV (73,7%, 70,0% y 75,0%).LIMITACIONES:Este estudio estuvo limitado por su diseño de estudio retrospectivo.CONCLUSIONES:La positividad de la citología de lavado es un factor pronóstico y regulador independiente del cáncer colorrectal en estadio IV. Consulte Video Resumen en http://links.lww.com/DCR/B770. (Traducción- Dr. Ingrid Melo).
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Young S, Ou R, Dehal A, O'Connor VV, DiFronzo LA. Peritoneal Lavage Cytology Following Neoadjuvant Chemotherapy for Gastric Adenocarcinoma: Low Yield in Detecting Peritoneal Metastases. Am Surg 2022; 88:1084-1089. [PMID: 33382351 DOI: 10.1177/0003134820984867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of neoadjuvant chemotherapy (NAC) on cytological detection of carcinomatosis is unknown. METHODS Using a 2012-2020 prospective database, we retrospectively reviewed patients with GC who underwent NAC followed by a staging laparoscopic peritoneal lavage with or without biopsy of suspicious peritoneal nodules. PLC results were considered discordant if they did not align with the peritoneal biopsy results. Patients with benign peritoneal cytology (Cyt-) or biopsy results who had postoperative time to carcinomatosis of <6 months were considered to have diagnostic failure of peritoneal lavage. RESULTS Fifty-five patients with GC who underwent NAC followed by staging diagnostic laparoscopy with peritoneal lavage were identified. The majority of the patients in the cohort had Cyt- lavage (89.1%). Of the patients who underwent resection, 76.1% had T3 or greater disease on final pathology and 66% had nodal metastases. In 23 patients (41.8%) who had both peritoneal lavage and biopsy, four cases (17.4%) had discordant results. Diagnostic failure rate was 20% at 6 months and 42.2% at 12 months. The median time to carcinomatosis in patients who were Cyt- or biopsy negative was 7.9 months. CONCLUSION PLC after NAC has a high diagnostic failure rate and inaccurately predicts carcinomatosis in 20% of patients with GC. Novel methods for identifying cytology positive GC after NAC should also be developed and evaluated, since the risk of peritoneal dissemination is high.
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Affiliation(s)
- Stephanie Young
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Ryan Ou
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Ahmed Dehal
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Victoria V O'Connor
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - L Andrew DiFronzo
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
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Lee TY, Hsu CH, Fan HL, Liao GS, Chen TW, Chan DC. Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1972-1979. [DOI: 10.1016/j.ejso.2022.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/09/2022] [Accepted: 04/22/2022] [Indexed: 11/17/2022]
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Bausys A, Gricius Z, Aniukstyte L, Luksta M, Bickaite K, Bausys R, Strupas K. Current treatment strategies for patients with only peritoneal cytology positive stage IV gastric cancer. World J Clin Cases 2021; 9:9711-9721. [PMID: 34877310 PMCID: PMC8610919 DOI: 10.12998/wjcc.v9.i32.9711] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/28/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and surgery remains the only potentially curative treatment option for it. Although a significant proportion of GC patients are found with distant metastases already at the initial diagnosis. Peritoneal dissemination is the most common site of metastases. Positive peritoneal cytology (Cy1) is associated with poor long-term outcomes; thus, these patients are considered as stage IV even if macroscopic carcinomatosis is absent. Currently, there is no clear evidence for the most optimal treatment for this distinct subpopulation of the stage IV cohort. Available strategies vary from palliative chemotherapy to upfront gastrectomy. This comprehensive review summarized current evidence of different treatment strategies for Cy1 GC including roles of surgery, systemic and intraperitoneal chemotherapy.
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Affiliation(s)
- Augustinas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | - Zilvinas Gricius
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Laura Aniukstyte
- Faculty of Medicine, Vilnius University, Vilnius 08406, Lithuania
| | - Martynas Luksta
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius 03101, Lithuania
| | | | - Rimantas Bausys
- Department of Abdominal Surgery and Oncology, National Cancer Institute, Vilnius 08406, Lithuania
| | - Kestutis Strupas
- Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius University, Vilnius 03101, Lithuania
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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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17
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Takebayashi K, Murata S, Kodama H, Kaida S, Yamaguchi T, Ishikawa K, Shimoji M, Miyake T, Ueki T, Kojima M, Iida H, Maehira H, Shimizu T, Tani M. Long-term prognosis of patients with cancer-related genes detected in postoperative peritoneal washings obtained during curative gastrectomy. Eur J Surg Oncol 2021; 48:177-182. [PMID: 34034940 DOI: 10.1016/j.ejso.2021.05.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/03/2021] [Accepted: 05/03/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Cancer cells in intraoperative peritoneal washings (PW) indicate increased peritoneal recurrence. Detection of CEA or CK20 genes indicates poor prognosis. We assessed long-term prognosis of patients with amplification of cancer-related genes in PW obtained intraoperatively during curative gastric cancer surgery. METHODS PW was collected before and immediately after curative gastrectomy. CEA, CK20, TFF1, MUC2, and FABP1-mRNA were selected as marker genes for reverse transcription polymerase chain reaction. Peritoneal recurrence-free survival (PRFS) and overall survival (OS) after >7-year follow-up were examined using the Kaplan-Meier method. RESULTS Of 138 patients who underwent gastrectomy with negative cytological findings at laparotomy, 80 patients showed negative cancer-related gene amplification in preoperative PW. Fifty-eight patients were excluded due to positive gene amplification, which suggested presence of preoperative peritoneal cancer cells. The 80 patients had mRNA amplification in PW after surgery. Amplification of multiple and single cancer-related marker genes was observed in 38 and 21 patients; 21 cases had marker-negative results. Five-year PRFS was 69.1%, 95.2%, and 100% in multi-marker-positive, single marker-positive, and marker-negative cases, respectively. Multi-marker-positive patients had significantly worse PRFS than the other groups (p < 0.05). Multivariate analysis in the Cox proportional hazards model identified multi-marker-positivity as an independent prognostic factor for PRFS (hazard ratio, 7.6; 95% confidence interval, 1.07-62.63; p = 0.046), and multi-marker-positive patients had significantly worse OS than other groups (p < 0.01). CONCLUSION Multi-marker cancer-related gene amplification in PW is associated with worse prognosis in PRFS and OS even after a long follow-up; PRFS can be stratified by the number of genes amplified.
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Affiliation(s)
- Katsushi Takebayashi
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Satoshi Murata
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan; Cancer Center, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
| | - Hirokazu Kodama
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Tsuyoshi Yamaguchi
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Ken Ishikawa
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Miyuki Shimoji
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Tomoyuki Ueki
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Masatsugu Kojima
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Hiroya Iida
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Hiromitsu Maehira
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Tomoharu Shimizu
- Medical Safety Section, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
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Fujita K, Omori T, Hara H, Shinno N, Yamamoto M, Aoyama Y, Sugimura K, Kanemura T, Takeoka T, Yasui M, Matsuda C, Takahashi H, Wada H, Nishimura J, Haraguchi N, Hasegawa S, Nakai N, Asukai K, Mukai Y, Miyata H, Ohue M, Sakon M. Clinical importance of carcinoembryonic antigen messenger RNA level in peritoneal lavage fluids measured by transcription-reverse transcription concerted reaction for advanced gastric cancer in laparoscopic surgery. Surg Endosc 2021; 36:2514-2523. [PMID: 33999253 DOI: 10.1007/s00464-021-08539-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 04/30/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer. METHODS We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity. RESULTS A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence. CONCLUSIONS TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy.
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Affiliation(s)
- Kohei Fujita
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Takeshi Omori
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan.
| | - Hisashi Hara
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Naoki Shinno
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masaaki Yamamoto
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Yoshimasa Aoyama
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Keijiro Sugimura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Takashi Kanemura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Tomohira Takeoka
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masayoshi Yasui
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Chu Matsuda
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hidenori Takahashi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Junichi Nishimura
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Naotsugu Haraguchi
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Shinichiro Hasegawa
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Nozomu Nakai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Kei Asukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Yosuke Mukai
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Hiroshi Miyata
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masayuki Ohue
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
| | - Masato Sakon
- Department of Gastroenterological Surgery, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan
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Harris MC, Cockbain AJ, McQuillan PW, Kanhere HA. Survey and literature review on the importance of peritoneal cytology in staging and treatment of gastric cancer: always wash it before you treat it. ANZ J Surg 2021; 91:13-18. [PMID: 33590628 DOI: 10.1111/ans.16295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Mark C Harris
- Division of Surgery, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.,School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Andrew J Cockbain
- Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Patrick W McQuillan
- Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Harsh A Kanhere
- Division of Surgery, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.,School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.,Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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20
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Yamaguchi T, Takashima A, Nagashima K, Terashima M, Aizawa M, Ohashi M, Tanaka R, Yamada T, Kinoshita T, Matsushita H, Ishiyama K, Hosoda K, Yuasa Y, Haruta S, Kakihara N, Nishikawa K, Yunome G, Satoh T, Fukagawa T, Katai H, Boku N. Impact of preoperative chemotherapy as initial treatment for advanced gastric cancer with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) or localized peritoneal metastasis (P1a): a multi-institutional retrospective study. Gastric Cancer 2021; 24:701-709. [PMID: 33179192 DOI: 10.1007/s10120-020-01137-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 10/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer (GC) patients with peritoneal metastasis are defined as stage IV in the Japanese classification of GC. For patients with peritoneal metastasis limited to positive peritoneal lavage cytology (CY1) and/or localized peritoneal metastasis (P1a), gastrectomy followed by S1 monotherapy is one of the most widely accepted therapeutic strategy in Japan. This study investigated the efficacy of preoperative chemotherapy as initial treatment in GC patients with CY1 and/or P1a. METHODS We retrospectively reviewed GC patients diagnosed with CY1 and/or P1a at 34 institutions in Japan between 2008 and 2012. Selection criteria were: adenocarcinoma, no distant metastasis except CY1 or P1a, and no prior treatment. The subjects were divided into an Initial-Chemotherapy group and an Initial-Surgery group, according to the initial treatment. RESULTS A total of 824 patients were collected and 713 eligible patients were identified for this study. As the initial treatment, 150 patients received chemotherapy (Initial-Cx), and 563 patients underwent surgery (Initial-Sx). Initial-Cx regimens were cisplatin plus S1/docetaxel plus cisplatin plus S1/others (n = 90/37/23). Both overall survival (OS) and progression-free survival (PFS) were similar between the Initial-Cx and Initial-Sx groups (median OS 24.8 and 24.0 months, HR 1.07, 95% CI 0.87-1.3; median PFS 14.9 and 13.9 months, HR 1.04, 95% CI 0.85-1.27). The 5-year OS rates were 22.3% in the Initial-Cx group and 21.5% in the Initial-Sx group. CONCLUSIONS Although, the preoperative chemotherapy did not show a survival benefit for GC patients with CY1 and/or P1a, initial-Cx showed favorable survival in patients who converted to P0 and CY0.
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Affiliation(s)
- Toshifumi Yamaguchi
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Atsuo Takashima
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
| | - Kengo Nagashima
- Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
| | | | - Masaki Aizawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan
| | - Ryo Tanaka
- Department of General and Gastroenterological Surgery, Osaka Medical College Hospital, Takatsuki, Japan
| | - Tatsuya Yamada
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Takahiro Kinoshita
- Gastric Surgery Division, National Cancer Center Hospital East, Kashiwa, Japan
| | | | - Koshiro Ishiyama
- Department of Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Kei Hosoda
- Department of Upper Gastrointestinal Surgery, Kitasato University School of Medicine, Tokyo, Japan
| | - Yasuhiro Yuasa
- Department of Gastroenterological Surgery, Tokushima Red Cross Hospital, Komatsu, Japan
| | - Shusuke Haruta
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | - Naoki Kakihara
- Department of Surgery, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Kazuhiro Nishikawa
- Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Gen Yunome
- Department of Surgery, Sendai Medical Center, Sendai, Japan
| | - Taroh Satoh
- Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takeo Fukagawa
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Hitoshi Katai
- Division of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Narikazu Boku
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
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21
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Fan B, Bu Z, Zhang J, Zong X, Ji X, Fu T, Jia Z, Zhang Y, Wu X. Phase II trial of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer after curative surgery. BMC Cancer 2021; 21:216. [PMID: 33653317 PMCID: PMC7923597 DOI: 10.1186/s12885-021-07925-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 02/17/2021] [Indexed: 11/10/2022] Open
Abstract
Background HIPEC is an emerging procedure to treat peritoneal metastasis of gastric cancer. Data about HIPEC in locally advanced gastric cancer is scarce. The purpose of this trial is to evaluate the safety and toxicity of prophylactic HIPEC with cisplatin for patients with locally advanced gastric cancer. Methods From March 2015 to November 2016, a prospective, randomized phase II trial was conducted. After radical gastrectomy, patients in the experimental group underwent HIPEC with cisplatin followed by adjuvant chemotherapy with SOX regime. Patients in the other group were treated with SOX regime alone. Postoperative complications and patient survival were compared. Results In total, 50 patients were eligible for analyses. No significant difference was found in the incidence of postoperative complications including anastomotic/intestinal leakage, liver dysfunction, bone marrow suppression, wound infection and ileus (P > 0.05). Mean duration of hospitalization after radical gastrectomy was 11.7 days. 12.2 days in experimental group and 10.8 days in control group respectively (P = 0.255). The percentage of patients with elevated tumor markers was 12.1% in experimental group, which was significantly lower than 41.2% in control group (P = 0.02). 3-year RFS of patients who treated with or without prophylactic HIPEC were 84.8 and 88.2% respectively (P = 0.986). In the multivariate analysis, pathological T stage was the only independent risk factor for the RFS of patients (P = 0.012, HR =15.071). Conclusion Additional intraoperative HIPEC with cisplatin did not increase postoperative complications for locally advanced gastric cancer after curative surgery. Prophylactic HIPEC with cisplatin was safe and tolerable, while it did not reduce the risk of peritoneal recurrence in this trial, supporting further studies to validate the efficacy of it. Trial registration Chinese Clinical Trial Registry, ChiCTR2000038331. Registered 18 September 2020 - Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=59692.
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Affiliation(s)
- Biao Fan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Xianglong Zong
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Tao Fu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Ziyu Jia
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Yinan Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer center, Peking University Cancer Hospital and Institute, Fu-Cheng Road 52#, Hai-Dian District, Beijing, 100142, China.
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22
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Parray A, Gupta V, Chaudhari VA, Shrikhande SV, Bhandare MS. Role of intraperitoneal chemotherapy in gastric cancer. SURGERY IN PRACTICE AND SCIENCE 2021. [DOI: 10.1016/j.sipas.2020.100025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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23
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Yoshida M, Esaki M, Satoh T, Yamakawa S, Nakajima N, Ono H, Gotoda T. Transrectal laparoscopy using flexible endoscopy with a submucosal tunneling method: Porcine survival model. Dig Endosc 2021; 33:133-140. [PMID: 32275783 DOI: 10.1111/den.13683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 03/27/2020] [Accepted: 04/01/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Transrectal laparoscopy (TRLS) using a flexible endoscope was recently proposed for peritoneal observation. Although previous studies have reported its feasibility, follow-up durations were insufficient to ascertain technical safety. Moreover, knowledge about the technical feasibility of collecting peritoneal cytological lavage or ascites during TRLS is limited. Thus, this study aimed to confirm the safety and efficacy of TRLS in a porcine survival model. METHODS After creating artificial ascites in 10 animals, TRLS was performed as follows: submucosal tunnel creation on the anterior wall of the rectum, intentional perforation at the distal end of the tunnel, endoscopic ascites collection and intraperitoneal observation, and clip closure at the mucosal incision site. The pigs were administered antibiotics orally for 7 days after TRLS and killed for histological evaluation and bacterial culture after 28 days of observation. RESULTS The technical success rates of insertion into the abdominal cavity, ascites collection, and clip closure were 100%. All frequent anatomical sites for peritoneal dissemination including the stomach, subdiaphragmatic space, and pelvic space were fully observable without adverse events. The median procedure time was 36.3 min. Full 28-day survival was observed in all cases without any infection. The autopsies showed no infection, including abscess formation. Bacterial cultures of the peritoneal cavity were negative 28 days after TRLS in all cases. CONCLUSIONS Transrectal laparoscopy enabled ascites collection and intraperitoneal observation without adverse events. All animals survived without peritonitis. Therefore, TRLS can be an option for intraperitoneal examination.
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Affiliation(s)
- Masao Yoshida
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Mitsuru Esaki
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Tatsunori Satoh
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Shun Yamakawa
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Noriko Nakajima
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Hiroyuki Ono
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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Takahashi K, Kurashina K, Saito S, Kanamaru R, Ohzawa H, Yamaguchi H, Miyato H, Hosoya Y, Lefor AK, Sata N, Kitayama J. Flow cytometry-based analysis of tumor-leukocyte ratios in peritoneal fluid from patients with advanced gastric cancer. CYTOMETRY PART B-CLINICAL CYTOMETRY 2020; 100:666-675. [PMID: 33277773 PMCID: PMC9290827 DOI: 10.1002/cyto.b.21978] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 10/29/2020] [Accepted: 11/19/2020] [Indexed: 01/08/2023]
Abstract
Background The frequency of tumor cell dissemination in the peritoneal cavity is critically related to the progression of peritoneal metastases (PM). Recently, flow cytometry (FCM) has been successfully used to detect tumor cells in malignant effusions. Methods A total of 143 single cell suspensions derived from ascites or peritoneal lavages from patients with advanced gastric cancer (GC) were stained with monoclonal antibodies to CD45 and to CD326 as well as 4,6‐diamidino‐2‐phenylindole (DAPI) and FVS780. Using FCM, tumor‐leukocyte ratio (TLR) were calculated from CD45(−)CD326(+) tumor cell counts/ CD45(+)CD326(+) leukocyte counts in DAPI (+) FVS780(−) gated area. In 54 patients, the ratios of CD11b(+), CD4(+) and CD8(+) cells in CD45(+) leukocytes were evaluated in parallel. Results TLR of 69 patients with PM were significantly higher than those of 74 without PM (p < .001) and log(TLR) showed strong correlation with peritoneal cancer index scores in 51 PM (+) patients (r = 0.439). TLR in PM (+) patients also correlated with the ratio of CD11b (+) myeloid cells (r = 0.547), and correlated inversely with those of CD4(+) (r = −0.490) and CD8(+) T cells (r = −0.648). In PM (−) patients who underwent gastrectomy, TLR never exceeded 0.1% in patients with primary GC without serosal involvement (<T4). However, TLR in patients with T4 GC were significantly higher (p < .05) and peritoneal recurrence occurred in 6/8 patients whose TLR exceeded 0.1%. Conclusion TLR in peritoneal fluid reflects tumor burden and the immune environment in peritoneal cavity. Multicolor FCM may provide additional information which can be used for the treatment of the patients with PM.
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Affiliation(s)
- Kazuya Takahashi
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Kentaro Kurashina
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Shin Saito
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Rihito Kanamaru
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Hideyuki Ohzawa
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan
| | - Hironori Yamaguchi
- Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan
| | - Hideyo Miyato
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Yoshinori Hosoya
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Alan Kawarai Lefor
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Naohiro Sata
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
| | - Joji Kitayama
- Department of Gastrointestinal Surgery, Jichi Medical University, Shimotsuke, Japan
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He Q, Zhu J, Wang A, Ji K, Ji X, Zhang J, Wu X, Li X, Bu Z, Ji J. A decision analysis comparing three strategies for peritoneal lavage cytology testing in staging of gastric cancer in China. Cancer Med 2020; 9:8940-8949. [PMID: 33047873 PMCID: PMC7724308 DOI: 10.1002/cam4.3518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Positive peritoneal cytology (PCY) indicates metastasis (M1) in gastric cancer (GC) patients; both the American and Chinese guidelines recommend laparoscopic peritoneal lavage (LPL) for cytology. However, relatively high costs impair the widespread use of LPL in some resource-limited regions in China, and the cost-effectiveness of PCY testing remains unclear. Therefore, we performed a decision analysis to evaluate the cost-effectiveness of PCY testing by comparing the guideline-recommended intraoperative LPL, a newly proposed preoperative percutaneous peritoneal lavage (PPL), and a third strategy of exploratory laparotomy with no cytology testing (ELNC) among GC patients. METHODS We developed a decision-analytic Markov model of the aforementioned three strategies for a hypothetical cohort of GC patients with curative intent after initial imaging, from the perspective of Chinese society. We estimated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) as primary outcomes; we also conducted one-way and probabilistic sensitivity analyses to investigate the model's robustness. RESULTS We found that ELNC was dominated (i.e., more expensive and less effective) by PPL and LPL. LPL was the most cost-effective method with an ICER of US$17,200/QALY compared to PPL, which was below the Chinese willingness-to-pay (WTP) threshold of US$29,313 per QALY gained. In sensitivity analyses, PPL was more likely to be cost-effective with a lower WTP threshold. CONCLUSIONS Cytology testing through either LPL or PPL was less expensive and more effective than ELNC among GC patients. Moreover, LPL was the most cost-effective modality at the current WTP threshold, while PPL could potentially be cost-effective in lower-income areas.
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Affiliation(s)
- Qifei He
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Jinyi Zhu
- Center for Health Decision ScienceHarvard T.H. Chan School of Public HealthBostonMAUSA
| | - Anqiang Wang
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Ke Ji
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Xin Ji
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Ji Zhang
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Xiaojiang Wu
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Xia Li
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
| | - Zhaode Bu
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
| | - Jiafu Ji
- Department of Gastrointestinal SurgeryKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education)Peking University Cancer Hospital & InstituteBeijingChina
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Alavi S, Haeri A, Mahlooji I, Dadashzadeh S. Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy. Pharm Res 2020; 37:119. [DOI: 10.1007/s11095-020-02818-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 04/06/2020] [Indexed: 12/12/2022]
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Fu Q, Yu Z. Phosphoglycerate kinase 1 (PGK1) in cancer: A promising target for diagnosis and therapy. Life Sci 2020; 256:117863. [PMID: 32479953 DOI: 10.1016/j.lfs.2020.117863] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/26/2020] [Accepted: 05/27/2020] [Indexed: 12/22/2022]
Abstract
Phosphoglycerate kinase 1 (PGK1) is the first critical enzyme to produce ATP in the glycolytic pathway. PGK1 is not only a metabolic enzyme but also a protein kinase, which mediates the tumor growth, migration and invasion through phosphorylation some important substrates. Moreover, PGK1 is associated with poor treatment and prognosis of cancers. This manuscript reviews the structure, functions, post-translational modifications (PTMs) of PGK1 and its relationship with tumors, which demonstrates that PGK1 has indispensable value in the tumor progression. The current review highlights the important role of PGK1 in anticancer treatments.
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Affiliation(s)
- Qi Fu
- Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, PR China.; College of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, PR China
| | - Zhenhai Yu
- Department of Reproductive Medicine, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, PR China..
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Allen CJ, Blumenthaler AN, Das P, Minsky BD, Blum M, Roy-Chowdhuri S, Ajani JA, Ikoma N, Mansfield PF, Badgwell BD. Staging laparoscopy and peritoneal cytology in patients with early stage gastric adenocarcinoma. World J Surg Oncol 2020; 18:39. [PMID: 32066454 PMCID: PMC7026970 DOI: 10.1186/s12957-020-01813-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Accepted: 02/06/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Staging laparoscopy and peritoneal cytology can detect occult metastatic disease prior to treatment of gastric cancer. The yield of peritoneal staging in patients with early stage disease is lacking. We assess the yield of peritoneal staging in early stage gastric cancer and its impact on survival. METHODS Data were obtained from a prospective database of patients who underwent staging laparoscopy and peritoneal cytology for gastric cancer at our institution between July 1995 and July 2018. Clinical stage was determined by endoscopic ultrasound, and early stage was defined as cT1-2 and cN0. Rates of positive cytology and carcinomatosis at time of laparoscopy were obtained. Univariate analyses were used to compare groups, and Kaplan-Meier survival analyses were used to assess survival outcomes. RESULTS Eight hundred sixty-seven patients underwent staging laparoscopy and peritoneal cytology; 56 were defined as early stage. Age was 61 ± 12 years, 66.4% were male, and 62.3% were white. Of the patients with early stage disease, 17.9% had either gross carcinomatosis (10.7%) and/or positive peritoneal cytology (10.9%). All cases of peritoneal disease were in patients with cT2 disease. There were no differences in age, gender, or race based on peritoneal disease (all p > 0.05). The presence of carcinomatosis or positive cytology significantly affected overall survival (p < 0.001), regardless of clinical T or N stage. CONCLUSIONS Peritoneal staging identifies metastatic disease in a significant number of patients with early stage disease. Given its poor prognosis and alternate therapy options, independent staging laparoscopy and peritoneal cytology should be considered in patients with early stage gastric adenocarcinoma.
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Affiliation(s)
- Casey J Allen
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6010, Houston, TX, 77030, USA
| | - Alisa N Blumenthaler
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6010, Houston, TX, 77030, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mariela Blum
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sinchita Roy-Chowdhuri
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6010, Houston, TX, 77030, USA
| | - Paul F Mansfield
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6010, Houston, TX, 77030, USA
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler Street, FCT17.6010, Houston, TX, 77030, USA.
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Togano S, Yashiro M, Miki Y, Yamamato Y, Sera T, Kushitani Y, Sugimoto A, Kushiyama S, Nishimura S, Kuroda K, Okuno T, Yoshii M, Tamura T, Toyokawa T, Tanaka H, Muguruma K, Tanaka S, Ohira M. Microscopic distance from tumor invasion front to serosa might be a useful predictive factor for peritoneal recurrence after curative resection of T3-gastric cancer. PLoS One 2020; 15:e0225958. [PMID: 31940352 PMCID: PMC6961828 DOI: 10.1371/journal.pone.0225958] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 11/15/2019] [Indexed: 12/23/2022] Open
Abstract
Background Peritoneal recurrence is one of the most frequent recurrent diseases in gastric cancer. Although the exposure of cancer cells to the serosal surface is considered a common risk factor for peritoneal recurrence, there are some cases of peritoneal recurrence without infiltration to the serosal surface even after curative surgery. This study sought to clarify the risk factors of peritoneal recurrence in the absence of invasion to the serosal surface. Materials and methods Ninety-six patients with gastric cancer who underwent curative surgery were enrolled. In all 96 cases, the depth of tumor invasion was subserosal (T3). The microscopic distance from the tumor invasion front to the serosa (DIFS) was measured using tissue slides by H&E staining and pan-cytokeratin staining. E-cadherin expression was evaluated by immunohistochemical staining. Results Among the 96 patients, 16 developed peritoneal recurrence after curative surgery. The DIFS of the tumors with peritoneal recurrence (156±220 μm) was significantly shorter (p = 0.011) than that without peritoneal recurrence (360±478 μm). Peritoneal recurrence was significantly correlated with DIFS ≤234 μm (p = 0.023), but not with E-cadherin expression. The prognosis of DIFS ≤234 μm was significantly poorer than that of DIFS >234 μm (log rank, p = 0.007). A multivariate analysis of the patients' five-year overall survival revealed that DIFS ≤234 μm and lymph node metastasis were significantly correlated with survival (p = 0.005, p = 0.032, respectively). Conclusion The measurement of the DIFS might be useful for the prediction of peritoneal recurrence in T3-gastric cancer patients after curative surgery.
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Affiliation(s)
- Shingo Togano
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masakazu Yashiro
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
- Cancer Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka, Japan
- * E-mail:
| | - Yuichiro Miki
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yurie Yamamato
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
- Cancer Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomohiro Sera
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Yukako Kushitani
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Sugimoto
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shuhei Kushiyama
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Sadaaki Nishimura
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenji Kuroda
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tomohisa Okuno
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
- Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Mami Yoshii
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Tatsuro Tamura
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Takahiro Toyokawa
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Tanaka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kazuya Muguruma
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Sayaka Tanaka
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masaichi Ohira
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Long Term Survival after Cytoreductive Surgery Combined with Perioperative Chemotherapy in Gastric Cancer Patients with Peritoneal Metastasis. Cancers (Basel) 2020; 12:cancers12010116. [PMID: 31906405 PMCID: PMC7016959 DOI: 10.3390/cancers12010116] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 12/24/2019] [Accepted: 12/29/2019] [Indexed: 12/18/2022] Open
Abstract
The present study demonstrated prognostic factors for long-term survival in patients after a comprehensive treatment (CHT) for peritoneal metastasis (PM) from gastric cancer (GC). Materials and Methods: Among 419 patients treated with neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), 266 (63.5%) patients received complete resection (CC-0) of the macroscopic tumors. In total, 184 (43.9%) patients were treated with postoperative systemic chemotherapy. Results: All patients treated who received incomplete cytoreduction (CC-1) died of GC within 6 years. In contrast, 10- year survival rates (-YSR) of CC-0 resection were 8.3% with median survival time (MST) of 20.5 months. Post-NIPS peritoneal cancer index (PCI) ≤11, and pre-NIPS PCI ≤13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors ≤5 survived significant longer than those with ≥6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (≤13 vs. ≥14), and cytology after NIPS (negative cytology vs. positive cytology) as independent prognostic factors. Ten year-survivors were found in patients with involvement of the greater omentum (9%), pelvic peritoneum (3%), para-colic gutter (13.9%), upper jejunum (5.6%), lower jejunum (5.5%), spermatic cord (21.9%), rectum (9.5%), ureter (6.3%), ovary (6.7%), and diaphragm (7.0%) at the time of cytoreduction. Twenty-one patients survived longer than 5 years, and 17 patients are still alive without recurrence. Conclusions: GC-PM should be removed aggressively, in patients with PCI after NIPS ≤11, PCI before NIPS ≤13, mall bowel PCI ≤2, and complete cytoreduction should be performed for metastasis in ≤5 peritoneal sectors.
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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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Huang C, Liu Z, Xiao L, Xia Y, Huang J, Luo H, Zong Z, Zhu Z. Clinical Significance of Serum CA125, CA19-9, CA72-4, and Fibrinogen-to-Lymphocyte Ratio in Gastric Cancer With Peritoneal Dissemination. Front Oncol 2019; 9:1159. [PMID: 31750248 PMCID: PMC6848261 DOI: 10.3389/fonc.2019.01159] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Accepted: 10/17/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Relevant serum tumor markers have been indicated to be associated with peritoneal dissemination (PD) of gastric cancer (GC). Fibrinogen has been shown to play an important role in the systemic inflammatory response (SIR) and in tumor progression. However, the clinical significance of the fibrinogen-to-lymphocyte ratio (FLR) in GC with PD has not been studied. Methods: The clinical data of 391 patients with GC were collected, including 86 cases of PD. Then, 1:3 matching was performed by propensity score matching (PSM), and the clinical data of the matched 344 patients were analyzed by univariate and multivariate conditional logistic regression. Classification tree analysis was used to obtain the decision rules and a random forest algorithm to extract the important risk factors of PD in GC. A nomogram model for risk assessment of PD in GC was established by using the rms package of R software. Results: Univariate analysis showed that the factors related to PD in GC were: carbohydrate antigen (CA) 125 (P < 0.0001), CA19-9 (P < 0.0001), CA72-4 (P < 0.0001), FLR (P < 0.0001), neutrophil-to-lymphocyte ratio (NLR) (P < 0.0001), albumin-to- lymphocyte ratio (ALR) (P < 0.0001), platelet-to-lymphocyte ratio (PLR) (P = 0.013), and carcinoembryonic antigen (CEA) (P = 0.031). Conditional logistic regression found that CA125 (OR: 1.046; P < 0.0001), CA19-9 (OR: 1.002; P < 0.0001), and FLR (OR: 1.266; P = 0.024) were independent risk factors for GC with PD. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the decision rules for detecting PD of GC were 89.5, 77.4, 94.0, 82.8, and 91.8%, respectively. According to the important variables identified by the classification tree and random forest algorithm, the risk assessment model of PD in GC was established. The accuracy, sensitivity, and specificity of the model were 91, 89.5, and 79.5%, respectively. Conclusion: CA125 > 17.3 U/ml, CA19-9 > 27.315 U/ml, and FLR > 2.555 were the risk factors for GC with PD. The decision rules and nomogram model constructed by CA125, CA19-9, CA72-4, and FLR can correctly predict the risk of PD in GC.
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Affiliation(s)
| | | | | | | | | | | | | | - Zhengming Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Conversion Surgery with HIPEC for Peritoneal Oligometastatic Gastric Cancer. Cancers (Basel) 2019; 11:cancers11111715. [PMID: 31684115 PMCID: PMC6896107 DOI: 10.3390/cancers11111715] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 10/22/2019] [Accepted: 10/30/2019] [Indexed: 12/13/2022] Open
Abstract
Peritoneal metastases (PM) of gastric cancer (GC) are characterized by a particularly poor prognosis, with median survival time of 6 months, and virtually no 5-year survival reported. Conversion therapy for GC is defined as a surgical treatment aiming at an R0 resection after systemic chemotherapy for tumours that were originally unresectable (or marginally resectable) for technical and/or oncological reasons. The aim of the present study was to evaluate early and late outcomes in GC patients with PM who underwent the cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant (conversion) chemotherapy. Thirty patients with stage IV GC underwent CRS plus HIPEC. Severe grade III/IV (Clavien-Dindo classification) complications occurred in 13 (43%) patients. The Comprehensive Complication Index (CCI) ranged from 8.7 to 100 (median, 42.4). In the multivariate survival analysis, ypT2 and P3 (according to the Japanese classification of the PM severity) were favourable and adverse prognostic factors p = 0.031 and o = 0.035, respectively. Estimated 1- and 3-year survival was 73.9% and 36.6%, respectively. The median survival was 19.3 months. Conclusion: Conversion surgery, including extended gastrectomy and multi-organ resections followed by HIPEC performed after systemic chemotherapy therapy for GC with PM is justified in downstaged patients with ypT2 and limited (less than P3) PM.
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Nakanishi K, Kanda M, Umeda S, Tanaka C, Kobayashi D, Hayashi M, Yamada S, Kodera Y. The levels of SYT13 and CEA mRNAs in peritoneal lavages predict the peritoneal recurrence of gastric cancer. Gastric Cancer 2019; 22:1143-1152. [PMID: 31055693 DOI: 10.1007/s10120-019-00967-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 04/25/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although peritoneal lavage cytology often serves as a sensitive method to detect free cancer cells in the abdominal cavity, some patients experience peritoneal recurrence despite negative cytology. The aim of this study was to evaluate mRNAs in peritoneal lavage fluid as potential markers for predicting the peritoneal recurrence of gastric cancer (GC). METHODS Peritoneal lavage fluid samples were obtained during surgery conducted on 187 patients with GC and from 30 patients with non-malignant disease (controls). The mRNA levels of nine candidate markers were quantified, and analysis of a receiver-operating characteristic curve compared their accuracies. The cutoff was defined as the highest value of the controls. RESULTS Synaptotagmin XIII (SYT13) and carcinoembryonic antigen (CEA) mRNA levels were analyzed further. SYT13 levels were significantly associated with shorter peritoneal recurrence-free survival (PRFS) and overall survival. Among patients with negative peritoneal lavage cytology, those positive for either SYT13 or CEA mRNA experienced significantly shorter peritoneal recurrence-free survival compared with those with negative fluid (hazards ratio [HR] 4.21, P = 0.0114; HR 3.53; P = 0.0426, respectively). Univariate analysis revealed that SYT13 and CEA mRNA levels were significant predictors of peritoneal recurrence. Positive levels of both SYT13 and CEA mRNA demonstrated the highest HR for peritoneal recurrence (HR 12.27, P = 0.0064). Multivariable analysis revealed that SYT13 positivity was a significant independent prognostic factor (HR 3.69; 95% confidence interval, 1.18-12.74; P = 0.0246). CONCLUSIONS Combined measurement of SYT13 and CEA mRNA levels in peritoneal lavage fluid could serve as a promising approach to predict peritoneal recurrence of GC.
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Affiliation(s)
- Koki Nakanishi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Shinichi Umeda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Masamichi Hayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Suguru Yamada
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
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Shitanaka S, Yamanoi K, Ogura J, Ohara T, Inayama Y, Hirayama T, Sakai M, Suzuki H, Yasumoto K, Suginami K. A Case of Synchronous Primary Corpus and Ovarian Cancer with Pseudo-Meigs Syndrome: Utilization of a Diagnostic Laparoscopy for the Accurate Diagnosis. Gynecol Minim Invasive Ther 2019; 8:188-191. [PMID: 31741847 PMCID: PMC6849096 DOI: 10.4103/gmit.gmit_18_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Revised: 06/13/2019] [Accepted: 08/27/2019] [Indexed: 11/04/2022] Open
Abstract
We report a case of synchronous primary corpus and ovarian cancer (SPC) with massive ascites due to Pseudo-Meigs syndrome (PMS). A 48-year-old woman presented with complaints of abnormal genital bleeding and abdominal discomfort. Massive ascites and tumors in the endometrium and right ovary were detected. Although imaging tests showed no evidence of dissemination, and ascites cytology was negative, we performed a diagnostic laparoscopy to exclude the possibility of microdissemination because pathological findings of the corpus tumor were suggested to be so-called Type-2 endometrial cancer. Laparoscopy clearly confirmed no dissemination in the peritoneum. We ultimately diagnosed this patient with SPC with massive nonmalignant ascites due to PMS and performed an appropriate treatment. This report is the first case of SPC that developed PMS.
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Affiliation(s)
- Shimpei Shitanaka
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Koji Yamanoi
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan,Address for correspondence: Dr. Koji Yamanoi, Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA, USA. E-mail:
| | - Jumpei Ogura
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Tsutomu Ohara
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Yoshihide Inayama
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Takahiro Hirayama
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Mie Sakai
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Haruka Suzuki
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Koji Yasumoto
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
| | - Koh Suginami
- Department of Obstetrics and Gynecology, Toyooka Public Hospital, Toyooka, Japan
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Beeharry MK, Zhu ZL, Liu WT, Yao XX, Yan M, Zhu ZG. Prophylactic HIPEC with radical D2 gastrectomy improves survival and peritoneal recurrence rates for locally advanced gastric cancer: personal experience from a randomized case control study. BMC Cancer 2019; 19:932. [PMID: 31533660 PMCID: PMC6751672 DOI: 10.1186/s12885-019-6125-z] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 09/03/2019] [Indexed: 02/07/2023] Open
Abstract
Background To investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized case control study. Method Eighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m2 at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored. Results Faster recovery of bowel function (43 ± 5 h vs 68 ± 7, P < 0.05) and shorter postoperative stay (8d vs 14d, P < 0.05) were noted in the HIPEC group. Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The 3 year DFS rate analysis showed that the prophylactic HIPEC group had a higher DFS rate (93% vs 65%, P = 0.0054). The peritoneal recurrence rate was lower in the HIPEC group (3% vs 23%, P < 0.05). Conclusion Prophylactic HIPEC with radical D2 Gastrectomy improves survival and peritoneal recurrence rates for AGC with favorable post-operative recovery at low and acceptable morbidity.
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Affiliation(s)
- Maneesh Kumarsing Beeharry
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zheng-Lun Zhu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Wen-Tao Liu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Xue-Xin Yao
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Min Yan
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Zheng-Gang Zhu
- Department of Surgery, Ruijin Hospital affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
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Yamaguchi T, Takashima A, Nagashima K, Makuuchi R, Aizawa M, Ohashi M, Tashiro K, Yamada T, Kinoshita T, Hata H, Kawachi Y, Kawabata R, Tsuji T, Hihara J, Sakamoto T, Fukagawa T, Katai H, Higuchi K, Boku N. Efficacy of Postoperative Chemotherapy After Resection that Leaves No Macroscopically Visible Disease of Gastric Cancer with Positive Peritoneal Lavage Cytology (CY1) or Localized Peritoneum Metastasis (P1a): A Multicenter Retrospective Study. Ann Surg Oncol 2019; 27:284-292. [PMID: 31535301 DOI: 10.1245/s10434-019-07697-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.
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Affiliation(s)
- Toshifumi Yamaguchi
- Cancer Chemotherapy Center and Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan.,Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan
| | - Atsuo Takashima
- Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
| | - Kengo Nagashima
- Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan
| | - Rie Makuuchi
- Division of Gastric Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masaki Aizawa
- Department of Gastroenterological Surgery, Niigata Cancer Center Hospital, Niigata, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan
| | - Keitaro Tashiro
- Departments of General and Gastroenterological Surgery, Osaka Medical College Hospital, Osaka, Japan
| | - Tatsuya Yamada
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Takahiro Kinoshita
- Gastric Surgery Division, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hiroaki Hata
- Department of Surgery, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Yasuyuki Kawachi
- Department of Surgery, Nagaoka Chuo General Hospital, Niigata, Japan
| | | | - Toshikatsu Tsuji
- Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Japan
| | - Jun Hihara
- Department of Surgery, Hiroshima City Asa Citizens Hospital, Hiroshima, Japan
| | - Takeshi Sakamoto
- Department of Gastroenterology, Hyogo Cancer Center, Hyogo, Japan
| | - Takeo Fukagawa
- Department of Surgery, Teikyo University Hospital, Tokyo, Japan
| | - Hitoshi Katai
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kazuhide Higuchi
- Cancer Chemotherapy Center and Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan
| | - Narikazu Boku
- Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan
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Soeda N, Iinuma H, Suzuki Y, Tsukahara D, Midorikawa H, Igarashi Y, Kumata Y, Horikawa M, Kiyokawa T, Fukagawa T, Fukushima R. Plasma exosome-encapsulated microRNA-21 and microRNA-92a are promising biomarkers for the prediction of peritoneal recurrence in patients with gastric cancer. Oncol Lett 2019; 18:4467-4480. [PMID: 31611956 PMCID: PMC6781766 DOI: 10.3892/ol.2019.10807] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2018] [Accepted: 07/03/2019] [Indexed: 12/17/2022] Open
Abstract
In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC.
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Affiliation(s)
- Naruyoshi Soeda
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Hisae Iinuma
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Yusuke Suzuki
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Daisuke Tsukahara
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Hironori Midorikawa
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Yuichi Igarashi
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Yoshimasa Kumata
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Masahiro Horikawa
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Takashi Kiyokawa
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Takeo Fukagawa
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
| | - Ryoji Fukushima
- Department of Surgery, Teikyo University School of Medicine, Itabashi, Tokyo 173-0003, Japan
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Yarema R, Mielko J, Fetsych T, Ohorchak M, Skorzewska M, Rawicz‐Pruszyński K, Mashukov A, Maksimovsky V, Jastrzębski T, Polkowski W, Gyrya P, Kovalchuk Y, Safiyan V, Karelin I, Kopetskiy V, Kolesnik O, Kondratskiy Y, Paskonis M. Hyperthermic intraperitoneal chemotherapy (HIPEC) in combined treatment of locally advanced and intraperitonealy disseminated gastric cancer: A retrospective cooperative Central-Eastern European study. Cancer Med 2019; 8:2877-2885. [PMID: 31033239 PMCID: PMC6558472 DOI: 10.1002/cam4.2204] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 04/10/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Clinical experience in Western Europe suggests that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are promising methods in the management of gastric cancer (GC) with peritoneal metastases. However, there are almost no data on such treatment results in patient from Central-Eastern European population. METHODS A retrospective cooperative study was performed at 6 Central-Eastern European HIPEC centers. HIPEC was used in 117 patients for the following indications: treatment of GC with limited overt peritoneal metastases (n = 70), adjuvant setting after radical gastrectomy (n = 37) and palliative approach for elimination of severe ascites without gastrectomy (n = 10). RESULTS Postoperative morbidity and mortality rates were 29.1% and 5.1%, respectively. Median overall survival in the groups with therapeutic, adjuvant, and palliative indications was 12.6, 34, and 3.5 months. The only long-term survivors occurred in the group with peritoneal cancer index (PCI) of 0-6 points without survival difference in groups with PCI 7-12 vs PCI 13 or more points. CONCLUSIONS GC patients with limited peritoneal metastases can benefit from CRS + HIPEC. Hyperthermic intraperitoneal chemotherapy could be an effective method of adjuvant treatment of GC with a high risk of intraperitoneal progression. No long-term survival may be expected after palliative approach to HIPEC.
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Affiliation(s)
- Roman Yarema
- Danylo Halytsky Lviv National Medical UniversityLvivUkraine
| | | | - Taras Fetsych
- Danylo Halytsky Lviv National Medical UniversityLvivUkraine
| | - Myron Ohorchak
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | | | | | | | | | | | | | - Petro Gyrya
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Yuriy Kovalchuk
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Victor Safiyan
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | - Ivan Karelin
- Lviv State Oncological Regional Treatment and Diagnostic CenterLvivUkraine
| | | | | | | | - Marius Paskonis
- Vilnius universtiy hospital Santaros klinikosVilniusLithuania
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Kitano T, Aisu Y, Yasukawa D, Hori T. Aggressive Graphic/Surgical R0 Resection and Jejunal Interposition with Preservation of Mesojejunal Autonomic Nerves in Patients with Stage IV Esophagogastric Junction Adenocarcinoma: A Report of 3 Cases. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:465-473. [PMID: 30952831 PMCID: PMC6463956 DOI: 10.12659/ajcr.913960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 01/26/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Three patients with stage IV esophagogastric junction cancer (EGJC) underwent extended resection to achieve a graphic/surgical R0 status (no visible remnant of viable tumor in imaging/surgical findings) and adjuvant chemotherapy from the early postoperative period. We also introduced use of our digestive reconstruction technique in these patients. CASE REPORT We used jejunal interposition for digestive reconstruction, which involved end-to-end jejunojejunostomy with a biofragmentable anastomosis ring. The mesojejunal autonomic nerves of the lifted jejunum were preserved. The first adenocarcinoma involved the perilesional lymph nodes (LNs). Graphic/surgical R0 resection was completed by para-aortic LN dissection. The diagnosis (Japanese Classification of Gastric Carcinoma) was stage IV [pM1(LYM)]. Adjuvant chemotherapy began on postoperative day (POD) 11. The second adenocarcinoma was accompanied by a solitary lung metastasis. Intraoperative cytology of ascitic fluid was positive, and cisplatin was intraperitoneally administered. Adjuvant chemotherapy began on POD 10. The solitary lung metastasis was then resected, and graphic/surgical R0 resection was achieved. The diagnosis was stage IV [pM1(PUL) and CY1]. The third adenocarcinoma was accompanied by multiple liver metastases and metastatic regional LNs. The diagnosis was stage IV [H1]. Systemic chemotherapy was repeated. Only a solitary liver metastasis remained and was treated by radiofrequency ablation. Conversion surgery was conducted, achieving graphic/surgical R0 resection. Systemic chemotherapy was continued from POD 10. CONCLUSIONS For patients with stage IV EGJC, extended resection to achieve a graphic/surgical R0 status is still controversial, and systemic chemotherapy is important. The results of the present study suggest that our physiological reconstruction technique does not affect the efficacy of other therapies, such as adjuvant chemotherapy.
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Taniguchi K, Ota M, Yamada T, Serizawa A, Noguchi T, Amano K, Kotake S, Ito S, Ikari N, Omori A, Yamamoto M. Staging of gastric cancer with the Clinical Stage Prediction score. World J Surg Oncol 2019; 17:47. [PMID: 30849974 PMCID: PMC6408856 DOI: 10.1186/s12957-019-1589-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Accepted: 02/28/2019] [Indexed: 12/13/2022] Open
Abstract
Background Chemotherapy with or without surgery is the first-line treatment for stage III/IV gastric cancer, while surgery is the first-line treatment for stage I/II gastric cancer. Accordingly, it is important to distinguish between stage III/IV and stage I/II gastric cancer, but clinical staging is less accurate than pathological staging. This study was performed to develop a clinical score that could distinguish stage III/IV gastric cancer from stage I/II gastric cancer. Methods We reviewed 2722 patients who underwent gastrectomy at our hospital from January 1996 to December 2015. As pretreatment factors potentially related to tumor stage, we assessed age, sex, tumor markers, tumor diameter, tumor location, tumor histology, and macroscopic type. Factors showing significance on multivariate analysis were used to develop the Clinical Stage Prediction score (CSP score), and a cutoff value for the score was determined by receiver operating characteristics analysis. Results According to multivariate analysis, clinical factors associated with stage III/IV disease were elevation of the carcinoembryonic antigen level, tumor diameter ≥ 60 mm, circumferential gastric involvement, esophageal infiltration, mucinous adenocarcinoma, and macroscopic types 2–4. The CSP score was obtained by weighting these factors according to the non-standardized β-coefficient. Receiver operating characteristics analysis indicated that the optimum cutoff value of the CSP score was 17 points. Among 1042 patients with a CSP score ≥ 17 points, 820 patients (78.7%) had stage III/IV gastric cancer. Conversely, among 1680 patients with a CSP score < 17 points, 1547 patients (92.1%) had stage I/II gastric cancer. When discrimination of stage III/IV gastric cancer from stage I/II gastric cancer by the CSP score was assessed, the sensitivity was 78.7%, specificity was 92.1%, positive predictive value was 86.0%, and negative predictive value was 87.5%. Conclusions The CSP score can be helpful for differentiating stage III/IV gastric cancer from stage I/II gastric cancer based on pretreatment clinical factors.
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Affiliation(s)
- Kiyoaki Taniguchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Masaho Ota
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Takuji Yamada
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Akiko Serizawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Takeharu Noguchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Kunihiko Amano
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Sho Kotake
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Shunichi Ito
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Naoki Ikari
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Akiko Omori
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
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Sakata T, Takahata T, Kimura T, Yasuhara I, Kojima T, Akazai Y, Mimura T, Lefor AK. A single-institution retrospective analysis of gastric carcinoma with positive peritoneal lavage cytology and without serosal invasion: A case series. Ann Med Surg (Lond) 2019; 39:10-15. [PMID: 30792857 PMCID: PMC6370578 DOI: 10.1016/j.amsu.2019.01.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 12/21/2018] [Accepted: 01/23/2019] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Peritoneal dissemination of gastric cancer is often associated with serosal infiltration. The aim of this study was to evaluate the clinical importance of peritoneal lavage cytology in patients with gastric carcinoma without serosal invasion. The incidence and impact on prognosis of positive cytology were analyzed. METHODS Of 2768 patients with gastric cancer, outcomes and pathological characteristics of 973 patients were reviewed retrospectively. All patients underwent peritoneal lavage at laparotomy for curative or palliative resection of gastric cancer between 1999 and 2017. Among these, 479 who underwent surgery from January 1999 to March 2012 were also reviewed to analyze 5-year survival. RESULTS Of 973 patients enrolled, 338 (35%) did not have serosal invasion, and peritoneal cytology was positive in 4/338 (1.2%). Of these four patients, one had submucosal invasion and three had muscularis propria invasion. Of 635 patients with serosal invasion, peritoneal cytology was positive in 74/635 (12%). Of 479 patients reviewed for survival, cytology was positive in 32/479, with 3/32 (9%) surviving for five years, and cytology was negative in 447 patients with 266/447 (60%) surviving for five years. CONCLUSIONS Cytologic evaluation should be routinely performed in patients with early-stage gastric cancer.
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Affiliation(s)
- Taizo Sakata
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Takaomi Takahata
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Toshikazu Kimura
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Isao Yasuhara
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Toru Kojima
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Yoshihiro Akazai
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
| | - Tetsushige Mimura
- Department of Surgery, Okayama Saiseikai General Hospital, Okayama, Japan
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Okabe H, Hata H, Hosogi H, Ueda S, Ota S, Kinjo Y, Hoshino N, Hisamori S, Tsunoda S, Obama K, Sakai Y. A Phase 2 Study of Induction Chemotherapy Using Docetaxel, Cisplatin, and S-1 for Gastric Cancer with Peritoneal Metastasis (KUGC06). Ann Surg Oncol 2019; 26:1779-1786. [DOI: 10.1245/s10434-019-07229-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Indexed: 01/19/2023]
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45
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Wang A, Li Z, Wang Q, Bai Y, Ji X, Fu T, Ji K, Xue Y, Han T, Wu X, Zhang J, Yang Y, Xu G, Bu Z, Ji J. Diagnostic value of negative enrichment and immune fluorescence in situ hybridization for intraperitoneal free cancer cells of gastric cancer. Chin J Cancer Res 2019; 31:945-954. [PMID: 31949396 PMCID: PMC6955163 DOI: 10.21147/j.issn.1000-9604.2019.06.10] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Objective To explore the intraperitoneal free cancer cell (IFCC) detection value of negative enrichment and immune fluorescence in situ hybridization (NEimFISH) on chromosomes (CEN) 8/17.
Methods To verify the reliability of NEimFISH, 29 gastric cancer tumors, their adjacent tissues and greater omental tissues were tested. Our study then included 105 gastric cancer patients for IFCC. We defined patients as IFCC-positive if a signal was detected, regardless of the detailed cancer cell numbers. A comparison of clinicopathological features was conducted among IFCC groups. We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods. The comparison of IFCC number was also conducted among different groups. Results A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97% of malignant tissue samples in our study. Compared to intestinal gastric cancer, patients with diffuse gastric cancer tended to have more IFCCs (6 vs. 4, P=0.002). The IFCC counts were often higher in the lymphovascular invasion positive group than negative group (3 vs. 1, P=0.022). All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH. When compared to conventional cytology and paraffin pathology, NEimFISH had a higher IFCC positive rate (68.9%) and higher one-year peritoneal recurrence predictive value with area under the curve (AUC) of 0.922.
Conclusions Gastric cancer could be effectively diagnosed by NEimFISH. The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer. NEimFISH is a reliable detection modality with a higher positive detection rate, higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.
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Affiliation(s)
- Anqiang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhongwu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Qian Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yali Bai
- Cyttel Biosciences INC, Taizhou 225316, China
| | - Xin Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Tao Fu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ke Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yanwen Xue
- Cyttel Biosciences INC, Taizhou 225316, China
| | - Tingxu Han
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Clinical Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiaojiang Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ji Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | | | - Guobin Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Clinical Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhaode Bu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Center of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China
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Hu Q, Mimori K. ASO Author Reflections: ARL4C and Peritoneal Dissemination in Gastric Cancer. Ann Surg Oncol 2018; 26:547. [PMID: 30556117 DOI: 10.1245/s10434-018-7056-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Indexed: 11/18/2022]
Affiliation(s)
- Qingjiang Hu
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.,Department of Surgery and Science, Kyushu University Hospital, Fukuoka, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
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Yepuri N, Bahary N, Jain A, Dhir M. Review and Update on the Role of Peritoneal Cytology in the Treatment of Gastric Cancer. J Surg Res 2018; 235:607-614. [PMID: 30691849 DOI: 10.1016/j.jss.2018.10.049] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 08/12/2018] [Accepted: 10/26/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Positive peritoneal cytology (Cyt+) even in the absence of macroscopic disease is associated with poor prognosis in patients with gastric cancer and deemed as M1 disease. Recent years have seen advancements in the evaluation strategies for peritoneal washings and management of patients with Cyt+. The aim of this review was to describe the newest paradigms in the management of patients with gastric cancer who have Cyt+ without macroscopic peritoneal metastases. METHODS A comprehensive literature review was performed to identify studies on the management of gastric cancer and thereby to summarize relevant information on the accuracy of various diagnostic tests and controversies involved in the treatment of patients with Cyt+. RESULTS Although conventional cytology remains the standard technique for assessment of peritoneal washings, it is limited by low sensitivity. The role of immunohistochemistry and molecular techniques for the assessment of peritoneal washings is evolving. Although systemic chemotherapy remains the standard of care for patients with Cyt+ disease, the role of gastrectomy, intraperitoneal chemotherapy, extensive intraperitoneal saline lavage, and hyperthermic intraperitoneal chemotherapy is being evaluated. CONCLUSIONS Clinical decision-making in patients with Cyt+ remains controversial given the seemingly technical resectable albeit biologically unresectable or aggressive disease that portends an overall poor prognosis. Current management strategies are evolving, and further studies are needed to develop an optimal treatment strategy for these patients.
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Affiliation(s)
- Natesh Yepuri
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York
| | - Nathan Bahary
- Division of Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Ajay Jain
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York
| | - Mashaal Dhir
- Division of Surgical Oncology, Department of Surgery, SUNY Upstate Medical University, Syracuse, New York.
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Hasbahceci M, Akcakaya A, Guler B, Kunduz E, Malya FU, Muslumanoglu M. Use of peritoneal washing cytology for the detection of free peritoneal cancer cells before and after surgical treatment of gastric adenocarcinoma. J Cancer Res Ther 2018; 14:1225-1229. [PMID: 30488834 DOI: 10.4103/0973-1482.184518] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
AIM Cytological detection of peritoneal-free gastric cancer cells is considered as the gold standard with variable sensitivity. Seeding of cancer cells after radical surgery for gastric cancer is a controversial issue. In this study, it was aimed to detect the rate of positive peritoneal washing cytology and the incidence of spreading of tumor cells after radical surgery. MATERIALS AND METHODS Patients with pathologically proven and surgically treated gastric adenocarcinoma were enrolled. Three peritoneal washing samples were examined cytologically: at the beginning, after completion of resection, and before closure of the abdomen. Identification of peritoneal-free gastric cancer cells was regarded as the main outcome. RESULTS Thirty-four patients with a mean age of 60.7 ± 12 years were enrolled. T3 and N0 were the most common stages seen in 16 (47%) and 12 patients (35.3%), respectively. There were two positive results (5.9%) as the first peritoneal sample. Considering T3- or N-positive patients, the incidence increased to 9.1%. There was no conversion of negative to positive cytology. Cytological positivity remained only in one case (2.9%) after the second and the third peritoneal samples. CONCLUSION Rate of positive peritoneal washing cytology in patients with gastric cancer is influenced by clinicopathological findings and the technique used. Use of cytology alone is thought to be failed to detect free cancers cells within the peritoneal cavity.
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Affiliation(s)
- Mustafa Hasbahceci
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Adem Akcakaya
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Beril Guler
- Department of Pathology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Enver Kunduz
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Fatma Umit Malya
- Department of General Surgery, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
| | - Mahmut Muslumanoglu
- Department of General Surgery, Faculty of Medicine, İstanbul University, Istanbul, Turkey
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Watanabe M, Kagawa S, Kuwada K, Hashimoto Y, Shigeyasu K, Ishida M, Sakamoto S, Ito A, Kikuchi S, Kuroda S, Kishimoto H, Tomida S, Yoshida R, Tazawa H, Urata Y, Fujiwara T. Integrated fluorescent cytology with nano-biologics in peritoneally disseminated gastric cancer. Cancer Sci 2018; 109:3263-3271. [PMID: 30076658 PMCID: PMC6172043 DOI: 10.1111/cas.13760] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/01/2018] [Accepted: 08/01/2018] [Indexed: 12/29/2022] Open
Abstract
Gastric cancer patients positive for peritoneal cytology are at increased risk of tumor recurrence, but although a certain proportion of cytology‐positive patients relapse rapidly with aggressive progression, others survive longer with conventional chemotherapies. This heterogeneity makes it difficult to stratify patients for more intensive therapy and poses a substantial challenge for the implementation of precision medicine. We developed a new approach to identify biologically malignant subpopulations in cytology‐positive gastric cancer patients, using a green fluorescent protein (GFP)‐expressing attenuated adenovirus in which the telomerase promoter regulates viral replication (TelomeScan, OBP‐401). The fluorescence emitted from TelomeScan‐positive cells was successfully quantified using a multi‐mode microplate reader. We then analyzed clinical peritoneal washes obtained from 68 gastric cancer patients and found that patients positive for TelomeScan had a significantly worse prognosis. In 21 cytology‐positive patients, the median survival time of those who were TelomeScan positive (235 days) was significantly shorter than that for those who were TelomeScan negative (671 days; P = 0.0062). This fluorescent virus‐guided cytology detects biologically malignant cancer cells from the peritoneal washes of gastric cancer patients and may thus be useful for both therapy stratification and precision medicine approaches based on genetic profiling of disseminated cells.
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Affiliation(s)
- Megumi Watanabe
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shunsuke Kagawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kazuya Kuwada
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Yuuri Hashimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Kunitoshi Shigeyasu
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Michihiro Ishida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shuichi Sakamoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Atene Ito
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Satoru Kikuchi
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shinji Kuroda
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroyuki Kishimoto
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shuta Tomida
- Translational Research Network Project, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Ryuichi Yoshida
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Hiroshi Tazawa
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.,Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | | | - Toshiyoshi Fujiwara
- Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
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Alves LB, Tsukazan MT, Serafim AE, Mendoza R, Padoin AV, Baú PC, Moreira LF. PROGNOSTIC VALUE OF CARCINOEMBRYONIC ANTIGEN LEVELS IN TRANSOPERATIVE PERITONEAL LAVAGE IN PATIENTS WITH GASTRIC CANCER. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2018; 31:e1358. [PMID: 29947692 PMCID: PMC6049989 DOI: 10.1590/0102-672020180001e1358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 02/16/2018] [Indexed: 11/22/2022]
Abstract
Background: The carcinoembryonic antigen level in peritoneal lavage has been showing to be a reliable prognostic factor in gastric cancer. Aim: To identify any association between carcinoembryonic antigen level in peritoneal lavage, in gastric cancer patients, with mortality, peritoneal recurrence, tumor relapse or other prognostic factors. Methods: In total, 30 patients (22 men, 8 women; median age 66 years) with resectable gastric cancer (mainly stage III and IV) were studied. Carcinoembryonic antigen level in peritoneal lavage was detected at operation by immunocytochemical method and a level over 210 ng/g of protein was considered as positive. Results: There were detected 10 positive cases (33.3%) of plCEA levels. These levels were associated with mortality, RR: 2.1 (p=0.018); peritoneal recurrence, OR: 9.0 (p=0.015); and relapse or gastric cancer progression, OR: 27.0 (p=0.001). Conclusion: Increased levels of plCEA fairly predicts mortality, peritoneal recurrence tumor relapse or cancer progression.
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Affiliation(s)
- Letícia Biscaino Alves
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul.,Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
| | | | | | | | - Alexandre Vontobel Padoin
- Center for Obesity and Metabolic Syndrome, São Lucas Hospital, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS).,Post-Graduate Program in Medicine and Health Sciences, PUCRS
| | | | - Luis Fernando Moreira
- Post-Graduate Program in Surgery, Hospital de Clínicas of Porto Alegre, Federal University of Rio Grande do Sul
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