Clinical impact of gastrectomy for gastric cancer patients with positive lavage cytology without gross peritoneal dissemination.

BACKGROUND: The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established. PATIENTS AND METHODS: In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care. RESULTS: One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p < 0.001). CONCLUSION: Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.

Clinical significance of initial treatment for peritoneal lavage cytology-positive gastric cancer: outcomes according to treatment strategy.

BACKGROUND: Although patients with positive lavage cytology (CY1) are classified as having stage IV disease, long-term survival without other unresectable factors (P0CY1) has been reported. Conversion gastrectomy in patients with a change in cytology status after induction chemotherapy might improve survival, but appropriate treatment remains controversial. Here, we reviewed our experience in treating CY1 gastric cancer to evaluate the best treatment strategy. METHODS: Clinical and pathological findings of patients with a diagnosis of P0CY1 gastric cancer at Toranomon Hospital between February 2006 and April 2019 were retrospectively analyzed. Patients were classified into two groups according to initial treatment: a surgery-first group and a chemotherapy-first group. In addition, the patients were categorized into subgroups based on the subsequent treatment pattern. The surgery-first group was divided into two subgroups: adjuvant chemotherapy and palliative gastrectomy only. The chemotherapy-first group was divided into three subgroups with the subsequent treatment pattern depending on the response to chemotherapy: conversion gastrectomy, palliative gastrectomy after induction therapy, and palliative chemotherapy. RESULTS: In total, 38 patients were eligible for inclusion in this study. After initial assessment of cytology status, 21 patients underwent gastrectomy as initial treatment (surgery first) and 17 received induction chemotherapy (chemotherapy first). Ten patients underwent surgery first with adjuvant chemotherapy, 11 underwent palliative gastrectomy alone, 5 underwent conversion surgery, 5 with CY1 disease after induction chemotherapy underwent palliative gastrectomy, and 7 received palliative chemotherapy only. The 3-year survival rate was 23.4% (median survival, 17.7 months) in the surgery-first group and 27.3% (median survival, 19.7 months) in the chemotherapy-first group. The 3-year survival rate was 75% for conversion gastrectomy, 16.7% for palliative chemotherapy, and 0% for palliative gastrectomy after induction chemotherapy. CONCLUSIONS: There was no significant difference in outcome according to whether surgery or chemotherapy was performed first. The prognosis of conversion surgery with curative resection was better than that of the other types of treatment. However, the outlook after induction chemotherapy was poor. Patients with advanced gastric cancer should be treated cautiously until more effective treatment options become available.

Is curative gastrectomy justified for gastric cancer with cytology positive as the only stage IV factor?

AIMS: The prognosis of patients with gastric cancer and stage IV factors is poor. However, several recent studies have identified that curative surgery followed by S-1 chemotherapy for cytology positive (CY1) only patients contributed to a better prognosis. This study was designed to compare the prognosis between curative and palliative gastrectomy followed by chemotherapy in CY1 only stage IV gastric cancer. METHODS: Between 2001 and 2016, 1507 patients underwent gastrectomy for gastric cancer. Of these, 51 consecutive patients with only CY1 factor who underwent gastrectomy followed by chemotherapy were enrolled in this study. RESULTS: (1) Twenty three (45%) patients underwent curative D2 or D2+ gastrectomy, and the remaining 28 (55%) patients underwent palliative gastrectomy, followed by S-1 based or another historical recommended chemotherapy postoperatively. (2) Compared with patients undergoing palliative gastrectomy, patients undergoing curative gastrectomy had a significantly better prognosis (P = 0.042; median survival time: curative vs. palliative, 22.6 months vs. 11.8 months) and a lower incidence of recurrences (P = 0.091). Two- and five-year overall survival rates of patients following curative gastrectomy were 48.2% and 18.2%, respectively. A multivariate analysis showed that venous invasion [P = 0.006; hazard ratio (HR), 3.70 (95% CI: 1.27-9.43)] and curative gastrectomy [P < 0.005; HR, 0.28 (95% CI: 0.12-0.87)] were independent prognostic factors. CONCLUSION: Curative gastrectomy followed by chemotherapy might be justified to improve the prognosis of patients with only CY1 Stage IV gastric cancer.

Retrospective comparison of S-1 plus cisplatin versus S-1 monotherapy for the treatment of advanced gastric cancer patients with positive peritoneal cytology but without gross peritoneal metastasis.

BACKGROUND: Peritoneal cytology positive for carcinoma cells (CY+) is an independent poor prognostic factor in gastric cancer, and patients with CY+ are diagnosed with stage IV disease. However, there is no standard treatment strategy for CY+ gastric cancer, whereas combination chemotherapy with fluoropyrimidine and platinum has been established as the standard treatment for unresectable advanced gastric cancer or after R2 resection. Herein, we assessed whether adding cisplatin to S-1 (SP) could improve the outcome of CY+ gastric cancer patients, as compared to S-1 monotherapy. METHODS: This retrospective study was conducted at a single Japanese institute between June 2005 and March 2014. Patients diagnosed with CY+ advanced gastric cancer and treated with S-1-based therapy were enrolled. Patients with incurable factors other than CY+ were excluded. RESULTS: Forty-four patients were enrolled; 25 and 19 were administered S-1 and SP, respectively. The 2-year survival rates were 52.0% [95% confidence interval (CI), 31.2-69.2%] and 52.6% (28.7-71.9%) in the S-1 and SP groups, respectively. The median overall survival (OS) and progression-free survival (PFS) were 28.2 and 15.6 months in the S-1 group and 24.0 and 18.8 months in the SP group, respectively; they were not significantly different. The relative dose intensities were 0.79 (S-1) in the S-1 group and 0.69 (S-1)/0.70 (cisplatin) in the SP group. CONCLUSION: Adding cisplatin to long-term S-1 monotherapy did not significantly improve the outcome of CY+ advanced gastric cancer patients.

Impact of skeletal muscle loss during conversion therapy on clinical outcomes in lavage cytology positive patients with gastric cancer.

Background: The relationship between sarcopenia and clinical outcomes during conversion therapy in patients with lavage cytology positive gastric cancer (GC-CY1) remains unclear. This study aimed to investigate the impact of sarcopenia and skeletal muscle loss on the efficacy of conversion therapy, tumour response and survival in GC-CY1 patients. Methods: Retrospective analysis of data from a prospective trial of conversion therapy conducted between April 2018 and August 2019 in patients with GC-CY1 (NCT03718624). Skeletal muscle index (SMI) was measured at the level of the third lumbar (L3) vertebra and the sarcopenia was defined using published cut-off points in all patients. We defined ΔSMI (%)/50 days above 9.53% for men and ΔSMI (%)/50 days above 8.81% for women as significant muscle loss (SML) and analysed the changes in skeletal muscle during conversion therapy in relation to treatment efficacy, survival and tumour response. Results: Of the 36 patients, 7 patients (19.44%) developed sarcopenia before conversion therapy, 6 (16.67%) developed new sarcopenia after conversion therapy, and 8 (22.22%) developed SML during treatment. Multivariate analysis showed that sarcopenia before treatment [Odds Ratio (OR) =8.923, 95%CI: 1.341-25.321, p=0.002] and SML during treatment (OR=7.803, 95%CI: 1.106-16.189, p=0.001) had a negative impact on the success rate of conversion therapy. Cox multifactorial analysis found that pre-treatment sarcopenia [overall survival (OS): Hazard Ratio (HR) =6.341, 95%CI: 1.269-18.943, p=0.001; progression-free survival (PFS): HR=8.212, 95%CI: 1.569-36.582, p=0.001], newly developed sarcopenia after conversion therapy (OS: HR=3.189, 95%CI: 1.023-9.811, p=0.012; PFS: HR=3.084, 95%CI: 1.042-14.236, p=0.013) and the presence of SML during treatment (OS: HR=10.234, 95%CI: 2.532-54.231, p=0.002; PFS: HR=9.562, 95%CI: 2.341-38.092, p=0.002) were independent risk factor for OS and PFS in GC-CY1 patients. Conclusion: Pre-treatment sarcopenia and the presence of SML during treatment are strongly correlated with the immediate and long-term outcomes of GC-CY1 patients and can be used as imaging markers to predict the treatment efficacy and prognosis of patients in clinical practice.

The impact of peritoneal lavage cytology in biliary tract cancer (KHBO1701): Kansai Hepato-Biliary Oncology Group.

BACKGROUND: Only few studies in literature have analyzed the clinical effects of peritoneal lavage status in biliary tract cancers. AIM: We aimed to assess the effect of cytology-positive peritoneal lavage on survival for patients with biliary tract cancer who underwent curative resection. METHODS: The KHBO1701 study was a multi-institutional retrospective study that assessed the clinical effects of peritoneal lavage cytology in biliary tract cancers. Using clinicopathological data from 11 Japanese institutions, we compared long-term outcomes between patients with cytology-positive and cytology-negative peritoneal lavage. RESULTS: Of 169 patients who underwent curative resection, 164 were cytology-negative, and five were cytology-positive. The incidence of portal invasion and preoperative carbohydrate antigen 19-9 levels were higher in the cytology-positive group than in the cytology-negative group. The incidence of peritoneal metastatic recurrence was also higher, and overall survival tended to be worse in the cytology-positive group. In contrast, recurrence-free survival was similar between the cytology-negative and cytology-positive groups. CONCLUSIONS: The positive status of peritoneal lavage cytology could moderately affect the survival of patients with biliary tract cancers. Given that surgical resection is the only curative treatment option, it may be acceptable to resect biliary tract cancers without other non-curative factors, regardless of peritoneal lavage cytology status.

Neoadjuvant intraperitoneal and systemic paclitaxel combined with apatinib and S-1 chemotherapy for conversion therapy in gastric cancer patients with positive exfoliative cytology: a prospective study.

BACKGROUND: To explore the efficacy and safety of neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel chemotherapy combined with apatinib and S-1 in the treatment of gastric cancer patients with positive exfoliative cytology. METHODS: Patients with gastric cancer (P0CY1) who were confirmed to have free cancer cells (FCCs) in the abdominal cavity after laparoscopic exploration from April 2018 to August 2019 were enrolled. All patients underwent NIPS chemotherapy using paclitaxel combined with apatinib and S-1 treatment. Laparoscopic exploration was performed after 3 cycles of conversion therapy. The primary study endpoint was the FCC negative rate, and the secondary study endpoints were overall survival time (OS), progression-free survival time (PFS), objective response rate (ORR), disease control rate (DCR), and safety indicators. RESULTS: Out of 312 advanced gastric cancer patients who underwent laparoscopic exploration, 36 patients with P0CY1 gastric cancer were identified and enrolled in this study. After 3 cycles of conversion therapy, the ORR was 80.56% and the DCR was 94.44%. All patients underwent secondary laparoscopic exploration, and the FCC conversion rate was 77.78%. All patients with negative FCC underwent R0 surgical resection, with a median follow-up time of 11.4 months. The median survival time was 15.5 months, and the 1-year OS was 80.55%. The median PFS was 14.4 months, and the 1-year PFS was 75.00%. Treatment-related grade 3 adverse reactions were mainly leukopenia and neutropenia. No grade 4 adverse reactions were observed. There were no reported deaths related to chemotherapy or surgery in the study cohort. CONCLUSIONS: NIPS with paclitaxel combined with apatinib and S-1 treatment may increase the FCC negative rate of P0CY1 gastric cancer patients.

Predictive Effect of Systemic Immune-Inflammation Index Combined With Prognostic Nutrition Index Score on Efficacy and Prognosis of Neoadjuvant Intraperitoneal and Systemic Paclitaxel Combined With Apatinib Conversion Therapy in Gastric Cancer Patients With Positive Peritoneal Lavage Cytology: A Prospective Study.

BACKGROUND: Gastric cancer with only peritoneal lavage cytology (GC-CY1) is a special type of gastric cancer, which is defined as stage IV. The pre-treatment systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) are representative blood indexes of systemic inflammatory response and nutritional status. However, the clinical significance of combined detection of these two indexes is still unclear. This study aims to evaluate the clinical value of the new score system by combining SII and PNI (SII-PNI score) as a predictor of efficacy and prognosis after neoadjuvant intraperitoneal and systemic (NIPS) paclitaxel combined with Apatinib conversion therapy for GC-CY1 patients. METHODS: We registered a prospective clinical study involving 36 GC-CY1 patients from April 2018 to August 2019 (NCT03718624). All patients underwent re-laparoscopic exploration after treatment. According to free cancer cells (FCCs) status, these patients were divided into FCCs group and non-FCCs group. The SII-PNI score ranged from 0 to 2 as follows: score of 2, high SII (≥512.1) and low PNI (≤52.9); score of 1, either high SII or low PNI; score of 0, no high SII nor low PNI. RESULTS: All patients underwent re-laparoscopic exploration after 3 cycles of NIPS paclitaxel and Apatinib conversion therapy. Among them, 28 cases (77.78%) were in non-FCCs group, and 8 cases (22.22%) were in FCCs group. The SII-PNI score of non-FCCs patients was significantly lower than that of FCCs patients (p=0.041). The prognosis of patients with high SII-PNI score was significantly worse than that of patients with low SII-PNI score (p<0.001). Multivariate analysis showed that SII-PNI score was an independent prognostic factor for predicting overall survival and progression-free survival (p=0.001, 0.002). CONCLUSION: Pretreatment SII-PNI score is an important predictor for the efficacy of GC-CY1 patients after NIPS paclitaxel combined with Apatinib conversion therapy, which can help to identify high-risk groups and predict prognosis.

Survival and the prognosticators of peritoneal cytology-positive pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy.

BACKGROUND: The factors associated with the survival and prognosis of peritoneal cytology (CY)-positive pancreatic cancer patients who undergo curative resection followed by adjuvant chemotherapy have not been established. PATIENTS AND METHODS: Both overall survival (OS) and recurrence-free survival (RFS) were examined in 23 peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy between 2005 and 2015. RESULTS: When the length of OS was evaluated using a log-rank test, significant differences were observed in the number of metastatic lymph nodes. In addition, univariate and multivariate analyses demonstrated that the number of metastatic lymph nodes was a significant independent risk factor for OS and a marginally significant risk factor for RFS. The 3-year OS rate was 20.2% in patients with ≤8 metastatic lymph nodes, and it was 0% in those with the ≥9 metastatic lymph nodes (P = 0.017). The 3-year RFS rate was 6.3% in patients with ≤8 metastatic lymph nodes, whereas it was 0% in those with ≥9 metastatic lymph nodes (P = 0.062). CONCLUSIONS: The number of metastatic lymph nodes is the most important prognostic factor for OS and RFS in peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy. To improve the survival of these patients, it is necessary to establish optimal treatments.