Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis.

BACKGROUND: Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy. METHODS: Embase, MEDLINE, Web of Science and Cochrane were searched for articles studying the use of repeated administration of palliative intraperitoneal chemotherapy in patients with gastric cancer and peritoneal metastases, published up to January 2024. The primary outcome was overall survival. RESULTS: Twenty-three studies were included, representing a total of 999 patients. The pooled median overall survival was 14.5 months. The pooled hazard ratio of the two RCTs using intraperitoneal paclitaxel and docetaxel favoured the intraperitoneal chemotherapy arm. The median overall survival of intraperitoneal paclitaxel, intraperitoneal docetaxel and PIPAC with cisplatin and doxorubicin were respectively 18.4 months, 13.2 months and 9.0 months. All treatment methods had a relatively safe toxicity profile. Conversion surgery after completion of intraperitoneal therapy was performed in 16% of the patients. CONCLUSIONS: Repeated intraperitoneal chemotherapy, regardless of method of administration, is safe for patients with gastric cancer and peritoneal metastases. Conversion surgery after completion of the intraperitoneal chemotherapy is possible in a subset of patients.

Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

BACKGROUND: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. PATIENTS AND METHODS: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. RESULTS: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. CONCLUSIONS: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC. METHODS: We performed a retrospective analysis of our prospectively maintained CRS/HIPEC database and evaluated all patients with CRC peritoneal metastases between 2012 and 2022. We divided the cohorts between those with low operative PCI (PCI<20) and high operative PCI (PCI =>20). We examined demographic, clinicopathologic data, perioperative, and oncological outcomes between the cohorts. RESULTS: Of the 691 patients who underwent CRS/HIPEC, 289 were evaluable with CRC metastases, 234 with PCI <20 and 43 with PCI => 20. Median radiologic preoperative and operative PCI was 4 and 10 versus 7 and 24.5 in the low and high PCI cohorts, respectively. Operative time was longer (6 vs. 4 h) and blood loss higher (500 vs. 400 mL) in the high PCI cohort. All other demographic, clinicopathological, and operative characteristics were similar. Median disease free survival (DFS) was longer in the low PCI cohort (11.5 vs. 7 months) but overall survival (OS) showed benefit (41.3 vs. 31.8 months), (p = 0.001 and p = 0.189, respectively), comparatively with an only chemotherapy strategy. CONCLUSIONS: Appropriately selected patients with CRC metastases and extremely high PCI demonstrate similar perioperative safety outcomes in experienced tertiary referral centers. Despite a shorter median DFS, these carefully selected patients demonstrated similar median OS.

Long term survival outcomes of surgery combined with hyperthermic intraperitoneal chemotherapy for perforated low-grade appendiceal mucinous neoplasms: A multicenter retrospective study.

BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are very rare, accounting for approximately 0.2%-0.5% of gastrointestinal tumors. We conducted a multicenter retrospective study to explore the impact of different surgical procedures combined with HIPEC on the short-term outcomes and long-term survival of patients. METHODS: We retrospectively analyzed the clinicopathological data of 91 LAMN perforation patients from 9 teaching hospitals over a 10-year period, and divided them into HIPEC group and non-HIPEC group based on whether or not underwent HIPEC. RESULTS: Of the 91 patients with LAMN, 52 were in the HIPEC group and 39 in the non-HIPEC group. The Kaplan-Meier method predicted that 52 patients in the HIPEC group had 5- and 10-year overall survival rates of 82.7% and 76.9%, respectively, compared with predicted survival rates of 51.3% and 46.2% for the 39 patients in the non-HIPEC group, with a statistically significant difference between the two groups (χ2 = 10.622, p = 0.001; χ2 = 10.995, p = 0.001). Compared to the 5-year and 10-year relapse-free survival rates of 75.0% and 65.4% in the HIPEC group, respectively, the 5-year and 10-year relapse-free survival rates of 48.7% and 46.2% in the non-HIPEC group were significant different between the two outcomes (χ2 = 8.063, p = 0.005; χ2 = 6.775, p = 0.009). The incidence of postoperative electrolyte disturbances and hypoalbuminemia was significantly higher in the HIPEC group than in the non-HIPEC group (p = 0.023; p = 0.044). CONCLUSIONS: This study shows that surgery combined with HIPEC can significantly improve 5-year and 10-year overall survival rates and relapse-free survival rates of LAMN perforation patients, without affecting their short-term clinical outcomes.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis.

PURPOSE: The purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy. METHODS: This retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression. RESULTS: The PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than -15% had significantly longer OS. CONCLUSION: CT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Correlation between peritoneal cancer index and survival in advanced epithelial ovarian cancer with complete resection.

OBJECTIVE: The aim of this study was to investigate the relation between the peritoneal cancer index, overall survival, and recurrence free survival, in patients with epithelial ovarian cancer. METHODS: Patients treated at the Gustave-Roussy Institute between December 2004 and November 2017 for advanced epithelial ovarian cancer in complete resection were included. The correlation between the peritoneal cancer index and survival was studied using statistical modeling. Multivariate analysis was performed with a logistic regression model. RESULTS: Of the 351 patients included, 94 (27%) had initial surgery and 257 (73%) had interval surgery. Median follow-up was 52.7 months (range 47.6-63.9). Median peritoneal cancer index was 10 (range 0-32). The linear model best represented the relationship between peritoneal cancer index and overall survival. Patients with neoadjuvant chemotherapy had a greater instantaneous risk of baseline death than those with initial surgery, as well as a more rapid increase in this risk as the peritoneal cancer index increased. Overall survival and recurrence free survival were better in the initial surgery group (103.4 months (79.1-not reached (NR)) vs 66.5 months (59.1-95.3) and 31.8 months (23.7-48.7) vs 25.9 months (23.2-29), respectively). Risk factors for death were body mass index, peritoneal cancer index, and need for neoadjuvant chemotherapy. CONCLUSION: The peritoneal cancer index is a prognostic indicator, but its linear relationship with survival precluded setting a unique peritoneal cancer index cut-off. Moreover, the prognostic impact of peritoneal cancer index was stronger in the setting of neoadjuvant chemotherapy.

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study.

BACKGROUND: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. METHODS: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009-2015 and 2016-2021). RESULTS: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009-2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016-2021 (30.2% in expert centers, 22.6% in referring centers). In 2009-2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02-2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66-0.96). In 2016-2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76-2.13) and survival (HR 1.00, 95% CI 0.76-1.32). CONCLUSION: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

Retrospective Evaluation of the Prognostic Value of Histological Growth Pattern in Patients with Colorectal Peritoneal Metastases Undergoing Curative-Intent Cytoreductive Surgery.

BACKGROUND: Two distinct histological growth patterns (HGPs) were described in patients with peritoneal metastasis of colorectal cancer origin (PMCRC) with limited Peritoneal Cancer Index (PCI) ≤ 6 who did not receive neoadjuvant chemotherapy (NAC) and were treated with cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC): pushing HGP (P-HGP) and infiltrating HGP (I-HGP). Patients with dominant P-HGP (> 50%) had significantly better disease-free survival (DFS) and overall survival (OS). OBJECTIVE: We aimed to determine whether these previous observations regarding the prognostic value of HGP in patients with PMCRC with low PCI (≤ 6) are also valid in all operable patients, regardless of whether they received NAC or not and regardless of PCI score. METHODS: This was a retrospective study including 76 patients who underwent complete CRS ± HIPEC for PMCRC between July 2012 and March 2019. In each patient, up to five of the largest excised peritoneal nodules were analyzed for their tumor-to-peritoneum interface. Correlations between NAC, HGP, and prognosis were further explored. RESULTS: Thirty-seven patients (49%) had dominant P-HGP and 39 (51%) had dominant I-HGP. On univariate analysis, patients with P-HGP ≤ 50% had significantly lower OS than those with dominant P-HGP > 50% (39 versus 60 months; p = 0.014) confirmed on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.3-4.5; p = 0.006). There were no significant associations between NAC and type of HGP. CONCLUSIONS: This study confirms the prognostic value and reproducibility of the two previously reported HGPs in PMCRC. Dominant P-HGP is associated with better DFS and OS in patients undergoing curative-intent CRS ± HIPEC compared with I-HGP, independently of the extent of peritoneal disease burden.

Pediatric, Adolescent and Young Adult (AYA) Peritoneal and Pleural Mesothelioma: A National Cancer Database Review.

PURPOSE: Malignant peritoneal and pleural mesothelioma are rare in young patients, with a paucity of data regarding clinical characteristics and outcomes. We aimed to describe the clinical characteristics, treatment strategies, and outcomes for pediatric and adolescent/young adult (AYA) patients. METHODS: The National Cancer Database (NCDB) was queried for malignant peritoneal and pleural mesothelioma in pediatric and AYA patients (ages 0-39) from 2004 to 2019. Stratification was performed for pediatric (age 0-21) and young adult (age 22-39) patients. Chi-squared, multivariable cox regression, and Kaplan-Meier analyses were performed. RESULTS: We identified 570 total patients, 46 pediatric and 524 young adult, with mesothelioma (363 peritoneal and 207 pleural). There were significant differences in sex distribution as patients with peritoneal mesothelioma were more frequently female (63.1%). Patients with peritoneal mesothelioma were more likely to have radical surgery compared to pleural mesothelioma (56.7% v. 24.6%, respectively). A majority of patients with peritoneal and pleural mesothelioma received chemotherapy (66.4% and 61.4%, respectively). For peritoneal mesothelioma, surgical resection was associated with improved overall survival, whereas male sex, neoadjuvant chemotherapy, and radiation were associated with worse overall survival. For pleural mesothelioma, intraoperative chemotherapy was associated with improved overall survival, whereas Black race was associated with worse overall survival. Mean overall survival was greater for patients with peritoneal mesothelioma (125 months) compared to those with pleural mesothelioma (69 months), which remained significant after stratification of pediatric and young adult patients. CONCLUSION: By analyzing a large cohort of pediatric and AYA mesothelioma, this study highlights clinical, prognostic, and survival differences between peritoneal and pleural disease. LEVEL OF EVIDENCE: Level III. TYPE OF STUDY: Retrospective.

Morbimortality after 1321 consecutive CRS+HIPEC procedures: seeking excellence in surgery for peritoneal surface malignancy

Purpose Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) treatment has classically presented a percentage of associated complications that have limited its expansion. The aim of this study is to describe the morbimortality results obtained from a referral center implemented with the support of a governmental health agency and directed by a surgical team experienced in CRS for Peritoneal Surface Malignancies (PSM). Methods Data from the Peritoneal Carcinomatosis Program of Catalonia (PCPC) prospective database, including patients who underwent CRS + HIPEC between September 2006 and January 2021, were analyzed. Results A total of 1151 consecutive patients underwent 1321 CRS + HIPEC procedures. Colonic origin of peritoneal metastasis was the most frequent (47.3%). Median PCI was 7 and most patients had CC0-1 (96.1%). Multivisceral resection was performed in 44% of all patients, 57% required digestive anastomosis. Median hospital stay was 11 days (range 6–144 days). High-grade complications occurred in 20% of all patient, most of them surgical complications. Anastomotic leak occurred in 0.6% of all cases. The overall in-stay and 30-day mortality rate was 0.4%. The low-rate of complications and the high rate of complete CRS were achieved from the beginning of the PCPC. Median overall survival was 54.7 months, with a 5-year survival rate of 47.5%. Conclusions Implementation of a CRS + HIPEC referral program for the treatment of PSM with preferably an experienced surgical team enables acceptable rates of severe morbidity (20%) and mortality (< 1%) (AU)

Prophylactic hyperthermic intraperitoneal chemotherapy may benefit the long-term survival of patients after radical gastric cancer surgery.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proven to improve the survival rate of gastric cancer and reduce peritoneal recurrence. We aimed to evaluate the effectiveness and safety of prophylactic HIPEC after radical gastric cancer surgery in this study. Researchers searched for studies published in PubMed, Embase, Web of science, Scopus, Cochrane, Clinical key databases and Microsoft Academic databases to identify studies that examine the impact of prophylactic HIPEC on the survival, recurrence and adverse events of patients undergoing radical gastric cancer surgery. RevMan 5.3 was used to analyze the results and risk of bias. The PROSERO registration number is CRD42021262016. This meta-analysis included 22 studies with a total of 2097 patients, 12 of which are RCTs. The results showed that the 1-, 3- and 5-year overall survival rate was significantly favorable to HIPEC (OR 5.10, 2.07, 1.96 respectively). Compared with the control group, the overall recurrence rate and peritoneal recurrence rate of the HIPEC group were significantly lower (OR 0.41, 0.24 respectively). Significantly favorable to the control group in terms of renal dysfunction and pulmonary dysfunction complications (OR 2.44, 6.03 respectively). Regarding the causes of death due to postoperative recurrence: liver recurrence, lymph node and local recurrence and peritoneal recurrence, the overall effect is not significantly different (OR 0.81, 1.19, 0.37 respectively). 1-, 3- and 5-year overall survival follow-up may be incremented by the prophylactic HIPEC, and which reduce the overall recurrence rate and peritoneal recurrence rate. HIPEC may have high-risk of pulmonary dysfunction and renal dysfunction complications. No difference has been found in the deaths due to recurrence after surgery.

Postoperative Treatment of Resectable Pancreatic Cancer With Positive Peritoneal Lavage Cytology: A Multicentre Retrospective Study.

BACKGROUND/AIM: We aimed to evaluate pancreatic cancer (PC) with positive peritoneal lavage cytology (CY1) outcomes following a change in adjuvant therapy. PATIENTS AND METHODS: The clinicopathological data of patients with pancreatic adenocarcinoma with CY1 at 14 institutions, between 2007 and 2015, were collected and analyzed. RESULTS: Of the 124 eligible patients, 114 underwent macroscopically curative resection. Of the 114 patients, 80 (70%) did not have early recurrence and received postoperative chemotherapy that was S-1 in 43 (54%), gemcitabine in 31 (39%), and others in six (7%). The median overall survival was 21.0 months in S-1 and 19.2 in gemcitabine therapy (p=0.23), whereas the median relapse-free survival was 10.2 and 7.1 months (p=0.03), respectively. CONCLUSION: Following the change in adjuvant therapy, most PC patients with CY1 who underwent macroscopically curative resection received S-1; however, it was insufficient. Further development of postoperative chemotherapy is required.

Assessment of the use of computed tomography colonography in early detection of peritoneal metastasis in patients with gastric cancer: A prospective cohort study.

Peritoneal metastasis (PM) is one of the most frequent forms of gastric cancer recurrence. In this study, we aimed to use computed tomography (CT) colonography (CTC) to detect signs of PM earlier in patients in whom PM was suspected but not yet diagnosed. CTC was used to evaluate patients with clinical symptoms or general CT findings that were suspicious but not sufficient to confirm PM. In total, 18 patients with suspected PM were enrolled. Ten patients (55.6%) had PM on CTC. Abnormal colonic deformities were identified at locations other than those of the lesions detected by general CT in seven patients. The sensitivity and specificity of CTC for the detection of PM were 83.3% and 100%, respectively. The median overall survival after CTC was 201 days in the CTC-positive group, which was significantly shorter than that in the CTC-negative group (945 days, p = 0.01). In the multivariate analysis, a positive CTC finding was the only factor independently associated with survival (p = 0.005). According to our experience with 18 patients, CTC can be an alternative to conventional imaging for early detection of PM. Further prospective studies with larger sample sizes are warranted to confirm and validate these findings. University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000044167.

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.

The concept of oligometastatic disease in gastric cancer: reality or fiction?

Positive results in the RENAISSANCE Trial will establish oligometastatic gastric cancer as a real independent entity where total surgical treatment will become the standard of care.

Oxaliplatin plus S-1 with intraperitoneal paclitaxel for the treatment of Chinese advanced gastric cancer with peritoneal metastases.

BACKGROUND: In this study, we tried to access the efficacy and safety of oxaliplatin plus S-1 with intraperitoneal paclitaxel (PTX) for the treatment of Chinese advanced gastric cancer with peritoneal metastases. PATIENTS AND METHODS: Thirty patients diagnosed with advanced gastric cancer underwent laparoscopic exploration and were enrolled when macroscopic disseminated metastases (P1) were confirmed. PTX was diluted in 1 l of normal saline and IP administered through peritoneal port at an initial dose of 40 mg/m2 over 1 h on day1,8, respectively. Oxaliplatin was administered intravenously at an initial dose of 100 mg/m2 on day1, and S-1 was administered orally at an initial dose of 80 mg/m2 for 14 days followed by 7 days rest, repeated by every 3 weeks. RESULTS: Of all these 30 patients, the median number of cycles was 6 (range 2-16) due to the limitation of hematotoxicity and peripheral neuropathy by oxaliplatin. There were 11 (36.7%) patients received conversion surgery. The median progression free survival (PFS) was 6.6 months (95% CI = 4.7-8.5 months) and the median overall survival (OS) was 15.1 months (95% CI = 12.4-17.8 months). The grade 3-4 hematological toxicities were leucopenia (23.3%), neutropenia (23.3%), anemia (16.7%), and thrombocytopenia (20%), respectively. The grade 3-4 non-hematological toxicities were tolerated, most of which were peripheral sensory neuropathy (40%) due to oxaliplatin, diarrhea (20%), nausea and vomiting (26.7%). CONCLUSIONS: SOX+ip PTX regimen was effective in advanced gastric cancer with peritoneal metastasis. Survival time was significantly prolonged by conversion surgery. Grade 3-4 toxicities were uncommon. Large scale clinical trial is necessary to get more evidence to identify its efficacy. TRAIL REGISTRATION: ChiCTR, ChiCTR-IIR-16009802 . Registered 9 November 2016.

Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study.

OBJECTIVES: To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery. DESIGN: Population based cohort study. SETTING: Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017. PARTICIPANTS: 200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17). EXPOSURES: Bilateral salpingo-oophorectomy versus ovarian conservation. MAIN OUTCOMES MEASURES: The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant. RESULTS: Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter. CONCLUSION: In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.

Peritoneal Spread of Low-grade Appendiceal Tumours - 2 Days of Early Postoperative Intra-peritoneal Chemotherapy Are Enough.

BACKGROUND/AIM: While controversial, cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) and early postoperative intra-peritoneal chemotherapy (EPIC) remains the mainstay of treatment for low grade appendiceal neoplasm with pseudomyxoma peritonei (PMP). Our study aimed to investigate the difference in survival when administering HIPEC alone vs. HIPEC + EPIC. Additionally, we examined whether the duration of EPIC affects survival. PATIENTS AND METHODS: We compared the difference in survival in 238 patients who underwent CRS + HIPEC alone vs. CRS + HIPEC/EPIC combination for low grade appendiceal cancer. We also compared short course (1-2 days) vs. long course (3-5 days) of EPIC. RESULTS: HIPEC/EPIC combination group (n=179) showed a significantly better 5-year survival of 95% compared to 71% in HIPEC alone (n=59). There was no statistically significant difference in 5-year survival between short course (n=22) and long course of EPIC (n=157). CONCLUSION: Combined use of HIPEC and EPIC improves 5-year survival in low-grade appendiceal neoplasm. Two days of EPIC are sufficient.

Postoperative Pancreatic Fistula After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Update on Incidence, Risk Factors, Management, and Clinical Sequelae in 1,141 Patients.

BACKGROUND/AIM: An update on the incidence, risk factors, clinical sequalae, and management of postoperative pancreatic fistula (POPF) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Retrospective analysis of prospectively collected data from the St George CRS/HIPEC database. RESULTS: Sixty-five (5.7%) out of 1,141 patients developed a POPF. Patients with POPFs were older, had a higher peritoneal cancer index, longer operation time, and required more units of blood intraoperatively. Splenectomy and distal pancreatectomy were significant risk factors for developing POPFs. While there was no effect on overall long-term survival in POPF patients, they did suffer higher rates of Clavien-Dindo grade 3/4 complications, in-hospital deaths, and longer hospital length of stay. Of the 65 POPF patients, 23 were taken back to theatre, 48 required radiological drains and 7 underwent endoscopic retrograde cholangiopancreatography. CONCLUSION: There are multiple risk factors for developing POPFs that are non-modifiable. While POPFs are associated with increased postoperative morbidity, long-term survival does not appear to be affected.