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.

Utility of hyperthermic intraperitoneal chemotherapy in cases of incomplete cytoreductive surgery.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions. METHODS: Retrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score. RESULTS: A total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS-HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS-HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low-grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS-HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC. CONCLUSION: HIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low-grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).

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.

Half of Postoperative Deaths After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Could be Preventable: A French Root Cause Analysis on 5562 Patients.

OBJECTIVE: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures. BACKGROUND: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality. METHODS: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram. RESULTS: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%). CONCLUSION: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.

Ki67 does not predict recurrence for low-grade appendiceal mucinous neoplasms with peritoneal dissemination after cytoreductive surgery and HIPEC.

Low-grade appendiceal mucinous neoplasms (LAMN) can disseminate to become low-grade mucinous carcinoma peritonei (LGMCP), which is optimally treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Approximately half of the patients with LGMCP recur despite complete cytoreduction, and risk factors for recurrence are poorly understood. We sought to evaluate if Ki67 predicts progression of LGMCP after CRS/HIPEC. A retrospective review of a prospectively maintained database was performed to identify patients treated with complete CRS/HIPEC for LGMCP from 2008 to 2019 with Ki67 assessed. Patient characteristics, histologic data, average and focally high "hotspot") Ki67 index, progression-free survival (PFS), and overall survival (OS) were analyzed. Ki-67 immunostain was performed on the histologic section with the highest cellularity and architectural complexity. Forty-four patients with LGMCP (55% male, median age 61) were identified. The median Ki67 score and hotspot Ki67 score was 15% (1-70) and 50% (1-90), respectively. On univariate analysis, average Ki67 and hotspot Ki67 were not predictive of PFS when analyzed as continuous normalized values (HR 1.0, p = 0.79 and HR 1.1, p = 0.38, respectively) or as categorical values when stratified by the median (HR 0.9, p = 0.67 and HR 1.0, p = 0.93). This remained true on multivariate analysis when stratified for peritoneal cancer index, CEA, and completeness of cytoreduction score for both normalized Ki67 and hotspot Ki67 (HR 0.9 [95% CI 0.8-1.3], p = 0.94 and HR 1.04 [95% CI 0.8-1.3], p = 0.73, respectively). Ki67 failed to predict disease recurrence for patients with LGMCP in this cohort.

Surgical and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at a nonacademic center: 25-year experience.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is predominantly performed and studied in academic centers. While developing CRS/HIPEC programs in nonacademic hospitals can increase accessibility, its safety and oncological efficacy remains unclear. We evaluated CRS/HIPEC outcomes in a nonacademic setting. METHODS: A single-center descriptive study was conducted using a prospective database. Data of all CRS/HIPEC attempts in peritoneal surface malignancies (PSM) patients from October 1994 to November 2019 were extracted. Surgical and survival outcomes were measured. Center experience was assessed by quartiles of cases. RESULTS: Overall, 856 patients underwent 948 CRS/HIPEC attempts: 788 (83%) completed CRS/HIPECs, 144 (15%) aborted HIPECs, and 16 (2%) complete cytoreductions (CC-0/1) without chemoperfusion. For completed CRS/HIPECs, median peritoneal cancer index was 24 (interquartile range: 10-33) and CC-0/1 rate was 88%. Major complications occurred in 23.5% with 30- and 100-day mortality of 1.0% and 2.3%, respectively. Median overall survival was 68 months (95% confidence interval [CI]: 50-86). Median progression-free survival was 37 months (95%CI: 28-46). Incomplete cytoreduction and major complication rates decreased over time, while mortality remained low and constant. CONCLUSIONS: CRS/HIPEC at a nonacademic center with advanced surgical and auxiliary services is a safe option to treat PSM with favorable surgical and oncological outcomes.

High-grade postoperative complications affect survival outcomes of patients with colorectal Cancer peritoneal metastases treated with Cytoreductive surgery and Hyperthermic Intraperitoneal chemotherapy.

BACKGROUND: This study aimed to evaluate the impact of postoperative complications on long-term survival in patients with peritoneal metastasis (PM) arising from colorectal cancer (CRC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Patients with PM arising from CRC treated with CRS and HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. High-grade complications that occurred within 30 days were defined as grade 3 to 4 events according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Univariate and multivariable Cox regression models for overall survival were created. Predictors of high-grade postoperative complications were evaluated with univariate and multivariate logistic regression analyses. RESULTS: In all, 86 consecutive cases were included in this study. Forty-one patients (47.7%) developed postoperative complications, while 22 patients (25.6%) experienced high-grade complications. No mortality occurred during the postoperative period. The median survival of all patients was 25 months, and the estimated 3-year overall survival (OS) rate was 35.0%. In the multivariable Cox regression analysis, a high peritoneal carcinomatosis index (PCI) score (HR, 1.07, 95% CI, 1.01-1.14; P=0.015) and grade 3-4 postoperative complications (HR, 1.86, 95% CI, 1.22-3.51; P=0.044) correlated with worse overall survival. High estimated blood loss (OR, 1.01, 95% CI, 1.01-1.02; P< 0.001) was identified as an independent risk factor for developing high-grade complications. CONCLUSION: Careful patient selection, high levels of technical skill and improved perioperative management are crucial to ensure patient survival benefits after CRS+HIPEC.

Tumor characteristics and clinical outcome of peritoneal metastasis of gastric origin treated with a hyperthermic intraperitoneal chemotherapy procedure in the PERISCOPE I trial.

INTRODUCTION: The PERISCOPE I (Treatment of PERItoneal dissemination in Stomach Cancer patients with cytOreductive surgery and hyPErthermic intraperitoneal chemotherapy) study was conducted to investigate the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients with limited peritoneal dissemination. In this study, tumor characteristics and clinical outcome of the patients treated in the PERISCOPE I trial were investigated. METHODS: Patients who had undergone the full study protocol were selected; that is, preoperative systemic chemotherapy, followed by a surgical procedure consisting of a (sub)total gastrectomy, cytoreductive surgery, and HIPEC with oxaliplatin (460 mg/m2 ) and docetaxel (in escalating doses). RESULTS: Twenty-five PERISCOPE I patients underwent the full study protocol. Most patients had an ypT3-4 tumor (96%) and the diffuse-type histology was predominant (64%). Seven patients (28%) had a microscopically irradical (R1) resection. In all patients, a complete cytoreduction was achieved. Median follow-up was 37 (95% confidence interval [CI]: 34-39) months. Disease recurrence was detected in 17 patients (68%). Median disease-free and overall survival were 12 and 15 months, respectively. CONCLUSION: In this series of gastric cancer patients with limited peritoneal dissemination who underwent HIPEC surgery, unfavorable tumor characteristics were common. Survival might be encouraging but disease recurrence was frequent. The efficacy of an HIPEC procedure in improving prognosis is currently being investigated in the PERISCOPE II trial.

Effect of platinum sensitivity on the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery (CRS) is a treatment strategy that has been evaluated in recurrent ovarian cancer. The aim of this study was to examine if survival was similar regardless of platinum sensitivity. METHODS: A retrospective study of women with recurrent platinum sensitive or resisteant epithelial ovarian cancer who were treated with cytoreductive surgery (CRS) and HIPEC between the years 2010-2018 was performed. Recurrence free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Thirty-five (72.9 %) were platinum sensitive (PS) and 13 (27.1 %) were platinum resistant (PR). The complete cytoreduction (R0) rate was higher in the PS patients as compared to PR (85.7 % vs 53.8 %; p = 0.017). Median follow-up was 16.9 (range, 11.7-34.5) months. The median recurrence free survival in the patients who had a R0 resection was 22.3 months in PS and 11.1 months in PR patients (p = 0.017), respectively. Median overall survival was 26.9 months in the PR patients, while it had not been reached in the PS patients. In the patients with PS recurrence, the mean treatment free interval (TFI) prior to HIPEC was 1.6 years and following HIPEC, 40 % of those patients were recurrence free at 2 years. In the patients with PR recurrence, the mean TFI prior to HIPEC was 4.6 months and following HIPEC, 61.5 % of those patients had a longer TFI, with a mean increase of 10.1 months. CONCLUSION: Although surgery is not considered standard treatment in PR ovarian cancer, in carefully selected patients, surgery with HIPEC could extend the treatment-free interval.

Upfront or intermediate treatment of advanced ovarian cancer patients with cytoreduction plus HIPEC: Results of a retrospective study.

BACKGROUND: Newly diagnosed advanced-stage ovarian cancer patients are treated with neoadjuvant chemotherapy, primary or intermediate cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to evaluate the optimal timing of cytoreduction plus HIPEC for advanced ovarian cancer patients. METHODS: Advanced ovarian cancer patients treated with cytoreductive surgery plus HIPEC at three different hospitals between 2005 and 2019 were subgrouped regarding their time of management with cytoreduction plus HIPEC, upfront or intermediate. We retrospectively assessed the overall survival (OS), the progression-free survival (PFS), and the disease-free survival (DFS) of these groups. RESULTS: A total of 112 ovarian cancer patients were contained. Of whom, 47 patients were in the upfront group with 24 (51.1%) to be alive, while 65 patients were included in the intermediate group with 34 (52.3%) to be alive. OS (48 vs. 30 months) and DFS (42 vs. 20 months) indicated no significant difference. Although the same median PFS was observed in both groups (10 months), a higher mean PFS was observed in the upfront group (11.9 vs. 9 months, p = 0.023). CONCLUSION: The treatment of advanced ovarian cancer patients with upfront cytoreductive surgery plus HIPEC is feasible with the same survival results. Further, larger prospective studies need to verify our results.

Neoadjuvant systemic and hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery for gastric cancer patients with limited peritoneal metastasis: a prospective cohort study.

BACKGROUND: There is no currently available treatment for peritoneal metastasis of gastric cancer. This phase II study aimed to evaluate the efficacy and safety of neoadjuvant systemic chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) for the treatment of these patients. METHODS: Neoadjuvant chemotherapy comprised two cycles of HIPEC and four cycles of S-1 plus paclitaxel. HIPEC was administered intraperitoneally with paclitaxel (75 mg/m2). For systemic chemotherapy, paclitaxel was administered intravenously(150 mg/m2) on day 1, and S-1 was administered orally(80 mg/m2/day)on days 1-14 of a 3-week cycle. Another two cycles of HIPEC and four cycles of S-1 plus paclitaxel were administered after second diagnostic staging laparoscopy or CRS. The primary endpoints were treatment efficiency and safety; the secondary endpoint was 3-year overall survival (OS). RESULTS: A total of 40 patients were enrolled and 38 patients have been analyzed. Of these, 18 (47.4%) patients received neoadjuvant systemic chemotherapy, HIPEC and CRS (conversion therapy group), while 20 patients received only chemotherapy and HIPEC (palliative chemotherapy group). Median OS was markedly improved in the conversion therapy group (21.1 months, 95% confidence interval [CI] 16.7-25.6 months) in comparison with the palliative chemotherapy group(10.8 months, 95%CI 7.3-14.2 months, p = 0.002). After neoadjuvant systemic chemotherapy and HIPEC, a second laparoscopic exploration was performed, and the prognosis of patients with low peritoneal cancer index (PCI) (PCI < 6) was significantly better than that of patients with high PCI (PCI ≥ 6)(20.1 vs.11.3 months, p = 0.006). CONCLUSION: Neoadjuvant systemic chemotherapy and HIPEC combined with CRS is safe and feasible, and could potentially improve the prognosis of gastric cancer patients with limited peritoneal metastasis. However, further clinical trials are still warranted. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov as NCT02549911 . Trial registration date: 15/09/2015.

HIPEC plus EPIC paclitaxel for maximal perioperative treatments of advanced epithelial ovarian cancer. Long-term results of a pilot study.

BACKGROUND: A unique time in which to effectively treat an intraabdominal malignancy is the time at which the surgeon attempts complete removal of the malignant process. Although surgery is effective for visible disease, micrometastases or multiple small cancer nodules are not amenable to resection. Alternative interventions to deal with residual disease disseminated on peritoneal surfaces are needed. MATERIALS AND METHODS: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be combined with early postoperative intraperitoneal chemotherapy (EPIC) in order to maximally treat gross disease within the abdomen and pelvis and also the minimal residual disease that exists in many patients after resection. The third component of this treatment for ovarian malignancy was EPIC paclitaxel in this study. The clinical features, pharmacologic assessments, and survival were determined in ovarian cancer patients in whom EPIC was added to the perioperative treatment plan. RESULTS: Patients with high grade serous ovarian cancer underwent CRS, HIPEC with cisplatin/doxorubicin, and EPIC paclitaxel. These treatments combined as a single intervention were studied in 10 patients. The median number of peritonectomy procedures was 1, the median number of visceral resections was 5, and the median time required in the operating room was 8 h. Two patients had a class 3 adverse event. The median survival of patients was 50 months. Pharmacokinetic analysis of the intraperitoneal paclitaxel showed 252 ± 153 times exposure of peritoneal surfaces as compared to intravenous exposure when the drug was instilled into the peritoneal space. CONCLUSIONS: EPIC paclitaxel was successfully combined with CRS and HIPEC in 10 patients with ovarian cancer. The treatment was tolerated approximately the same as other major cytoreductive surgical procedures for ovarian cancer or other malignancies. Survival of these ovarian cancer patients seemed unusually prolonged as compared to other patients with stage 3b or recurrent disease. In this pilot study CRS, HIPEC and EPIC were safe and effective.

[Outcome of Icelandic patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) abroad].

BACKGROUND: Peritoneal carcinomatosis is a known complication of colorectal cancer and has long been considered very difficult to manage. The survival has been reported to be under two years after systemic chemotherapy with or without palliative surgery. The most recent method of treatment is compiled of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and has been suggested to significantly increase survival. The aim of this study was to research the cases of Icelandic patients undergoing this treatment overseas and the impact it has had on their disease. METHODS: A retrospective study of all Icelandic patients who have undergone CRS-HIPEC treatment abroad 2008-2017. Information was retrieved from medical records and from registry of the Icelandic Health Insurance committee of medical treatments abroad. RESULTS: A total of 11 patients have undergone CRS-HIPEC treatment after having received their initial treatment in Landspitali University Hospital. All of the surgeries were performed in the United States by the same surgeon in the years 2008-2017. The group consists of 10 women and 1 man with a mean age of 53 years. The cause of peritoneal carcinomatosis was appendiceal cancer for 7 patients (67%) and colon cancer for 3 patients (27%). One patient had a primary malignancy of the peritoneum, mesothelioma. Three patients suffered complications within 30 days of surgery, 2 had infection and 1 had an anastomotic leak. Another patient had a late complication of bowel stenosis and later a fistula. Five patients have completed their five year observation period post surgery without diagnosis of recurrence and mean follow-up time was 44 months. Out of 11 patients, 10 are still alive. Five have been diagnosed with recurrence of disease. CONCLUSION: Icelandic patients who have undergone CRS-HIPEC treatment have in most cases done well and survival is comparable to other studies. Half of the survivors did not have recurrence of disease within 5 years of surgery. Prognosis has improved since the introduction of this treatment and every reason to keep sending selected Icelandic patients abroad to receive it.

A population-based study on the prognostic impact of primary tumor sidedness in patients with peritoneal metastases from colon cancer.

Primary tumor location is an established prognostic factor in patients with (metastatic) colon cancer. Colon tumors can be divided into left-sided and right-sided tumors. The aim of this study was to determine the impact of primary tumor location on treatment and overall survival (OS) in patients with peritoneal metastases (PM) from colon cancer. This study is a retrospective, population-based cohort study. Records of patients diagnosed with colon cancer and synchronous PM, from 1995 through 2016, were retrieved from the Netherlands Cancer Registry (NCR). Data on diagnosis, staging, and treatment were extracted from the medical records by specifically trained NCR personnel. Information on survival status was updated annually using a computerized link with the national civil registry. In total, 7930 patients were included in this study; 4555 (57.4%) had a right-sided and 3375 (42.6%) had a left-sided primary tumor. In multivariable analysis right-sided primary tumor was associated with worse OS (HR: 1.11, 95% CI 1.03-1.19, P = .007). Of all patients diagnosed with PM, 564 (7.1%) underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Patients with left-sided primary tumors were more often candidates for CRS-HIPEC (6.5% vs. 8.0%, P = .008). OS of patients with right- and left-sided tumors who underwent CRS-HIPEC did not significantly differ. In conclusion, primary right-sided colon cancer was an independent prognostic factor for decreased OS in patients diagnosed with synchronous PM. In patients treated with CRS-HIPEC location of the primary tumor did not influence survival.

Clinicopathological analysis of appendiceal goblet cell adenocarcinoma with peritoneal metastasis: World Health Organization grade predicts survival following cytoreductive surgery with intraperitoneal chemotherapy.

AIMS: Peritoneal spread is the most common route of metastasis in appendiceal goblet cell adenocarcinoma. The aim of this study was to assess the prognostic significance of the World Health Organization (WHO) 5th edition grading criteria in peritoneal metastases of goblet cell adenocarcinoma. METHODS AND RESULTS: We evaluated the clinicopathological features and survival of 63 patients with peritoneal metastasis of goblet cell adenocarcinoma who underwent cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), stratified according to the WHO 5th edition and the Tang et al. grading schemes. The patients were also compared with 120 patients with peritoneal metastasis of appendiceal mucinous neoplasia. Most (73%) peritoneal metastases of goblet cell adenocarcinoma were WHO Grade 3 (G3), there being fewer cases of Grade 2 (G2) (16%) and Grade 1 (G1) (11%) disease. No significant differences in overall survival were observed between WHO G1 and G2 tumours or between the three Tang grades. In the multivariable model of survival, WHO G3 [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.02-7.70] and the presence of >50% extracellular mucin (HR 2.30, 95% CI 1.09-4.88) were associated with reduced overall survival for patients with goblet cell adenocarcinoma. As compared with patients with peritoneal metastasis of mucinous neoplasia, patients with goblet cell adenocarcinoma had significantly reduced survival (median overall survival of 37 months versus 102 months, P < 0.001), which was attributed to the reduced survival of patients with G1/G2 goblet cell adenocarcinoma as compared with patients with G1 mucinous neoplasia (median survival of 98 months versus 204 months, P < 0.001). CONCLUSIONS: Grade of peritoneal goblet cell adenocarcinoma determined according to the WHO 5th edition criteria is a clinically relevant measure that independently predicts survival in patients treated with CRS-HIPEC.