Clinical benefits of FOLFOXIRI combined with bevacizumab for advanced-stage primary signet ring cell carcinoma of the appendix: A case report.

RATIONALE: Signet-ring cell carcinoma, which is an infrequent type of colorectal cancer. Abdominal pain is the primary presenting complaint of patients with acute appendicitis. It is difficult to diagnose patients with appendiceal carcinomas accompanying with symptoms of acute appendicitis. PATIENT CONCERNS: A 33-year-old female patient was admitted to our hospital, with chief complaints of "bilateral pelvic space-occupying lesions for 1 month, aggravated abdominal distension, and she accompanied with diarrhea for 3 days." DIAGNOSIS: The patient was with primary signet ring cell carcinoma of the appendix, presented with acute appendicitis, as well as bilateral ovarian metastasis and peritoneal implantation metastasis. INTERVENTIONS: She was then treated with irinotecan, oxaliplatin, calcium folinate, 5-FU combined with bevacizumab, surgical treatment, and postoperative adjuvant treatment with oxaliplatin, capecitabine regimen to consolidate the efficacy. OUTCOMES: The patient is in good conditions, and postoperative adjuvant chemotherapy is in progress as well. CONCLUSION: The outcomes highlighted the importance of strict histopathologic assessment for appendiceal adenocarcinoma, and provided new ideas for the diagnosis and treatment of advanced-stage signet ring cell carcinoma of the appendix.

Alternative medicine: therapeutic effects on gastric original signet ring carcinoma via ascorbate and combination with sodium alpha lipoate.

BACKGROUND: Gastric signet ring cell carcinoma (SRCC) is an aggressive gastric adenocarcinoma with a poor prognosis when diagnosed at an advanced stage. As alternative medicine, two natural supplements (ascorbate (AA) and sodium alpha lipoate (LA)) have been shown to inhibit various cancers with mild side effects. METHODS: These two natural supplements and a series of combinations (AA&LA, AA+LA and LA + AA) were incubated with non-SRCC cells (GPM-1), patient-derived gastric origin SRCC (GPM-2), gastric-origin SRCCs (HSC-39 and KATO-3), human pancreatic (MIA PaCa-2) and ovarian (SKOV-3) cells for evaluating their therapeutic effects. Moreover, these treatments were applied in 3D-cultured organoids to reveal the feasibility of these approaches for in vivo study. RESULTS: Analyzing their antioxidant capabilities and dose-response curves, we observed that all four gastric cell lines, including three patient-derived cell lines were sensitive to ascorbate (~ 10 mM). The influence of ascorbate incubation time was studied, with a 16-h incubation found to be optimal for in vitro studies. Moreover, a simultaneous combination of AA and LA (AA&LA) did not significantly inhibit cell proliferation, while prior LA treatment increased the growth inhibition of AA therapy (LA + AA). Anti-cancer efficacy of AA was further confirmed in 3D-cultured SRCC (KATO-3) organoids. CONCLUSIONS: This study highlights the potential of AA and LA + AA in treating gastric origin SRCC, and demonstrates the influence of order in which the drugs are administered.

Esophageal adenocarcinoma with any component of signet ring cells portends poor prognosis and response to neoadjuvant therapy.

BACKGROUND: Multiple investigations have shown inferior outcomes for esophageal cancer patients with signet ring cell (SRC) histology. Traditionally, SRC adenocarcinoma has been defined by ≥50% of the tumor composed of SRC. We hypothesized that patients with SRC even <50% would show resistance to standard multimodality therapy with poorer long-term outcomes. METHODS: Patients treated with trimodality therapy for adenocarcinoma from 2006 to 2018 were evaluated for SRC on pretreatment biopsy specimens. Available hematoxylin and eosin slides containing SRC tumors were re-reviewed by an esophageal pathologist to quantify the percent composition of SRC. RESULTS: SRC histology was identified on at least 1 pathologic specimen in 106 of 819 (13%) patients. Rates of pathologic complete response (pCR) among usual-type and SRC tumors were 25% (177/713) and 10% (11/106), respectively (P = .006). The pretreatment SRC components did not independently affect the rate of pCR (1%-10% SRC: 4% [2/46] pCR; 11%-49% SRC: 25% [7/28] pCR; 50%-100% SRC: 7% [2/30] pCR). Kaplan-Meier analysis demonstrated worse survival among patients with any degree of SRC present on pretreatment biopsy, as compared with usual-type esophageal adenocarcinoma (P < .0001). Cox multivariable analysis failed to identify a relationship between increasing SRC component and poorer survival. CONCLUSIONS: We present the only known evaluation of the percentage of SRC component in esophageal carcinoma. Our data support the hypothesis that esophageal adenocarcinoma with any component of SRC are more resistant to chemoradiation with poorer survival. Pathologic reporting of esophageal adenocarcinoma should include any component of SRC. Alternative therapies in patients with any SRC component may be indicated.

Quality of life in rectal cancer patients with or without oxaliplatin in the randomised CAO/ARO/AIO-04 phase 3 trial.

BACKGROUND: The CAO/ARO/AIO trial has shown that oxaliplatin added to preoperative chemoradiotherapy and postoperative chemotherapy significantly improved disease-free survival in locally advanced rectal cancer (LARC). Here, we present a post-hoc analysis of quality of life (QoL) in disease-free patients. PATIENTS AND METHODS: Between 2006 and 2010, 1236 patients with LARC were randomly assigned either to preoperative chemoradiotherapy followed by total mesorectal excision and postoperative chemotherapy (N = 623) or combined with oxaliplatin (N = 613). QoL questionnaires (EORTC QLQ-C30, colorectal module CR38) were completed at baseline, after postoperative chemotherapy and during follow-up. Analysis was performed according intent-to-treat. RESULTS: Available questionnaires (baseline) were 82% (N = 512) in the control and 84% (N = 513) in the investigational group. Response rates were 49% (533 of 1086) at 1 year and 43% (403 of 928) at 3 years. Global health status (GHS) for disease-free patients was stable in both groups (range 0-100). At baseline: standard arm 62.0 (mean, SD 21.6; N = 491) versus oxaliplatin arm 63.2 (mean, SD 22; N = 503); at 3 years: 69.4 (SD 19.3; N = 187) versus 65.4 (SD 22.2; N = 202). After treatment and at 3 years, no significant differences (≥10 points) between groups were found in QoL subscales. Disease-free patients experiencing neurotoxic side-effects (grade 1-4) showed reduced GHS at 3 years versus patients without neurotoxicity (mean 59.2 versus 69.3; P < 0.001), while grade 3-4 rate was low. CONCLUSION: The addition of oxaliplatin was not associated with worse overall QoL. This information is of interest to patients in many ongoing rectal cancer trials. TRIAL REGISTRATION INFORMATION: NCT00349076.

Impact of adjuvant chemotherapy on outcomes in appendiceal cancer.

BACKGROUND: The impact of using adjuvant chemotherapy following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal adenocarcinoma is not known. The aim of this study was to assess the impact of adjuvant chemotherapy following complete cytoreduction in patients with appendiceal adenocarcinoma. METHODS: Retrospective medical record review of all patients with appendiceal adenocarcinoma treated at our institution between 2006 and 2015. Kaplan-Meier plots were used to summarize overall survival (OS) and relapse-free survival over time, and log-rank tests and Cox proportional hazards models were used to test for differences in survival between groups. RESULTS: A total of 103 patients with appendiceal adenocarcinoma received care at our institution during the study period. Complete cytoreduction (cytoreductive score 0-1) was achieved in 68 patients (66%). Of these 68 patients, 26 received adjuvant chemotherapy. The most common regimens were capecitabine (n = 11), capecitabine plus oxaliplatin (n = 7), and 5-FU plus oxaliplatin (n = 6). Tumor histopathology and grade, and the ability to achieve complete cytoreduction were significant predictors of overall survival. The median OS for non-low-grade and well-differentiated tumor patients who received adjuvant chemotherapy following complete cytoreduction was 9.03 years, compared to 2.88 years for patients who did not receive adjuvant chemotherapy (P = .02). Among low-grade and well-differentiated tumor patients who underwent complete cytoreduction, there was no statistically significant difference in OS between those who received adjuvant chemotherapy and those who did not. CONCLUSION: Adjuvant chemotherapy seems to have benefit in appendiceal cancer patients with non-low-grade or well-differentiated tumor type but not in low-grade or well-differentiated tumors.

Intra-abdominal recurrence from colorectal carcinoma: Differences and similarities between local and peritoneal recurrence.

BACKGROUND: Peritoneal recurrences from colo-rectal cancer can be isolated (PR) or associated with local recurrences (LR). The purpose of this study was to analyze patterns and outcomes of LR and PR. METHODS: Analyze from a prospective database of 108 patients treated with CCS plus HIPEC at two cancer centers between 2008 and 2015. RESULTS: The population was divided into an LPR group (presence of LR with or without PR, n = 56) and a PR group (isolated PR, n = 52). The patients characteristics (age, sex, Charlson score, PCI) or perioperative treatments were comparable between the groups. The median number of resected organs for tumor involvement (respectively, 2 vs 1; p < 0.001), the percentage of patients with metastatic lymph nodes (LN+) from the resected specimen (respectively, 25% vs 7%; p = 0.016) and the mortality rate (respectively, 9% vs 0%; p = 0.023) were significantly higher in the LPR group. After a median follow-up of 32 (1-108) months, median overall survival was comparable between the two groups (respectively, 46 vs 42 months; p = 0.262). CONCLUSIONS: LR is associated with a higher incidence of organ invasion, LN involvement (25%) and postoperative mortality. Optimal surgical resection of LR with systematic lymphadenectomy of invaded organs seems mandatory.

Metachronous Signet Ring Cell Bladder Metastasis as First Sing of Cancer Recurrence.

We describe the case of a 74-year-old woman with previous history of gastric signet cell carcinoma who develops bladder metastasis as first sign of recurrence 6 years later. Bladder metastasis due to signet cell carcinoma is extremely rare with only 19 cases reported. Treatment includes radical cystectomy or chemotherapy.

Systemic chemotherapy before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with high-grade mucinous carcinoma peritonei of appendiceal origin.

BACKGROUND: The role of systemic chemotherapy (SC) before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in appendiceal high-grade mucinous carcinoma peritonei (HGMCP) is controversial. We analyzed the effect of SC prior to CRS/HIPEC in HGMCP. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP without signet ring cells and with signet ring cells (HGMCP-S) from 1998 to 2017 was reviewed. Exclusion criteria was prior surgery >5 regions or >2 regimens of prior SC. Perioperative variables were analyzed. RESULTS: There were 140 HGMCP/HGMCP-S identified: 64 with prior SC (preSC) and 76 without (noSC). Groups were balanced for lymph node status, complete cytoreduction rate, disease burden, complications, and postoperative SC. PreSC had more HGMCP-S, moderately/poorly differentiated histology, and longer time-to-surgery (median: 6 vs 2 months, p < 0.001). Median overall survival (mOS) was 40 vs 86 and median progression-free survival (mPFS) was 19 vs 43 months for preSC vs noSC, respectively (p = 0.006 and p = 0.007). In HGMCP-S subanalysis, mOS was 25 vs 39 and mPFS 16 vs 29 months for preSC vs noSC, respectively (p = 0.188 and p = 0.063). In moderately/poorly differentiated histology subanalysis, mOS was 38 vs 56 and mPFS 18 vs 29 months in preSC vs noSC, respectively (p = 0.199 and 0.082). Prior SC was not linked to improved OS or PFS in non-signet ring HGMCP or well-differentiated histology subanalysis. CONCLUSION: Prior SC was not associated with less disease burden, better cytoreduction rates, or improved clinical outcomes in HGMCP, regardless of histopathologic subtype. Traditional SC agents may not be effective in HGMCP in the neoadjuvant setting.

Selection and Characteristics of Patients with Peritoneal Dissemination from Appendiceal Cancer with Exceptional/Poor Survival After CRS/HIPEC.

BACKGROUND: Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. METHODS: Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. RESULTS: LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). CONCLUSIONS: Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.

Signet ring cell features with peritoneal carcinomatosis in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are associated with poor overall survival.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective in select patients with peritoneal carcinomatosis (PC). Signet ring cell (SRC) pathology is associated with poor prognosis. The role of CRS/HIPEC in this population is unclear. METHODS: Patients diagnosed with PC due to appendiceal (AC), colorectal (CRC), and gastric cancer (GC) undergoing CRS/HIPEC 2007-2016 were included. RESULTS: A total of 268 patients were referred for CRS/HIPEC. Of the 204 patients who underwent complete CRS/HIPEC, 101 (49.5%) had AC, 85 (41.7%) CRC, and 18 (8.8%) GC. Patients with GC had higher rates of SRC pathology than AC and CRC: 12 (66.7%) vs 16 (15.8%) and 10 (11.7%). The 3-year survival rate after CRS/HIPEC was 5.7% for the SRC group and 66.1% for the non-SRC group (P < 0.001). This was true for both AC and CRC subgroups (P < 0.001 for both). Overall, patients with SRC were more likely to have a peritoneal carcinomatosis index (PCI) score > 15 (P = 0.046). Upon multivariate analysis of the SRC population, PCI > 20 (P = 0.007) and GC (P = 0.008) were found to be independent predictors of poor overall survival. CONCLUSIONS: Performing CRS/HIPEC for PC from gastrointestinal malignancies presenting SRC features is recommended on patients with select diseases of appendiceal and colorectal origins.

Outcomes in Peritoneal Dissemination from Signet Ring Cell Carcinoma of the Appendix Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard treatment for peritoneal dissemination from appendiceal cancer (AC); however, its role in high-grade histopathologic subtypes (high-grade mucinous carcinoma peritonei [HGMCP] and HGMCP with signet ring cells [HGMCP-S]) is controversial due to their aggressive behavior. This study analyzed clinical outcomes of high-grade AC after CRS/HIPEC. METHODS: A prospective database of CRS/HIPEC procedures for HGMCP performed from 1998-2017 was reviewed. Perioperative variables and survival were analyzed. RESULTS: Eighty-six HGMCP and 65 HGMCP-S were identified. HGMCP had more positive tumor markers (TM) (CEA/CA-125/CA-19-9) than HGMCP-S (63% vs 40%, p = 0.005). HGMCP had higher Peritoneal Cancer Index (32 vs 26, p = 0.097) and was less likely to have positive lymph nodes (LN) than HGMCP-S (28% vs 69%, p = < 0.001). Complete cytoreduction was achieved in 84% and 83%, respectively. PFS at 3- and 5-years was 59% and 48% for HGMCP vs 31% and 14% for HGMCP-S. Median PFS was 4.3 and 1.6 years, respectively (p < 0.001). OS at 3- and 5-years was 84% and 64% in HGMCP vs 38% and 25% in HGMCP-S. Median OS was 7.5 and 2.2 years, respectively (p < 0.001). LN negative HGMCP-S had longer median PFS and OS than LN positive HGMCP-S (PFS: 3.4 vs 1.5 years, p = 0.03; OS: 5.6 vs 2.1 months, p = 0.021). CONCLUSIONS: The aggressive histology of HGMCP-S is associated with poor OS, has fewer abnormal TM, and is more likely to have positive LN. However, CRS/HIPEC can achieve a 5-year survival of 25%, which may improve to 51% with negative LN.

Sites of Recurrence After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Patients with Peritoneal Carcinomatosis from Colorectal and Appendiceal Adenocarcinoma: A Tertiary Center Experience.

BACKGROUND: This report describes patterns of disease recurrence after optimal cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of colorectal (CRC) and appendiceal adenocarcinoma (AC) origin. METHODS: Patients undergoing optimal CRS/HIPEC (2007-2016) at the authors' institution were retrospectively reviewed from a prospectively maintained database. Data regarding disease recurrence were analyzed. RESULTS: Of 74 patients who underwent CRS/HIPEC for PC from CRC (n = 46) or AC (n = 28), 49 (66%) had recurrence during a median follow-up period of 39.5 months. The sites of recurrence were peritoneal-only (n = 34, 69%), hematogenous-only (n = 6, 12%), and combined peritoneal and hematogenous (n = 9, 19%) sites. No patients with AC had hematogenous-only recurrence. The median disease-free survival (DFS) time for all the patients was 15 months (95% confidence interval [CI] 12.5-17.5 months). The recurrence rate after CRS/HIPEC was 41% at 1 year, 73% at 3 years, and 76% at 5 years. All the patients with hematogenous-only metastases experienced recurrence within 12 months after CRS/HIPEC. Mucinous or signet ring features predicted peritoneal recurrence (p = 0.041), whereas a complete cytoreduction of 1 was a predictor of early recurrence (p = 0.040). Patients who underwent repeat cytoreduction survived longer than those who received systemic chemotherapy alone. The median survival time after peritoneal-only recurrence was 33 months (95% CI 27.8-38.9 months). CONCLUSION: Recurrence for patients with PC is common, even after optimal CRS/HIPEC. Hematogenous-only recurrence occurs early after CRS/HIPEC, suggesting occult disease at the time of treatment and highlighting the need for methods to identify micro-metastases and improve patient selection. Patients experiencing peritoneal-only recurrence had long survival period after CRS/HIPEC, suggesting its effectiveness at controlling peritoneal disease for a time.

Angiogenesis-Related Markers and Prognosis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND: Patients presenting with peritoneal metastases (PM) of colorectal cancer (CRC) can be curatively treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Angiogenesis is under control of multiple molecules of which HIF1a, SDF1, CXCR4, and VEGF are key players. We investigated these angiogenesis-related markers and their prognostic value in patients with PM arising from CRC treated with CRS and HIPEC. PATIENTS AND METHODS: Clinicopathological data and tissue specimens were collected in 2 tertiary referral centers from 52 patients who underwent treatment for isolated PM of CRC. Whole tissue specimens were subsequently analyzed for protein expression of HIF1a, SDF1, CXCR4, and VEGF by immunohistochemistry. Microvessel density (MVD) was analyzed by CD31 immunohistochemistry. The relationship between overall survival (OS) and protein expression as well as other clinicopathological characteristics was analyzed. RESULTS: Univariate analysis showed that high peritoneal cancer index (PCI), resection with residual disease and high expression of VEGF were negatively correlated with OS after treatment with CRS and HIPEC (P < 0.01, P < 0.01, and P = 0.02, respectively). However, no association was found between the other markers and OS (P > 0.05). Multivariate analysis showed an independent association between OS and PCI, resection outcome and VEGF expression (multivariate HR: 6.1, 7.8 and 3.8, respectively, P ≤ 0.05). CONCLUSIONS: An independent association was found between high VEGF expression levels and worse OS after CRS and HIPEC. The addition of VEGF expression to the routine clinicopathological workup could help to identify patients at risk for early treatment failure. Furthermore, VEGF may be a potential target for adjuvant treatment in these patients.

T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: FOLFOX-based adjuvant chemotherapy is a benefit for high-risk stage II and stage III colon cancer after curative resection. But, the prognostic factor or predictive marker for the efficacy of FOLFOX remains unclear. This study was aimed to identify the prognostic value and cumulative impact of adjuvant FOLFOX on the stage II and III colon cancer patients. METHODS: A total of 196 stage II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They underwent curative resection followed by FOLFOX4 adjuvant chemotherapy. The oncological outcomes included the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate. Cox-regression analysis was performed to identify the prognostic value, and its cumulative impact was analyzed. RESULTS: The 5-year DFS rate of the patients was 71.94% and the 5-year OS rate was 81.5%. The prognostic values for the 5-year DFS rate and 5-year OS rate were T4 stage and preoperative anemia in a multivariate analysis. Each patient group who had no prognostic value, single, or both factors revealed 95.35%, 69.06%, and 28.57% in the 5-year DFS rate, respectively (p < 0.0001). The 5-year OS rate also showed the significant differences in each group who had no prognostic value, single, or both factors revealed 100%, 79.3%, and 45.92%, respectively (p < 0.0001). CONCLUSION: Our results showed similar efficacy to MOSAIC study in stage II and stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy after curative resection. Patients who had T4 stage and/or preoperative anemia showed worse prognosis than patients without any prognostic value. These findings suggest that FOLFOX could not be effective in the patients with T4 stage colon cancer accompanied by preoperative anemia.

Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology.

BACKGROUND: Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC. METHODS: Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations. RESULTS: Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05). CONCLUSION: Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC.

Adjuvant chemoradiotherapy after D2 resection in gastric cancer: a single-center observational study.

PURPOSE: Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery. METHODS: This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at least D2 lymph node resection. Median three cycles of fluorouracil chemotherapy were administered, and 45-Gy radiotherapy was delivered at 1.8 Gy/fraction concomitantly during the second cycle of chemotherapy. Local control, regional control, distant metastasis and overall survival rates were estimated. RESULTS: The median age of the patients was 54 years (range 25-74 years). The most common grade III toxicities were nausea (10%) and neutropenia (9%). During radiotherapy, grade IV local skin reaction occurred in one patient. Median duration of follow-up was 47 months. Local, regional and distant recurrence developed in 9 (4%), 41 (18%) and 45 (20%) patients, respectively. Overall 5-year survival rate was 57.2%, and disease-free 5-year survival rate was 53.8%. Multivariate analysis identified less than 15 lymph node involvement as an independent predictor of better survival (p < 0.001). CONCLUSIONS: Concomitant 5-FU-based chemoradiotherapy seems to be an effective and tolerable adjuvant regimen on local control and survival in curatively resected node-positive stomach cancer, particularly when combined with D2 resection.

Predictors of progression in high-grade appendiceal or colorectal peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Long-term survival of patients with appendiceal or colorectal peritoneal carcinomatosis (PC) may be achieved by combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, such favorable outcomes are realized in a minority of patients. Given the morbidity of the CRS/HIPEC and the uncertain role of postresection systemic therapy, it is important that prognostic factors in high-grade PC be clearly defined. METHODS: This single center, retrospective, cohort study examined the outcomes of CRS/HIPEC performed on patients with high-grade PC secondary to appendiceal or colorectal adenocarcinoma between 2007 and 2013. Cox regression analysis was utilized to evaluate the association between potential prognostic factors [age, sex, primary site, lymph node (LN) status, peritoneal cancer index (PCI) score, completeness of cytoreduction score (CC score), number of visceral resections, and systemic chemotherapy] and progression-free survival (PFS). RESULTS: A total of 70 patients with high-grade appendiceal or colorectal PC underwent CRS/HIPEC during the study period; 82.9 % underwent complete (CC-0) cytoreduction with a median PFS of 9.7 months. Positive LNs at the time of CRS/HIPEC were predictors of worse PFS on univariate and multivariate analysis. No association was demonstrated between pre- or post-HIPEC systemic chemotherapy and PFS. CONCLUSIONS: High-grade PC secondary to appendiceal or colorectal adenocarcinoma can be managed with CRS/HIPEC. The number of LN metastases at the time of CRS/HIPEC is the strongest predictor of progression and must be considered when determining patient eligibility for this aggressive treatment.

Adjuvant radiotherapy for gastric carcinoma: 10 years follow-up of 244 cases from a single institution.

BACKGROUND: Postoperative chemoradiotherapy (CRT) of gastric carcinoma improves survival among high- risk patients. This study was undertaken to analyse long-term survival probability and the impact of certain covariates on the survival outcome in affected individuals. MATERIALS AND METHODS: Between January 2000 and December 2005, 244 patients with gastric cancer underwent adjuvant radiotherapy (RT) in our institution. Data were retrieved retrospectively from patient files and analysed with SPSS version 21.0. RESULTS: A total of 244 cases, with a male to female ratio of 2.2:1, were enrolled in the study. The median age of the patients was 52 years (range, 20-78 years). Surgical margin status was positive or close in 72 (33%) out of 220 patients. Postoperative adjuvant RT dose was 46 Gy. Median follow-up was 99 months (range, 79-132 months) and 23 months (range, 2-155 months) for surviving patients and all patients, respectively. Actuarial overall survival (OS) probability for 1-, 3-, 5- and 10-year was 79%, 37%, 24% and 16%, respectively. Actuarial progression free survival (PFS) probability was 69%, 34%, 23% and 16% in the same consecutive order. AJCC Stage I-II disease, subtotal gastrectomy and adjuvant CRT were significantly associated with improved OS and PFS in multivariate analyses. Surgical margin status or lymph node dissection type were not prognostic for survival. CONCLUSIONS: Postoperative CRT should be considered for all patients with high risk of recurrence after gastrectomy. Beside well-known prognostic factors such as stage, lymph node status and concurrent chemotherapy, the type of gastrectomy was an important prognostic factor in our series. With our findings we add to the discussion on the definition of required surgical margin for subtotal gastrectomy. We consider that our observations in gastric cancer patients in our clinic can be useful in the future randomised trials to point the way to improved outcomes.

Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis.

BACKGROUND: When peritoneal carcinomatosis (PC) is diagnosed during emergency surgery for colorectal cancer (CRC), further treatment with curative intent may seem futile given the known poor prognosis of both PC and emergency surgery. The aim of the current study was to investigate the feasibility and effectiveness of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRC patients who previously underwent emergency surgery in the presence of PC. METHODS: All patients with synchronous PC of CRC referred to two tertiary centers between April 2005 and November 2013 were included in this study. Operative, postoperative and survival details were compared between patients presenting in an emergency or elective setting. RESULTS: In total, 149 patients with synchronous PC underwent CRS and HIPEC. Amongst these patients, 36 (24.2 %) initially presented with acute symptoms requiring emergency surgery. Acute presentation did not result in a longer interval between the initial operation and HIPEC (2.2 vs. 2.1 months; P = 0.09). When comparing operative outcomes, no significant differences were found in blood loss (P = 0.47), operation time (P = 0.39), or completeness of cytoreduction (P = 0.97). In addition, complication rates, degree and types of complication did not differ between the groups. Median survival was 36.1 months for emergency presentation compared with 32.1 in the elective group (P = 0.73). CONCLUSION: CRS + HIPEC may be performed safely in patients with PC of colorectal origin presenting with acute symptoms requiring emergency surgery. More importantly, the 5-year survival rate in these patients was equal to elective cases. This should be regarded as promising and therefore considered for these patients.