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Background This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. Methods Sixty-eight gastric PC patients were randomized into CRS alone ( n  = 34) or CRS + HIPEC ( n  = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60–90 min. The primary end point was overall survival, and the secondary end points were safety profiles. Results Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2–36 (median 15) in the CRS + HIPEC and 3–23 (median 15) in the CRS groups ( P  = 0.489). The completeness of CRS score (CC 0–1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups ( P  = 1.000). At a median follow-up of 32 months (7.5–83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8–8.2 months) in CRS and 11.0 months (95% confidence interval 10.0–11.9 months) in the CRS + HIPEC groups ( P  = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events ( P  = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0–1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival. Conclusions For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

Background: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). Methods: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. Results: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. Conclusion: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.

Background Systemic chemotherapy is the key treatment for advanced gastric cancer. The benefit of adjuvant surgery following preoperative chemotherapy in gastric cancer with liver metastasis has not been well established. Methods Forty-nine gastric cancer patients diagnosed with synchronous liver metastasis initially treated with chemotherapy were categorized into the following two groups: surgery group: 25 patients who underwent gastrectomy and subsequently received postoperative chemotherapy and control group: 24 patients who received chemotherapy alone. Results The median overall survival of patients in the surgery group and control group was 20.5 and 9.1 months, respectively, ( P = 0.006). The median progression-free survival in the surgery group was 10.9 months, with statistical significance when compared with 5.0 months in the control group ( P = 0.001). Multivariate analysis demonstrated that response to chemotherapy was the only independent factor in predicting prognosis. The survival of patients who achieved partial response (PR) was prolonged if they received adjuvant surgery ( P = 0.024). No significant difference in the survival of patients underwent combined hepatic resection when compared with patients performed gastrectomy only. Conclusions For gastric cancer with synchronous liver metastasis, adjuvant gastrectomy followed by chemotherapy might be beneficial for survival comparing with chemotherapy alone, especially in patients response to initial preoperative chemotherapy.

Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional colon resection. Data for all patients who underwent elective resection for Union for International Cancer Control (UICC) stage I–III colon adenocarcinomas in the Capital Region of Denmark between June 1, 2008, and Dec 31, 2011, were retrieved for this population-based study. The CME group consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients were excluded if they had stage IV disease, metachronous colorectal cancer, rectal cancer (≤15 cm from anal verge) in the absence of synchronous colon adenocarcinoma, tumour of the appendix, or R2 resections. Survival data were collected on Nov 13, 2014, from the DCCG database, which is continuously updated by the National Central Office of Civil Registration. The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85·8% (95% CI 81·4–90·1) after CME and 75·9% (72·2–79·7) after non-CME surgery (log-rank p=0·0010). 4-year disease-free survival for patients with UICC stage I disease in the CME group was 100% compared with 89·8% (83·1–96·6) in the non-CME group (log-rank p=0·046). For patients with UICC stage II disease, 4-year disease-free survival was 91·9% (95% CI 87·2–96·6) in the CME group compared with 77·9% (71·6–84·1) in the non-CME group (log-rank p=0·0033), and for patients with UICC stage III disease, it was 73·5% (63·6–83·5) in the CME group compared with 67·5% (61·8–73·2) in the non-CME group (log-rank p=0·13). Multivariable Cox regression showed that CME surgery was a significant, independent predictive factor for higher disease-free survival for all patients (hazard ratio 0·59, 95% CI 0·42–0·83), and also for patients with UICC stage II (0·44, 0·23–0·86) and stage III disease (0·64, 0·42–1·00). After propensity score matching, disease-free survival was significantly higher after CME, irrespective of UICC stage, with 4-year disease-free survival of 85·8% (95% CI 81·4–90·1) after CME and 73·4% (66·2–80·6) after non-CME (log-rank p=0·0014). Our data indicate that CME surgery is associated with better disease-free survival than is conventional colon cancer resection for patients with stage I–III colon adenocarcinoma. Implementation of CME surgery might improve outcomes for patients with colon cancer. Tvergaards Fund and Edgar and Hustru Gilberte Schnohrs Fund.

Background The significance of lateral pelvic lymph node (LPLN) metastasis in advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT) remains unclear. The objective of this study was to evaluate the outcomes of selective LPLN dissection (LPLD) based on the pretreatment imaging in patients with advanced low rectal cancer treated with preoperative CRT. Methods We reviewed 127 consecutive patients with clinical stage II–III low rectal cancer below the peritoneal reflection who underwent preoperative CRT and curative resection. LPLD was performed in patients with suspected LPLN metastasis based on MDCT or MRI before CRT (LPLD group, N  = 38), and only total mesorectal excision (TME) was performed in patients without suspected LPLN metastasis (TME group, N  = 89). Clinical characteristics and the oncological outcome were compared between groups. Results The median tumor-to-anal verge distance was 40 mm in both groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3 patients (3.4 %) in the TME group and in none (0 %) of the LPLD group. Multivariate analysis showed that only ypN was an independent prognostic factor for relapse-free survival (RFS), but LPLN metastasis was not associated with poor RFS. Conclusions The incidence of LPLN metastasis is high even after preoperative CRT, and LPLD might improve local control and survival of patients with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.

Previous studies have demonstrated that the prognosis of disseminated mucinous appendiceal neoplasms is highly dependent upon tumor grade. Reflecting this, the 7th edition of the American Joint Committee on Cancer (AJCC) staging system now incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. In order to address this issue, we evaluated clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at our institution between 2004 and 2012. We identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all with P<0.0001). We used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature (except a signet ring cell component); and AJCC grade G3 were defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P<0.0001 for each). A trend toward worse overall survival was identified for patients with AJCC grade G3 adenocarcinomas compared with AJCC grade G2 adenocarcinomas (P=0.07). Our multivariate analysis found that this three-tier grading system was a significant predictor of outcome (P=0.008), independent of other prognostic variables. After controlling for other prognostic variables, AJCC grade G2 was associated with a 2.7-fold increased risk of death (95% confidence interval (CI), 1.2–6.2) and AJCC grade G3 was associated with a 5.1-fold increased risk of death (95% CI, 1.7–14) relative to grade G1 tumors. Our results indicate that evaluation of a limited set of adverse histologic features allows for the separation of disseminated mucinous neoplasms of appendiceal origin into three morphologically defined and prognostically relevant grades as advocated by the AJCC.

Purpose This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol. Methods In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival. Results Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III–V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0–166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36–46 months). Median progression-free survival was 15 months (95 % CI 13–17 months) for CRC patients and 53 months (95 % CI 40–66 months) for PMP patients. Overall median survival was 33 (95 % CI 28–38 months) months for CRC patients and 130 months (95 % CI 98–162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients. Conclusions The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.

Purpose We evaluated clinical features and survival outcomes among patients with signet ring and mucinous histologies of colorectal adenocarcinoma by using data from the National Cancer Data Base (NCDB). Methods Patients aged 18–90 years with colorectal adenocarcinoma diagnosed between 1998 and 2002 were identified from the NCDB. Site-stratified (colon vs. rectum) survival analysis was performed by multivariate relative survival adjusted for multiple clinicopathologic and treatment variables. Results The study included 244,794 patients: 25,546 (10%) with mucinous, 2,260 (1%) with signet ring, and 216,988 (89%) with nonmucinous, non–signet ring adenocarcinoma. Mucinous and signet ring cancers were more frequently right-sided (60% and 62%, respectively) than were nonmucinous, non–signet ring adenocarcinomas (42%, P  < 0.001). Signet ring histology was associated with a higher stage ( P  < 0.001), and 77.2% of signet ring tumors were high-grade lesions, compared with 20% of mucinous and 17% of non–signet ring, nonmucinous adenocarcinomas ( P  < 0.001). After adjustment for covariates, signet ring histology was independently associated with higher risk of death [hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51, and HR 1.57, CI 1.38–1.77, for tumors located in the colon and rectum, respectively]. Mucinous tumors of the rectum (HR 1.22, CI 1.16–1.29), but not the colon (HR 1.03, CI 1.00–1.06), were associated with increased risk of death. Conclusions Signet ring cell adenocarcinomas of the colon and rectum and mucinous adenocarcinomas of the rectum are associated with poorer survival. These aggressive histologic variants of colorectal adenocarcinoma should be targeted for research initiatives to improve outcomes.

Signet Ring Cell Adenocarcinoma (SRCA) of the appendix is a rare tumor with a poor prognosis and limited information to help guide treatment. We reviewed patients diagnosed with SRCA between 1998 and 2024 ​at all Mayo Clinic sites. Among 84 patients, the most common presentation was non-specific abdominal pain (31 ​%). The majority of tumors were high grade (81 ​%), and most patients had metastatic disease (69 ​%). The best overall survival at 5 years was 25 ​% with complete cytoreduction, which was not significantly improved with the addition of systemic therapy. The addition of HIPEC to cytoreduction surgery showed a clinically significant but not a statistically significant improvement in 5-year survival (20 ​% vs 5 ​%, p ​= ​0.059). Cytoreductive surgery with HIPEC showed the best survival outcomes for SRCA, with no demonstrated efficacy for systemic chemotherapy. Overall outcomes remain poor and new treatment modalities are needed. •Signet ring cell carcinoma of the appendix is associated with a poor prognosis and low 5-year survival.•The standard treatment approach of cytoreductive surgery with HIPEC (CRS/HIPEC) provided a survival advantage.•Systemic chemotherapy offered no survival benefits in patients with or without CRS/HIPEC.

BackgroundSignet ring cell adenocarcinoma is a histological classification based on the WHO classification. The presence of this specific histological type is associated with a worse pathological appearance. The prognosis of signet ring cell adenocarcinoma in gastric cancer patients after curative surgery is still under debate.MethodsFrom January 1988 to December 2012, a total of 2971 patients, including 819 early and 2152 advanced gastric cancer patients underwent curative resection for gastric cancer. Among them, there were 185 cases of signet ring cell adenocarcinoma in early gastric cancer patients, while there were 570 cases in advanced gastric cancer patients.ResultsThe overall incidence of signet ring cell adenocarcinoma was 25.4%. Our results showed that the 5-year overall survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 90.7 and 83.2%, respectively (P = 0.001). The 5-year disease-free survival rates of early gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 87.4 and 81.6%, respectively (P = 0.003). The 5-year overall survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 32.1 and 37.9%, respectively (P = 0.041). The 5-year disease-free survival rates of advanced gastric cancer patients with signet ring cell adenocarcinoma and non-signet ring cell adenocarcinoma were 28.6 and 35.2%, respectively (P = 0.037). Signet ring cell adenocarcinoma was an independent predictor for overall survival in advanced gastric cancer (P = 0.017).ConclusionThe clinical features and prognosis of signet ring cell adenocarcinoma are different between early and advanced gastric cancer. Signet ring cell adenocarcinoma is a poor prognostic factor in advanced gastric cancer after curative resection.