Therapeutic and prophylactic gastrectomy in a family with hereditary diffuse gastric cancer secondary to a CDH1 mutation: a case series.

BACKGROUND: Gastric cancer is the fifth most prevalent and the third most lethal cancer worldwide, causing approximately 720,000 deaths annually. Although most cases of gastric cancers are sporadic, one of its inherited forms, hereditary diffuse gastric cancer (HDGC), constitutes about 1-3% of cases. Interestingly, females in families with HDGC are also predisposed to developing lobular breast cancer (LBC). Recent analyses have identified loss-of-function germline mutations in cadherein-1 (CDH1) as a culprit in HDGC and LBC. This discovery fueled several sequencing analyses and case series reports analyzing the pattern of inheritance of CDH1 and its propensity to induce HDGC. In 2015, a multinational and multidisciplinary task force updated the guidelines and criteria for screening, diagnosing, and managing HDGC. CASE PRESENTATION: Here, we present a case series of three siblings with family history of HDGC who tested positive for the CDH1 mutation and describe their surgical treatment course, post-operative management, and follow-up as they pertain to the updated guidelines. CONCLUSIONS: Despite recent updates in guidelines in the diagnosis and management of HDGC, the disease remains challenging to address with patients given the high level of uncertainty and the comorbidities associated with prophylactic intervention. We strongly recommend that an interdisciplinary team inclusive of clinical and surgical oncologists, along with geneticists, social work, and psychological support, should follow the patients in a longitudinal and comprehensive manner in order to achieve full recovery and return to normalcy, as with our patients.

Neoplasms of the appendix: current treatment guidelines.

The purpose of this article is to update the medical community on the current management of patients with appendiceal neoplasms. The authors discuss clinical evidence of medical and surgical treatment with emphasis on presentation, diagnosis, pathology, and surgical technique. Current available clinical evidence on the use of systemic chemotherapy is included. The authors describe in detail management of peritoneal carcinomatosis arising from tumors of the appendix with cytoreductive surgery and hyperthermic intraperitoneal therapy as standard of care.

Delay of cytoreductive surgery and heated intraperitoneal chemotherapy in patients with appendiceal neoplasm.

Cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) has been shown to be effective for selected patients with advanced appendiceal cancer. We propose that delaying CRS/HIPEC leads to disease progression and affects outcome. A retrospective analysis of a prospective database was carried out. Patients were divided into two groups based on time from diagnosis to CRS/HIPEC (less than 6 months = early, greater than 6 months = delayed). Comparison was made of Peritoneal Cancer Index (PCI), Prior Surgery Score (PSS), complete cytoreduction (CC), and lymph node status. Overall survival (OS) was calculated using Kaplan-Meier estimates. Of 127 patients, 50 had disseminated peritoneal adenomucinosis and 77 had peritoneal mucinous carcinomatosis (PMCA). Of patients with PMCA, 41 had early CRS/HIPEC and 36 delayed. PCI was less than 20 in 46 and 17 per cent (P = 0.007) of the early and delayed groups, respectively. CC was achieved in 88 and 61 per cent (P = 0.009) of the early and delayed groups, respectively. PSS was (2 of 3) in 51 and 91 per cent (P = 0.001) of the early and delayed groups, respectively. Five-year OS was 54 per cent for the early group and 45 per cent for the delayed group (P = 0.2). Delaying CRS/HIPEC was associated with higher tumor load and lower chance for complete cytroreduction. Longer follow-up and larger numbers are needed to determine if OS difference will reach statistical significance.

The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with high-grade appendiceal carcinoma and extensive peritoneal carcinomatosis.

BACKGROUND: Patients with peritoneal mucinous carcinomatosis (PMCA) of appendiceal origin and extensive disease are commonly advised against CRS/HIPEC. We hypothesize that CRS/HIPEC is a beneficial treatment for this group. METHODS: Retrospective analysis of 134 patients with appendiceal cancer treated with CRS/HIPEC was performed from a prospective database. Extent of disease, measured by peritoneal cancer index (PCI), was related to completeness of cytoreduction (CC), lymph node (LN) status, and prior surgery score (PSS). Overall survival (OS) was estimated by Kaplan-Meier curves. Test differences were calculated using log-rank test. RESULTS: A total of 77 patients (57%) had PMCA. Mean follow-up was 22 months with a median of 18 months. OS was 88%, 56%, and 40% for 1, 3, and 5 years, respectively. 68% had PCI ≥ 20. LN metastasis was found in 44% of patients in PCI ≥ 20 and PCI < 20 groups. 73% and 60% of patients had PSS of 2 or 3 in PCI ≥ 20 and PCI < 20 groups, respectively (P = .196). Complete cytoreduction was achieved in 65% of PCI ≥ 20 group and 96% of PCI < 20 group (P = .004). With complete cytoreduction, the 5-year OS was 45% in PCI ≥ 20 group and 66% in PCI < 20 group (P = .139). 18 of 19 patients with incomplete cytoreduction had PCI ≥ 20, with 3- and 5-year OS of 27% and 0%. Hazard ratios (by Cox regression) were 2.8 (95% confidence interval [95% CI] 0.8-10.2) and 3.6 (95% CI 1.5-8.8) for PCI < 20 and complete cytoreduction, respectively. CONCLUSIONS: Meaningful long-term survival could be achieved in patients with PMCA even with extensive peritoneal disease. PCI ≥ 20 should not be used as an exclusion criterion when selecting these patients for CRS/HIPEC, and every effort should be made to achieve complete cytoreduction.

Prognostic significance of lymph node metastases in patients with high-grade appendiceal cancer.

BACKGROUND: In treating high-grade appendiceal cancer, appropriate patient selection for cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is essential. The effect of lymph node (LN) status on survival is not clear. We hypothesize that LN metastases negatively affect long-term survival. METHODS: Retrospective analysis of peritoneal mucinous carcinomatosis (PMCA) patients from a prospective database was conducted. Using Kaplan-Meier survival curves and Cox proportional hazards ratio analysis, the effect of LN status, completeness of cytoreduction (CC), and peritoneal cancer index (PCI) was studied. RESULTS: Of 134 patients with appendiceal cancer who underwent CRS/HIPEC, 77 (57%) had PMCA. Mean follow-up was 22 (range, 3-90) months. Overall survival (OS) was 88, 56, and 40% for 1, 3, and 5-year, respectively. Thirty-four patients (44%) had LN metastases, 23 of whom (68%) had CC, whereas in LN negative patients 35 of 43 (81%) had CC (p = 0.191). PCI ≥ 20 was seen in 23 of 34 patients (68%) with LN metastases and 29 of 43 (67%) without metastases (p = 0.191). Five-year OS for patients with LN metastases was 11% compared with 76% for LN negative (p < 0.001). Among patients with complete cytoreduction, 5-year OS for LN positive vs. negative was 21 and 73%, respectively (p = 0.002). On multivariate regression analysis of LN status, CC score and PCI, the following hazard ratios were obtained: 3.4 (95% confidence interval (CI), 1.3-9.0), 2.6 (95% CI, 1.03-6.7), and 2.8 (95% CI, 0.8-10.4), respectively. CONCLUSIONS: Patient selection for CRS/HIPEC should take into consideration LN status, but it should not be a contraindication if preoperative evaluation revealed a high likelihood of complete cytoreduction.

Clinical results of various reconstructions employed after total gastrectomy.

Methods of restoring continuity after total gastrectomy, particularly those creating a "reservoir," have led to many publications over the last 20 years. These publications are herein reviewed in an attempt to answer questions regarding the clinical value of a jejunal "reservoir". The conclusion we reached from this review was that such a reconstruction does reduce unpleasant symptoms, aids weight maintenance, and is a valuable operative approach.