Background: We sought to identify an optimal combination of survival risk stratification markers in patients with pathological (p) stage II/III gastric cancer (GC) after curative resection. Methods: We measured the expression levels of 127 genes in pStage II/III GC tissues of two patient cohorts by quantitative polymerase chain reaction (qPCR) and the expression of 1756 proteins between two prognosis (good and poor) groups by proteomic analysis to identify candidate survival stratification markers. Further, immunohistochemistry (IHC) using tumor microarrays (TMAs) in another cohort of patients was performed to identify an optimal biomarker combination for survival stratification in GC patients. Results: secreted protein acidic and rich in cysteine (SPARC), erb-b2 receptor tyrosine kinase 2 (ERBB2), inhibin subunit beta A (INHBA), matrix metallopeptidase-11 (MMP11), tumor protein p53 (TP53), and platelet-derived growth factor receptor-beta (PDGFRB) were identified as candidate biomarkers from qPCR analysis, and SPARC and galectin-10 were obtained from the proteomic analysis. The combination of PDGFRB, INHBA, MMP11, and galectin-10 was identified as the optimal combination of survival risk stratification markers. Conclusions: A combination of four proteins in GC tissues may serve as useful survival risk stratification markers in patients with pStage II/III GC following curative resection. Our results may facilitate future multicenter prospective clinical trials. Full article

In pancreatic neuroendocrine tumors (PNETs), the impact of minimally invasive (MI) versus open resection on outcomes remains poorly studied. We queried a multi-institutional pancreatic cancer registry for patients with resected non-metastatic PNET from 1996–2020. Recurrence-free (RFS), disease-specific survival (DSS), and operative complications were evaluated. Two hundred and eighty-two patients were identified. Operations were open in 139 (49%) and MI in 143 (51%). Pancreaticoduodenectomy was performed in 77 (27%, n = 23 MI), distal pancreatectomy in 184 (65%, n = 109 MI), enucleation in 13 (5%), and total pancreatectomy in eight (3%). Median follow-up was 50 months. Thirty-six recurrences and 13 deaths from recurrent disease yielded 5-year RFS and DSS of 85% and 95%, respectively. On multivariable analysis, grade 1 (HR 0.07, p < 0.001) and grade 2 (HR 0.20, p = 0.002) tumors were associated with improved RFS, while T3/T4 tumors were associated with worse RFS (OR 2.78, p = 0.04). MI resection was not associated with RFS (HR 0.53, p = 0.14). There was insufficient mortality to evaluate DSS with multivariable analysis. Of 159 patients with available NSQIP data, incisional surgical site infections (SSIs), organ space SSIs, Grade B/C pancreatic fistulas, reoperations, and need for percutaneous drainage did not differ by operative approach (all p > 0.2). Nodal harvest was similar for MI versus open distal pancreatectomies (p = 0.16) and pancreaticoduodenectomies (p = 0.28). Minimally invasive surgical management of PNETs is equivalent for oncologic and postoperative outcomes. Full article

Introduction: Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable. Methods: We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher’s exact test. Results: In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (p = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (p = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again. Conclusions: Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable. Full article

Pancreatic neuroendocrine tumors (PNETs) are described by the World Health Organization (WHO) classification by grade (1–3) and degree of differentiation. Grade 1 and 2; well differentiated PNETs are often characterized as relatively “indolent” tumors for which locoregional therapies have been shown to be effective for palliation of symptom control and prolongation of survival even in the setting of advanced disease. The treatment of liver metastases includes surgical and non-surgical modalities with varying degrees of invasiveness; efficacy; and risk. Most of these modalities have not been prospectively compared. This paper reviews literature that has been published on treatment of pancreatic neuroendocrine liver metastases using surgery; liver directed embolization and peptide receptor radionuclide therapy (PRRT). Surgery is associated with the longest survival in patients with resectable disease burden. Liver-directed (hepatic artery) therapies can sometimes convert patients with borderline disease into candidates for surgery. Among the three embolization modalities; the preponderance of data suggests chemoembolization offers superior radiographic response compared to bland embolization and radioembolization; but all have similar survival. PRRT was initially approved as salvage therapy in patients with advanced disease that was not amenable to resection or embolization; though the role of PRRT is evolving rapidly Full article

Complete surgical resection of pancreatic neuroendocrine tumors (pNETs) has been suggested as the only potentially curative treatment. A proportion of these tumors will present late during disease progression, and invade or encase surrounding vasculature; therefore, surgical treatment of locally advanced disease remains controversial. The role of surgery with vascular reconstruction in pNETs is not well defined, and there is considerable variability in the use of aggressive surgery for these tumors. Accurate preoperative assessment is critical to evaluate individual considerations, such as anatomical variants, areas and lengths of vessel involvement, proximal and distal targets, and collateralization secondary to the degree of occlusion. Surgical approaches to address pNETs with venous involvement may include thrombectomy, traditional vein reconstruction, a reconstruction-first approach, or mesocaval shunting. Although the amount of literature on pNETs with vascular reconstruction is limited to case reports and small institutional series, the last two decades of studies have demonstrated that aggressive resection of these tumors can be performed safely and with acceptable long-term survival. Full article

Neoadjuvant treatment strategies for resectable proximal gastric, gastroesophageal junction (GEJ), and distal esophageal cancer have evolved over several decades. Treatment recommendations differ based on histologic type—squamous cell carcinoma (SCC) versus adenocarcinoma (AC)—as well as the exact location of the tumor. Recent and older clinical trials in this area were critically reviewed. Neoadjuvant chemoradiation with concurrent taxane- or fluoropyrimidine-based chemotherapy has an established role for both AC and SCC of the distal esophagus and GEJ. The use of perioperative chemotherapy for gastric AC is based on the FLOT4 and MAGIC trials; however, the utility of neoadjuvant chemoradiation in this setting requires further evaluation. Additional clinical trials evaluating chemotherapy, targeted therapy, immunotherapy, and radiation that are currently in process are highlighted, given the need for further disease control. Full article

Gastric cancer carries a poor prognosis and is a leading cause of cancer-related mortality worldwide. Patients with gastric cancer who develop peritoneal metastases have an even more dismal prognosis, with median survival time measured in months. Since studies have demonstrated that systemic chemotherapy has poor penetration into the peritoneum, multimodal treatment with intraperitoneal chemotherapy has been proposed for the treatment of peritoneal metastases and has become the foundation for newer therapeutic techniques and clinical trials. These include heated intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS), which involves the application of heated chemotherapy into the abdomen with or without tumor debulking surgery; normothermic intraperitoneal chemotherapy (NIPEC), in which non-heated chemotherapy can be delivered into the abdomen via a peritoneal port allowing for repeat dosing; and pressurized intraperitoneal aerosolized chemotherapy (PIPAC), a newer technique of pressurized and aerosolized chemotherapy delivered into the abdomen during laparoscopy. Early results with intraperitoneal chemotherapy have shown promise in increasing disease-free and overall survival in select patients. Additionally, there may be a palliative effect of these regional therapies. In this review, we explore and summarize these different intraperitoneal chemotherapy treatment regimens for gastric cancer with peritoneal metastases. Full article