Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors

BackgroundThe American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included.MethodsWe collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs.ResultsCompared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762).ConclusionThese findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.     

Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients

BackgroundExtra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions.MethodsAll patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012–December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates.ResultsFrom 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up.ConclusionsThe majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.     

Role of NK T cells in transplantation with particular emphasis on corneal transplantation

Natural killer T cells (NKT cells) are a unique subset of the immune system that possess characteristics of both an innate and adaptive immune response. This study reviews the reported roles of NKT cells in different solid transplantations such as cardiac, skin, liver, and corneal grafts as well as investigates a novel role of NKT cells in steroid-resistant corneal rejections. It is unknown why there is late corneal graft rejection despite being treated with immunosuppression. Our experimental data suggests NKT cells are playing a crucial part in steroid-resistant late graft rejections. While the pathophysiology of acute rejection is better understood, the process of chronic graft rejection is much less clear. Our data suggests NKT cells as a potential therapeutic target to prevent chronic transplant rejection which needs further investigation.     

Risk of lymph node metastasis and prognostic outcome in early gastric cancer patients with mixed histologic type

BackgroundWhether early gastric cancer with mixed histologic type should be considered for endoscopic submucosal dissection (ESD) remains controversial. The objective of this study was to evaluate the risk of lymph node metastasis (LNM) and prognostic significance for early gastric cancer with mixed histologic type.MethodsWe retrospectively reviewed clinicopathologic and survival data of 302 patients who underwent surgical resection for early gastric cancer. Based on the histologic components, all patients were classified as pure differentiated type, pure undifferentiated type and mixed histologic type. The prognostic differences between different types were compared and predictive factors for LNM were evaluated.ResultsHistopathologically, the proportion of mixed histologic type was 12.3% in early gastric cancer. In terms of LNM, mixed histologic type had a more frequent incidence than pure differentiated type (32.4% vs 11.1%, P < 0.01). However, there was no significant difference between mixed type and pure undifferentiated type for LNM (32.4% vs 21.1%, P = 0.139). Multivariate analysis revealed that tumor size >2 cm (odds ratio [OR]: 2.153, 95% confidence interval [CI]: 1.113-4.164, P < 0.05), submucosal invasion (OR: 3.881, 95%CI: 1.832-8.222, P < 0.001), lymphovascular invasion (OR: 8.797, 95% CI: 2.643-29.277, P < 0.001), undifferentiated type (OR: 3.146, 95% CI: 1.352-7.320, P < 0.01), and mixed histologic type (OR: 3.635, 95% CI: 1.272-10.390, P < 0.05) were independent risk factors for LNM in early gastric cancer patients. However, mixed histologic type did not affect the survival outcome of these patients (hazard ratio: 0.629, 95% CI: 0.074-5.311, P > 0.05).ConclusionMixed histologic type was an independent risk factor for lymph node metastasis in early gastric cancer patients. The decisions regarding endoscopic submucosal dissection for mixed histologic type should be carefully considered.     

A Clinical and Economic Evaluation of Endoscopic Ultrasound for Patients at Risk for Familial Pancreatic Adenocarcinoma

Background and Aims: Approximately 10% of pancreatic adenocarcinoma is familial. Approximately 50% of Ist-degree relatives (FDRs) have endoscopic ultrasound (EUS) findings of chronic pancreatitis. We modeled the natural history of these patients to compare 4 management strategies. Methods: We performed a systematic review, and created a Markov model for 45-year-old male FDRs, with findings of chronic pancreatitis on screening EUS. We compared 4 strategies: doing nothing, prophylactic total pancreatectomy (PTP), annual surveillance by EUS, and annual surveillance with EUS and fine needle aspiration (EUS/FNA). Outcomes incorporated mortality, quality of life, procedural complications, and costs. Results: In the Do Nothing strategy, the lifetime risk of cancer was 20%. Doing nothing provided the greatest remaining years of life, the lowest cost, and the greatest remaining quality-adjusted life years (QALYs). PTP provided the fewest remaining years of life, and the fewest remaining QALYs. Screening with EUS provided nearly identical results to PTP, and screening with EUS/FNA provided intermediate results between PTP and doing nothing. PTP provided the longest life expectancy if the lifetime risk of pancreatic cancer was at least 46%, and provided the most QALYs if the risk was at least 68%. Conclusions: FDRs from familial pancreatic cancer kindreds, who have EUS findings of chronic pancreatitis, have increased risk for cancer, but their precise risk is unknown. Without the ability to further quantify that risk, the most effective strategy is to do nothing.