Spontaneous Regression of Hepatocellular Carcinoma with Multiple Lung Metastases: A Case Report and Review of the Literature.

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare event. Here we present a case of spontaneous regression of metastatic HCC. A 53-year-old man with hepatitis C and alcoholic cirrhosis was found to have a large liver mass consistent with HCC based on its radiographic features. Imaging also revealed left portal and hepatic vein thrombosis, as well as multiple lung nodules concerning for metastases. Approximately 2 months after the initial diagnosis, both the primary liver lesion and the lung metastases decreased in size and eventually resolved without any intervention. Thereafter, the left hepatic vein thrombus progressed into the inferior vena cava and the right atrium, and the patient died due to right heart failure. In this case report and literature review, we discuss the potential mechanisms for and review the literature on spontaneous regression of metastatic HCC.

Submucosal Necrotic Nodule of the Colon: An Enigmatic Entity Potentially Related to Anisakis Infection.

CONTEXT.­: Discrete submucosal necrotic nodules may rarely manifest as colon polyps. OBJECTIVE.­: To characterize the clinical and pathologic features of this lesion, which has been under-studied in the literature. DESIGN.­: We conducted an international search to compile a series. For each potential case, photomicrographs were centrally reviewed to confirm the diagnosis. We gathered clinical and pathologic information on each confirmed case. RESULTS.­: The final cohort included 25 patients, with 23 having 1 lesion and 2 having several (31 lesions total). Mean patient age was 62 years; 13 patients (52%) were male. Symptoms were nonspecific, although 4 patients (16%) had blood in stool; 14 patients were asymptomatic. Patient history and medications appeared noncontributory. Most cases were located in the right colon (n = 18; 58%). Mean lesion size was 0.4 cm (range, 0.1-1.7 cm). Histology typically showed a centrally necrotic nodule with peripheral fibrosis, chronic inflammation, and sometimes palisading granulomatous inflammation. Percent necrosis ranged from 5% to 95% (average, 70%), and percent fibrosis ranged from 3% to 70% (average, 25%). In 3 cases, degenerated parasitic structures consistent with Anisakis could be seen on hematoxylin-eosin and trichrome special stain. No patient experienced disease recurrence. CONCLUSIONS.­: Submucosal necrotic nodules can present as colon polyps. Most cases are unifocal, and patients do well on follow-up. At least some examples appear to be caused by Anisakis, implicating patient diet. Patients are often asymptomatic, and many cases show no histologic evidence of the causative agent.

Foxo3a tempers excessive glutaminolysis in activated T cells to prevent fatal gut inflammation in the murine IL-10-/- model of colitis.

Mutations in susceptibility alleles correlate with gut-inflammatory diseases, such as Crohn's disease; however, this does not often impact the disease progression indicating the existence of compensatory genes. We show that a reduction in Foxo3a expression in IL-10-deficient mice results in a spontaneous and aggressive Crohn's- like disease with 100% penetrance, which is rescued by deletion of myeloid cells, T cells and inhibition of mTORC1. In Foxo3a-/- IL-10-/- mice, there is poor cell death of myeloid cells in the gut, leading to increased accumulation of myeloid and T cells in the gut. Myeloid cells express high levels of inflammatory cytokines, and regulatory T cells are dysfunctional despite increased abundance. Foxo3a signaling represses the transcription of glutaminase (GLS/GLS2) to prevent over-consumption of glutamine by activated T cells and its conversion to glutamate that contributes to the TCA cycle and mTORC1 activation. Finally, we show that Foxo3a restricts the abundance of colitogenic microbiota in IL-10-deficient mice. Thus, by suppressing glutaminolysis in activated T cells Foxo3a mediates a critical checkpoint that prevents the development of fulminant gut inflammatory disease.

NKR-P1B expression in gut-associated innate lymphoid cells is required for the control of gastrointestinal tract infections.

Helper-type innate lymphoid cells (ILC) play an important role in intestinal homeostasis. Members of the NKR-P1 gene family are expressed in various innate immune cells, including natural killer (NK) cells, and their cognate Clr ligand family members are expressed in various specialized tissues, including the intestinal epithelium, where they may play an important role in mucosal-associated innate immune responses. In this study, we show that the inhibitory NKR-P1B receptor, but not the Ly49 receptor, is expressed in gut-resident NK cells, ILC, and a subset of γδT cells in a tissue-specific manner. ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria. The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin. The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 and γδT cells in the gut lamina propria. However, the function of gut-resident ILC3, NK, and γδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium, resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice. Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.

Pancreatic Neuroendocrine Tumors Complicated by Sinistral Portal Hypertension: Insights into Pathogenesis.

Purpose: To investigate the association between pancreatic neuroendocrine tumors (panNETs) and sinistral portal hypertension (SPH) and provide insights into the pathogenesis. Methods: A retrospective review of panNETs was conducted from our institution for 12 years. Medical imaging findings were analyzed to determine any association with splenic vein thrombosis (SVT) at diagnosis. The cases were further selected based on the criteria for SPH, namely, (1) presence of SVT, (2) gastric varices, (3) patent portal vein, and (4) normal liver function tests. Results: There were 61 patients with panNETs and 8 (8/61) had SVT and gastric varices at diagnosis. Four (4/8) met the strict criteria for SPH while the other four had more conventional portal hypertension. The four with SPH had large tumors located in the tail with splenic vein invasion and three of four presented with bleeding gastric varices. All four patients underwent surgical resection. Mean follow-up was 8.5 years and the hematemesis never recurred. The other four patients (four of eight) with gastric varices had unresectable disease and all died after a mean survival of 29 months. Conclusion: PanNETs appear to be more commonly associated with SVT and SPH compared with other tumors. This could be related to their relatively indolent nature and their intrinsic vascularity. From a surgical viewpoint, the decision to operate depends on many factors including but not limited to the size/stage, grade, and functionality of the tumor and comorbidities. These considerations notwithstanding, the association between panNETs and SPH suggests that there is benefit in timely resection of panNETs located in the tail.

Achieving High Reliability in Histology: An Improvement Series to Reduce Errors.

OBJECTIVES: Despite sweeping medical advances in other fields, histology processes have by and large remained constant over the past 175 years. Patient label identification errors are a known liability in the laboratory and can be devastating, resulting in incorrect diagnoses and inappropriate treatment. The objective of this study was to identify vulnerable steps in the histology workflow and reduce the frequency of labeling errors (LEs). METHODS: In this 36-month study period, a numerical step key (SK) was developed to capture LEs. The two most prevalent root causes were targeted for Lean workflow redesign: manual slide printing and microtome cutting. The numbers and rates of LEs before and after interventions were compared to evaluate the effectiveness of interventions. RESULTS: Following the adoption of a barcode-enabled laboratory information system, the error rate decreased from a baseline of 1.03% (794 errors in 76,958 cases) to 0.28% (107 errors in 37,880 cases). After the implementation of an innovative ice tool box, allowing single-piece workflow for histology microtome cutting, the rate came down to 0.22% (119 errors in 54,342 cases). CONCLUSIONS: The study pointed out the importance of tracking and understanding LEs by using a simple numerical SK and quantified the effectiveness of two customized Lean interventions. Overall, a 78.64% reduction in LEs and a 35.28% reduction in time spent on rework have been observed since the study began.