Acute appendicitis secondary to hypertriglyceridemia-induced acute pancreatitis: A case report.

Hypertriglyceridemia led acute pancreatitis secreted exudative fluid tacked to the right iliac fossa may cause irritation of retroperitoneum leading to acute periappendicular inflammation and acute appendicitis.

Curative intent treatment of late presented extragastrointestinal stromal tumor: two identical case reports with literature review.

Gastrointestinal stromal tumors (GISTs) occurring outside the gastrointestinal tract are known as extragastrointestinal stromal tumors (EGIST). They share some common histopathologic and molecular characteristics. This report describes two female patients who were suspected of having a mesenteric GIST, but opted for surveillance rather than definitive treatment. Upon reassessment, both patients demonstrated increased tumor mass with no evidence of distant metastasis. The intraoperative findings confirmed the conclusion of clinical and imaging studies performed preoperatively and radical excisions were performed. Histopathological examination (spindle cell neoplasm) and immunohistochemistry (CD117) confirmed EGIST. Both patients underwent Imatinib therapy following surgery with no evidence of disease recurrence or metastasis upon follow up. Although sharing histologic features with GIST, EGIST frequently demonstrates distinct characteristics that facilitate the proper diagnosis and management of EGIST. Since it is a rare and aggressive disease with a poor outcome, early detection and curative surgical resection remains the mainstay of treatment.

A neglected case of chronic abdominal pain due to Lapsi seeds: A unique foreign body at unusual location.

INTRODUCTION: Foreign body ingestion is less common in healthy adult population. Obstructive symptom caused by foreign body at unusual site of gastrointestinal (GI) tract is even rarer. PRESENTATION OF CASE: A 60-year-old female presented to the surgery outpatient department (SOPD) with 40-years of non-specific abdominal pain. Over the years, at various health facilities, multiple abdominal and pelvic ultrasounds were performed. No etiology was identified. A contrast enhanced computed tomography (CECT) of the abdomen found a short segment stricture in distal jejunum and dilated proximal jejunum with multiple hyper dense foreign bodies within the distal part of dilated jejunum. An exploratory laparotomy revealed multiple seed stones of Nepali Hog Plum (Scientific name: Choerospondias axillaris; Nepali Language: Lapsi) resided freely within the dilated and inflamed distal jejunum along with two marked strictures and a narrowed lumen at 7 cm apart at the terminal part of unhealthy jejunum. The seeds were successfully removed and a jejunoileal bypass was performed. The patient had an uneventful postoperative recovery. DISCUSSION: Lapsi seeds could reside in human gastrointestinal tract for prolonged period and are indigestible in human digestive system that could lead to various inflammatory changes in gastrointestinal tracts causing obstructive symptoms. Widely consumed fruits in Nepal, lapsi seeds when swallowed even by healthy individuals, could effect in gastrointestinal tract. CONCLUSION: Lapsi seeds could act as foreign body and obstruct human gastrointestinal tract. Healthcare professionals must approach mystery cases with diligence and thoroughness and timely referral to well equipped center could prevent significant morbidity.

Current perspectives of cancer-associated fibroblast in therapeutic resistance: potential mechanism and future strategy.

The goal of cancer eradication has been overshadowed despite the continuous improvement in research and generation of novel cancer therapeutic drugs. One of the undeniable existing problems is drug resistance due to which the paradigm of killing all cancer cells is ineffective. Tumor microenvironment plays a crucial role in inducing drug resistance besides cancer development and progression. Recently, many efforts have been devoted to understand the role of tumor microenvironment in cancer drug resistance as it provides the shelter, nutrition, and paracrine niche for cancer cells. Cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, reside in symbiotic relationship with cancer cells, supporting them to survive from cancer drugs. The present review summarizes the recent understandings in the role of CAFs in drug resistance in various tumors. Acknowledging the fact that drug resistance depends not only upon cancer cells but also upon the microenvironment niche could guide us to formulate novel cancer drugs and provide the optimal cancer treatment.

The dual blockade of MET and VEGFR2 signaling demonstrates pronounced inhibition on tumor growth and metastasis of hepatocellular carcinoma.

BACKGROUND: The application of VEGF signaling inhibitors have been associated with more invasive or metastatic behavior of cancers including hepatocellular carcinoma (HCC). We explored the contribution of MET pathway to the enhanced HCC invasion and metastasis by VEGF signaling inhibition, and investigated the antitumor effects of NZ001, a novel dual inhibitor of MET and VEGFR2, in HCC. METHODS: Immunocompetent orthotopic mice model of hepal-6 was established to investigate the effects of either VEGF antibody alone or in combination with the selective MET inhibitor on tumor aggressiveness. The antitumor effects of NZ001 were examined in cultured HCC cells as well as in vivo models. MET gene amplification was determined by SNP 6.0 assay. MET/P-MET expression was detected by IHC. RESULTS: Selective VEGF signaling inhibition by VEGF antibody significantly reduced in vivo tumor growth of the orthotopic mice models, simultaneously also enhanced tumor invasion and metastasis, but inhibiting MET signaling attenuated this side-effect. Further study revealed that hypoxia caused by VEGF signaling inhibition induced HIF-1α nuclear accumulation, subsequently leading to elevated total-MET expression, and synergized with HGF in inducing invasion. NZ001, a novel dual inhibitor of MET and VEGFR2, markedly inhibited both tumor growth and metastasis of HCC, which showed obvious advantages over sorafenib in not inducing more invasive and metastatic behaviors. This effect is more pronounced in HCC with MET amplification and overexpression. CONCLUSIONS: The activation of MET is responsible for the metastasis-promoting effects induced by VEGF inhibition. MET and VEGFR2 dual blockade, NZ001, has advantages over sorafenib in not inducing more invasive and metastatic behaviors; MET amplification and overexpression can be used to identify the subgroup of patients most likely to get the optimal benefit from NZ001 treatment.

Targeting mTORC1/2 Complexes Inhibit Tumorigenesis and Enhance Sensitivity to 5-Flourouracil (5-FU) in Hepatocellular Carcinoma: A Preclinical Study of mTORC1/2-Targeted Therapy in Hepatocellular Carcinoma (HCC).

BACKGROUND Although 5-Flourouracil(5-FU) is used as the first-choice treatment for advanced hepatocellular carcinoma (HCC), it is associated with acquired and intrinsic resistance. Hyperactivation of mTOR signaling has been linked to tumorigenesis and chemoresistance in HCC. The aim of this study was to evaluate and compare the antitumor effects of mTORC1 inhibitor everolimus and mTORC1/2 inhibitor AZD8055 and to examine the interaction between 5-FU and mTORC1/2 inhibitor in HCC. MATERIAL AND METHODS Using cultured HCC cells and mouse xenograft, the antitumor effects of everolimus and AZD8055 were analyzed as mono- and combination therapy with 5-Flourouracil. RESULTS TSC2-deficient HCC cell lines were more sensitive to everolimus and AZD8055. AZD8055, but not everolimus, potently prevented cells from transitioning from G1 phase to S phase in TSC2-high-expressing HCC cells. AZD8055 reduced phosphorylation of both mTORC1 and mTORC2 substrates. In contrast, everolimus reduced the phosphorylation of mTORC1 substrates, but increased the phosphorylation of AKT. Notably, AZD8055, but not everolimus, synergistically enhanced the efficacy of 5-FU via reversing 5-FU-induced upregulation of P-glycoprotein (P-gp). The synergistic antitumor effect of AZD8055 and 5-FU was also observed in a HCC xenograft mouse model. CONCLUSIONS TSC2 in HCC is a promising efficacy-predicting biomarker for the treatment of mTORC1/2 inhibitor. AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells. Moreover, the combination of mTORC1/2 inhibitor with 5-FU appears to be a promising option for HCC patients refractory to chemotherapy.

The prognostic influence of body mass index, resting energy expenditure and fasting blood glucose on postoperative patients with esophageal cancer.

BACKGROUND: Body mass index (BMI), resting energy expenditure (REE) and fasting blood glucose (FBG) are major preoperative assessments of patients' nutrition and metabolic state. The relations and effects of these indices on esophageal cancer patients' postoperative short-term and long-term outcomes remain controversial and unclear. We aimed to study the impact of BMI, REE and FBG in esophageal cancer patients undergoing esophagectomy. METHODS: Three hundred and six esophageal cancer patients who underwent esophagectomy were observed retrospectively. Clinical characteristics, postoperative complications and survival analysis were compared among different BMI, REE and FBG groups. RESULTS: There were significant linear relationships between REE, BMI and FBG indices, patients with low BMI tended to have low REE (p < 0.001) and low FBG (p = 0.003). No significant difference was found in case of mortality and postoperative complications among different groups. Low BMI (X 2 = 6.141, p = 0.046), REE (X 2 = 6.630, p = 0.010) and FBG (X 2 = 5.379, p = 0.020) were related to poor survival. FBG ≤90 mg/dL was independently associated with poor survival (HR = 0.695; 95 % CI 0.489-0.987, p = 0.042). BMI and REE came to be stronger prognostic factors on lymph node-negative patients and proved to be independent prognostic indicators (HR = 0.540; 95 % CI 0.304-0.959, p = 0.035 and HR = 0.457; 95 % CI 0.216-0.967, p = 0.041, respectively). CONCLUSIONS: BMI, REE and FBG are important prognostic factors in patients with esophageal cancer undergoing esophagectomy and preoperative evaluation of these indices help to determine the prognosis in these patients.

''Minimizing tacrolimus'' strategy and long-term survival after liver transplantation.

AIM: To investigate the effect of the ''minimizing tacrolimus'' strategy on long-term survival of patients after liver transplantation (LT). METHODS: We conducted a retrospective study of 319 patients who received LT between January 2009 and December 2011 at the First Affiliated Hospital of Zhejiang University School of Medicine. Following elimination of ineligible patients, 235 patients were included in the study. The relationship between early tacrolimus (TAC) exposure and survival period was analyzed by Kaplan Meier curves. Adverse effects related to TAC were evaluated by the χ(2) test. Routine monitoring of blood TAC concentration (TC) was performed using the PRO-Trac(TM) II Tacrolimus Elisa Kit (Diasorin, United States). RESULTS: Of 235 subjects enrolled in the study, 124 (52.8%) experienced adverse effects due to TAC. When evaluating mean TC, the survival time of patients with a mean TC < 5 ng/mL was significantly shorter than that in the other groups (911.3 ± 131.6 d vs 1381.1 ± 66.1 d, 911.3 ± 131.6 d vs 1327.3 ± 47.8 d, 911.3 ± 131.6 d vs 1343.2 ± 83.1 d, P < 0.05), while the survival times of patients with a mean TC of 5-7, 7-10 and 10-15 ng/mL were comparable. Adverse effects due to TAC in all four groups were not significantly different. When comparing the standard deviation (SD) of TC among the groups, the survival time of patients with a SD of 2-4 was significantly longer than that in the other groups (1388.8 ± 45.4 d vs 1029.6 ± 131.3 d, 1388.8 ± 45.4 d vs 1274.9 ± 57.0 d, P < 0.05), while in patients with a SD < 2 and SD > 4, the survival time was not statistically different. Adverse effects experienced in all three groups were not statistically different. In Cox regression analysis, male patients and those with a primary diagnosis of benign disease, mean TC > 5 ng/mL and TC SD 2-4 had better outcomes. CONCLUSION: The early ''minimizing tacrolimus'' strategy with a mean TC of 5-10 ng/mL and SD of 2-4 was beneficial in terms of long-term survival after LT.