Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: A single center experience

Systemic chemotherapy or chemoradiotherapy is the initial primary option for patients with locally advanced pancreatic cancer (LAPC). This study analyzed the effect of FOLFIRINOX and assessed the factors influencing conversion to surgical resectability for LAPC.Sixty-four patients with LAPC who received FOLFIRINOX as initial chemotherapy were enrolled retrospectively. Demographic characteristics, tumor status, interval/dosage/cumulative relative dose intensity (cRDI) of FOLFIRINOX, conversion to resection, and clinical outcomes were reviewed and factors associated with conversion to resectability after FOLFIRINOX were analyzed.After administration of FOLFIRINOX (median 9 cycles, 70% of cRDI), the median patient overall survival (OS) was 17.0 months. Fifteen of 64 patients underwent surgery and R0 resection was achieved in 11 patients. During a median follow-up time of 9.4 months after resection, cumulative recurrence rate was 28.5% at 18 months after resection. The estimated median OS was significantly longer for the resected group (>40 months vs 13 months). There were no statistical differences between the resected and non-resected groups in terms of baseline characteristics, tumor status and hematologic adverse effects. The patients who received standard dose of FOLFIRINOX had higher probability of subsequent resection compared with patients who received reduced dose, although cRDIs did not differ between groups.FOLFIRINOX is an active regimen in patients with LAPC, given acceptable resection rates and promising R0 resection rates. Additionally, our data demonstrate it is advantageous for obtaining resectability to administer FOLFIRINOX without dose reduction

Maintenance of skeletal muscle mass during FOLFIRINOX is a favorable prognostic factor in pancreatic cancer patients

Objective The study aimed to investigate the effect of body composition changes during chemotherapy on clinical outcomes in patients with pancreatic cancer. Results In patients with locally advanced pancreatic cancer (LAPC), the cross-sectional area of skeletal muscle (SM) and adipose tissue (AT) at the level of third lumbar vertebra was measured. The SM and AT ratios indicated the changes during chemotherapy. The patients were classified into three groups based on these ratios: group 1, ≥ 1.00; group 2, 0.85–0.99; group 3, < 0.85. The overall survival (OS) and surgical resection rates were estimated. Fifty-eight patients with LAPC who received first-line FOLFIRINOX were analyzed. Fifteen (25.9%) patients who underwent resection showed maintained BMI, SM, and AT as compared to the patients who did not undergo resection. As the SM ratio decreased, the risk for death increased significantly. Further, the resection rate was significantly higher in patients with maintained SM compared to those with low SM ratio. On the contrary, the change in AT ratio was not associated with OS and resection rate; however, significant decrease in AT more than 15% showed poor clinical outcomes. Maintenance of SM during chemotherapy is a reliable prognostic factor indicating longer OS and higher resection rate

A Case of Adenocarcinoma in situ of the Distal Common Bile Duct Diagnosed by Percutaneous Transhepatic Cholangioscopy

Extrahepatic cholangiocarcinoma is often clinically challenging to diagnose. Even multidisciplinary approaches which include computed tomography, magnetic resonance imaging, and endoscopic retrograde cholangiography are unsatisfactory in some cases, especially with biliary stricture. Percutaneous transhepatic cholangioscopy (PTCS) with its direct visualization for biopsy appears to be a promising technique for detecting cholangiocarcinoma at an early stage. We report a case of adenocarcinoma in situ of the distal common bile duct (CBD) that was confirmed by PTCS. This case suggests the useful role of PTCS in the differential diagnosis of a distal CBD obstruction, particularly when other diagnostic modalities do not provide definitive information

Castleman Disease Presenting with Jaundice: A Case with the Multicentric Hyaline Vascular Variant

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown etiology with different clinical manifestations. A previous healthy 50 year-old man was hospitalized for right upper quadrant (RUQ) abdominal pain. He had jaundice and a 1 cm-sized lymph node in the right supraclavicular area. Pancreas and biliary computed tomography (CT) showed masses at the right renal hilum and peripancreatic areas. Positron emission tomography (PET) showed widespread systemic lymphadenopathy. Excisional biopsy of the right supraclavicular node revealed a hyaline vascular variant of CD. Corticosteroid therapy was started and the extent of disease decreased. We here report a case of multicentric CD, the hyaline vascular variant, presenting with jaundice, diagnosed by excisional biopsy and successfully treated with corticosteroids

Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer

IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3–28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4–30.3) and 16.7 months (95% CI: 13.0–20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042–3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival

A Case of Acute Q Fever with Severe Acute Cholestatic Hepatitis

Minimal hepatic dysfunction can be common in acute Q fever, but severe acute cholestatic hepatitis is rarely reported. We report on a 55-year-old male with acute Q fever and severe acute cholestatic hepatitis. He complained of fever, jaundice, ascites, and restlessness on admission. A liver biopsy revealed the presence of compact fibrin-ring granulomas. Serologic titers for C. burnetii IgM and IgG were 2048:1 and 1024:1, respectively. C. burnetii DNA was detected by a nested polymerase chain reaction on the liver tissue

Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study

Background/AimsVitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome.MethodsA retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85).ResultsThe PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period.ConclusionsShort-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E

Effect of chitinase- 3- like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study

We investigated the effect of chitinase- 3- like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP- activated protein kinase (AMPK)- dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1- mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/2/fsb220907.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/1/fsb220907_am.pd