Fatal acquired coagulation factor V deficiency after hepatectomy for advanced hepatocellular carcinoma as a possible immune checkpoint inhibitor-related adverse event: a case report.

BACKGROUND: Atezolizumab plus bevacizumab therapy was recently introduced as the first line for unresectable advanced hepatocellular carcinoma (HCC), but immune-related adverse events (IrAEs) due to atezolizumab are a great concern. Here, we report the case of a patient who developed fatal acquired coagulation factor deficiency after hepatectomy for HCC, treated with atezolizumab and bevacizumab before surgery. CASE PRESENTATION: A 70-year-old man received right trisegmentectomy of the liver with hepaticojejunostomy for advanced HCC with bile duct invasion, after atezolizumab and bevacizumab therapy. The patient suffered the sudden onset of severe multiple coagulation factor deficiency (II, V, VII, VIII, IX, X, XI and XII) immediately following reoperation for anastomotic leakage of hepaticojejunostomy, 7 days after hepatectomy. The coagulation factor deficiency did not reverse even with intensive treatment, and the patient died of uncontrollable bleeding 32 days after hepatectomy. An IrAE due to atezolizumab was suspected because the patient had developed the possible IrAE of enthesitis of the right gastrocnemius muscle before surgery, and specific inhibitors against factor V and anti-factor V autoantibodies were detected, leading to an ultimate diagnosis of autoimmune FV/5 deficiency (AiF5D). CONCLUSION: Severe acquired coagulopathy should be recognized as a possible life-threatening IrAE when using atezolizumab and bevacizumab for HCC.

Human chorionic gonadotropin-ß promotes pancreatic cancer progression via the epithelial mesenchymal transition signaling pathway.

Background: The human chorionic gonadotropin free beta-subunit (hCGß) is ectopically produced in various epithelial cancers and is associated with poor prognoses. However, its molecular mechanism remains unclear. In this study, we examined the biological role of hCGß in pancreatic cancer progression. Methods: Tissue specimens of 30 patients with pancreatic cancer were examined immunohistochemically to investigate the relationship between hCGß expression and clinicopathological features. We also evaluated the molecular effects of hCGß-downregulated pancreatic cell lines. Results: Total of 21 cases were positive for immunostaining, and 17 of 25 metastatic lymph nodes were positive. hCGß expression levels were correlated with pancreatic cancer T and N factors. hCGß expression was significantly associated with poor overall and recurrence-free survival (P<0.001). In a multivariate analysis, hCGß expression was independently associated with overall survival (HR 14.0; 95% CI: 1.5-130; P=0.019). The proliferative, invasive, and migratory abilities of hCGß-downregulated cell lines were reduced compared with the control cell lines. Moreover, downregulation of hCGß reduced vimentin, slug, and α-smooth muscle actin expression and increased E-cadherin expression. Conclusions: hCGß expression is related to cancer progression and poor prognoses via epithelial mesenchymal transition. hCGß is a potential prognostic marker and molecular target in pancreatic cancer.

National survey of hepatobiliary and pancreatic surgery in hemophilia patients in Japan.

BACKGROUND: Approximately 8300 hemophiliacs are registered in Japan, but no comprehensive reports on hepatobiliary and pancreatic surgery (HBPS) have been conducted. This report investigates the current status of HPBS in hemophilia patients in Japan. METHODS: The subjects were hemophiliac patients seen between January 1 2007, and December 31 2017, at facilities participating in this study among the facilities for performing high-difficulty cases nationwide designated by the Japanese Society for HBPS. A retrospective examination of short-term outcomes in 49 cases was conducted to assess patient background, disease, surgical procedure, and complications. RESULTS: The types of hemophilia were A: 43 cases, B: four cases, and von Willebrand disease: two cases (hemophilia severity: mild 32, moderate seven, severe 10). The target malignant diseases for surgery were hepatocellular carcinoma (HCC) in 20 cases, intrahepatic cholangiocellular carcinoma (CCC) in four cases, combined HCC-CCC in two cases, hilar CCC in two cases, and pancreatic cancer in four cases. As for the surgical procedure, limited resection (subsegmentectomy and partial hepatectomy) was performed in 16 cases of HCC even with normal liver function tests. Pancreaticoduodenectomy and distal pacreatectomy were performed for pancreatic cancers as in the standard procedure. Postoperative complications were postoperative bleeding in two cases after hepatectomy and one after pancreatectomy in one case. When compared with Japanese National Clinical Data base, the complication rates after hepatectomy and pancreatectomy were not conspicuous in hemophilic patients. CONCLUSIONS: As long as they are performed in qualified centers, complication rate is not increased in hemophilic patients undergoing HBPS.

Hepatocellular Carcinoma in a Patient With Crohn's Disease.

A 44-year-old woman with a 26-year history of Crohn's disease (CD) presented with intermittent fever, vomiting, and watery diarrhea. Her medication included an elemental diet, mesalazine, and infliximab. Liver profile and viral hepatitis markers were normal. Computed tomography scans showed a hepatic tumor by chance. Serum tumor markers disclosed elevated protein induced by vitamin K absence-II. With a diagnosis of hepatocellular carcinoma (HCC), she underwent a hepatic resection of the tumor, revealing well-to-moderately differentiated HCC. The nontumor region of the liver disclosed the absence of cirrhosis or other diseases. Here, the development of HCC in CD without underlying liver diseases is discussed with a review of the literature.

Evaluation of psychophysiological asymmetry in patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is characterized by systemic pain of unknown etiology, and is often accompanied by various psychological symptoms. In the present study, differences in surface electromyographic (SEMG) levels of the trapezius muscle, skin temperature (TEMP) and skin conductance level (SCL) were compared between the right and left side of the body in 31 FMS and 47 control subjects (Control Group). We observed significant asymmetries of SEMG level, TEMP and SCL in the FMS Group. These asymmetries might be related to central, peripheral and autonomic nervous system dysfunctions. Marked increase of SEMG levels, and a decrease of TEMP and SCL were observed at the dominant side in the FMS Group, and a negative correlation of SEMG levels with TEMP and SCL was found. These results suggest that continued antalgic postures in response to pain at the dominant side in FMS patients might lead to asymmetries of SEMG level, TEMP and SCL. Thus, a focus on pain related behaviors and muscle asymmetry might be a useful therapeutic approach.

Paradoxical results of psychophysiological stress profile in functional somatic syndrome: correlation between subjective tension score and objective stress response.

Mind-body interactions are important in functional somatic syndromes (FSS). Therefore, in the assessment of the psychophysiological stress response in patients with FSS, both subjective feelings and psychophysiological activity should be simultaneously measured. In this study, "Objective Tension Score" (OTS) was defined as an objective parameter of tension; it consisted of surface electromyography and skin conductance level as indicators of muscle and mental tension, respectively. "Subjective Tension Score" (STS) was defined as a subjective parameter of tension. Changes in OTS and STS in response to the stress task were investigated in 30 FSS patients and 28 controls. Objective tension was significantly hyporeactive to the stress task and STS was significantly higher in the patient group than in the control group. There was a significant negative correlation between OTS response and STS in the patient group, but no significant correlation in the control group. Our results suggested the existence of dissociation between subjective and objective responses in FSS patients. This may indicate that FSS patients had difficulty with the awareness of bodily feelings, thus supporting the concept of "alexisomia" or "escaped bodily feelings" in FSS patients.