Barriers in Hepatitis C Treatment in Somali Patients in the Direct Acting Antiviral Therapy Era.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) treatment has changed dramatically in the last few years. Our observations suggest that a minority of HCV infected Somalis are treated. In this study, we aimed to evaluate for treatment and health outcome disparities between Somali and non-Somali patients during the direct acting antiviral (DAA) era. METHODS: Patients with HCV seen in the gastroenterology clinic in 2015 were included in the study. Patients were identified using ICD9 and 10 codes. Electronic medical records were analyzed to evaluate for treatment candidacy, acceptance and reasons for refusal of treatment. RESULTS: Genotype 4 followed by 3 were the most common genotypes in the Somalis while genotype 1 was the most common in the non-Somalis. Majority of patients were offered treatment, active alcohol and substance abuse was a common reason for not offering treatment in non-Somalis while the presence of hepatocellular carcinoma was the most common reason in Somalis. Somalis had higher rates of declining treatment given the asymptomatic nature of their disease and the feeling that treatment is not needed. Sustained virologic response rates were comparable in both groups. CONCLUSIONS: Disparities in acceptance of HCV treatment persist in the DAA era. The asymptomatic nature of the infection and potential cultural mistrust makes patients hesitant to undergo treatment. Healthcare providers must find interventions aimed at reducing barriers to treatment and increasing acceptance of HCV treatment.

Outcomes of Simultaneous Peritoneal Dialysis and Arteriovenous Fistula Placement in End-Stage Renal Disease Patients.

Peritoneal dialysis (PD) interruption requiring hemodialysis (HD) is not uncommon and its frequently abrupt nature prevents timely creation of permanent HD access and avoidance of central venous catheters (CVC). We retrospectively studied a cohort of 24 end-stage renal disease (ESRD) patients (mean age 50.7 years, 83.3% African-Americans, 58.3% females, time on dialysis interquartile range [IQR] 0 - 65 days) who had simultaneous PD catheter insertion and backup arteriovenous fistula (AVF) creation between January 1, 2012, and December 31, 2013. The primary outcome of interest was the percent of patients receiving HD through the backup AVF at the time of PD interruption. A median (IQR) for PD catheter use after its insertion was 10.5 (2 - 20) days. After the mean follow-up of 19.6 months, 12 patients remained on PD, 2 patients received a kidney transplant, and 1 patient died. The overall AVF patency was 66.7%. A total of 9 (37.5%) patients had PD interruption requiring permanent (8 patients) or temporary (1 patient) HD after the mean (standard deviation [SD]) follow-up of 12.3 (8.2) months. Arteriovenous fistula was used as the initial access in 4 patients, and in 3 patients the original AVF was used after additional surgical revision. Forty-four percent of patients with a backup AVF fistula avoided CVC at the time of PD interruption requiring HD. The simultaneous AVF creation at the time of PD catheter insertion reduced but did not fully eliminate CVC at the time of PD interruption. Larger studies are needed to evaluate the utility of a backup AVF in PD patients.

Antitumor effect of FGFR inhibitors on a novel cholangiocarcinoma patient derived xenograft mouse model endogenously expressing an FGFR2-CCDC6 fusion protein.

Cholangiocarcinoma is a highly lethal cancer with limited therapeutic options. Recent genomic analysis of cholangiocarcinoma has revealed the presence of fibroblast growth factor receptor 2 (FGFR2) fusion proteins in up to 13% of intrahepatic cholangiocarcinoma (iCCA). FGFR fusions have been identified as a novel oncogenic and druggable target in a number of cancers. In this study, we established a novel cholangiocarcinoma patient derived xenograft (PDX) mouse model bearing an FGFR2-CCDC6 fusion protein from a metastatic lung nodule of an iCCA patient. Using this PDX model, we confirmed the ability of the FGFR inhibitors, ponatinib, dovitinib and BGJ398, to modulate FGFR signaling, inhibit cell proliferation and induce cell apoptosis in cholangiocarcinoma tumors harboring FGFR2 fusions. In addition, BGJ398 appeared to be superior in potency to ponatinib and dovitinib in this model. Our findings provide a strong rationale for the investigation of FGFR inhibitors, particularly BGJ398, as a therapeutic option for cholangiocarcinoma patients harboring FGFR2 fusions.

Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells.

Sphingosine kinase 2 (Sphk2) has an oncogenic role in cancer. A recently developed first-in-class Sphk2 specific inhibitor ABC294640 displays antitumor activity in many cancer models. However, the role of Sphk2 and the antitumor activity of its inhibitor ABC294640 are not known in cholangiocarcinoma. We investigated the potential of targeting Sphk2 for the treatment of cholangiocarcinoma. We found that Sphk2 is overexpressed in five established human cholangiocarcinoma cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient-derived cholangiocarcinoma cell line (LIV27) compared to H69 normal cholangiocytes. Inhibition of Sphk2 by ABC294640 inhibited proliferation and induced caspase-dependent apoptosis. Furthermore, we found that ABC294640 inhibited STAT3 phosphorylation, one of the key signaling pathways regulating cholangiocarcinoma cell proliferation and survival. ABC294640 also induced autophagy. Inhibition of autophagy by bafilomycin A1 or chloroquine potentiated ABC294640-induced cytotoxicity and apoptosis. In addition, ABC294640 in combination with sorafenib synergistically inhibited cell proliferation of cholangiocarcinoma cells. Strong decreases in STAT3 phosphorylation were observed in WITT and HuCCT1 cells exposed to the ABC294640 and sorafenib combination. These findings provide novel evidence that Sphk2 may be a rational therapeutic target in cholangiocarcinoma. Combinations of ABC294640 with sorafenib and/or autophagy inhibitors may provide novel strategies for the treatment of cholangiocarcinoma.

A new clinically based staging system for perihilar cholangiocarcinoma.

OBJECTIVES: Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials. METHODS: Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system. RESULTS: Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1-2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival. CONCLUSIONS: This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.

Not every recurrent pelvic mass in a female is a leiomyoma.

Desmoid tumors are rare neoplasms. They occur mostly in females in their reproductive age and may present with pelvic pain and intestinal obstruction. These connective tissue neoplasms are because of uncontrolled proliferation of differentiated myofibroblasts. The cells may synthesize vast amounts of collagen fibers in response to various stimuli. We describe a case of a pelvic desmoid tumor simulating a uterine leiomyoma recurrence. We review the literature on the epidemiology and the treatment options for desmoid tumors and suggest a strong index of suspicion when a new pelvic mass arises in an adult with previous pelvic surgery. We advise a planned multidisciplinary treatment approach at the first hint of the diagnosis of desmoid tumor.

Klippel-trenaunay syndrome: an often overlooked risk factor for venous thromboembolic disease.

Klippel-Trenaunay syndrome (KTS) is a congenital condition redefined by Oduber et al (2008) by the coexistence of vascular malformations and disturbed soft tissue or bony growth, including hypertrophy or hypotrophy in the same or opposite sides of the body. The anomalies may involve part of a limb, a whole limb, a limb girdle, or a hemibody. Vascular malformations may involve veins, capillaries, or lymphatics although venous or capillary malformations are essential for the diagnosis. Associated venous anomalies include dysplasia, valvular malformations, and varicosities. Congenital venous anomalies are often associated with disturbances of blood flow and should be considered as prothrombotic states. However, such anomalies are not considered in Wells scores and used to determine the risk for venous thromboembolism (VTE). We present the case of a male with unrecognized crossed dissociated form of KTS and unsuspected VTE. The pathophysiology and the treatment of VTE in KTS are discussed. We suggest physicians to be aware of KTS and that its recognition in a critically ill patient should prompt consideration for appropriate prophylaxis for high-risk category for VTE. Dedicated duplex sonography should be obtained if VTE is suspected. We also suggest a modification of the Wells scores to reflect the association of KTS and VTE.

Non-islet cell tumor hypoglycemia associated with uterine leiomyomata.

OBJECTIVE: We report a case of non-islet cell tumor hypoglycemia (NICTH) in a patient with large leiomyomata. METHODS: We present the clinical, laboratory, and pathologic findings of a diabetic patient who presented with recurrent hypoglycemia later linked to uterine leiomyomata. RESULTS: An 80-year-old woman with diabetes was admitted after falling at home. She reported dizziness and had recorded low capillary blood glucose despite discontinuing her diabetic medication prior to admission. Her physical examination was remarkable for nonorthostatic vital signs, normal cardiovascular and lung examination, and a pelvi-abdominal mass the size of a gravid uterus at 28 weeks of gestation. After receiving a 50% dextrose infusion, she became alert with no focal neurological deficit. Capillary blood glucose rose from 31 mg/dL to 110 mg/dL. A pelvic sonogram confirmed fibromyomata. She was initially treated with steroids after a hormonal profile suggested NICTH (normal fasting insulin, C-peptide, cosyntropin and glucagon stimulation tests, and negative insulin antibodies). Insulinlike growth factor (IGF) levels were IGF-1, 69 ng/mL and IGF-2, 782 ng/mL, and the IGF-2/IGF-1 ratio was 10.8. The patient underwent a total abdominal hysterectomy. Pathology reported a 3-kg uterus with multiple, large cellular fibromyomas. After steroids were discontinued, she became hyperglycemic requiring insulin and oral diabetic agents. Repeat IGF-2 and IGF-1 measurements were 261 ng/mL and 36 ng/mL, respectively. She was discharged 2 weeks after surgery. CONCLUSION: NICTH is a rare complication associated with large neoplasms. Leiomyomata should be included in the differential diagnoses of NICTH. Surgery is curative in such cases.

An obscure case of hepatic subcapsular hematoma.

Spontaneous liver bleeding is often reported in preeclampsia. It is otherwise rare and has been linked to gross anatomical lesions and coagulopathy. We report a case of subcapsular hematoma of the liver without any apparent lesion and in the absence of coagulopathy. A 41-year-old male, paraplegic for 16 years, presented to the emergency department 3 days after sudden onset of right upper quadrant and shoulder pain. He had been on vitamins and 5,000 units subcutaneous heparin 12-hourly at the nursing home for the last month. He was in no distress, afebrile, with stable vitals. Physical examination showed a diverting colostomy, tender hepatomegaly and sacral decubiti. A fecal occult blood test was negative. There was spastic paraplegia below the level of T12. Two days after admission, the patient was afebrile and hemodynamically stable. PTT, PT, liver profile, BUN and creatinine were all normal, however his hemoglobin had dropped from 11.3 to 7.6 g/dl. An abdominal CT scan revealed an isolated 9.0 × 1.8 cm subcapsular hematoma. The patient received blood transfusion in the intensive care unit and was discharged 7 days later. In conclusion, spontaneous liver hemorrhage occurs in the nonobstetrical population in the setting of gross anatomical lesions or coagulopathy. This is the first report of an isolated subcapsular liver hematoma.

An unusual cause of postoperative gastric volvulus.

BACKGROUND: Gastric volvulus presents with nonspecific abdominal symptoms and therefore may be missed. Its diagnosis has increased with improving imaging techniques such as computed tomography scan with contrast. Volvulus around a surgical drain has not been previously reported. OUR CASE: We report the case of a 44-year-old lady who suffered with symptoms of persistent postprandial nausea and vomiting after distal pancreatectomy and splenectomy. A computed tomography scan of the abdomen demonstrated a surgical drain slinging up the pylorus and a partial gastric volvulus. The symptoms resolved after the drain was removed. CONCLUSIONS: Gastric volvulus is a differential diagnosis of persistent postprandial vomiting after surgical disruption of the gastrosplenic ligament. However, if this occurs in the early postoperative period the drains should be removed to ensure resolution.

Autogenous brachio-cephalic arterio-venousautogenous brachio-cephalic arterio-venous fistulae: effect of age, diabetes,fistulae: effect of age, diabetes, atherosclerosis, and anticoagulation on theatherosclerosis, and anticoagulation on the long-term outcomelong-term outcome.

Age, diabetes, and generalized atherosclerosis are thought to be limiting factors forAge, diabetes, and generalized atherosclerosis are thought to be limiting factors for creating an autogenous arterio-venous fistula (AVF) unlike the use of anticoagulants. Wecreating an autogenous arterio-venous fistula (AVF) unlike the use of anticoagulants. We retrospectively assessed the effect of these factors on the outcome of 75 autogenousretrospectively assessed the effect of these factors on the outcome of 75 autogenous brachio-cephalic AVFs created between January 1, 2002 and August 31, 2005. Differentbrachio-cephalic AVFs created between January 1, 2002 and August 31, 2005. Different groups of patients were compared and the longevity of the AVFs was calculated. Fifty-twogroups of patients were compared and the longevity of the AVFs was calculated. Fifty-two percent of the patients were >65 years old, 41.3% werepercent of the patients were >65 years old, 41.3% were diabetic, 48% were arteriopaths,diabetic, 48% were arteriopaths, and 41.3% were not using anticoagulants. The maximum follow-up was 35 months (mean,and 41.3% were not using anticoagulants. The maximum follow-up was 35 months (mean, 11.2 +/- 10.3 months; median, 7 months). The success rate of the operation was 93.3% (mean 11.2 +/- 10.3 months; median, 7 months). The success rate of the operation was 93.3% (70 patent AVFs); 79.3% of the AVFs were functioning at 35 months. Age >65 years old,patent AVFs); 79.3% of the AVFs were functioning at 35 months. Age >65 years old, diabetes, generalized atherosclerosis, and the lack of use of anticoagulants were notdiabetes, generalized atherosclerosis, and the lack of use of anticoagulants were not associated with an increased rate of technical failures or a decreased long-term patencyassociated with an increased rate of technical failures or a decreased long-term patency rate of the AVFs.rate of the AVFs.