Finasteride induced depression: a prospective study

BACKGROUND: Finasteride is a competitive inhibitor of 5 alpha-reductase enzyme, and is used for treatment of benign prostatic hyperplasia and androgenetic alopecia. Animal studies have shown that finasteride might induce behavioral changes. Additionally, some cases of finasteride-induced depression have been reported in humans. The purpose of this study was to examine whether depressive symptoms or anxiety might be induced by finasteride administration. METHODS: One hundred and twenty eight men with androgenetic alopecia, who were prescribed finasteride (1 mg/day) were enrolled in this study. Information on depressed mood and anxiety was obtained by Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS). Participants completed BDI and HADS questionnaires before beginning the treatment and also two months after it. RESULTS: Mean age of the subjects was 25.8(± 4.4) years. At baseline, mean BDI and HADS depression scores were 12.11(± 7.50) and 4.04(± 2.51), respectively. Finasteride treatment increased both BDI (p < 0.001) and HADS depression scores significantly (p = 0.005). HADS anxiety scores were increased, but the difference was not significant (p = 0.061). CONCLUSION: This preliminary study suggests that finasteride might induce depressive symptoms; therefore this medication should be prescribed cautiously for patients with high risk of depression. It seems that further studies would be necessary to determine behavioral effects of this medication in higher doses and in more susceptible patients

Malpositioned endoscopically inserted biliary stent causing massive hematemesis managed with vascular plug and stenting

A 46-year-old man with a history of hepatitis B cirrhosis and hepatocellular carcinoma (HCC) status post liver transplantation two years ago complicated by HCC recurrence and biliary stenosis presented with hypovolemic shock and melena one month after endoscopic exchange of plastic biliary stents. During endoscopic retrograde cholangiopancreatography, patient was found to have hemobilia and developed uncontrollable bleeding after a common bile duct (CBD) sweep managed by insertion of a stent-graft across major papilla into presumed CBD. The bleeding continued with subsequent negative angiography, and a computed tomography angiography showed malpositioned stent-graft between major papilla and inferior vena cava (IVC). This was successfully managed by the deployment of a vascular plug inside the stent graft and excluding it by deploying a stent across the affected area in IVC

Genotype Directed Therapy in Murine Mismatch Repair Deficient Tumors

The PI3K/AKT/mTOR pathway has frequently been found activated in human tumors. We show that in addition to Wnt signaling dysfunction, the PI3K/AKT/mTOR pathway is often upregulated in mouse Msh2−/− initiated intestinal tumors. NVP-BEZ235 is a dual PI3K/mTOR inhibitor toxic to many cancer cell lines and currently involved in clinical trials. We have treated two mouse models involving Msh2 that develop small intestinal and/or colonic tumors with NVP-BEZ235, and a subset of animals with NVP-BEZ235 and MEK inhibitor ADZ4266. The disease phenotype has been followed with pathology, 18F FDG PET imaging, and endoscopy. Intestinal adenocarcinomas are significantly decreased in multiplicity by both drug regimens. The majority of tumors treated with combined therapy regress significantly, while a small number of highly progressed tumors persist. We have examined PTEN, AKT, MEK 1&2, MAPK, S6K, mTOR, PDPK1, and Cyclin D1 and find variable alterations that include downregulation of PTEN, upregulation of AKT and changes in its phosphorylated forms, upregulation of pMEK 1&2, p42p44MAPK, pS6K, and Cyclin D1. Apoptosis has been found intact in some tumors and not in others. Our data indicate that NVP-BEZ235 alone and in combination with ADZ4266 are effective in treating a proportion of colorectal cancers, but that highly progressed resistant tumors grow in the presence of the drugs. Pathways upregulated in some resistant tumors also include PDPK1, suggesting that metabolic inhibitors may also be useful in treating these tumors

Definitive locoregional therapy (LRT) versus bridging LRT and liver transplantation with wait-and-not-treat approach for very early stage hepatocellular carcinoma

PURPOSE:Since the change in the United Network for Organ Sharing (UNOS) policy excluding patients with very early stage hepatocellular carcinoma (veHCC, single tumor nodule <2 cm) from receiving Model for End-stage Liver Disease (MELD) exception points, patients eligible to receive liver transplantation (LT) who fall in this category are commonly treated with locoregional therapy (LRT) after progression to UNOS T2 stage (1 nodule of 2–5 cm or up to 3 nodules, none above 3 cm). The aim of the current study is to compare the outcomes of patients treated with bridging LRT and LT with wait-and-not-treat approach with patients treated with definitive LRT.METHODS:A retrospective study has been performed on patients with veHCC evaluated in multidisciplinary liver tumor clinic of a large academic center between 2004–2011. Patients eligible for LT were assigned to the wait-and-not-treat group while patients who were not eligible were assigned to the definitive LRT group. Tumor size, time to treatment, severity of liver disease, recurrence and survival from time of detection were reviewed and recorded.RESULTS:A total of 19 patients were identified and treated with definitive LRT while 57 patients were treated with bridging LRT prior to LT after disease progression to T2 stage. Patients in the definitive LRT group were older (70.4±10.2 years vs. 58.7±5.9 years, P < 0.001) and had more comorbid conditions compared with the wait-and-not-treat group. Mean survival for definitive LRT group at the end of 5 years was 34.3±6.0 months with a median of 30.3 months (95% CI, 5.7–55.0 months) compared with 48.7±2.6 months for the wait-and-not-treat group, respectively (median not reached). The 3- and 5-year survival rates were 53.3% and 33.3% for the definitive LRT group compared with 78.9% and 68.4% for the patients in the wait-and-not-treat group. Survival rate at the end of 5 years was significantly better for the wait-and-not-treat group (P = 0.013).CONCLUSION:Based on the findings of current retrospective study, treating veHCC (UNOS T1 stage) patients listed for LT with bridging LRT after disease progression to T2 stage appears to be safe and effective with high 5-year survival rates

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64$\pm$0.14 and 4.50$\pm$0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88$\pm$0.04 and 0.81$\pm$0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions

Mechanical Venous Thrombectomy for Deep Venous Thrombosis in Cancer Patients: A Single-Center Retrospective Study

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (\u3c 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients\u27 VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected

Evaluation of Ventriculoperitoneal Shunt malfunction Regarding Ventricular Catheter Placement

Backgroundline of treatment for management of hydrocephalus despite available new techniques andsystems of shunting.Associated complications should be recognized and managed properly,but the most recognized complications are shunt obstruction which its prevalencethrough surgical approach is discussed here. Two approaches (frontal and parietal) are usedto insert ventriculoperitoneal shunt. In this study we retrospectively examined patterns ofshunt failure in patients with symptoms of shunt malfunction. Factors analyzed includedsite of failure, time from shunt placement or last revision of failure,age of patient at time offailure,infection and primary etiology of hydrocephalus.Two approaches were comparedto determine which one is more associated with shunt failure.: Shunting procedures specifically ventriculoperitoneal shunts are the mainMethodsretrospectively examined, in 126 cases who were shunted through frontal approach,48 casesand in 124 patients whose shunts were inserted through parietal approach 64 cases ofmalfunction observed.All data was analyzed with SPSS software and with T-test,and thenthe failure rate for frontal versus parietal approach was compared.:250 patients with symptoms of shunt malfunction over 4 years period wereResultsof underlying cause of ventriculoperitoneal shunt failure was observed, with theless failure rates through frontal approach.:Significant difference in malfunction rate between these two approaches regardlessConclusionshunt failure and frontal approach demonstrated less failure rate, but as it isknown placing the catheter tip away from the choroids plexus is the most important factoravoiding obstruction.: Although proximal obstruction is the most common cause of ventriculoperitonea