Endoscopic Management of Biliary Leaks and Strictures After Living Donor Liver Transplantation: Optimizing Techniques for Successful Management

Digestive Diseases and Sciences - Biliary complications (BCs) occur in up to 40% of living donor liver transplant (LDLT) recipients. The aim of this study was to evaluate the efficacy of endoscopic...     

Prevention of cadmium bioaccumulation by herbal adaptogens

Objectives:

To evaluate the effect of various herbal adaptogens such as shade-dried powders of Withania somnifera, Ocimum sanctum, Asperagus recemosus, Andrographis paniculata, Asphaltum panjabinum (Shilajith), Gymnema sylvestre, Spirulina platensis, and Panex ginseng on cadmium (Cd)-induced oxidative stress and its accumulation in broiler chicken.

Materials and Methods:

A total of 80 male broiler chicks of day old age were randomly assigned to 10 equal groups. Group 1 birds were fed with basal diet throughout the experiment (1–42 days). Group 2–10 chicks were fed with basal diet containing cadmium at 100 ppm from day 1 to day 28 (4 weeks). From 29^th to 42^nd day (2 weeks), basal diet alone was fed to group 2 chicks which acted as toxic control and group 3–10 birds were fed with feed containing 0.1% powder of W. somnifera, O. sanctum, Aspe. recemosus, An. paniculata, Asph. panjabinum (Shilajith), G. sylvestre, S. platensis, and P. ginseng, respectively. Body weight gain, levels of non-enzymatic antioxidants such as reduced glutathione (GSH), lipid peroxidation markers such as thiobarbituric acid reacting substances (TBARS), liver functional markers such as serum alanine transaminase (ALT), kidney functional markers such as blood urea nitrogen (BUN) and serum creatinine and concentration of cadmium in liver and kidney were investigated.

Results:

Body weight gains were significantly decreased in birds of groups 2–10 compared to group 1 at the end of 4^th week. Supplementation of various medicinal herbs in feed after 4^th week significantly improved the body weight gain compared to that in group 2 chicks. The increase in TBARS and decrease in GSH concentrations of liver and kidney tissues in cadmium intoxicated birds were significantly reversed by the above-said herbs. The liver and kidney functional markers were also restored to normal levels. Highest concentration of cadmium was found accumulated in kidney, followed by liver in birds of group 2. Herbal supplementation in groups 3–10 prevented Cd bioaccumulation which was most evident in liver, followed by kidney.

Conclusions:

Administration of herbal adaptogens at the rate of 0.1% in feed significantly prevented the bioaccumulation of Cd and reversed the Cd-induced oxidative tissue damage.     

Robot-assisted radical cystectomy: An expert panel review of the current status and future direction

ObjectiveAt the 9th Annual Meeting of the Society of Urologic Oncology (SUO), an expert panel discussed the current status of robot-assisted radical cystectomy (RARC).Materials and methodsThe presentations were derived from: (1) review of published literature, unpublished addendums, and SUO abstracts, (2) initial abstract data of pooled results of 528 patients from the International Robot-Assisted Cystectomy Consortium (IRCC), and (3) an internet-based survey of the SUO membership (n = 54) on training and practice patterns related to RARC.ResultsUsing pathologic assessment of surgical margins as a surrogate for cancer control, the results are favorable with organ confined disease, with select expert series showing no positive margins and the IRCC group reporting 4%. In non-organ-confined disease, select expert series also show no positive margins, while for the IRCC group it was 15%. The median lymph node yield in all series is 12–19 with 5%–33% positive. The S-model robot is preferred for an extended node dissection to the aortic bifurcation. In experienced hands, estimated blood loss is <500 cc, and hospital discharge by postoperative d 4–5. Complications appear similar to open and decrease with experience. In one study comparing RARC to open, pain scales were similar but morphine use was consistently lower for RARC. The technique is most often applied to the bladder and lymph nodes only with a mini-laparotomy for the diversion; technical considerations for female patients were described. The membership surveys showed that 37% of respondents have attempted RARC, but < 20% received robot console training during fellowship. The greatest area of concern was the adequacy of the lymph node dissection in the higher regions—common iliac to peri-caval/aortic.ConclusionsInitial reports of RARC demonstrate feasibility of technique, early oncologic outcomes, and learning curve experiences. Surgeons learning RARC should select patients without clinical evidence of locally advanced disease, and consider a second look open node dissection. Experienced surgeons have demonstrated the possibility of reduced blood loss, opiate requirement, and hospital stay. Moving forward, an international consortium has been organized to address the unmet needs of prospective comparisons with long-term oncologic outcomes, standardized complication reporting, and quality of life.     

Association of rash with outcomes in a randomized phase II trial evaluating cetuximab in combination with mitoxantrone plus prednisone after docetaxel for metastatic castration-resistant prostate cancer

Purpose

Cetuximab (C), a chimeric monoclonal antibody that binds epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cancer cell lines and might enhance the activity of chemotherapy. The efficacy of combining cetuximab with mitoxantrone (M) plus prednisone (MP) was evaluated in progressive metastatic castrate-resistant prostate cancer (CRPC) after receiving docetaxel.

Materials and Methods

Patients with progression after receiving docetaxel were eligible and randomized 2:1 to CMP or MP. Therapy was mitoxantrone 12 mg/m² intravenously (I.V.) on day 1, oral prednisone 10 mg daily in both arms, and cetuximab 250 mg/m² I.V. (400 mg/m² day 1, cycle 1) on days 1, 8, and 15 in the CMP arm. Cycles were repeated every 21 days. Radiologic assessments of disease and PSA (prostate-specific antigen) occurred every 4 cycles. The primary endpoint was time to progression (TTP).

Results

A total of 115 patients were enrolled, 75 in the CMP and 40 in the MP arm: the median TTP was 4.9 and 6.6 months, respectively; the measurable disease response rate was 2% and 4%, the PSA response rate 7.7% and 17.6%, and median survival 11.9 and 15.7 months, respectively. Key grade 3-4 toxicities were neutropenia 44% and 25.6%, anemia 6.7% and 7.7%, thrombocytopenia 6.7% and 2.6%, and fatigue 8% in both arms. In an unplanned exploratory analysis, median TTP with (n = 24) and without rash (n = 51) in the CMP arm was 10.3 months vs. 2.8 months (P = .004). On multivariable analysis,rash was significantly associated with TTP (hazard ratio [HR] = 0.43; P = .01).

Conclusions

The treatment with CMP is not recommended in unselected men with docetaxel-treated CRPC, although rash might help develop tailored therapy.     

Neutropenia as a Potential Pharmacodynamic Marker for Docetaxel-Based Chemotherapy in Men With Metastatic Castration-Resistant Prostate Cancer

BackgroundDocetaxel clearance appears increased in men who are castrated. Neutropenia in cycle 1 may be a pharmacodynamic marker for docetaxel, which may enable tailored dosing in metastatic castration-resistant prostate cancer (mCRPC).Patients and MethodsThe association of cycle 1 neutropenia with overall survival (OS) was examined post hoc in a randomized phase II trial of 221 men with mCRPC who received docetaxel-prednisone combined with placebo or AT-101 (bcl-2 inhibitor); weekly blood cell counts were performed during the first cycle. Patients from both arms were combined because no outcome and toxicity differences were observed. OS was calculated from randomization by the Kaplan-Meier method, and Cox proportional hazards regression models were used to estimate the association with OS.ResultsThe difference in OS between men with day 8 ≥grade 3 neutropenia and those with ≤grade 2 neutropenia was significant after adjusting for trial stratification factors, pain, and performance status (hazard ratio [HR] 0.64; 2P = .048). Results were similar for logarithmic neutrophil counts adjusted for the risk group based on anemia, visceral metastasis, progression by bone scan and pain (HR 1.18; 2P = .07) for stratification factors (HR 1.20; 2P = .052) or both (HR, 1.20; 2P = .046). Men with ≥grade 3 neutropenia and ≥30% prostate-specific antigen level decline by day 90 had improved OS compared with men exhibiting neither (HR 0.51; 2P = .014).ConclusionsFor patients with mCRPC who received docetaxel, ≥grade 3 neutropenia on day 8 was prognostic for improved OS, which suggests its utility as a pharmacodynamic marker, in this hypothesis-generating analysis. Exploration of dose escalation of docetaxel to attain ≥grade 3 neutropenia on day 8 may be warranted.     

Current status of home blood pressure monitoring in Asia: Statement from the HOPE Asia Network

Hypertension represents a major burden in Asia, with a high prevalence rate but poor level of awareness and control reported in many countries in the region. Home blood pressure monitoring has been validated as an accurate and reliable measure of blood pressure that can help guide hypertension treatment as well as identify masked and white‐coat hypertension. Despite its benefits, there has been limited research into home blood pressure monitoring in Asia. The authors reviewed the current evidence on home blood pressure monitoring in Asia, including but not limited to published literature, data presented at congresses, and national hypertension management guidelines to determine the current utilization of home blood pressure monitoring in clinical practice in the region. Public policies to enable greater access to home blood pressure monitoring and its use in clinical care would add considerably to improving hypertension outcomes in Asia.