Treatment of Refractory Gastrointestinal Bleeding in Patients With Portal Hypertension: A Case Series and Treatment Algorithm.

In patients with portal hypertension, ectopic varices can develop at any site along the gastrointestinal tract outside the classically described gastroesophageal location. Like esophageal variceal hemorrhage, bleeding from ectopic varices can be life-threatening. Diagnosis and treatment of ectopic varices can be challenging; to date, no effective treatment algorithm has been described. A systematic teamwork approach to diagnosing and treatment of ectopic varices is required to successfully manage hemorrhage from ectopic varices.

Mini-incision living donors nephrectomy using anterior muscle-splitting approach with hybrid technique.

BACKGROUND: Significant morbidity is associated with standard open flank living donor nephrectomy. Laparoscopic donor nephrectomy is criticized for a steep learning curve and a tendency to avoid the right kidney. The anterior muscle-splitting technique uses principles or advantages of an open extraperitoneal approach with minimal morbidity and the advantageous muscle-splitting (instead of cutting) procedure. OBJECTIVE: To compare mini-incision laparoscopic instrument-assisted (MILIA) live donor nephrectomy using a muscle-splitting technique to the standard open-flank donor nephrectomy (ODN) approach for efficacy and safety. METHODS: MILIA living donor nephrectomies were performed in 119 donors and compared to a cohort of open-flank nephrectomy donors (n=38) from the same center. Both donor groups were matched for body mass index as well as other personal characteristics. RESULTS: The mean donor age was 35 (range: 18-60) years. The right kidney was procured in 28% of cases. The majority of donors were female (58%) and Caucasian (60%). No differences were observed between MILIA and ODN donors for the age, gender and ethnicity. However, MILIA donors experienced a longer mean±SD operative time (234±47 vs. 197±33 min, p<0.0001) but a shorter hospital stay (4±1 vs. 6±3 days for the ODN group, p<0.0001) and less intraoperative blood loss (215±180 vs. 331±397 mL, p<0.02). No difference was found in the number of units of blood transfused (0.13±0.6 vs. 0.34±1.0 units, p=0.13). Right-sided kidneys were almost equally harvested in both groups (29% of MILIA donors vs. 26% of ODN donors). Post-operatively, MILIA donors had a significantly lower mean pain scores at one week and one month after surgery (p<0.001). They showed significant better post-operative recovery-earlier stopping of pain medications and restoration of other preoperative activities. Moreover, they were better satisfied with their scar appearance. Scores on the short form-36 quality of life questionnaire were comparable for both groups. CONCLUSION: MILIA is a viable option as an alternative for pure laparoscopic donor nephrectomy. MILIA appears to be as safe as open donor nephrectomy and may provide advantages over ODN, such as smaller incision, shorter hospital stay, and less incisional pain. Patient recovery and satisfaction after MILIA are excellent. This technique avoids the possibility of adhesive intestinal obstruction and also improves handling of major complications (e.g., bleeding) of laparoscopic donor nephrectomy. Utilization of this hybrid technique is particularly feasible on smaller (BMI<24 kg/m(2)) and medium-sized (BMI<28 kg/m(2)) donors. We believe that this technique should be adopted by centers that have limited advanced laparoscopic surgical experience and also it could be used selectively for the right donor nephrectomies, even in centers performing hand assisted donor nephrectomies by including a small patch of inferior vena cava for a better quality of right donor kidney during transplantation.

FEN1 contributes to telomere stability in ALT-positive tumor cells.

Abrogation of telomere stability through loss-of-function mutations in telomere binding proteins contributes to genomic instability and cancer progression. Recently, Flap endonuclease 1 (FEN1) was shown to contribute to telomere stability in human cells that had not yet activated a telomere maintenance mechanism, suggesting that abrogation of FEN1 function influences the transformation process by compromising telomere stability and driving genomic instability. Here, we analyse the telomeres in human cancer cells following FEN1 depletion. We show that FEN1 is required for telomere stability in cells that rely on the alternative lengthening of telomere (ALT) mechanism. Indeed, FEN1 depletion resulted in telomere dysfunction, characterized by formation of telomere dysfunction-induced foci (TIFs) and end-to-end fusions in ALT-positive cells. In contrast, no telomere phenotype was observed in telomerase-positive cells on FEN1 depletion, suggesting that ongoing telomerase activity protected telomeres. In consonance with this, we found that expression of the catalytic component of telomerase (hTERT) but not an inactive allele rescued telomere dysfunction on FEN1 depletion in ALT cells. Our data suggest that mutations that arise in FEN1 affect telomere stability and genome fidelity by promoting telomere fusions and anaphase-bridge-breakage cycles, which further drive genome instability and thereby contribute to the transformation process.

Radiation induced sarcoma following treatment of breast cancer.

The occurrence of radiation induced sarcoma following treatment of breast cancer is rare. It has an average latency of ten years and it correlates with the dose and technique of radiation. The prognosis is poor due to delay in diagnosis. We present a case where a female patient developed a chondrosarcoma of sternoclavicular joint 19 years after radiotherapy for breast cancer.