UV-Protection Timer Controls Linkage between Stress and Pigmentation Skin Protection Systems.

Skin sun exposure induces two protection programs: stress responses and pigmentation, the former within minutes and the latter only hours afterward. Although serving the same physiological purpose, it is not known whether and how these programs are coordinated. Here, we report that UVB exposure every other day induces significantly more skin pigmentation than the higher frequency of daily exposure, without an associated increase in stress responses. Using mathematical modeling and empirical studies, we show that the melanocyte master regulator, MITF, serves to synchronize stress responses and pigmentation and, furthermore, functions as a UV-protection timer via damped oscillatory dynamics, thereby conferring a trade-off between the two programs. MITF oscillations are controlled by multiple negative regulatory loops, one at the transcriptional level involving HIF1α and another post-transcriptional loop involving microRNA-148a. These findings support trait linkage between the two skin protection programs, which, we speculate, arose during furless skin evolution to minimize skin damage.

Laparoscopic partial nephrectomy for tumors 7cm and above. Perioperative outcomes

ABSTRACT Purpose: To assess and report the outcomes of laparoscopic partial nephrectomy) LPN) for T2 renal masses. Materials and Methods: Retrospective review of patients undergoing LPN for clinically localized renal masses ≥7cm between the years 2005-2016. Descriptive analyses were generated for demographics, lesion characteristics, perioperative variables (operative time, warm ischemia time (WIT), estimated blood loss (EBL), intra-operative and postoperative complications (IOC and POC) and pathologic variables (pathology, subtype and Fuhrman grade). Results: A total of 27 patients underwent LPN for a T2 renal mass at our institution between 2005 and early 2016 of which 19 were males. The mean age was 66 (52-72). All procedures were transperitoneal with 16 on the right and 11 on the left. Median operative time was 200 minutes (IQR 181-236) and median WIT 19 minutes (IQR 16-23). EBL was 125mL (IQR 75-175). One case was converted to laparoscopic radical nephrectomy due to suspected tumor thrombus in the renal vein. Surgical margins were positive in one renal tumor in a patient with multiple tumors. There was a total of 2 IOC (7.4%) and 3 POC (11%) classified as Clavien grade 3. Conclusions: To our knowledge, this series is the first to describe the outcomes of LPN for cT2 renal masses. In our series, LPN for larger renal masses appears feasible with favorable perioperative outcomes. Additional data are needed to further explore the benefits of minimally invasive surgical approaches to larger renal masses.

Laparoscopic partial nephrectomy for tumors 7cm and above. Perioperative outcomes.

PURPOSE: To assess and report the outcomes of laparoscopic partial nephrectomy )LPN) for T2 renal masses. MATERIALS AND METHODS: Retrospective review of patients undergoing LPN for clinically localized renal masses ≥7cm between the years 2005-2016. Descriptive analyses were generated for demographics, lesion characteristics, perioperative variables (operative time, warm ischemia time (WIT), estimated blood loss (EBL), intra-operative and post-operative complications (IOC and POC) and pathologic variables (pathology, subtype and Fuhrman grade). RESULTS: A total of 27 patients underwent LPN for a T2 renal mass at our institution between 2005 and early 2016 of which 19 were males. The mean age was 66 (52-72). All procedures were transperitoneal with 16 on the right and 11 on the left. Median operative time was 200 minutes (IQR 181-236) and median WIT 19 minutes (IQR 16-23). EBL was 125mL (IQR 75-175). One case was converted to laparoscopic radical nephrectomy due to suspected tumor thrombus in the renal vein. Surgical margins were positive in one renal tumor in a patient with multiple tumors. There was a total of 2 IOC (7.4%) and 3 POC (11%) classified as Clavien grade 3. CONCLUSIONS: To our knowledge, this series is the first to describe the outcomes of LPN for cT2 renal masses. In our series, LPN for larger renal masses appears feasible with favorable perioperative outcomes. Additional data are needed to further explore the benefits of minimally invasive surgical approaches to larger renal masses.

Routine diagnostic ureteroscopy for suspected upper tract transitional-cell carcinoma.

BACKGROUND AND PURPOSE: Upper tract transitional-cell carcinoma (utTCC) is uncommon. Standard evaluation includes imaging, cytology, and cystoscopy and gold standard treatment is nephroureterectomy (NU) with solid oncologic outcomes and elevated morbidity. In this study, we report on the value of including routine ureteroscopy (URS) for evaluating suspected utTCC in shifting the treatment toward less morbid options and increasing preoperative diagnostic accuracy. PATIENTS AND METHODS: Records of patients presenting between 2002 and 2013 with suspected utTCC were reviewed. Since 2010, URS has been included routinely in the evaluation protocol. Demographic, clinical, and pathologic characteristics were recorded and compared between earlier experience (group 1) and with routine URS (group 2). In addition, the number needed to treat (NNT) was calculated with respect to shifting the procedure choice from NU to other options as well as in reducing the rates of misdiagnoses. RESULTS: A total of 118 patients were included: 63 in group 1 and 55 in group 2. The pathology-confirmed TCC rates were comparable between the two groups (78 vs 85%). The rates of NU decreased with routine URS use from 89% to 69% (P=0.011, NNT=5.05) whereby patients were treated endoscopically or with distal ureterectomy. Misdiagnoses decreased from 15.5% to 2.1% with routine URS (P=0.021, NNT=7.44). Sepsis occurred in two patients after URS. CONCLUSIONS: In this initial study, routine URS evaluation for suspected utTCC appears to enable an increased use of other treatment choices rather then NU, with an estimated five URS avoiding one NU. Moreover, routine URS reduced the rates of misdiagnosis of TCC. Complications associated with URS may add an additional morbidity burden, however.

Laparoendoscopic single-site plus one port nephroureterectomy: single center initial experience.

BACKGROUND AND PURPOSE: Nephroureterectomy (NU) with bladder cuff excision is the gold standard treatment for patients with upper urinary tract urothelial cancer. We report our initial experience with laparoendoscopic single-site plus one port (LESS POP) technique for NU and bladder cuff excision. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients undergoing LESS POP NU between 2011 and 2012. We describe in detail our surgical technique and summarized the outcomes in this initial series. RESULTS: Ten patients (7 male, 3 female) aged 55 to 84 years underwent LESS POP NU. There were no conversions to open technique or additions of conventional laparoscopic ports. Median (range) operative time was 217 minutes. Specimens were extracted through the umbilical incision in five patients and through an extension of the lower quadrant port in five. One patient experienced urine leak followed by umbilical wound dehiscence (Clavien grade IIIb complication). CONCLUSIONS: In this series, LESS POP NU was feasible with encouraging outcomes. We believe that it is possible to extend the benefits of LESS to patients with upper tract tumors while adhering to strict oncologic principles.

Laparoscopic partial nephrectomy: beyond the straightforward T1a.

UNLABELLED: What's known on the subject? and What does the study add? Complex tumour features (e.g. size, hilar location, multifocality) are generally considered contraindicative for LPN and only a handful of studies reporting encouraging outcomes with more complex tumours. Herein we suggest that in experience hands the benefits of minimally-invasive surgery may be safely extended to patients with more complex renal masses. OBJECTIVE: To report on our experience in extending the indications for LPN beyond the single, T1a renal mass assessing the perioperative outcomes in a comparative fashion. PATIENTS AND METHODS: Retrospective review of consecutive patients undergoing LPN for a renal mass in an academic centre between 2005-2010. 150 patients were divided into two groups based on tumours characteristics: straightforward T1a (group 1: single, <4 cm, n = 84) and complex (group 2: multiple and/or hilar and/or ≥4 cm, n = 66). Comparison of demographic, clinical, radiographic and perioperative outcomes (operative times, blood loss, warm ischemia times, intra- and postoperative complications). RESULTS: In group 2, 19 tumours were hilar, 15 were multifocal and 44 measured ≥4 cm; 2 of these criteria were present in 7, and all three in 3 cases. Warm ischemia times and blood loss were comparable (medians of 21 vs 20 min, and 100 vs 100 mL). Operative times were longer in group 2 (190 vs 140min, P < 0.001). Complications occurred in 11.9% and 12.1% of patients in group 1 and 2, with Clavien grade 3 events in 8.3 and 10.9%, respectively (P = 1.00 and P = 0.547). There were 4 conversions to laparoscopic radical nephrectomy (1 in group 1, 3 in group 2). CONCLUSION: With adequate laparoscopic expertise, the indications for LPN can be safely extended beyond the single, small, peripheral T1a renal mass. In this series, more complex masses were effectively treated with LPN combining the advantages of minimally-invasive surgery to those of nephron-sparing approach.