Challenges of CYP21A2 genotyping in children with 21-hydroxylase deficiency: determination of genotype-phenotype correlation using next generation sequencing in Southeastern Anatolia.

BACKGROUND/PURPOSE: Although it is known that there is generally a good correlation between genotypes and phenotypes, the number of studies reporting discrepancies has recently increased, exclusively between milder genotypes and their phenotypes due to the complex nature of the CYP21A2 gene and methodological pitfalls. This study aimed to assess CYP21A2 genotyping in children with 21-hydroxylase deficiency (21-OHD) and establish their predictive genotype-phenotype correlation features using a large cohort in Southeastern Anatolia's ethnically diverse population. METHODS: The patients were classified into three groups: salt-wasting (SW), simple virilizing (SV) and non-classical (NC). The genotypes were categorized into six groups due to residual enzyme activity: null-A-B-C-D-E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes. RESULTS: A total of 118 unrelated children with 21-OHD were included in this study (61% SW, 24.5% SV and 14.5% NC). The pathogenic variants were found in 79.5% of 171 mutated alleles (60.2%, 22.2%, and 17.6% in SW, SV and NC, respectively). Patient distribution based on genotype groups was as follows: null-16.1%, A-41.4%, B-6.0%, C-14.4%, E-22%). In2G was the most common pathogenic variant (33.9% of all alleles) and the most common variant in the three phenotype groups (SW-38.8%, SV-22.2% and NC-23.3%). The total genotype-phenotype correlation was 81.5%. The correlations of the null and A groups were 100% and 76.1%, respectively, while it was lower in group B and poor in group C (71.4% and 23.5%, respectively). CONCLUSION: This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.

Robotic complete mesocolic excision for transverse colon cancer can be performed with a morbidity profile similar to that of conventional laparoscopic colectomy.

BACKGROUND: In minimally invasive surgery, complete mesocolic excision (CME) for transverse colon cancer is challenging; thus, non-CME resections are commonly preferred when laparoscopy is used. Robotic technology has been developed to reduce the limitations of laparoscopy. The aim of our study was to evaluate whether robotic CME for transverse colon cancer can be performed with short-term outcomes similar to those of laparoscopic conventional colectomy (CC). METHODS: A retrospective review of 118 consecutive patients having robotic CME or laparoscopic CC for transverse colon cancer in two specialized centers between May 2011 and September 2018 was performed. Perioperative 30-day outcomes of the two procedures were compared. RESULTS: There were 38 and 80 patients in the robotic CME group and laparoscopic CC group, respectively. The groups were comparable regarding preoperative characteristics. Intraoperative results were similar, including blood loss (median 50 vs 25 ml), complications (5.3% vs 3.8%), and conversions (none vs 7.5%). The rate of intracorporeal anastomosis was significantly higher (86.8% vs 20.0%), mean operative time was longer (325.0 ± 123.2 vs 159.3 ± 56.1 min (p < 0.001), and the mean number of harvested lymph nodes was higher in the robotic CME group (46.1 ± 22.2 vs 39.1 ± 17.8, p = 0.047). There were only minor differences in length of hospital stay (7.2 ± 3.1 vs 7.9 ± 4.0 days), anastomotic leak (none vs 2.6%), bleeding (none vs 1.3%), surgical site infections (10.5% vs 12.5%), and reoperations (2.6% vs 6.3%). CONCLUSIONS: Robotic CME can be performed with a similar morbidity profile as laparoscopic CC for transverse colon cancer along with a higher rate of intracorporeal anastomosis, and higher number of lymph nodes retrieved, but longer operative times.

The da Vinci Xi system for robotic total/subtotal colectomy vs. conventional laparoscopy: short-term outcomes.

BACKGROUND: The aim of this study was to evaluate the feasibility of robotic total/subtotal colectomy procedures with the Xi robot and to compare its short-term outcomes with those of conventional laparoscopy. METHODS: Between October 2010 and September 2018, consecutive patients with colonic neoplasia, inflammatory bowel disease, familial adenomatous polyposis or colonic inertia who underwent elective robotic or laparoscopic total/subtotal abdominal colectomy at two specialized centers in Turkey were included. Data on perioperative characteristics and 30-day outcomes were compared between the two approaches. RESULTS: There were a total of 82 patients: 26 and 56 patients in the robotic and laparoscopic group, respectively (54 men and 28 women, mean age 54.7 ± 17.4 years). The groups were comparable regarding preoperative characteristics. All the robotic procedures were completed with a single positioning of the robot. Estimated blood loss (median, 150 vs 200 ml), conversions (0% vs 14.3%), and complications (0% vs 7.1%) were similar but operative time was significantly longer in the robotic group (median, 350 vs 230 min, p < 0.001). No difference was detected in the length of hospital stay (7.9 ± 5.7 vs 9.5 ± 6.0 days, p = 0.08), anastomotic leak (3.8% vs 8.3%), ileus (15.4% vs 19.6%), septic complications, reoperations (7.7% vs 12.5%), and readmissions (19.2% vs 12.5%). The number of harvested lymph nodes in the subgroup of cancer patients was significantly higher in the robotic group (median, 66 vs 50, p = 0.01). CONCLUSIONS: In total/subtotal colectomy procedures, the robotic approach with the da Vinci Xi platform is feasible, safe, and associated with short-term outcomes similar to laparoscopy but longer operative times and a higher number of retrieved lymph nodes.

Laparoscopy reduces iatrogenic splenic injuries during colorectal surgery.

BACKGROUND: Splenic injury can occur during colorectal surgery especially in cases, where the splenic flexure is mobilized. The aim of this study was to analyze whether the operative approach (laparoscopic vs. open) was associated with an increased risk for splenic injury during colorectal surgery and to compare the outcomes of different management options. METHODS: All accidental injuries that occurred during colorectal resections performed in our department between January 2010 and June 2013 were identified from an administrative database. All patients with iatrogenic splenic injuries were classified into two groups according to the operative approach. Only procedures that required splenic flexure mobilization were included. Splenic injury management options and outcomes were compared. RESULTS: There were 2336 colorectal resections (1520 open, 816 laparoscopic) performed during the study period. There were 25 (1.1%) iatrogenic splenic injuries. 23 out of 25 splenic injuries occurred during open colorectal surgery. Overall, 16 (64%) patients were managed with topical hemostatic methods, 5 (20%) with splenectomy, and 4 (16%) with splenorrhaphy. It was possible to salvage the spleen in both laparoscopic patients. The laparoscopic approach was associated with a lower splenic injury rate (0.25% vs. 1.5%, p = 0.005) and a lower need for splenectomy/splenorrhaphy (p = 0.03). CONCLUSIONS: Our data suggest that laparoscopic colorectal surgery may be associated with a lower risk of iatrogenic splenic injury, and that most splenic injuries can be managed with spleen-preserving approaches.

"Top down no-touch" technique in robotic complete mesocolic excision for extended right hemicolectomy with intracorporeal anastomosis.

BACKGROUND: Proper identification of the mesocolic vessels is essential for achieving complete mesocolic excision (CME) in cases of colon cancer requiring an extended right hemicolectomy. In robotic procedures, we employed a "top down technique" to allow early identification of the gastrocolic trunk and middle colic vessels. The aim of our study was to illustrate the details of this technique in a series of 12 patients. METHODS: The top down technique consists of two steps. First, the omental bursa was entered to identify the right gastroepiploic vein. Tracing down this vein as a landmark, the gastrocolic trunk was exposed, branches of this trunk and the middle colic vessels were divided. Second, dissection was directed to the ileocolic region and proceeded in an inferior-to-superior direction along the superior mesenteric vein to divide the ileocolic and right colic vessels consecutively. The ileotranverse anastomosis was created intracorporeally. RESULTS: There were 8 males and 4 females with a mean age of 64.8 ± 16.9 years and a mean body mass index of 25.6 ± 3.7 kg/m2. All the procedures were completed successfully. No conversions occurred. The mean operative time and blood loss were 312.1 ± 93.9 min and 110.0 ± 89.9 ml, respectively. The mean number of harvested lymph nodes was 45.2 ± 11.1. The mean length of hospital stay was 7.6 ± 4.7 days. Two patients had intraoperative complications and two had postoperative complications. There was no disease recurrence at a mean follow-up period of 10.4 ± 7.1 months. CONCLUSIONS: The top down technique appears to be useful in robotic CME for an extended right hemicolectomy. Early identification of the gastrocolic trunk and middle colic vessels via this technique may prevent inadvertent vascular injury at the mesenteric root of the transverse colon.

The usefulness of the H-pouch configuration in salvage surgery for failed ileal pouches.

AIM: Abdominal salvage surgery for a failed ileal pouch-anal anastomosis (5) is safe and feasible in experienced hands. When salvaging an ileal pouch or creating a new J, S or W pouch may not be feasible, construction of an H-pouch may be the final option. This study reports a single colorectal surgeon's experience on H-pouch anal anastomosis in patients referred with a failed ileal pouch. METHOD: Patients undergoing transabdominal salvage surgery with H-pouch formation for a failed pouch from February 2012 to May 2016 were evaluated. RESULTS: Five patients were identified with a mean age of 46 (22-63) years. The pathological diagnosis was mucosal ulcerative colitis in all patients. Three patients had an initial traditional two-stage J-pouch creation and two patients had an initial three-stage approach. The median time to redo pouch surgery after the index IPAA creation was 99 (11-158) months. One patient required excision of the pouch and two patients had a complication within 30 days of surgery. CONCLUSION: The H-pouch is a good alternative for a failed IPAA when another type of reservoir is not an option.

Incidence, Management, and Risk Factors for Lower Gastrointestinal Bleeding in Renal Transplant Recipients.

BACKGROUND: There are limited convincing data regarding management and outcomes of lower gastrointestinal bleeding (LGB) in renal transplant recipients (RTR). The aim of this study was to evaluate incidence, management strategies, and risk factors associated with LGB in RTR. METHODS: Between January 2004 and December 2013, RTR with LGB were analyzed. LGB was defined as having clinical evidence of hemorrhage after upper gastrointestinal etiology was ruled out. RESULTS: There were 1578 RTR with a mean age of 50 ± 14 years at the time of transplantation. Mean follow-up time after transplantation was 57 ± 45 months. Forty-five (2.9%) patients had a documented site of LGB. The most common causes of bleeding were colitis and angiodysplasia (n = 17). Mean time to LGB after transplantation was 43 ± 36 months. Twelve patients with LGB required intervention. Three underwent colectomy, endoscopic treatment was utilized in 8, and 1 patient had angiographic embolization to control bleeding. Recurrent LGB developed in 11 patients of 42 patients who did not have surgery at the time of index bleeding. Surgical (n = 1) or endoscopic intervention (n = 4) was required in 5 of recurrent bleeders. LGB was more commonly seen in RTRs who had development of a nonfunctioning kidney (P < .0001). RTR who had an LGB had an increased overall mortality rate (not directly related to the bleeding episode) compared with those who did not have a LGB (P = .001). We did not observe any increased risk of LGB bleeding among patients who were receiving anticoagulant or anti-aggregant treatment agents (P = .76). CONCLUSIONS: Nonfunctioning kidney after transplant is a risk factor for LGB. Overall mortality rates increased after LGB in RTR. Strategies aiming to prolong transplanted kidney function may reduce the incidence of LGB and improve life expectancy in RTR.