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.

Genotype-defined cancer risk in juvenile polyposis syndrome.

BACKGROUND: Germline mutations in SMAD4 and BMPR1A disrupt the transforming growth factor ß signal transduction pathway, and are associated with juvenile polyposis syndrome. The effect of genotype on the pattern of disease in this syndrome is unknown. This study evaluated the differential impact of SMAD4 and BMPR1A gene mutations on cancer risk and oncological phenotype in patients with juvenile polyposis syndrome. METHODS: Patients with juvenile polyposis syndrome and germline SMAD4 or BMPR1A mutations were identified from a prospectively maintained institutional registry. Medical records were reviewed and the clinical patterns of disease were analysed. RESULTS: Thirty-five patients had germline mutations in either BMPR1A (8 patients) or SMAD4 (27). Median follow-up was 11 years. Colonic phenotype was similar between patients with SMAD4 and BMPR1A mutations, whereas SMAD4 mutations were associated with larger polyp numbers (number of patients with 50 or more gastric polyps: 14 versus 0 respectively). The numbers of patients with rectal polyps was comparable between BMPR1A and SMAD4 mutation carriers (5 versus 17). No patient was diagnosed with cancer in the BMPR1A group, whereas four men with a SMAD4 mutation developed gastrointestinal (3) or extraintestinal (1) cancer. The gastrointestinal cancer risk in patients with juvenile polyposis syndrome and a SMAD4 mutation was 11 per cent (3 of 27). CONCLUSION: The SMAD4 genotype is associated with a more aggressive upper gastrointestinal malignancy risk in juvenile polyposis syndrome.

Long-term outcomes after circular stapled hemorrhoidopexy versus Ferguson hemorrhoidectomy.

BACKGROUND: We aimed to compare long-term outcomes and quality of life in patients undergoing circular stapled hemorrhoidopexy to those who had Ferguson hemorrhoidectomy. METHODS: Patients who underwent Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy between 2000 and 2010 were reviewed. Long-term follow-up was assessed with questionnaires. RESULTS: Two hundred seventeen patients completed the questionnaires. Mean follow-up was longer in the Ferguson hemorrhoidectomy subgroups (7.7 ± 3.4 vs. 6.3 ± 2.9 years, p = 0.003). Long-term need for additional surgical or medical treatment was similar in the Ferguson hemorrhoidectomy and circular stapled hemorrhoidopexy groups (3 vs. 5%, p = 0.47 and 3% in both groups, p > 0.99, respectively). Eighty-one percentage of Ferguson hemorrhoidectomy and 83% of circular stapled hemorrhoidopexy patients stated that they would undergo hemorrhoid surgery again if needed (p = 0.86). The symptoms were greatly improved in the majority of patients (p = 0.06), and there was no difference between the groups as regards long-term anorectal pain (p = 0.16). The Cleveland global quality of life, fecal incontinence severity index, and fecal incontinence quality of life scores were similar (p > 0.05). CONCLUSIONS: This is one of the longest follow-up studies comparing the outcomes after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy. Patient satisfaction, resolution of symptoms, quality of life, and functional outcome appear similar after circular stapled hemorrhoidopexy and Ferguson hemorrhoidectomy in long term.

Laparoscopic versus open fecal diversion: does laparoscopy offer better outcomes in short term?

BACKGROUND: Laparoscopic fecal diversion is performed in patients with complicated colon and rectal diseases. We aim to compare operative and short-term outcomes between laparoscopic and open fecal diversion. METHODS: After obtaining institutional review board approval, patients undergoing laparoscopic or open fecal diversion between February 2010 and September 2012 were reviewed. A straight comparison of the open and laparoscopic groups was made initially; then, patients who underwent laparoscopic fecal diversion were case-matched with open counterparts based on stoma type and primary diagnosis. RESULTS: While body mass index (BMI) was higher in the laparoscopy group (p = 0.04), American Society of Anesthesiologists (ASA) score (p = 0.33) and gender (p = 0.74) were comparable between the study groups in the straight comparison. In the case-matched analysis, type of prior operations (p > 0.05), age (p = 0.79), gender (p > 0.99), BMI (p = 0.1), and ASA (p = 0.25) score were comparable between the groups. Open surgery was associated with increased estimated blood loss (p = 0.01), longer hospital stay (p = 0.0002), higher postoperative ileus (p = 0.03), and higher readmission rates (p = 0.002). CONCLUSIONS: Considering the short-term benefits as regards postoperative recovery and morbidity, fecal diversions should be performed laparoscopically when feasible.

Comparison of hospital costs for single-port and conventional laparoscopic colorectal resection: a case-matched study.

BACKGROUND: Whether single-port laparoscopic (SPL) colorectal resection is cost-effective in comparison to conventional laparoscopy remains unclear. The aim of this study is to compare hospital costs for single-port versus conventional laparoscopic colorectal resections. METHODS: Patients with available cost data who underwent (SPL) colorectal resection between December 2007 and December 2010 were matched with conventional (multiport) laparoscopic (CL) counterparts for age, gender, American Society of Anesthesiologists score, body mass index, operation type and year of surgery. Patients who underwent hand-assisted laparoscopic surgery were not included in the study. Direct hospital costs for the two groups were compared. RESULTS: There were 90 patients in the SPL group and 90 patients in the CL group. Age (p = 0.79), gender (p = 0.88), body mass index (p = 0.82), American Society of Anesthesiologists score (p = 1) and diagnosis (p = 0.85) were similar in both groups. Operation type (p = 1), estimated blood loss (p = 0.17) and length of hospital stay (p = 0.06) were comparable between the groups. Operation time was significantly shorter in the SPL group (p < 0.001), thus anesthesia cost was significantly lower in this group (p = 0.003). Total costs (p = 0.5), operating room (p = 0.65), nursing (p = 0.13), pharmacy (p = 0.6), radiology (p = 0.27), professional (p = 0.38) and pathology/laboratory (p = 0.46) costs were similar between the two groups. CONCLUSIONS: Single-port laparoscopic colorectal resection can be performed with comparable hospital costs to conventional multiport laparoscopy.

Factors affecting morbidity after conversion of laparoscopic colorectal resections.

BACKGROUND: The impact of conversion on postoperative outcomes of laparoscopic colorectal surgery remains controversial. The purpose of this study was to assess whether a conversion results in increased postoperative morbidity and mortality, and to evaluate whether any specific factors affect the outcomes of converted procedures. METHODS: Outcomes of procedures requiring conversion among patients undergoing elective laparoscopic colorectal resection between 1992 and 2011 were compared with those for operations completed laparoscopically. Subset analyses were also performed to evaluate the selective impact of patient-, disease- and treatment-related factors and the timing of conversion during surgery on outcomes. Primary endpoints were postoperative mortality and morbidity. RESULTS: Of 2483 patients undergoing laparoscopic colorectal resection, 270 (10.9 per cent) required conversion to open surgery. The 30-day postoperative mortality rate was comparable after laparoscopically completed and converted procedures (0.4 versus 0 per cent respectively; P = 0.610). Factors significantly associated with morbidity after conversion were smoking, cardiovascular co-morbidity, previous abdominal operations (particularly colectomy or hysterectomy) and adhesions. Overall morbidity was not affected by conversion (27.0 per cent at 30 days in both groups; P > 0.999). However, patients experiencing morbidity tended to have had earlier conversions: median (range) 40 (15-90) min into surgery versus 50 (15-240) min for those who did not develop morbidity (P = 0.006). The risk of reoperation for postoperative morbidity was higher following conversion because of complications (13 versus 2.9 per cent; P = 0.024). CONCLUSION: Conversions of laparoscopic colorectal resection are not associated with increased overall morbidity, regardless of the timing of conversion.

Risk of infection and hernia recurrence for patients undergoing ventral hernia repair with non-absorbable or biological mesh during open bowel procedures.

BACKGROUND: Ventral hernia repair (VHR) with mesh performed concurrently with colorectal surgery is presumably associated with significant risks of infection and recurrence. The purpose of this study is to evaluate the outcomes of patients undergoing VHR with non-absorbable mesh (NAM) or biological mesh (BM) at the same time as open colorectal surgery. METHODS: A retrospective review of short- and long-term outcomes for 25 patients undergoing repair of VHR with NAM or BM at the same time as an open colorectal procedure from 1991 to 2007 was performed. RESULTS: The mean age of the patients was 50.8 ± 12.7 years. Fifteen patients (60 %) underwent VHR with NAM versus 10 (40 %) with BM at the time of colorectal surgery. Mean follow-up after surgery was 32.9 ± 38.2 months. Overall wound infection, mesh infection and hernia recurrence rates were 44, 36 and 36 %, respectively. There was no difference between the NAM and BM mesh repair groups in terms of operative indications (p = 0.23) and operations performed (p = 0.47). Both groups had similar gender, ASA score, age, BMI, operating time, hernia recurrence rate, wound infection and follow-up. CONCLUSIONS: Although a proportion of patients who undergo concomitant use of mesh for VHR during colorectal resection has reasonable outcomes, there is a high associated risk of wound and mesh infection. Thus, a judicious decision regarding the use of mesh for hernia repair needs to be made on a case-by-case basis for patients undergoing open bowel surgery at the same time.