Mucosal advancement flap for recurrent complex anal fistula: a repeatable procedure.

PURPOSE: Mucosal advancement flap (MAF) is the best option for complex anal fistula (AF) treatment. Recurrence is not rare and the best surgical option for his handling is a challenge considering the incontinence risk and the healing rate. We aimed to determine the feasibility and outcomes of a second MAF for recurrent complex AF previously treated with mucosal advancement flap. METHODS: We retrospectively identified 32 patients undergoing two or more MAF for recurrent AF in a larger cohort of 121 consecutive cases of MAF operated by the same senior colorectal surgeon. Only complex AF of cryptoglandular origin was enrolled. A long-term follow-up was performed collecting clinical and functional data. RESULTS: Among 121 patients (group A) treated with mucosal advancement flap, 32 (26.4%) (group B) recurred with a complex AF requiring a second mucosal advancement flap procedure. Success rate of group B is 78.1%. Six patients of group B recurred a second time, another MAF was performed with healing in all cases. Complication rate (Clavien Dindo 3b) of group B is 9.4% compared to 8.3% of group A. A slight continence deficit (Miller score 1, 2, and 4) was detected after the first MAF in 3 patients. The Miller score for these patients did not change after the subsequent MAF. CONCLUSIONS: MAF is effective for treatment of complex recurrent AF. A pre-existing MAF procedure does not worsen the healing rate of the second flap. The rate of surgical complications is similar with those reported in the literature for MAFs.

Correction to: Mucosal advancement flap for recurrent complex anal fistula: a repeatable procedure.

The name of the second author of this article was incorrectly presented as "Riccardo Scarpa Cosimo" this should have been "Cosimo Riccardo Scarpa".

Successful pregnancy and delivery after simultaneous islet-kidney transplantation.

Allogeneic islet of Langerhans transplantation is a recognized beta-cell replacement therapy for patients affected by type 1 diabetes mellitus. Type 1 diabetes mellitus is a condition associated with an increased risk of adverse outcomes for pregnant women and fetuses. We report the case of a 29-year-old woman with type 1 diabetes mellitus, who underwent successful allogeneic islet transplantation with simultaneous kidney transplantation. She achieved durable insulin independence after 2 islet infusions. Pregnancy was desired and planned 2 years after the last islet infusion. Multidisciplinary monitoring of pregnancy was carried out and the immunosuppressive regimen was adapted. Euglycemia was maintained throughout pregnancy without the need for exogenous insulin. After an uneventful pregnancy, she delivered on term an otherwise healthy male child with imperforate anus that was immediately surgically corrected. In conclusion, allogeneic islet transplantation is a suitable treatment for women of childbearing age with complicated type 1 diabetes mellitus, allowing physiologic glycemic control during pregnancy with a low risk of graft loss. This target can be achieved only by a tight multidisciplinary follow-up, including immunosuppressive therapy adaptation and adequate diabetes and obstetrical monitoring.

Robotic single-site versus multiport laparoscopic cholecystectomy: a case-matched analysis of short- and long-term costs.

BACKGROUND: Multiport laparoscopy is the gold-standard approach for cholecystectomy, and single-port laparoscopy has been developed to further reduce its invasiveness. A specific robotic single-port platform (da Vinci single-site, Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2011, which could technically facilitate single-site cholecystectomy. Current data show its feasibility; however, detailed short- and long-term analyses of costs and comparisons relative to multiport laparoscopy are not available to date. METHODS: Patients who underwent robotic single-site cholecystectomy for benign, clinically noninflammatory disease between 2011 and 2015 were matched for disease, age, gender, BMI, ASA classification, diagnosis, and elapsed year of surgery to a cohort of multiport cholecystectomies. Demographic, perioperative, and long-term data were collected retrospectively and analyzed. Perioperative and long-term costs including re-operations due to the primary procedure until February 2017 were compared across both cohorts. RESULTS: 99 patients who underwent robotic single-site cholecystectomy were matched to 99 patients with multiport cholecystectomy. A higher rate of outpatient procedures in the robotic cohort (31.3 vs. 17.2%, p = 0.0305) was found, and demographic parameters and perioperative clinical outcomes were similar. Perioperative costs were significantly higher for the robotic single-site patients (6158.0 vs. 4288.0 USD, p < 0.0001). With similar follow-up times of 59.0 and 58.9 months, respectively (p = 0.9552), significantly more patients of the robotic Single-Site cohort underwent follow-up surgery (7.1 vs. 0.0%, p = 0.0140), and follow-up costs were significantly higher for the robotic cohort (694.7 vs. 0.0 USD, p = 0.0145). CONCLUSION: With similar early postoperative clinical results and a higher rate of re-operations, perioperative and long-term costs are significantly higher with robotic Single-Site cholecystectomy compared with multiport cholecystectomy. Considering the unclear clinical value of robotic single-site cholecystectomy and the significant short- and long-term costs, a call for further research and a debate as to who should bear the costs beyond the ones of the gold-standard treatment appear reasonable.

Traumatic perforated duodenal diverticulum after a fight, a case report.

INTRODUCTION: Fewer than 200 cases of Perforated Duodenal Diverticulum ("PDD") have been reported in the literature. The percentage of caused by trauma is generally very low and similar to rates recorded for duodenal injuries caused by trauma in the absence of diverticula (3 %-5 %). As a rare cause of abdominal pain after trauma, perforated duodenal diverticula are seldom diagnosed preoperatively. Despite preoperative CT scan demonstrating duodenal perforation, a diverticular origin is often only identified intraoperatively. PRESENTATION OF CASE: A 36-year-old man was admitted to the emergency department with severe upper abdominal pain that began after blunt trauma by a kick to his upper abdomen during a fight. A duodenal injury was identified by CT. Exploratory laparotomy then revealed a retroperitoneal perforation of a diverticulum located at the second segment of the duodenum. DISCUSSION: A review of the literature found few cases reporting perforated duodenal diverticulum secondary to trauma. Most cases identified the diverticulum at intraoperative exploration, with most approaches being through open surgery. CONCLUSION: Perforation of a duodenal diverticulum secondary to trauma is an extremely rare event, which is why it is often overlooked in the differential diagnosis of acute abdomen. As the presenting signs are often suggestive of duodenal perforation without a clear notion of duodenal diverticula at CT scan, a surgical approach and exploration is most frequently described. In our experience, the management of traumatic PDD aligns with the literature favoring the open surgical approach.

Roux-en-Y gastric bypass, sleeve gastrectomy, or one-anastomosis gastric bypass? A systematic review and meta-analysis of randomized-controlled trials.

OBJECTIVE: This study aimed to determine which bariatric procedure allows patients to obtain the best weight-loss outcomes and a remission of type 2 diabetes. METHODS: Databases were searched for randomized-controlled trials comparing Roux-en-Y gastric bypass (RYGB) with sleeve gastrectomy (SG) or one-anastomosis gastric bypass (OAGB). The mean difference (MD) or the relative risk was determined. RESULTS: Twenty-five randomized-controlled trials were analyzed. Excess weight loss (EWL, percentage) was greater for RYGB patients at 3 years (MD: 11.93, p < 0.00001) and 5 years (MD: 13.11, p = 0.0004). Higher excess BMI loss (percentage) was found in RYGB at 1 year (MD: 11.66, p = 0.01). Total weight loss (percentage) was greater for RYGB patients after 3 months (MD: 2.41, p = 0.02), 6 months (MD: 3.83, p < 0.00001), 1 year (MD: 6.35, p < 0.00001), and 5 years (MD: 3.90, p = 0.005). No difference in terms of remission of type 2 diabetes was seen between RYGB and SG. EWL was significantly more important after OAGB than after RYGB after 1 year (MD: -10.82, p = 0.003). CONCLUSIONS: RYGB is more efficient than SG in the midterm. OAGB offers greater EWL than RYGB after 1 year, but further evidence is needed to confirm this result.

Low-grade fibromatosis-like spindle cell metaplastic carcinoma: a basal-like tumor with a favorable clinical outcome. Report of two cases.

Fibromatosis-like spindle-cell metaplastic carcinoma (FLSpCC) is an atypical variant of spindle-cell carcinoma with a particular clinical behavior characterized by frequent local recurrence, very low potential for axillary lymph node metastasis, and uncommon distant metastases. Although it presents the typical immunoprofile of basal-like carcinomas, FLSpCC is associated with a favorable clinical outcome and conservative treatment is generally indicated. Because of the lack of specific clinical and radiological characteristics, the criteria for the differential diagnosis from other benign and malignant tumors are based only on histological findings and immunostaining. We report on two FLSpCC patients treated with wide local excision and mastectomy associated with axillary lymph node dissection. Although the biological behavior of this subtype of breast cancer has not been adequately evaluated, wide local excision or mastectomy with clear resection margins but no axillary dissection appears to be an adequate treatment approach.

Efficiency of Laparoscopic One-Step Revision of Failed Adjusted Gastric Banding to Gastric Sleeve: a Retrospective Review of 101 Consecutive Patients.

BACKGROUND: Until recently, laparoscopic adjustable gastric banding (LAGB) was one of the most commonly performed bariatric surgeries worldwide. Today, its high rate of complications and failure rates up to 70% requires revisional surgery. The one-stage conversion from LAGB to laparoscopic sleeve gastrectomy (LSG) has been shown to be safe, although there are some concerns on efficacy and long-term weight loss. OBJECTIVES: To demonstrate that one-step revision of LAGB to another restrictive procedure, such as LSG, might have efficient long-term outcomes. METHODS: The charts from 133 revisional LSGs for failed or complicated LAGB were retrospectively reviewed for the period between January 2010 and August 2017. Thirty-two patients were excluded for loss to follow-up. Demographics, complications, and percentage of excess weight loss (%EWL) were determined. RESULTS: One hundred one patients were included (85 women and 16 men), with a mean age of 48.5 years, and a mean body mass index of 47.1 kg/m2. During the follow-up, 15 patients (15%) underwent a second revisional surgery for weight loss failure (8 Roux-en-Y gastric bypass (RYGBP), 3 biliopancreatic diversion, 3 single anastomosis duodenal-ileal bypass, 1 revisional LSG). Ten patients (10%) had long-term complications (8 severe reflux and 2 stenosis) during this period and underwent a second revisional surgery (10 RYGBP). The remaining 76 had a mean follow-up of 4.3 years and a mean %EWL of 53.2%. CONCLUSION: Single-stage conversion to LSG is a safe and appropriate solution for failed or complicated LAGB with good long-term weight loss.

Oncocytic Adrenocortical Neoplasm with Concomitant Papillary Thyroid Cancer.

Adrenal oncocytoma (AO) is an extremely rare adrenocortical neoplasm and little is known about its malignant potential, secretory properties, and hereditary origin. We present the case of a benign AO with concomitant incidentally found papillary thyroid cancer (PTC) and review similar cases in the literature. Immunohistochemistry and next-generation sequencing (NGS) were performed. A 66-year-old women was incidentally found to have a large, androgen-secreting right adrenal mass. 18F-Fluorodeoxyglucose positron emission tomography showed intense uptake (SUVmax 88.7) of this mass and found a hypermetabolic right thyroid mass. Open adrenalectomy was performed for this highly suspicious adrenal mass. Histopathology revealed benign AO that was BRAFV600E negative, with low Ki-67, and no somatic mutation found on NGS. Thyroidectomy revealed invasive, BRAFV600E-positive PTC. At 6 months follow-up, androgen levels returned to normal, and no recurrence was seen on imaging. To our knowledge, this is the first report of an androgen-secreting AO with concomitant PTC. Possibly the simultaneous discovery of two independent neoplasms was observed. In conclusion, this case highlights that care should be given to exclude concomitant neoplasms. Long-term and regular imaging with biochemical follow-up is warranted, since the outcome and clinical behavior of AO remains uncertain.

Influence of Surgical Technique, Performance Status, and Peritonitis Exposure on Surgical Site Infection in Acute Complicated Diverticulitis: A Matched Case-Control Study.

BACKGROUND: Acute generalized peritonitis secondary to complicated diverticulitis is a life-threatening condition; the standard treatment is surgery. Despite advances in peri-operative care, this condition is accompanied by a high peri-operative complication rate (22%-25%). No definitive evidence is available to recommend a preferred surgical technique in patients with Hinchey stage III/IV disease. METHODS: A matched case-control study enrolling patients from four surgical units at Italian university hospital was planned to assess the most appropriate surgical treatment on the basis of patient performance status and peritonitis exposure, with the aim of minimizing the surgical site infection (SSI). A series of 1,175 patients undergoing surgery for Hinchey III/IV peritonitis in 2003-2013 were analyzed. Cases (n=145) were selected from among those patients who developed an SSI. THE CASE: control ratio was 1:3. Cases and control groups were matched by age, gender, body mass index, and Hinchey grade. We considered three surgical techniques: T1=Hartman's procedure; T2=sigmoid resection, anastomosis, and ileostomy; and T3=sigmoid resection and anastomosis. Six scoring systems were analyzed to assess performance status; subsequently, patients were divided into low, mild, and high risk (LR, MR, HR) according to the system producing the highest area under the curve. We classified peritonitis exposition as P1=<12 h; P2=12-24 h; P3=>24 h. Univariable and multivariable analyses were performed. RESULTS: The Apgar scoring system defined the risk groups according to performance status. Lowest SSI risk was expected when applying T3 in P1 (OR=0.22), P2 (OR=0.5) for LR and in P1 (OR=0.63) for MR; T2 in P2 (OR=0.5) in LR and in P1 (OR=0.61) in MR; T1 in P3 (OR=0.56) in LR; in P2 (OR=0.63) and P3 (OR=0.54) in MR patients, and in each P subgroup (OR=0.93;0.97;1.01) in HR. CONCLUSIONS: Pre-operative assessment based on Apgar scoring system integrated with peritonitis exposure in complicated diverticulitis may offer a ready-to-use tool for reducing SSI-related complications and applying appropriate treatment, reducing the need for disabling ostomy.

MicroRNAs in islet immunobiology and transplantation.

The ultimate goal of diabetes therapy is the restoration of physiologic metabolic control. For type 1 diabetes, research efforts are focused on the prevention or early intervention to halt the autoimmune process and preserve ß cell function. Replacement of pancreatic ß cells via islet transplantation reestablishes physiologic ß cell function in patients with diabetes. Emerging research shows that microRNAs (miRNAs), noncoding small RNA molecules produced by a newly discovered class of genes, negatively regulate gene expression. MiRNAs recognize and bind to partially complementary sequences of target messenger RNA (mRNA), regulating mRNA translation and affecting gene expression. Correlation between miRNA signatures and genome-wide RNA expression allows identification of multiple miRNA-mRNA pairs in biological processes. Because miRNAs target functionally related genes, they represent an exciting and indispensable approach for biomarkers and drug discovery. We are studying the role of miRNA in the context of islet immunobiology. Our research aims at understanding the mechanisms underlying pancreatic ß cell loss and developing clinically relevant approaches for preservation and restoration of ß cell function to treat insulin-dependent diabetes. Herein, we discuss some of our recent efforts related to the study of miRNA in islet inflammation and islet engraftment. Our working hypothesis is that modulation of the expression of specific microRNAs in the transplant microenvironment will be of assistance in enhancing islet engraftment and promoting long-term function.

Effect of the purinergic inhibitor oxidized ATP in a model of islet allograft rejection.

The lymphocytic ionotropic purinergic P2X receptors (P2X1R-P2X7R, or P2XRs) sense ATP released during cell damage-activation, thus regulating T-cell activation. We aim to define the role of P2XRs during islet allograft rejection and to establish a novel anti-P2XRs strategy to achieve long-term islet allograft function. Our data demonstrate that P2X1R and P2X7R are induced in islet allograft-infiltrating cells, that only P2X7R is increasingly expressed during alloimmune response, and that P2X1R is augmented in both allogeneic and syngeneic transplantation. In vivo short-term P2X7R targeting (using periodate-oxidized ATP [oATP]) delays islet allograft rejection, reduces the frequency of Th1/Th17 cells, and induces hyporesponsiveness toward donor antigens. oATP-treated mice displayed preserved islet grafts with reduced Th1 transcripts. P2X7R targeting and rapamycin synergized in inducing long-term islet function in 80% of transplanted mice and resulted in reshaping of the recipient immune system. In vitro P2X7R targeting using oATP reduced T-cell activation and diminished Th1/Th17 cytokine production. Peripheral blood mononuclear cells obtained from long-term islet-transplanted patients showed an increased percentage of P2X7R⁺CD4⁺ T cells compared with controls. The beneficial effects of oATP treatment revealed a role for the purinergic system in islet allograft rejection, and the targeting of P2X7R is a novel strategy to induce long-term islet allograft function.

Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets.

Nonspecific inflammation in the transplant microenvironment results in ß-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets. Islets exposed in vitro to proinflammatory cytokines and explanted syngeneic islet grafts were evaluated by miRNA arrays. A subset of 26 islet miRNAs was affected by inflammation both in vivo and in vitro. Induction of miRNAs was dependent on NF-κB, a pathway linked with cytokine-mediated islet cell death. RT-PCR confirmed expression of 8 miRNAs. The association between these miRNAs and mRNA target-predicting algorithms in genome-wide RNA studies of ß-cell inflammation identified 238 potential miRNA gene targets. Several genes were ontologically associated with regulation of insulin signaling and secretion, diabetes, and islet physiology. One of the most activated miRNAs was miR-21. Overexpression of miR-21 in insulin-secreting MIN6 cells downregulated endogenous expression of the tumor suppressor Pdcd4 and of Pclo, a Ca(2+) sensor protein involved in insulin secretion. Bioinformatics identified both as potential targets. The integrated analysis of miRNA and mRNA expression profiles revealed potential targets that may identify molecular targets for therapeutic interventions.