Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the In Vitro Integrity of T Cells from Cancer Patients.

PURPOSE: Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment. EXPERIMENTAL DESIGN: Patients with metastatic cancer (n = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14+HLA-DRno/lo MDSCs. Their suppressor function was assessed by in vitro coculture with autologous T cells, and the ability of anti-DC-HIL or anti-PDL1 mAb to reverse such function was determined. Tumor expression of these receptors was examined histologically, and the antitumor activity of the mAb was evaluated by attenuated growth of colon cancers in mice. RESULTS: Patients with metastatic cancer had high blood levels of DC-HIL+ MDSCs compared with healthy controls. Anti-DC-HIL mAb reversed the in vitro function in ∼80% of cancer patients tested, particularly for colon cancer. Despite very low expression on blood MDSCs, anti-PDL1 mAb was as effective as anti-DC-HIL mAb in reversing MDSC function, a paradoxical phenomenon we found to be due to upregulated expression of PDL1 by T-cell-derived IFNγ in cocultures. DC-HIL is not expressed by colorectal cancer cells but by CD14+ cells infiltrating the tumor. Finally, anti-DC-HIL mAb attenuated growth of preestablished colon tumors by reducing MDSCs and increasing IFNγ-secreting T cells in the tumor microenvironment, with similar outcomes to anti-PDL1 mAb. CONCLUSIONS: Blocking DC-HIL function is a potentially useful treatment for at least colorectal cancer with high blood levels of DC-HIL+ MDSCs.See related commentary by Colombo, p. 453.

Modified Transanosphincteric (York Mason) Repair of Nonradiated Rectourinary Fistulae: Patient-reported Fecal Continence Outcomes.

OBJECTIVE: To review our experience with the modified York Mason (MYM) procedure in the treatment of rectourinary fistulas (RUFs) and to assess fecal continence using patient-reported measures. MATERIALS AND METHODS: A retrospective review was performed of patients who underwent MYM repair of nonradiated RUF with gluteal free fat graft from 2008 to 2016 at a single institution. Success was defined as resolution of the fistula without need for further surgery. The Cleveland Clinic-Florida Wexner Fecal Incontinence Score (CCFFIS) and the Patient Global Impression of Improvement (PGI-I) surveys were administered by phone. RESULTS: Of 17 patients who underwent MYM repair with a mean age of 61.8 years old, the most common fistula etiologies were prostatectomy in 11 patients (65%), cryoablation in 2 patients (12%), and transanal tumor excision (12%). Three patients (18%) failed prior perineal repairs. The mean fistula size was 10.1 mm (range 2-25), the median operative time was 231 minutes (range 151-365), and the median length of stay was 2.0 days (range 1-13). At the median follow-up of 39.4 months, 16 of the 17 patients (94%) had successful primary closures. The condition of the 10 patients who responded to the phone survey was "much better" (median PGI-I score 2), with 89.5% mean improvement. The mean CCFFIS was 1.4 (range 0-5) on a scale of 0 (total continence) to 20 (complete incontinence). Two patients (20%) reported rare (<1 per month) fecal incontinence, and 2/10 (20%) reported frequent flatal incontinence, but none reported significant lifestyle change or sought further treatment for bowel symptoms. CONCLUSION: The MYM technique has a high success rate in the treatment of nonradiated RUF with negligible impact on fecal continence.

Single-site laparoscopic surgery for inflammatory bowel disease.

BACKGROUND AND OBJECTIVES: Single-site laparoscopic colorectal surgery has been firmly established; however, few reports addressing this technique in the inflammatory bowel disease population exist. METHODS: We conducted a case-matched retrospective review of 20 patients who underwent single-site laparoscopic procedures for inflammatory bowel disease compared with 20 matched patients undergoing multiport laparoscopic procedures. Data regarding these patients were tabulated in the following categories: demographic characteristics, operative parameters, and perioperative outcomes. RESULTS: A wide range of cases were completed: 9 ileocolic resections, 7 cases of proctocolectomy with end ileostomy or ileal pouch anal anastomosis, 2 cases of proctectomy with ileal pouch anal anastomosis, and 2 total abdominal colectomies with end ileostomy were all matched to equivalent multiport laparoscopic cases. No single-incision cases were converted to multiport laparoscopy, and 2 single-incision cases (10%) were converted to an open approach. For single-incision cases, the mean length of stay was 7.7 days, the mean time to oral intake was 3.3 days, and the mean period of intravenous analgesic use was 5.0 days. There were no statistically significant differences between single-site and multiport cases. CONCLUSIONS: Single-site laparoscopic surgery is technically feasible in inflammatory bowel disease. The length of stay and period of intravenous analgesic use (in days) appear to be higher than those in comparable series examining outcomes of single-site laparoscopic colorectal surgery, and the outcomes are comparable with those of multiport laparoscopy. This may be because of the nature of inflammatory bowel disease, limiting the benefits of a single-site approach in this population.

Incisional negative pressure wound therapy significantly reduces surgical site infection in open colorectal surgery.

BACKGROUND: Surgical site infections in colorectal surgery remain a common problem, and are associated with an increase in cost of care and length of stay. OBJECTIVE: This study aims to evaluate the effect of known risk factors and the use of incisional negative pressure wound therapy on surgical site infection rates. DESIGN: This is a single-center retrospective study with the use of chart review. SETTINGS: The study took place at a tertiary academic medical center. PATIENTS: All patients undergoing open colectomy at a single institution from 2009 through 2011 were studied. MAIN OUTCOME MEASURES: The primary outcome measured was the presence or absence of surgical site infection. RESULTS: Overall, 69 of the 254 patients (27.2%) experienced surgical site infection; 4 (12.5%) surgical site infections were seen in patients undergoing incisional negative pressure wound therapy and 65 (29.3%) were seen in patients undergoing standard closure. Multiple logistic regression revealed 2 significant factors: diabetes mellitus increased the chance of surgical site infection (OR, 1.98; p < 0.05), and the use of incisional negative pressure wound therapy decreased the chance of surgical site infection (OR, 0.32; p < 0.05). Obesity was associated with a trend toward increasing surgical site infection (OR, 1.64; p = 0.10). LIMITATIONS: This study is limited by its retrospective nature and the high baseline prevalence of surgical site infection. CONCLUSIONS: Incisional negative pressure wound therapy appears to reduce surgical site infection in open colorectal surgery. Further study may be helpful to identify patient populations who would have the greatest benefit from this technique(see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A115).

Assessing thrombosis risk in patients with idiopathic, diabetic, and postsurgical gastroparesis.

Patients with severe gastrointestinal motility disorders are often found to have intravenous access clots or deep venous thrombosis. It has previously been reported that many patients who have intravenous access thrombosis have concomitant thrombotic risk factors. In this study, the goal was to determine the underlying prevalence of hypercoagulable risk in a series of patients with documented gastroparesis. Investigators studied 62 consecutive patients (52 female; mean age, 42 y) who had symptoms of gastroparesis. All patients were evaluated for placement of a gastric neural stimulation device, or they had had one placed previously. Patients underwent a hematologic interview and standardized coagulation measures of thrombotic risk. Laboratory studies measured acquired elevations of Factor VII, Factor VIII, fibrinogen, lupus anticoagulant panel, antiphospholipid antibody panel, homocysteine (in the setting of kidney disease), and activated protein resistance. Investigators also measured congenital factors: Factor VIII (with C-reactive protein levels), antithrombin III, protein C, protein S (total and free), Factor II mutation, Factor V Leiden, methylenetetrahydrofolate reductase, and homocysteine. Fifty-five patients (89%) were found to have detectable hypercoagulable risk factors. Twenty-five of the 62 patients (40%) had a documented history of abnormal clotting, including deep venous thrombosis, intravenous access thrombosis, and pulmonary embolism. All patients with a previous history of thrombosis had detectable clotting abnormalities. Of 56 patients, 40 (71%) had hypercoagulability and did not have diabetes (P=.036), and 20 (36%) had hypercoagulability and no known history of infection. However, this value was not statistically significant when infection and hypercoagulability were compared (P=.408). A high prevalence of acquired and congenital hypercoagulable defects has been observed in patients with gastroparesis, which may predispose them to arterial and venous clots. This unique finding warrants consideration of coagulation evaluation in patients with severe gastroparesis, especially when these patients are placed in high-risk thrombophilic situations, such as hospitalization, prolonged intravenous access, and surgery.

Episiotomy dehiscence that required intestinal diversion.

Postpartum episiotomy dehiscence is a rare complication of vaginal delivery. Forceps-assisted vaginal delivery over mediolateral episiotomy was complicated by infection and dehiscence with rectal injury. A diverting ileostomy was used to permit healing. Episiotomy infection requires early recognition and thorough evaluation to exclude occult rectal injury.

Fecal impaction.

Fecal impaction is a common gastrointestinal problem and a potential source of major morbidity. Prompt identification and treatment minimize the risks of complications. Treatment options include manual extraction and proximal or distal washout. Following treatment, possible etiologies should be sought and preventive therapy instituted.