Simulated transanal NOTES sigmoidectomy training improves the responsiveness of surgical endoscopists.

BACKGROUND: There is no evidence demonstrating the feasibility of colorectal natural orifice transluminal endoscopic surgery (NOTES) resection with currently available endoscopic instrumentation. OBJECTIVE: This study aimed to evaluate the responsiveness of surgical endoscopists to simulated transanal NOTES sigmoidectomy training. DESIGN: Participants were trained in simulated NOTES sigmoidectomy by using disposable abdominal trays with tattooed sigmoid cancer in a hybrid simulator. SETTING: Endoscopy simulation laboratory in a university hospital. INTERVENTIONS: NOTES sigmoidectomy included 8 steps performed transanally with 2 colonoscopes, endoscopic scissors, and clip applier: (1) colonoscopic viscerotomy with a balloon; (2) retroperitoneal dissection; (3) left ureter identification, inferior mesenteric vessels division; (4) colonoscopy; (5) splenic flexure mobilization; (6) left side of the colon/rectal mobilization; (7) transanal specimen transection; (8) extracorporeal colorectal anastomosis. MAIN OUTCOME MEASUREMENTS: Responsiveness was defined as a change in performance over time and assessed comparing baseline testing with unmentored final testing. Content-valid measures included the length of the specimen, the distance of the anastomosis from the anal verge, and the proximal and distal resection margins and operating time (minutes). RESULTS: Four participants performed 21 resections. Tumor distance from the anal verge was 29.2 cm (range 26-2.5 cm). Operating time overall (127.5 vs 74 minutes, P = .068), viscerotomy (17.5 vs 9 minutes, P = .197), colonoscopy (4.5 vs 3.5 minutes, P = .655), flexure mobilization (19.5 vs 10 minutes, P = .144), colon mobilization (20 vs 14.5 minutes, P = .461), specimen extraction (9.5 vs 8.5 minutes, P = .465), and anastomosis (14 vs 11 minutes, P = .715) times improved. LIMITATIONS: Ceiling effects because of fixed anatomy. CONCLUSIONS: Simulated NOTES sigmoidectomy training affected responsiveness of surgical endoscopists with a 42% reduction in operating time.

Mentorship of Junior Surgical Faculty Across Academic Programs in Surgery.

Importance: Because mentorship is critical for professional development and career advancement, it is essential to examine the status of mentorship and identify challenges that junior surgical faculty (assistant and associate professors) face obtaining effective mentorship. Objective: To evaluate the mentorship experience for junior surgical faculty and highlight areas for improvement. Design, Setting, and Participants: This qualitative study was an explanatory sequential mixed-methods study including an anonymous survey on mentorship followed by semistructured interviews to expand on survey findings. Junior surgical faculty from 18 US academic surgery programs were included in the anonymous survey and interviews. Survey responses between "formal" (assigned by the department) vs "informal" (sought out by the faculty) mentors and male vs female junior faculty were compared using χ2 tests. Interview responses were analyzed for themes until thematic saturation was achieved. Survey responses were collected from November 2022 to August 2023, and interviews conducted from July to December 2023. Exposure: Mentorship from formal and/or informal mentors. Main Outcomes and Measures: Survey gauged the availability and satisfaction with formal and informal mentorship; interviews assessed broad themes regarding mentorship. Results: Of 825 survey recipients, 333 (40.4%) responded; 155 (51.7%) were male and 134 (44.6%) female. Nearly all respondents (319 [95.8%]) agreed or strongly agreed that mentorship is important to their surgical career, especially for professional networking (309 respondents [92.8%]), career advancement (301 [90.4%]), and research (294 [88.3%]). However, only 58 respondents (18.3%) had a formal mentor. More female than male faculty had informal mentors (123 [91.8%] vs 123 [79.4%]; P = .003). Overall satisfaction was higher with informal mentorship than formal mentorship (221 [85.0%] vs 40 [69.0%]; P = .01). Most male and female faculty reported no preferences in gender or race and ethnicity for their mentors. When asked if they had good mentor options if they wanted to change mentors, 141 (47.8%) responded no. From the interviews (n = 20), 6 themes were identified, including absence of mentorship infrastructure, preferred mentor characteristics, and optimizing mentorship. Conclusions and Relevance: Academic junior surgical faculty agree mentorship is vital to their careers. However, this study found that few had formal mentors and almost half need more satisfactory options if they want to change mentors. Academic surgical programs should adopt a framework for facilitating mentorship and optimize mentor-mentee relationships through alignment of mentor-mentee goals and needs.

Impact of preoperative antibiotics and other variables on integrated microbiome-host transcriptomic data generated from colorectal cancer resections.

BACKGROUND: Integrative multi-omic approaches have been increasingly applied to discovery and functional studies of complex human diseases. Short-term preoperative antibiotics have been adopted to reduce site infections in colorectal cancer (CRC) resections. We hypothesize that the antibiotics will impact analysis of multi-omic datasets generated from resection samples to investigate biological CRC risk factors. AIM: To assess the impact of preoperative antibiotics and other variables on integrated microbiome and human transcriptomic data generated from archived CRC resection samples. METHODS: Genomic DNA (gDNA) and RNA were extracted from prospectively collected 51 pairs of frozen sporadic CRC tumor and adjacent non-tumor mucosal samples from 50 CRC patients archived at a single medical center from 2010-2020. The 16S rRNA gene sequencing (V3V4 region, paired end, 300 bp) and confirmatory quantitative polymerase chain reaction (qPCR) assays were conducted on gDNA. RNA sequencing (IPE, 125 bp) was performed on parallel tumor and non-tumor RNA samples with RNA Integrity Numbers scores ≥ 6. RESULTS: PERMANOVA detected significant effects of tumor vs nontumor histology (P = 0.002) and antibiotics (P = 0.001) on microbial ß-diversity, but CRC tumor location (left vs right), diabetes mellitus vs not diabetic and Black/African Ancestry (AA) vs not Black/AA, did not reach significance. Linear mixed models detected significant tumor vs nontumor histology*antibiotics interaction terms for 14 genus level taxa. QPCR confirmed increased Fusobacterium abundance in tumor vs nontumor groups, and detected significantly reduced bacterial load in the (+)antibiotics group. Principal coordinate analysis of the transcriptomic data showed a clear separation between tumor and nontumor samples. Differentially expressed genes obtained from separate analyses of tumor and nontumor samples, are presented for the antibiotics, CRC location, diabetes and Black/AA race groups. CONCLUSION: Recent adoption of additional preoperative antibiotics as standard of care, has a measurable impact on -omics analysis of resected specimens. This study still confirmed increased Fusobacterium nucleatum in tumor.

Delayed Kock pouch nipple valve failure: is revision indicated?

PURPOSE: This study was designed to review our experience with patients who, after more than 10 years of normal Kock pouch valve function, required repair of the valve. In addition, we describe the surgical techniques employed for valve repair. METHODS: A retrospective chart review identified 31 patients who underwent Kock pouch revision after a minimum time interval between previous pouch surgery and the current revision of 10 (average, 19.7) years. RESULTS: The intraoperative findings included slipped valve, valve prolapse, and internal nipple valve fistulas. The procedures performed included standard valve reconstruction, turnaround procedures, pedicle repair, wall stapling, and oversewing of fistula. Twelve of the 31 patients failed the initial revision and required additional operations, with an overall pouch salvage success rate of 93 percent. Only two patients required excision of the pouch and conversion to a Brooke ileostomy. The procedures were performed with minimal morbidity and no mortality. CONCLUSION: Surgical revision can be offered to patients with a continent ileostomy complicated by delayed valve dysfunction with low morbidity and good functional outcome.

Hypoxia promotes colon cancer dissemination through up-regulation of cell migration-inducing protein (CEMIP).

Hypoxic stress drives cancer progression by causing a transcriptional reprogramming. Recently, KIAA1199 was discovered to be a cell-migration inducing protein (renamed CEMIP) that is upregulated in human cancers. However, the mechanism of induction of CEMIP in cancer was hitherto unknown. Here we demonstrate that hypoxia induces CEMIP expression leading to enhanced cell migration. Immunohistochemistry of human colon cancer tissues revealed that CEMIP is upregulated in cancer cells located at the invasive front or in the submucosa. CEMIP localization inversely correlated with E-cadherin expression, which is characteristic of the epithelial-to-mesenchymal transition. Mechanistically, hypoxia-inducible-factor-2α (HIF-2α), but not HIF-1α binds directly to the hypoxia response element within the CEMIP promoter region resulting in increased CEMIP expression. Functional characterization reveals that CEMIP is a downstream effector of HIF-2α-mediated cell migration. Expression of CEMIP was demonstrated to negatively correlate with the expression of Jarid1A, a histone demethylase that removes methyl groups from H3K4me3 (an activation marker for transcription), resulting in altered gene repression. Low oxygen tension inhibits the function of Jarid1A, leading to increased presence of H3K4me3 within the CEMIP promoter. These results provide insight into the upregulation of CEMIP within cancer and can lead to novel treatment strategies targeting this cancer cell migration-promoting gene.

miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14.

Upregulation of matrix metalloproteinase MMP-14 (MT1-MMP) is associated with poor prognosis in cancer patients, but it is unclear how MMP-14 becomes elevated in tumors. Here, we show that miR-181a-5p is downregulated in aggressive human breast and colon cancers where its levels correlate inversely with MMP-14 expression. In clinical specimens, enhanced expression of MMP-14 was observed in cancer cells located at the invasive front of tumors where miR-181a-5p was downregulated relative to adjacent normal cells. Bioinformatics analyses defined a potential miR-181a-5p response element within the 3'-untranslated region of MMP-14 that was validated in reporter gene experiments. Ectopic miR-181a-5p reduced MMP-14 expression, whereas miR-181a-5p attenuation elevated MMP-14 expression. In support of a critical relationship between these two genes, miR-181a-5p-mediated reduction of MMP-14 levels was sufficient to decrease cancer cell migration, invasion, and activation of pro-MMP-2. Furthermore, this reduction in MMP-14 levels was sufficient to reduce in vivo invasion and angiogenesis in chick chorioallantoic membrane assays. Taken together, our results establish the regulation of MMP-14 in cancers by miR-181a-5p through a posttranscriptional mechanism, and they further suggest strategies to elevate miR-181a-5p to prevent cancer metastasis.

Endovascular repair of a traumatic arteriovenous fistula 34 years after the injury: report of a case.

Penetrating extremity injuries can result in the development of arteriovenous fistulas (AVFs), whereby normal blood flow through the capillary bed is bypassed. Late complications of untreated AVFs include proximal arterial dilatation, venous congestion, congestive heart failure, and distal ischemia. We report the case of a 57-year-old man who was referred to us for treatment of a traumatic AVF with multiple sequelae, 34 years after he sustained a shrapnel injury to his right lower leg. We performed successful endovascular repair of this AVF with the patient under spinal anesthesia. Computed tomographic angiography (CTA) done 1 month and 6 months later confirmed AVF exclusion. Patients may present with sequelae of traumatic AVFs many years after their initial injury. Endovascular repair of AVFs offers several advantages over conventional repair and can be performed successfully even in the presence of complex anatomic abnormalities.