Combining staged laparoscopic colectomy with robotic completion proctectomy and ileal pouch-anal anastomosis (IPAA) in ulcerative colitis for improved clinical and cosmetic outcomes: a single-center feasibility study and technical description.

Robotic proctectomy has been shown to lead to better functional outcomes compared to laparoscopic surgery in rectal cancer. However, in ulcerative colitis (UC), the potential value of robotic proctectomy has not yet been investigated, and in this indication, the operation needs to be adjusted to the total colectomy typically performed in the preceding 6 months. In this study, we describe the technique and analyze outcomes of a staged laparoscopic and robotic three-stage restorative proctocolectomy and compare the clinical outcome with the classical laparoscopic procedure. Between December 2016 and May 2021, 17 patients underwent robotic completion proctectomy (CP) with ileal pouch-anal anastomosis (IPAA) for UC. These patients were compared to 10 patients who underwent laparoscopic CP and IPAA, following laparoscopic total colectomy with end ileostomy 6 months prior by the same surgical team at our tertiary referral center. 27 patients underwent a 3-stage procedure for refractory UC (10 in the lap. group vs. 17 in the robot group). Return to normal bowel function and morbidity were comparable between the two groups. Median length of hospital stay was the same for the robotic proctectomy/IPAA group with 7 days [median; IQR (6-10)], compared to the laparoscopic stage II with 7.5 days [median; IQR (6.25-8)]. Median time to soft diet was 2 days [IQR (1-3)] vs. 3 days in the lap group [IQR 3 (3-4)]. Two patients suffered from a major complication (Clavien-Dindo ≥ 3a) in the first 90 postoperative days in the robotic group vs. one in the laparoscopic group. Perception of cosmetic results were favorable with 100% of patients reporting to be highly satisfied or satisfied in the robotic group. This report demonstrates the feasibility of a combined laparoscopic and robotic staged restorative proctocolectomy for UC, when compared with the traditional approach. Robotic pelvic dissection and a revised trocar placement in staged proctocolectomy with synergistic use of both surgical techniques with their individual advantages will likely improve overall long-term functional results, including an improved cosmetic outcome.

Prognostic factors in patients with acute mesenteric ischemia-novel tools for determining patient outcomes.

BACKGROUND: Acute mesenteric ischemia (AMI) is a devastating disease with poor prognosis. Due to the multitude of underlying factors, prediction of outcomes remains poor. We aimed to identify factors governing diagnosis and survival in AMI and develop novel prognostic tools. METHODS: This monocentric retrospective study analyzed patients with suspected AMI undergoing imaging between January 2014 and December 2019. Subgroup analyses were performed for patients with confirmed AMI undergoing surgery. Nomograms were calculated based on multivariable logistic regression models. RESULTS: Five hundred and thirty-nine patients underwent imaging for clinically suspected AMI, with 216 examinations showing radiological indication of AMI. Intestinal necrosis (IN) was confirmed in 125 undergoing surgery, 58 of which survived and 67 died (median 9 days after diagnosis, IQR 22). Increasing age, ASA score, pneumatosis intestinalis, and dilated bowel loops were significantly associated with presence of IN upon radiological suspicion. In contrast, decreased pH, elevated creatinine, radiological atherosclerosis, vascular occlusion (versus non-occlusive AMI), and colonic affection (compared to small bowel ischemia only) were associated with impaired survival in patients undergoing surgery. Based on the identified factors, we developed two nomograms to aid in prediction of IN upon radiological suspicion (C-Index = 0.726) and survival in patients undergoing surgery for IN (C-Index = 0.791). CONCLUSION: As AMI remains a condition with high mortality, we identified factors predicting occurrence of IN with suspected AMI and survival when undergoing surgery for IN. We provide two new tools, which combine these parameters and might prove helpful in treatment of patients with AMI.

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients.

BACKGROUND: Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity. METHODS: We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design. RESULTS: Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients. CONCLUSION: As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

Single incision laparoscopic surgery (SILS) versus conventional laparoscopic technique for ileostomy: a retrospective cohort study.

PURPOSE: Minimal-invasive surgery has gained wide acceptance in colorectal surgery. Single incision laparoscopic surgery (SILS) was designed to minimize surgical trauma and improve postoperative outcome. However, the role of SILS in ileostomy formation is unclear. METHODS: In this retrospective cohort study 26 patients were included. Six patients were operated with SILS and 20 with conventional laparoscopic technique for ileostomy. We retrospectively evaluated patient charts for baseline characteristics including prior abdominal surgeries and combination of surgeries. Our primary efficacy objectives were operation time and postoperative hospitalization days. Our safety objectives included the prevalence of postoperative pain, parastomal hernia, incisional hernia, perforation, wound infection, ileus, and infections in general. RESULTS: Baseline characteristics including previous abdominal surgery and concomitant surgeries were comparable in both groups. Total operation time using SILS (37.5 ± 6.2 min [mean ± SD]), compared to laparoscopic surgery (82.2 ± 54.8 min [mean ± SD]) was significantly shorter (p = 0.0002). In a sensitivity analysis excluding patients with combined surgery, ileostomy formation by SILS was shorter (36.5 ± 6.2 min [mean ± SD]), compared to laparoscopy (59.7 ± 28.7 min [mean ± SD]; p = 0.024). Length of postoperative stay was not statistically different between the groups (SILS: 5.5 ± 2.4 days [mean ± SD]; laparoscopic: 13.8 ± 17.3 days [mean ± SD], p = 0.193). Postoperative complication rates were low and comparable in both groups. CONCLUSION: Placement of a loop ileostomy using SILS technique not only reduces surgical trauma but also operation time without affecting postoperative hospital stay or postoperative complication rates. Single-incision laparoscopic surgery for ileostomy is an appealing approach for ileostomy in selected patients.

MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model.

Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis. The aim of this project was to investigate in detail MMP-9 expression in different fistula types and to confirm that MMP-9 is a potential target for fistula therapy in CD patients.Immunohistochemistry for total and active MMP-9, Cytokeratin 8 (CK-8) and co-staining of active MMP-9/CK-8 was performed in specimen derived from perianal fistulas, entero-enteric fistulas and fistulas from patients not responding to anti-TNF therapy. In addition, fistulas from the xenograft mouse model (anti-TNF treated or untreated) were analyzed.Total and active MMP-9 protein was detectable in cells lining the tracts of perianal and entero-enteric fistulas. Of note, total and active MMP-9 was also expressed in fistulas of CD patients non-responding to anti-TNF treatment. Interestingly, we detected considerable co-staining of active MMP-9 and CK-8 in particular in cells lining the fistula tract and in transitional cells around the fistulas. Furthermore, total and active MMP-9 are detectable in both anti-TNF treated and untreated xenograft fistulas.Taken together, our data suggest that MMP-9 is involved in fistula pathogenesis in CD patients, in fistulas of different origins and particularly in patients non-responding to anti-TNF therapy. Our xenograft fistula model is suitable for in vivo studies investigating a possible therapeutic role for MMP-9 targeting as fistula therapy.

[Symptoms, diagnostic and therapy of perianal disease in patients with inflammatory bowel diseases]. / Klinik, Diagnostik und Therapie proktologischer Beschwerden bei Patienten mit chronisch entzündlichen Darmerkrankungen.

Symptoms, diagnostic and therapy of perianal disease in patients with inflammatory bowel diseases Abstract. Inflammatory bowel diseases (IBD) frequently affect the perianal region. Due to the great functional importance of the anorectum, this frequently results in a significant burden of disease for the patient. For assessment of perianal IBD symptoms, the clinical history is of great importance. Often, anorectal symptoms are not reported spontaneously by patients, and a respectful direct conversation remains crucial. More than 30 % of patients with Crohn's disease (CD) will develop perianal fistulas. Perianal fistulas can be further characterized by endoscopic ultrasound, MRI, and investigation under anesthesia. These investigations provide complementary information. Fistula therapy is based on symptoms; the short-term goal is improvement of pain and secretion; the long-term goal of treatment remains fistula closure. However, preservation of the anal sphincter is of utmost importance and incontinence needs to be avoided. Antibiotics and/ or seton drainage are the mainstay for acute fistula treatment. The anti-tumor necrosis factor antibody infliximab can improve fistula symptoms, as demonstrated in a randomized controlled study. Surgical fistula closure is only possible in a clinically stable situation without rectal inflammation or other symptoms of active CD. Several surgical strategies exist including 1) fistulotomy, 2) disconnection of the fistula, 3) filling of the fistula tract and 4) fistula ablation. The optimal strategy needs to be decided on an individual basis. Intraoperative application of mesenchymal donor stem cells into the fistula tract and surrounding tissue is possibly the most effective fistula therapy. Due to the significant logistic effort, this therapy is only available in a few selected centers. Currently, stem cell therapy for CD fistulas is limited to patients with no more than two external fistula openings. The therapy of fissures and hemorrhoids in IBD patients is similar to patients without intestinal inflammation; however, due to a high rate of complications, surgery should be avoided whenever possible in CD patients. Incontinence is a frequent problem in IBD patients leading to highly relevant restrictions in daily life. Therapy is directed against intestinal inflammation but also comprises measures for normalization of stool consistency and intestinal motility. However, there are no IBD-specific concepts for the treatment of incontinence. Functional intestinal diseases are frequent in IBD patients and can contribute to urge and incontinence. Some IBD patients might benefit from anorectal physiotherapy. IBD patients have an increased risk for colorectal carcinoma, fistula carcinoma and possibly also anal carcinoma. Therefore, malignancy needs to be excluded at reasonable intervals.

Combination of Vedolizumab With Tacrolimus Is More Efficient Than Vedolizumab Alone in the Treatment of Experimental Colitis.

BACKGROUND: Vedolizumab is a widely used and safe therapy in inflammatory bowel disease, particularly in ulcerative colitis (UC), making it a promising candidate for enhanced efficacy by combining it with additional immunomodulatory medications. In this study, we studied the impact of vedolizumab monotreatment vs vedolizumab coadministration with other immunomodulatory drugs on intestinal inflammation and intestinal immune cells in vivo. METHODS: Colon tissue from human patients with UC with active disease or in remission with or without vedolizumab treatment was stained by immunohistochemistry. We reconstituted NOD-SCID-SGM3 mice with human CD34+ cells and treated them with dextran sodium sulfate to induce acute colitis. Mice were treated with vedolizumab alone, or in combination with tacrolimus, ozanimid, or tofacitinib. RESULTS: Vedolizumab reduced the number of CD3+ T cells and CD68+ monocytes/macrophages in the colon of patients with UC with active disease. Vedolizumab moderately decreased immune cell numbers in acute dextran sodium sulfate-induced colitis. The combination of vedolizumab with tacrolimus further reduced the number of infiltrating CD3+ T cells and CD68+ monocytes/macrophages and was superior in ameliorating intestinal inflammation when compared to vedolizumab monotreatment. In contrast, cotreatment using vedolizumab with ozanimod or tofacitinib had no additive effect. CONCLUSIONS: Our data show that vedolizumab reduces the number of innate and adaptive immune cells in the mucosa of patients with UC. Further, the combination of vedolizumab with tacrolimus was more efficient to reduce immune cell numbers and to increase therapeutic efficacy than vedolizumab monotreatment. This finding indicates that combination treatment using these two drugs may be beneficial for patients who do not respond to vedolizumab monotherapy.

Long-term immune-related adverse events after discontinuation of immunotherapy.

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and ipilimumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Lay abstract Checkpoint inhibitors have revolutionized therapy for suitable cancers. However, they can cause side effects that are reminiscent of autoimmune diseases. While most adverse effects occur during ongoing therapy, there are increasing reports of late-onset adverse effects after discontinuation of therapy and of long-lasting adverse effects after discontinuation of treatment, which may remain latent even if symptom relief could be achieved by immunosuppression. We present a patient case with reappearance of a severe inflammation of the large bowel (colitis) after closure of an ostomy over 1 year after withdrawal of immune checkpoint inhibitor therapy. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

Colorectal cancer of the young displays distinct features of aggressive tumor biology: A single-center cohort study.

BACKGROUND: In recent years, a decrease in incidence and mortality of colorectal cancer (CRC) has been observed in developed nations, presumably through public disease awareness and increased screening efforts. However, a rising incidence of CRC in young patients below the age of 50 years has been reported in several studies. AIM: To study tumor biology in CRC patients below 50 years of age. METHODS: All patients with CRC were prospectively enrolled in our single-center oncologic database from January 2013 to December 2018 and were grouped and analyzed according to age (≥ 50 and < 50 years). Clinical as well as histopathological features were analyzed and compared. The study was approved by the local Ethics Committee. Fisher's exact test or t-test was used to test for differences between the groups, as appropriate. All statistical analysis was performed with IBM SPSS software Version 25 (SPSS Inc, Armonk, NY, United States) and with R-Studio using R Version 3.4.1 (RStudio, Boston, MA, United States). RESULTS: Seventeen percent of the 411 patients were younger than 50 years. Young patients were more often diagnosed with locally advanced T4-tumors and lymph node metastases (36.6% and 62% vs 17.7% and 42%; P < 0.01). In addition, a higher frequency of poorly differentiated (G3) tumors (40% vs 22.4% P < 0.05) was observed. More than every second patient below 40 years of age (51.8%) had distant metastases at diagnosis with a significant higher rate ring of signet cell differentiation compared to patients ≥ 50 years (14.8%, P < 0.05). Mutational status (KRAS, NRAS, BRAF, MSI) as well as selected behavioral risk factors showed no significant differences. CONCLUSION: Distinct histopathologic features of increased biologic aggressiveness are found in patients with CRC of young-onset. Those patients present more frequently with more advanced tumor stages compared to older patients. Features of aggressive tumor biology underscore the need for earlier uptake of routine screening measures.

Perianal fistulodesis - A pilot study of a novel minimally invasive surgical and medical approach for closure of perianal fistulae.

BACKGROUND: Perianal fistulae strongly impact on quality of life of affected patients. AIM: To challenge and novel minimally invasive treatment options are needed. METHODS: Patients with Crohn's disease (CD) in remission and patients without inflammatory bowel disease (non-IBD patients) were treated with fistulodesis, a method including curettage of fistula tract, flushing with acetylcysteine and doxycycline, Z-suture of the inner fistula opening, fibrin glue instillation, and Z-suture of the outer fistula opening followed by post-operative antibiotic prophylaxis with ciprofloxacin and metronidazole for two weeks. Patients with a maximum of 2 fistula openings and no clinical or endosonographic signs of a complicated fistula were included. The primary end point was fistula healing, defined as macroscopic and clinical fistula closure and lack of patient reported fistula symptoms at 24 wk. RESULTS: Fistulodesis was performed in 17 non-IBD and 3 CD patients, with a total of 22 fistulae. After 24 wk, all fistulae were healed in 4 non-IBD and 2 CD patients (overall 30%) and fistula remained closed until the end of follow-up at 10-25 mo. In a secondary per-fistula analysis, 7 out of 22 fistulae (32%) were closed. Perianal disease activity index (PDAI) improved in patients with fistula healing. Low PDAI was associated with favorable outcome (P = 0.0013). No serious adverse events were observed. CONCLUSION: Fistulodesis is feasible and safe for perianal fistula closure. Overall success rates is at 30% comparable to other similar techniques. A trend for better outcomes in patients with low PDAI needs to be confirmed.

Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management.

BACKGROUND: Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. METHODS: Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. RESULTS: In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P < 10-15), examinations (P < 10-12), medical therapies (P = 0.023) and weeks of hospitalisation (P = 0.0013) in a multivariate model. CONCLUSIONS: We detected an association between maximal abdominal pain in UC patients and two IBS-associated SNPs. Abdominal pain levels had a pronounced impact on diagnostic and therapeutic procedures in CD but not in UC patients.

Inequalities in access to minimally invasive general surgery: a comprehensive nationwide analysis across 20 years.

BACKGROUND: Minimally invasive surgery (MIS) has profoundly changed standards of care and lowered perioperative morbidity, but its temporal implementation and factors favoring MIS access remain elusive. We aimed to comprehensibly investigate MIS adoption across different surgical procedures over 20 years, identify predictors for MIS amenability and compare propensity score-matched outcomes among MIS and open surgery. METHODS: Nationwide retrospective analysis of all hospitalizations in Switzerland between 1998 and 2017. Appendectomies (n = 186,929), cholecystectomies (n = 57,788), oncological right (n = 9138) and left hemicolectomies (n = 21,580), rectal resections (n = 13,989) and gastrectomies for carcinoma (n = 6606) were included. Endpoints were assessment of temporal MIS implementation, identification of predictors for MIS access and comparison of propensity score-matched outcomes among MIS and open surgery. RESULTS: The rates of MIS increased for all procedures during the study period (p ≤ 0.001). While half of all appendectomies were performed laparoscopically by 2005, minimally invasive oncological colorectal resections reached 50% only by 2016. Multivariate analyses identified older age (p ≤ 0.02, except gastrectomy), higher comorbidities (p ≤ 0.001, except rectal resections), lack of private insurance (p ≤ 0.01) as well as rural residence (p ≤ 0.01) with impaired access to MIS. Rural residence correlated with low income regions (p ≤ 0.001), which themselves were associated with decreased MIS access. Geographical mapping confirmed strong disparities for rural and low-income areas in MIS access. Matched outcome analyses revealed benefits of MIS for length of stay, decreased surgical site infection rates for MIS appendectomies and cholecystectomies and higher mortality for open cholecystectomies. No consistent morbidity or mortality benefit for MIS compared to open colorectal resections was observed. CONCLUSION: Unequal access to MIS exists in disfavor of older and more comorbid patients and those lacking private insurance, living in rural areas, and having lower income. Efforts should be made to ensure equal MIS access regardless of socioeconomic or geographical factors.

Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) recently emerged as a promising cancer immunotherapy target. We set out to investigate the functional role of PTPN2 in the pathogenesis of human colorectal carcinoma (CRC), as its role in immune-silent solid tumors is poorly understood. We demonstrate that in human CRC, increased PTPN2 expression and activity correlated with disease progression and decreased immune responses in tumor tissues. In particular, stage II and III tumors displayed enhanced PTPN2 protein expression in tumor-infiltrating T cells, and increased PTPN2 levels negatively correlated with expression of PD-1, CTLA4, STAT1, and granzyme A. In vivo, T cell- and DC-specific PTPN2 deletion reduced tumor burden in several CRC models by promoting CD44+ effector/memory T cells, as well as CD8+ T cell infiltration and cytotoxicity in the tumor. In direct relevance to CRC treatment, T cell-specific PTPN2 deletion potentiated anti-PD-1 efficacy and induced antitumor memory formation upon tumor rechallenge in vivo. Our data suggest a role for PTPN2 in suppressing antitumor immunity and promoting tumor development in patients with CRC. Our in vivo results identify PTPN2 as a key player in controlling the immunogenicity of CRC, with the strong potential to be exploited for cancer immunotherapy.

Contribution of CD3+CD8- and CD3+CD8+ T Cells to TNF-α Overexpression in Crohn Disease-Associated Perianal Fistulas and Induction of Epithelial-Mesenchymal Transition in HT-29 Cells.

BACKGROUND: Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis. METHODS: CD3+CD8-, CD3+CD8+, or CD45+CD3- cells from healthy volunteers, patients with CD, and patients with CD with perianal fistula were co-cultured with HT-29 cells. The EMT, cytokine production, and mRNA expression were analyzed. Perianal CD fistula specimens were immunohistochemically stained for cytokines and their receptors. The effect of cytokines on EMT induction was investigated using an EMT spheroid model. RESULTS: Patients with CD with fistula revealed more CD3+CD8- and less CD3+CD8+ T cells in blood than healthy control patients and patients with CD without fistula. In perianal fistula specimens, CD4+ cells-and to a lesser extent CD8+ cells-were highly present around fistula tracts. When co-cultured with HT-29 cells, both cell subsets promoted EMT-related gene expression and TNF-α production in a time-dependent manner. The CD3+CD8- T cells from patients with CD with fistula also produced higher amounts of IL-13 than cells from healthy control patients or patients with CD without a fistula. We found that IL-22 and IL-22Rα1 were highly expressed in perianal CD fistula specimens and that IL-22 cotreatment potentiated TNF-α-induced EMT in HT-29 spheroids. CONCLUSIONS: Our data indicate that both CD3+CD8- and CD3+CD8+ T cells play an important role in the pathogenesis of perianal CD fistulas by the secretion of TNF-α. Our data support clinical evidence indicating that anti-TNF-α therapy is effective in fistula treatment and identify IL-13 and IL-22 as possible novel therapeutic targets for fistula therapy.

Complete Recovery of Immune Checkpoint Inhibitor-induced Colitis by Diverting Loop Ileostomy.

Checkpoint inhibitor-induced side effects such as diarrhea and colitis occur in up to 30% of patients. We present a case of recurrent episodes of checkpoint inhibitor-induced colitis and subsequent Fournier gangrene that resolved after ileostomy formation. Once the Fournier gangrene and colitis had resolved, the ileostomy was reversed. However, within only 4 days, another serious flare-up of colitis occurred, necessitating emergent re-formation of the ileostomy. Expertise in the management of side effects of immune checkpoint inhibitor therapy is currently limited. Although most side effects are mild to moderate and transient, a minority of patients suffer from life-threatening complications, such as colitis. The creation of an ileostomy might be a valid treatment option in severe or recurrent colitis due to immune checkpoint inhibitor therapy. Intestinal diversion surgery may be useful if conservative treatment has failed, similar to other forms of immune-mediated intestinal inflammation.

Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections.

PURPOSE: In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. METHODS: The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. RESULTS: All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4 cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10 mm (2-15 mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. CONCLUSION: The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

ß6 -integrin serves as a novel serum tumor marker for colorectal carcinoma.

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide and the need for novel biomarkers and therapeutic strategies to improve diagnosis and surveillance is obvious. This study aims to identify ß6 -integrin (ITGB6) as a novel serum tumor marker for diagnosis, prognosis, and surveillance of CRC. ITGB6 serum levels were validated in retro- and prospective CRC patient cohorts. ITGB6 serum levels were analyzed by ELISA. Using an initial cohort of 60 CRC patients, we found that ITGB6 is present in the serum of CRC, but not in non-CRC control patients. A cut-off of ≥2 ng/mL ITGB6 reveals 100% specificity for the presence of metastatic CRC. In an enlarged study cohort of 269 CRC patients, ITGB6 predicted the onset of metastatic disease and was associated with poor prognosis. Those data were confirmed in an independent, prospective cohort consisting of 40 CRC patients. To investigate whether ITGB6 can also be used for tumor surveillance, serum ITGB6-levels were assessed in 26 CRC patients, pre- and post-surgery, as well as during follow-up visits. After complete tumor resection, ITGB6 serum levels declined completely. During follow-up, a new rise in ITGB6 serum levels indicated tumor recurrence or the onset of new metastasis as confirmed by CT scan. ITGB6 was more accurate for prognosis of advanced CRC and for tumor surveillance as the established marker carcinoembryonic antigen (CEA). Our findings identify ITGB6 as a novel serum marker for diagnosis, prognosis, and surveillance of advanced CRC. This might essentially contribute to an optimized patient care.

The growing discrepancy between resident training in colonic surgery and the rising number of general surgery graduates.

PURPOSE: The decrease in resident operative experience due to working-hour directives and sub-specialization within general surgery is the subject of growing debate. This study aims to examine how the numbers of colectomies used for resident training have evolved since the introduction of working-hour directives and to place these results within the context of the number of new general surgeons. METHODS: Based on the nationwide database of the Swiss association for quality management in surgery, all segmental colectomies performed at 86 centers were analyzed according to the presence or absence of residents and compared to national numbers of surgical graduates. RESULTS: Of 19,485 segmental colectomies between 2006 and 2015, 36% were used for training purposes. Residents performed 4%, junior staff surgeons 31%, senior staff surgeons 55%, and private surgeons 10%. The percentage performed by residents decreased significantly, while the annual number of graduates increased from 36 to 79. Multivariate analysis identified statutory (non-private) health insurance (OR 7.6, CI 4.6-12.5), right colon resection (OR 3.5, CI 2.5-4.7), tertiary referral center (OR 1.9, CI 1.5-2.6), emergency surgery (OR 1.7, CI 1.3-2.3), and earlier date of surgery (OR 1.1, CI 1.0-1.1) as predictors for resident involvement. CONCLUSIONS: Only a low and declining percentage of colectomies is used for resident training, despite growing numbers of trainees. These data imply that opportunities to obtain technical proficiency have diminished since the implementation of working-hour directives, indicating the need to better utilize suitable teaching opportunities, to ensure that technical proficiency remains high.

Insurance status does not affect short-term outcomes after oncological colorectal surgery in Europe, but influences the use of minimally invasive techniques: a propensity score-matched analysis.

BACKGROUND AND PURPOSE: Controversy exists whether surgical treatment is influenced by insurance status. American studies suggest higher morbidity and decreased survival in uninsured patients with colorectal cancer (CRC). It remains elusive, however, whether these findings apply to European countries with mandatory, government-driven insurance systems. We aimed to analyze whether operative techniques, quality of surgery, and complication rates differ among patients covered by statutory (SI) versus private (PI) healthcare insurance. METHODS: Based on a prospective national surgical quality database, patients undergoing elective resection for CRC during 2007-2015 were identified. A propensity score match of eligible patients with SI and PI yielded 765 patients per group. RESULTS: Hierarchical status of the operating surgeon differed substantially (p = 0.001): junior surgeons operated on > 50% of patients with SI, whereas over 80% of patients with PI were operated by senior surgeons. Minimally invasive techniques were used more frequently in patients with PI (p = 0.001) and patients with SI undergoing colonic resection showed an increased conversion rate (OR 2.44). Median duration of surgery (p = 0.001) and blood loss (p = 0.002) were higher in patients with SI; however, length of hospital stay was equal. Neither the rate of positive resection margins nor the number of resected lymph nodes differed among groups. Complications and mortality occurred with similar frequencies for patients undergoing colon (p = 0.140) and rectal (p = 0.335) resection. CONCLUSION: The use of minimally invasive techniques was favored in patients with PI; however, the quality of oncological resection was not affected by insurance status and only minor differences in perioperative complications observed.

Eighty-nine-year-old woman with abdominal pain and vomiting.

CLINICAL INTRODUCTION: An 89-year-old female patient presented to the ED with mild abdominal pain and a history of vomiting for 3 days. Because of dementia, further history was unclear. Vital signs were normal. Clinical examination revealed mild abdominal pain without defence or signs of peritonism. Bowel sounds were normal. Lab results showed a white cell count of 16x109/L, otherwise normal. There was no episode of vomiting during the ED consultation. A supine AXR was performed (figure 1).emermed;35/9/576/F1F1F1Figure 1Supine AXR. WHAT IS THE DIAGNOSIS?: Foreign bodyGallstone ileusColon obstructionIntestinal volvulus.