Safety of perioperative treatment with biologics in patients with inflammatory bowel disease undergoing bowel surgery: Experience from a large urban center.

BACKGROUND AND AIMS: Risks of peri- and postoperative complications after bowel surgery in patients with inflammatory bowel disease (IBD) receiving biologics are still discussed controversially. We therefore addressed the safety of different biologics that were applied in our IBD center before surgery. METHODS: Data of IBD patients who underwent bowel resections between 2012 and 2022 at our hospital were analyzed retrospectively. Exposure to biologics was defined by receiving biologics within 12 weeks before resective abdominal surgery. Safety considerations included minor complications, such as infections and wound healing disorders and major complications, e.g., anastomotic insufficiency or abscess formation. RESULTS: A total of 447 IBD patients (334 with Crohn's disease, 113 with ulcerative colitis), 51.9% female, were included and followed for a median follow-up of 45 months [range 0-113]. A total of 73.9% (326/447) were undergoing medical treatment at date of surgery, 61.5% (275/447) were treated with biologics within 3 months and 42.3% (189/447) within 4 weeks before surgery. Most surgeries (97.1%) were planned electively and 67.8% were performed laparoscopically. Major and minor complications occurred in 20.8% (93/447) of patients. Serious complications were rare: Six patients had acute postoperative bleeding, one CD patient developed peritonitis and two CD patients died postoperatively. After adjusting for age, disease duration, disease activity, Montreal classification, and medical treatment at date of surgery, no significant differences were observed regarding complications and exposure to biologics. CONCLUSIONS: This retrospective single center study of 447 IBD patients goes to demonstrate that perioperative use of biologics is not associated with a higher risk of complications.

Damage control strategy in perforated diverticulitis with generalized peritonitis.

BACKGROUND: The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann's procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS. METHODS: DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24-48 h: definite reconstruction with colorectal anastomosis (-/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis). RESULTS: Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma. CONCLUSION: DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.

Role of Brain Biomarkers S-100-Beta and Neuron-Specific Enolase for Detection and Follow-Up of Hepatic Encephalopathy in Cirrhosis before, during and after Treatment with L-Ornithine-L-Aspartate.

INTRODUCTION: Hepatic encephalopathy (HE), in the context of liver cirrhosis, seems to result from low-grade cerebral edema of the astrocytes. Serum brain biomarkers S-100-beta und neuron-specific enolase (NSE) are often elevated in brain injury. We hypothesized that neuromarkers S-100-beta and NSE can be used in the diagnosis of HE, compared with standardized diagnostic tools. MATERIAL AND METHODS: A prospective non-randomized intervention study was performed using L-ornithine-L-aspartate (LOLA) for HE treatment. Primary endpoint was the evaluation of neuromarkers S-100-beta and NSE for detection and diagnosis of follow-up of HE. As secondary endpoints, the efficacy of LOLA on the course of HE and the diagnostic role of Portosystemic-Encephalopathy-Syndrome score (PHES) and critical flicker frequency (CFF) were analyzed. For diagnosis of covert (CHE) and overt (OHE) HE, West-Haven criteria (WHC), PHES and CFF were assessed at study entry. LOLA was applied (20 g i.v.) for 6 days. At the end of the study, HE evaluation was repeated. S-100-beta, NSE and ammonia were assessed in each patient before, during and after therapy with LOLA. RESULTS: 30 patients were included. At study entry, CHE was diagnosed in 50% and OHE in 50% of all subjects. A total of 25 participants completed the study. After LOLA therapy, deterioration of HE occurred in <11%, while most patients showed improvement (e.g. improved CFF in 79%). No significant correlation with HE severity (as diagnosed by WHC, PHES and CFF) could be demonstrated for any biochemical parameter. In addition, there were no significant changes in brain biomarkers during the treatment period. DISCUSSION: While CFF as well as PHES showed good correlation with treatment response, S-100-beta and NSE did not significantly correlate with HE severity compared to proven diagnostic methods, and do not seem reliable biochemical markers for the follow-up under therapy.

INTRODUÇÃO: A encefalopatia hepática (EH) na cirrose é vista como o resultado de edema cerebral de baixo grau dos astrócitos. Biomarcadores cerebrais serológicos S-100-beta e enolase neurónio-específica (NSE) estão frequentemente elevados na lesão cerebral. A nossa hipótese é que os neuromarcadores S-100-beta e NSE podem ser usados no diagnóstico de EH, quando comparados com os meios diagnósticos standard. MATERIAL E MÉTODOS: Estudo prospectivo não randomizado foi realizado usando L-ornitina-L-aspartato (LOLA) no tratamento da EH. O endpoint primário foi a avaliação dos neuromarcadores S-100-beta e NSE para a deteção e vigilância da EH. Foram endpoints secundários a eficácia da LOLA no curso da EH e o papel diagnóstico do Portosystemic-Encephalopathy-Syndrome score (PHES) e do critical flicker frequency (CFF). Para o diagnóstico de EH oculta (EHO) ou declarada (EHD) foram avaliados os West-Haven criteria (WHC), PHES e CFF à entrada do estudo. LOLA foi administrada (20 g ev) por 6 dias. No fim do estudo os testes de EH foram repetidos. Os níveis de S-100-beta, NSE e amónia foram avaliados em todos os doentes antes, durante e após a terapêutica com LOLA. RESULTADOS: Foram incluídos 30 doentes no estudo. À entrada EHO foi diagnosticada em 50% e EHD nos restantes 50% dos participantes. Um total de 25 doentes completaram o estudo. Após a terapêutica com LOLA, verificou-se deterioração da EH em < 11%, enquanto a maioria dos doentes melhorou (melhoria CFF em 79%). Não se demonstrou nenhuma correlação significativa com a gravidade da EH (tendo em conta os WHC, PHES e CFF) para nenhum dos parâmetros bioquímicos. Para além disso, não se demonstraram variaões significativa nos biomarcadores cerebrais durante o período de tratamento. DISCUSSÃO: Apesar do CFF e do PHES apresentarem boa correlação com a resposta terapêutica, a S-100-beta e a NSE não se correlacionaram significativamente com a gravidade da EH quando comparado com os outros métodos diagnósticos standard, não parecendo ser marcadores bioquímicos úteos para a vigilância da resposta terapêutica.

PREDICtors for health-related quality of life after elective sigmoidectomy for DIVerticular disease: the PREDIC-DIV study protocol of a prospective multicentric transnational observational study.

INTRODUCTION: Diverticulitis is among the most common abdominal disorders. The best treatment strategy for this complicated disease as well as for recurrent stages is still under debate. Moreover, little knowledge exists regarding the effect of different therapeutic strategies on the health-related quality of life (HrQoL). Therefore, the PREDIC-DIV (PREDICtors for health-related quality of life after elective sigmoidectomy for DIVerticular disease) study aims to assess predictors of a change in HrQoL in patients after elective sigmoidectomy for diverticular disease. METHODS AND ANALYSIS: A prospective multicentre transnational observational study was started in November 2017. Patients undergoing elective sigmoid resection for diverticular disease were included. Primary outcome includes HrQoL 6 months postoperatively, staged by the Gastrointestinal Quality of Life Index (GIQLI). Secondary outcomes include HrQoL 6 months after sigmoidectomy, assessed using the Short Form 36 Questionnaire and a custom-made Visual Analogue Scale-based inventory; HrQoL after 12 and 24 months; postoperative morbidity; mortality; influence of surgical technique (conventional laparoscopic multiport operation vs robotic approach); histological grading of inflammation and morphological characteristics of the bowel wall in the resected specimen; postoperative functional changes (faecal incontinence, faecal urge, completeness of emptying, urinary incontinence, sexual function); disease-specific healthcare costs; and changes in economic productivity, measured by the iMTA Productivity Cost Questionnaire. The total follow-up will be 2 years. ETHICS AND DISSEMINATION: The protocol was approved by the medical ethical committee of the Bavarian Medical Council (report identification number: 2017-177). The study was conducted in accordance with the Declaration of Helsinki. The findings of this study will be submitted to a peer-reviewed journal (BMJ Open, Annals of Surgery, British Journal of Surgery, Diseases of the Colon and the Rectum). Abstracts will be submitted to relevant national and international conferences. TRIAL REGISTRATION NUMBER: The study is registered with the ClinicalTrials.gov register as NCT03527706; Pre-results.

Risk of colectomy after conservative treatment of diverticulitis of the left hemicolon complicated by abdominal or pelvic abscess: protocol of a systematic review and meta-analysis.

INTRODUCTION: Acute diverticulitis of the sigmoid colon is increasingly treated by a non-operative approach. The need for colectomy after recovery from a flare of acute diverticulitis of the left colon, complicated diverticular abscess is still controversial. The primary aim of this study is to assess the risk of interval emergency surgery by systematic review and meta-analysis. METHODS AND ANALYSIS: The systematic review and meta-analysis will be conducted in accordance to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and EMBASE will be screened for the predefined searching term: (Diverticulitis OR Diverticulum) AND (Abscess OR pelvic abscess OR pericolic abscess OR intraabdominal abscess) AND (surgery OR operation OR sigmoidectomy OR drainage OR percutaneous drainage OR conservative therapy OR watchful waiting). All studies published in an English or German-speaking peer-reviewed journal will be suitable for this analysis. Case reports, case series of less than five patients, studies without follow-up information, systematic and non-systematic reviews and meta-analyses will be excluded. Primary endpoint is the rate of interval emergency surgery. Using the Review Manager Software (Review Manager/RevMan, V.5.3, Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration, 2012) meta-analysis will be pooled using the Mantel-Haenszel method for random effects. The Risk of Bias in Non-randomized Studies of Interventions tool will be used to assess methodological quality of non-randomised studies. Risk of bias in randomised studies will be assessed using the Cochrane developed RoB 2-tool. ETHICS AND DISSEMINATION: As no new data are being collected, ethical approval is exempt for this study. This systematic review is to provide a new insight on the need for surgical treatment after a first attack of acute diverticulitis, complicated by intra-abdominal or pelvic abscesses. The results of this study will be presented at national and international meetings and published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020164813.

Frequency of Polyps and Adenocarcinoma in Colon Interposition After Esophagectomy in Adulthood - A Systematic Review.

BACKGROUND/AIM: Colon interposition counts among the most common techniques for reconstruction after esophagectomy. Availability of data on metachronous mucosal pathologies is weak. The aim of this review was to identify all reports on the development of metachronous adenoma and adenocarcinoma in colon interposition after esophagectomy in adulthood. MATERIALS AND METHODS: A comprehensive search was conducted in MEDLINE/PubMed, Science Direct, Cochrane Library, Bayerische Staatsbibliothek München. All studies reporting on patients who received colon interposition as substitute after esophagectomy in adulthood for benign and malignant reasons were included. RESULTS: Five retrospective studies were included, reporting on 1016 patients. Therein, no interval lesion was identified. One further study, which formally must be excluded for a misfit to inclusion criteria reports on three interval carcinomas within 365 patients. Because these lesions were the only ones found within a cohort analysis, results were supplementary reported in this review. Additionally, 31 case reports including 32 patients with benign (n=7) or malignant (n=25) findings were analyzed. Median age was 63.5 years (interval carcinoma) and 69 years (benign lesion). Benign and malignant lesions were diagnosed after a median of 8.5 years. CONCLUSION: Due to the rareness of respective cohort studies, the frequency of metachronous lesions cannot be calculated accurately. The estimated rate of interval carcinoma is 0-0.22%. Life-long endoscopic surveillance of patients with colon interposition is recommended.

Disease phenotype rather than treatment strategy impacts the long-term quality of life in patients with diverticular disease.

PURPOSE: To identify the impact of the severity of diverticular disease on long-term quality of life. METHODS: Consecutive patients, hospitalized between October 2009 and November 2015 due to uncomplicated (UD) and complicated diverticulitis (CD) of the left colon, were analyzed. Patients undergoing emergent surgery for perforated disease were excluded. Primary endpoint was health-related quality of life (HrQol), measured by the Short Form 36 questionnaire (SF-36). Physical (PCS) and mental (MCS) compository scores were calculated from SF-36 subscales. To overcome bias, one-to-one propensity score matching and multivariable logistic regression analysis were performed. RESULTS: Two hundred eighty of the overall 392 patients (Male 138, Female 142; mean age 60.5 years, range 27-91) answered the SF-36 questionnaire. The median follow-up period was 37.8 months (range 15-85). After propensity score matching, each group consisted of 51 patients. Results of the SF-36 questionnaires showed a statistically significant difference, favoring patients with CD in 5 of 8 domains. Also, PCS (56.3 vs. 52.9, p = 0.13) and MCS (53.3 vs. 46.7, p = 0.005) were higher in patients treated for CD. By a multivariate analysis, complicated disease was independently associated with a better scoring on 6 out of 8 SF-36 subscales and on MCS. Treatment strategy (surgery or conservative) did not have any impact on SF-36 subscales, MCS, or PCS on multivariate analysis. CONCLUSION: In contrast to complicated disease, the uncomplicated diverticular disease is associated with an impaired long-term quality of life especially in domains composing mental health scores independently of chosen treatment strategy. STUDY REGISTRATION: The study is registered with the Research Registry at June 19, 2019. Research registry UIN: researchregistry4959 .

Perforated Diverticulitis with Generalized Peritonitis: Low Stoma Rate Using a "Damage Control Strategy".

PURPOSE: Optimal surgical management of perforated diverticulitis of the sigmoid colon has yet to be clearly defined. The purpose of this study was to evaluate efficacy of a "Damage Control Strategy" (DCS). MATERIALS AND METHODS: Patients with perforated diverticulitis of the sigmoid colon complicated by generalized peritonitis (Hinchey III and IV) surgically treated according to a damage control strategy between May 2011 and February 2017 were enrolled in the present multicenter retrospective cohort study. Data were collected at three surgical centers. DCS comprises a two-stage concept: [1] limited resection of the perforated colon segment with oral and aboral blind closure during the emergency procedure and [2] definitive reconstruction at scheduled second laparotomy (anastomosis ∓ loop ileostomy or a Hartmann's procedure) after 24-48 h. RESULTS: Fifty-eight patients were included into the analysis [W:M 28:30, median age 70.1 years (30-92)]. Eleven patients (19%) initially presented with fecal peritonitis (Hinchey IV) and 47 patients with purulent peritonitis (Hinchey III). An anastomosis could be created during the second procedure in 48 patients (83%), 14 of those received an additional loop ileostomy. In the remaining ten patients (n = 17%), an end colostomy was created at second laparotomy. A fecal diversion was performed in five patients to treat anastomotic complications. Thus, altogether, 29 patients (50%) had stoma at the end of the hospital stay. The postoperative mortality was 9% (n = 5), and median postoperative hospital stay was 18.5 days (3-66). At the end of the follow-up, 44 of 53 surviving patients were stoma free (83%). CONCLUSION: The use of the Damage Control strategy leads to a comparatively low stoma rate in patients suffering from perforated diverticulitis with generalized peritonitis.

Surgical management of acute appendicitis in adults: A review of current techniques.

Acute appendicitis is one of the most frequent disorders in abdominal surgery. Therefore, appendectomy is a matter of significant interest in that field. Yet, four different techniques are available: open appendectomy, (conventional) laparoscopic appendectomy, single port laparoscopic appendectomy and NOTES-appendectomy with its different variations. To evaluate the current state of the art in appendectomy a bibliographic search was conducted. All prospectively randomized trials and national register cohort studies published between 1/2010 and 5/2016 were included into the analysis. Overall, 25 respective studies were identified. All studies were screened for the following parameters: surgical site infection (SSI) (wound infection (WI) or intraabdominal abscess (IAA)), postoperative pain (PP), length of surgery (LoS), length of hospital stay (LHS), return to normal activities (RNA). Today the rate of laparoscopic appendectomy is reported to be up to 86% in the recent literature. Open appendectomy remains a safe and effective technique. Single port laparoscopic appendectomy presented almost equal in terms of safety and patient satisfaction. The method is still not as widespread as conventional three port laparoscopic appendectomy, presumably due to the necessity of special equipment and training. NOTES appendectomy is the newest development in appendectomy technique. First prospective cohort studies proved the safety and feasibility in experienced hands. However, the method is still experimental and further prospectively randomized trials are necessary. Concluding the current evidence, a laparoscopic approach, which is most commonly and increasingly frequently used, could be called "state of the art" in the treatment of appendicitis.

Intrapancreatic mass: A rare cause.

We found a case of pancreatic extraintestinal gastrointestinal stroma tumor (pEGIST) in 2014. The patient, initially suspected to suffer from pancreatic adenocarcinoma, underwent open left hemipancreatectomy and en bloc splenectomy in May 2014. Postoperative histopathology showed the unexpected manifestation of a pEGIST. Recovery was well, and a 23-month follow-up was free from recurrency by now.

Preservation of the superior rectal artery: influence of surgical technique on anastomotic healing and postoperative morbidity in laparoscopic sigmoidectomy for diverticular disease.

PURPOSE: To evaluate the impact of superior rectal artery (SRA) sparing technique on anastomotic leakage in laparoscopic sigmoidectomy for diverticular disease. MATERIAL AND METHODS: A retrospective multicenter analysis of all patients undergoing laparoscopic sigmoid resection for diverticular disease between 2002 and 2015 was conducted. Data were recorded in three hospitals: University Hospital Regensburg, Marienhospital Gelsenkirchen, and Städtisches Klinikum München Bogenhausen. The SRA was resected between 2002 and 2005. Since 2005, the artery was preserved in most cases. RESULTS: Two hundred sixty-seven patients were included. One hundred sixty patients presented with complicated diverticulitis (60%). The SRA was resected in 102 patients (group 1) and preserved in 157 patients (group 2, no data in eight cases). Anastomotic leakage occurred in 7% of patients in group 1 and 1.9% of patients in group 2 (p = 0.053). Duration of surgery was significantly shorter (157 vs. 183 min, p < 0.001) in group 2 patients. Length of hospital stay was without significant difference (group 1 8.2 days; group 2 8.3 days; p = 0.83). The conversion rate was higher in group 2 patients; however, the difference was not statistically significant (9 vs. 3%, p = 0.07). There was no significant difference between both groups regarding intraoperative complications and overall complication rate. The length of the resected specimen (19 vs. 21 cm, p = 0.001) was significantly shorter in group 2 patients. CONCLUSION: Preservation of the SRA seems to be associated with favorable outcome in patients undergoing laparoscopic sigmoid resection for diverticular disease.

Laparoscopic Appendectomy Is Safe: Influence of Appendectomy Technique on Surgical-site Infections and Intra-abdominal Abscesses.

PURPOSE: Surgical-site infections (SSIs) and intra-abdominal abscesses (IAAs) are the most frequent complications of appendectomy. The role of laparoscopy in the treatment of appendicitis remains controversial concerning the complication rate. The aim of this retrospective cohort study was to compare open and laparoscopic appendectomy for SSI and IAA. METHODS: All patients undergoing appendectomy between January 1, 2007 and May 31, 2010 were included in the study. Perioperative data and data on postoperative complications were collected from patient files. A questionnaire was used to assess complications after discharge. Main outcome parameters were SSI and IAA. Open appendectomy (OAG) and laparoscopic appendectomy (LAG) were compared with univariate and multivariate analyses for the outcome parameters. RESULTS: Four hundred thirty patients were included in the study. SSI (all: 10.6%, OAG: 11.7%, LAG: 7.5%, P=0.293) and IAA (all: 2.8%, OAG: 2.4%, LAG: 3.8%, P=0.506) were not significantly different between OAG and LAG. Risk factors for SSI were age (P=0.003), body mass index (P=0.017), ASA score (P=0.001), the intraoperative grade of inflammation (P=0.004), and the histologic grade of inflammation (P=0.015). The only risk factor for IAA was the intraoperative grade of inflammation (P=0.028). ASA score (odds ratio: 1.992, P=0.032) and the intraoperative grade of inflammation (odds ratio: 1.573, P=0.006) remained significant in the multivariate analysis for SSI. CONCLUSIONS: A higher ASA score correlates with SSI. A higher grade of intraoperative inflammation correlates with SSI and IAA. Laparoscopy has no impact on SSI and IAA in appendectomy.

Numerical and structural genomic aberrations are reliably detectable in tissue microarrays of formalin-fixed paraffin-embedded tumor samples by fluorescence in-situ hybridization.

Few data are available regarding the reliability of fluorescence in-situ hybridization (FISH), especially for chromosomal deletions, in high-throughput settings using tissue microarrays (TMAs). We performed a comprehensive FISH study for the detection of chromosomal translocations and deletions in formalin-fixed and paraffin-embedded (FFPE) tumor specimens arranged in TMA format. We analyzed 46 B-cell lymphoma (B-NHL) specimens with known karyotypes for translocations of IGH-, BCL2-, BCL6- and MYC-genes. Locus-specific DNA probes were used for the detection of deletions in chromosome bands 6q21 and 9p21 in 62 follicular lymphomas (FL) and six malignant mesothelioma (MM) samples, respectively. To test for aberrant signals generated by truncation of nuclei following sectioning of FFPE tissue samples, cell line dilutions with 9p21-deletions were embedded into paraffin blocks. The overall TMA hybridization efficiency was 94%. FISH results regarding translocations matched karyotyping data in 93%. As for chromosomal deletions, sectioning artefacts occurred in 17% to 25% of cells, suggesting that the proportion of cells showing deletions should exceed 25% to be reliably detectable. In conclusion, FISH represents a robust tool for the detection of structural as well as numerical aberrations in FFPE tissue samples in a TMA-based high-throughput setting, when rigorous cut-off values and appropriate controls are maintained, and, of note, was superior to quantitative PCR approaches.