Effect of Early Removal of Urinary Catheter in Patients Undergoing Abdominal and Thoracic Surgeries with Continuous Thoracic Epidural Analgesia on Postoperative Urinary Retention.

Background: Postoperative continuous thoracic epidural analgesia (TEA) is an integral aspect of pain management after major abdominal and thoracic surgery. Under TEA, postoperative urinary retention (POUR) is frequently noted, prompting a common practice of maintaining the transurethral catheter (UC) until the cessation of TEA to avoid the necessity for reinsertion of the UC. This study analyzes the effect of an early bladder catheter removal during TEA on POUR incidence. Methods: The retrospective study was conducted on 71 patients undergoing elective abdominal and thoracic operations with TEA for postoperative pain control. Patients were divided into two groups based on the UC removal time in relation to the epidural catheter removal. In the early removal group (ERG), the UC was removed within 3 days of surgery, while in the standard group (SG), it was removed after completion of TEA. All patients in the ERG were still receiving TEA at the time of the UC removal. The primary outcome assessed was the incidence of POUR, while secondary outcomes included urinary tract infections (UTI), hospital length of stay (LOS), and patient's comfort. Results: The overall prevalence of POUR was 7%, with five POUR cases - two (4.9%) of 41 patients in SG and three (10%) of 30 in ERG (p = 0.644). No significant difference was found in POUR occurrence between ERG and SG (p = 0.644). Additionally, no UTIs were observed in the study. The postoperative pain scores (visual analog scale [VAS]) 72 h and 96 h and the LOS (SG: 16.74 [±8.39] days; ERG: 14.53 [±6.99] days; p = 0.3) were similar between both study groups. Conclusion: Based on our results, it can be concluded that the removal of UC in the early postoperative period, even during TEA, can be performed safely without significantly increasing the risk of recatheterization.

Retroperitoneal cecal volvulus: a complication of a rare internal hernia - a case report.

Introduction and importance: The foramen of Winslow hernia (FWH) is a rare type of internal hernia. In one-third of cases, the cecum was found in the lesser sac. More rarely, the herniated cecum might be volvulated, which represents 1-1.5% of the causes of intestinal obstruction. Once diagnosed, surgical reduction and/or resection of the nonviable herniated bowel is crucial for a positive outcome. Case presentation: The authors report a case of retroperitoneal cecal volvulus that complicated FWH in a patient with a history of laparoscopic cholecystectomy. Clinical discussion: A delay in the diagnosis is associated with high morbidity and even higher mortality. Because of lacking a consensus, the treatment of FWH depends on the team's surgical experience. Conclusion: Reporting this case will help us to keep in mind this differential diagnosis while treating patients in our daily practice.

Recurrent sigmoid volvulus secondary to a large pedunculated colonic lipoma.

Symptomatic colon lipoma is a rare occurrence in clinical practice, and its association with sigmoid volvulus is even rarer. We present a case of a man in his 70s who presented to our emergency department with suspected intestinal obstruction. Upon examination, sigmoid volvulus was diagnosed and successfully treated endoscopically through decompression and detorsion. However, the patient experienced a recurrence, leading to the decision to perform sigmoid resection as a Hartmann's procedure. Subsequently, a prolapsed tumor was observed through the stoma, which was endoscopically resected, revealing a pedunculated submucous colonic lipoma. This case report highlights the potential association between sigmoid volvulus and the presence of a large colon lipoma. Thus, giant colonic lipoma should be considered as a differential diagnosis among the causes of colonic volvulus.

Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.

Conservative therapy of severe acute pancreatitis is a safe option - results of a 15-year long-term follow-up cohort study.

Treatment of severe acute pancreatitis can be challenging with high mortality. In 2012 we reported a significantly reduced in-hospital mortality if these patients are treated conservatively for at least the first 3 weeks in the course of the disease as compared to early necrosectomy. We performed a long-term follow-up and compared the outcome of these two study groups (group 1 - early necrosectomy, n=20 versus group 2 - primary conservative treatment, n=24). Materials and methods: Follow-up of the study patients by personal contact, phone survey, or data from primary care physician. Median follow-up was 15 years (range 10-22 years). This trial is registered at: Research Registry UIN researchregistry8697. Results: Eleven survivors of group 1 and 22 survivors of group 2 were discharged after initial treatment. Ten of 11 surviving patients of group 1 (90.9%) and 20 of 22 surviving patients of group 2 (90.9%) were included in this study. Between groups, there were no statistical differences in the rate of resubmission (P=0.23), development of diabetes (P=0.78), or development of exocrine insufficiency (P=1.0). However, long-term survival in group 2 was significantly better than that of group 1 (P=0.049). Conclusion: Primary conservative treatment of severe acute pancreatitis without early necrosectomy does not lead to early complications and even shows an advantage in long-term survival. Therefore conservative treatment of severe acute pancreatitis is safe and there is no absolute need for necrosectomy in severe acute pancreatitis.

Endoscopic Vacuum Therapy for Treating an Esophago-Pulmonary Fistula after Esophagectomy: A Case Report and Review of the Literature.

An acquired esophago-respiratory fistula represents an abnormal connection between the esophagus and the respiratory system. It is usually caused by malignancy and infection, or it occurs as a complication after surgery or radiation therapy. It can be divided according to its anatomical level into esophago-tracheal fistula, esophago-bronchial fistula, and in the rarest case, esophago-pulmonary fistula (EPF). We present a case of EPF aggravating an anastomotic leak (AL) after the Ivor-Lewis operation for esophageal cancer. The leak was treated with endoscopic vacuum therapy (EVT) using the Eso-Sponge® system (B. Braun Melsungen AG, Melsungen, Germany). In the further course of treatment, an EPF was suspected by a new onset of severe cough after oral fluid intake. The suspicion was confirmed by injecting methylene blue dye into the paraesophageal-extraluminal cavity during endoscopy and attesting to its presence in the respiratory tract by simultaneous bronchoscopy. Furthermore, an oral contrast computed tomography scan showed the presence of contrast in the right lower lobe of the lung. This complication was treated conservatively with EVT and antibiotics. Nutrition was administered through the existing jejunostomy. Both fistulas and the paraesophageal cavity were fully healed, oral intake was maintained, and the patient was discharged. This rare life-threatening complication can be treated conservatively. Its management is challenging, controversial, and lacks a general consensus.

Quality of Life after Desarda Technique for Inguinal Hernia Repair-A Comparative Retrospective Multicenter Study of 120 Patients.

Inguinal hernia repair, according to Desarda, is a pure tissue surgical technique using external oblique fascia to reinforce the posterior wall of the inguinal canal. This has provided an impetus for the rethinking of guideline adherence toward minimally invasive and mesh-based surgery of inguinal hernia. In this study, a retrospective analysis of this technique was conducted in two German hospitals. Between 6/2013 and 12/2020, 120 operations were performed. Analysis included patient characteristics, duration of operation, length of hospital stay, and perioperative complications. Data were used to achieve a matched-pair analysis comparing Desarda to laparoscopic transabdominal preperitoneal (TAPP) hernia repair. Propensity scores were calculated based on five preoperative variables, including sex, age, American Society of Anesthesiology classification, localization, and width of the inguinal hernia in order to achieve comparability. Additionally, we assessed pain level and quality of life (QoL) 12 months postoperatively. The focus of our study was a comparison of QoL to a reference population and TAPP cohort. The study population consisted of 106 male and 14 female patients, and the median age was 37.5 years. The median operation time was 50 min, and the median length of hospital stay was 2 days. At a follow-up of 17 months, the median recurrence rate was 0.8%, and two cases of chronic postoperative pain were recorded. Postoperative QoL does not significantly differ between Desarda and TAPP. In contrast, Desarda patients had a significantly higher QoL compared with the reference population. In summary, Desarda's procedure is a good option as a pure tissue method for inguinal hernia repair.

Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study.

OBJECTIVE: Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. DESIGN: Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). RESULTS: Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10-9, OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10-5, OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10-44). CONCLUSION: This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.

More than 30 Years of POSSUM: Are Scoring Systems Still Relevant Today for Colorectal Surgery?

BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) weights the patient's individual health status and the extent of the surgical procedure to estimate the probability of postoperative complications and death of general surgery patients. The variations Portsmouth-POSSUM (P-POSSUM) and colorectal POSSUM (CR-POSSUM) were developed for estimating mortality in patients with low perioperative risk and for patients with colorectal carcinoma, respectively. The aim of the present study was to evaluate the significance of POSSUM, P-POSSUM, and CR-POSSUM in two independent colorectal cancer cohorts undergoing surgery, with an emphasis on laparoscopic procedures. METHODS: For each patient, an individual physiological score (PS) and operative severity score (OS) was attributed to calculate the predicted morbidity and mortality, respectively. Logistic regression analysis was used to evaluate the possible correlation between the subscores and the probability of postoperative complications and mortality. RESULTS: The POSSUM equation significantly overpredicted postoperative morbidity, and all three scoring systems considerably overpredicted in-hospital mortality. However, the POSSUM score identified patients at risk of anastomotic leakage, sepsis, and the need for reoperation. Logistic regression analysis demonstrated a strong correlation between the subscores and the probability of postoperative complications and mortality, respectively. CONCLUSION: Our results suggest that the three scoring systems are too imprecise for the estimation of perioperative complications and mortality of patients undergoing colorectal surgery in the present day. Since the subscores proved valid, a revision of the scoring systems could increase their reliability in the clinical setting.

Adequate Management of Postoperative Complications after Esophagectomy: A Cornerstone for a Positive Outcome.

BACKGROUND: Esophagectomy for cancer is one of the most complex procedures in visceral surgery. Postoperative complications negatively affect the patient's overall survival. They are not influenced by the histology type (adenocarcinoma (AC)/squamous cell carcinoma (SCC)), or the surgical approach (open, laparoscopic, or robotic-assisted). Among those dreadful complications are anastomotic leak (AL), esophago-respiratory fistula (ERF), and chylothorax (CT). METHODS: In this review, we summarize the methods to avoid these complications, the diagnostic approach, and new therapeutic strategies. RESULTS: In the last 20 years, both centralization of the medical care, and the development of endoscopy and radiology have positively influenced the management of postoperative complications. For the purpose of their prevention, perioperative measures have been applied. The treatment includes conservative, endoscopic, and surgical approaches. CONCLUSIONS: Post-esophagectomy complications are common. Prevention measures should be known. Early recognition and adequate treatment of these complications save lives and lead to better outcomes.

The HSF1-CPT1a Pathway Is Differentially Regulated in NAFLD Progression.

Obesity and obesity-associated diseases represent one of the key health challenges of our time. In this context, aberrant hepatic lipid accumulation is a central pathological aspect of non-alcoholic fatty liver disease (NAFLD). By comparing methylation signatures of liver biopsies before and after bariatric surgery, we recently demonstrated the strong enrichment of differentially methylated heat shock factor 1 (HSF1) binding sites (>400-fold) in the process of liver remodeling, indicating a crucial role of HSF1 in modulating central aspects of NAFLD pathogenesis. Using cellular models of NAFLD, we were able to show that HSF1 is activated during fat accumulation in hepatocytes, mimicking conditions in patients before bariatric surgery. This induction was abolished by starving the cells, mimicking the situation after bariatric surgery. Regarding this connection, carnitine palmitoyltransferase 1 isoform A (CTP1a), a central regulator of lipid beta-oxidation, was identified as a HSF1 target gene by promoter analysis and HSF1 knockdown experiments. Finally, pharmacological activation of HSF1 through celastrol reduced fat accumulation in the cells in a HSF1-dependent manner. In conclusion, we were able to confirm the relevance of HSF1 activity and described a functional HSF1-CPT1a pathway in NAFLD pathogenesis.

An Extremely Rare Cause of an Obstructive Jaundice in Adults: Limited Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct.

Langerhans cell histiocytosis (LCH) is a rare group of idiopathic disorders (previously termed "histiocytosis X") which is characterized by the presence of cells with characteristics similar to bone marrow-derived Langerhans cells which infiltrate various tissues and organs. Like Langerhans cells located in the skin, they express histiocytic markers such as S100, CD1a, and CD68 and contain Birbeck granules, which are rod-shaped intracytoplasmic organelles best demonstrated in electron microscopy. LCH primarily affects the skeleton, but lung, skin, liver, and lymph node involvement may occur alike. Hepatic involvement is well recognized in children, with sclerosing cholangitis occurring in 10-15% of those with multisystemic involvement, whereas LCH confined to the liver appears to be very unusual in adults. Up to date, only one case of a solitary LCH affliction of the extrahepatic bile duct lacking liver involvement in adulthood has been reported on in the literature. We here report on a 60-year-old male patient with classical indolent progressive obstructive jaundice. The diagnostic workup revealed a tumorous lesion in the middle third of the common hepatic bile duct, initially being highly suspicious of an extrahepatic cholangiocarcinoma. CT scans further suspected an infiltration of the right portal vein, implicating a potentially extensive tumor growth, but a preoperative histological confirmation was not feasible. The serum tumor marker CA19-9 was 48 U/mL. The patient then underwent an explorative laparotomy with a pylorus preserving pancreaticoduodenectomy, as all frozen section tissue specimens revealed no tumor infiltration. The final result of the histopathological examination revealed an isolated LCH in the extrahepatic bile duct with a consecutive secondary sclerosing cholangitis. To complete the tumor staging, a thorax CT scan was performed and a generalized histiocytosis was ruled out, hence confirming the localized character of the disease. To the best of our knowledge and after a comprehensive literature review, we report on the second case globally, which describes a primary LCH limited to the extrahepatic bile duct in adulthood. A generalized sclerosing cholangitis in the liver was ruled out by radiological imaging. Preoperative histological affirmation of such findings is very confined due to the complexity and hence can only be diagnosed in the postoperative specimen. However, patients with nondisseminated sole findings, usually report a good prognostic outcome after surgical resection despite the paucity of corresponding data.

Global Association of Cause-specific Mortality between the Major Gastrointestinal Cancers and Parkinson's Disease for the First Two Decades of the New Millennium.

Parkinson's disease (PD) and gastrointestinal (GI) cancers are both "age-related diseases" sharing several environmental risk factors, but possess opposite underlying biological mechanisms. Aim of this study was to evaluate the correlations between GI cancers and PD using national cause-specific mortality data of 183 countries extracted from the Global Health Observatory database. The association between PD- and GI cancers- (i.e. esophagus cancer, EC; stomach cancer, SC; colorectal cancer, CRC; liver cancer, LC and pancreatic cancer, PC) specific mortality on the country level was evaluated using Spearman correlation and logistic regression analysis. A global increase in mortality from 2000 to 2019 was observed in PD, CRC and PC, whereas in EC, SC and LC it decreased. We see the consistent diminishment of correlation intensities between PD and GI cancer mortalities from 2000 to 2019 as a positive development. In 2019, PD inversely correlated with CRC (rs = -0.39) and PC (rs = -0.40, all P < 0.001) but not with EC and SC. Of note, an exceptionally positive correlation of PD with LC (rs = 0.26, P < 0.001) and its two hepatitis B and C virus-associated subtypes was revealed. Logistic regression analysis further determined that PD associated negatively with CRC (OR = 0.25) and PC (OR = 0.21, both P < 0.001), but positively with LC (OR = 2.27, P = 0.007). Consequently, future research aiming to unravel the functional biological link between neurodegeneration, hepatitis and tumor development holds great potential for developing novel therapeutics.

Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer.

Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8+ T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8+ T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8+ T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8+ T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC.

Eso-Sponge® for anastomotic leakage after oesophageal resection or perforation: outcomes from a national, prospective multicentre registry.

BACKGROUND: Anastomotic leakage (AL) after oesophagectomy and oesophageal perforations are associated with significant morbidity and mortality. Minimally invasive endoscopy is often used as first-line treatment, particularly endoluminal vacuum therapy (EVT). The aim was to assess the performance of the first commercially available endoluminal vacuum device (Eso-Sponge®) in the management of AL and perforation of the upper gastrointestinal tract (GIT). METHODS: The Eso-Sponge® registry was designed in 2014 as a prospective, observational, national, multicentre registry. Patients were recruited with either AL or perforation within the upper GIT. Data were collected with a standardized form and transferred into a web-based platform. Twenty hospitals were enrolled at the beginning of the study (registration number NCT02662777; http://www.clinicaltrials.gov). The primary endpoint was successful closure of the oesophageal defect. RESULTS: Eleven out of 20 centres recruited patients. A total of 102 patients were included in this interim analysis; 69 patients with AL and 33 with a perforation were treated by EVT. In the AL group, a closure of 91 per cent was observed and 76 per cent was observed in the perforation group. The occurrence of mediastinitis (P = 0.002) and the location of the defect (P = 0.008) were identified as significant predictors of defect closure. CONCLUSIONS: The Eso-Sponge® registry offers the opportunity to collate data on EVT with a uniform, commercially available product to improve standardization. Our data show that EVT with the Eso-Sponge® is an option for the management of AL and perforation within the upper GIT.

Management of Pulmonary Artery Synovial Sarcoma: The 3-Step Surgical Approach.

Primary pulmonary artery sarcoma is an uncommon neoplasm. Given its clinical and radiographic resemblance to pulmonary embolism, initial diagnostic steps may be complicated, leading to delay in diagnosis. This report presents the case of a 52-year-old-woman who was admitted with pulmonary embolism. She underwent pulmonary embolectomy, and histopathologic examination revealed synovial sarcoma.

A novel unconventional T cell population enriched in Crohn's disease.

OBJECTIVE: One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls. DESIGN: We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. RESULTS: We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs. CONCLUSIONS: We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies.

PSD3 downregulation confers protection against fatty liver disease.

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.