Torsion of the spiral colon in cattle- a retrospective analysis of 58 cases.

BACKGROUND: Torsion of the spiral colon (TSC) describes twisting of the spiral colon around its mesentery. The present study reviewed the medical records of 58 cows and heifers with TSC and described the findings, treatment and outcome. RESULTS: All cases had an abnormal general condition, and the main vital sign abnormalities were tachycardia (72.4%), tachypnoea (67.2%) and decreased rectal temperature (51.8%). Signs of colic were seen in 62.1% of the cows. The most common intestinal abnormalities were an empty or almost empty rectum (96.6%), reduced or absent rumen motility (93.2%), positive ballottement and/or percussion and simultaneous auscultation on the right side of the abdomen (87.9%), reduced or absent intestinal motility (84.5%) and dilatation of the large intestines (spiral colon and/or caecum, 70.7%) diagnosed by transrectal palpation. The main biochemical changes were hypermagnesaemia (70.8%), hypocalcaemia (70.8%), and acidosis (66.7%). Haemoconcentration was found in 63.8%. The main ultrasonographic findings were reduced to absent small intestinal motility (83.3%), dilated small intestines (69.6%) and ascites (66.7%). The spiral colon was dilated in 44.0% of the cows and the caecum in 24.0%. The actual site of torsion could not be visualised. Based on the clinical findings, TSC was diagnosed in 22.4% and caecal dilatation in 50.0% of the cows. A tentative diagnosis of small intestinal ileus was made in another 10.3% of the cows, and a definitive diagnosis of small intestinal ileus in 17.3%. Fifty-three cows underwent right flank laparotomy, and the TSC could be reduced in 26. Twenty-six of the 58 (44.8%) cows were discharged and 32 (55.2%) were euthanased before, during or after surgery. CONCLUSIONS: Acute illness, a sparse amount of faeces in the rectum and dilated spiral colon and caecum are characteristic findings of TSC. The final diagnosis often relies on the surgical or postmortem findings. Cattle with TSC should be treated surgically without delay. The prognosis is guarded with a survival rate of 44.8%.

Small intestinal volvulus in 47 cows.

Objective: To describe the findings, treatment, and outcome of small intestinal volvulus (SIV) in 47 cows. Animals and procedure: Retrospective analysis of medical records. Comparison of the findings for 18 surviving and 29 non-surviving cows. Results: The most common abnormal vital signs were tachycardia (68.0%), tachypnea (59.6%), and decreased rectal temperature (51.1%). Signs of colic occurred in 66.0% of cows in the study. Rumen motility was reduced or absent in 93.6% of cows, and intestinal motility in 76.6%. Clinical signs on ballottement and/or percussion and simultaneous auscultation were positive on the right side in 78.7% of cows. Transrectal examination showed dilated small intestines in 48.9% of cows. The rectum contained little or no feces in 93.6% of cows. The principal laboratory abnormalities were hypocalcemia (74.1%), hypokalemia (73.8%), azotemia (62.8%), hypermagnesemia (61.6%), and hemoconcentration (60.0%). The principal ultrasonographic findings were dilated small intestines (87.1%) and reduced or absent small intestinal motility (85.2%). Forty-one of the 47 cows underwent right flank laparotomy and the SIV was reduced in 21 cows. When comparing the clinical and laboratory findings of 18 surviving and 29 non-surviving cows, the groups differed significantly with respect to severely abnormal general condition (16.7 versus 37.9%), rumen stasis (22.2 versus 79.3%), intestinal atony (16.7 versus 48.3%), serum urea concentration (6.5 versus 9.8 mmol/L), and serum magnesium concentration (0.98 versus 1.30 mmol/L). In summary, 38.3% of the cows were discharged and 61.7% were euthanized before, during, or after surgery. Conclusion and clinical relevance: An acute course of disease, little or no feces in the rectum, and dilated small intestines were characteristic of SIV in this study population.

Volvulus de l'intestin grêle chez 47 vaches. Objectif: Décrire les données, le traitement et les résultats du volvulus de l'intestin grêle (SIV) chez 47 vaches. Animaux et procédure: Analyse rétrospective des dossiers médicaux. Comparaison des résultats pour 18 vaches survivantes et 29 vaches non survivantes. Résultats: Les signes vitaux anormaux les plus courants étaient la tachycardie (68,0 %), la tachypnée (59,6 %) et la diminution de la température rectale (51,1 %). Des signes de coliques sont apparus chez 66,0 % des vaches étudiées. La motilité du rumen était réduite ou absente chez 93,6 % des vaches et la motilité intestinale chez 76,6 %. Les signes cliniques de ballottement et/ou percussion et auscultation simultanée étaient positifs du côté droit chez 78,7 % des vaches. L'examen transrectal a montré une dilatation de l'intestin grêle chez 48,9 % des vaches. Le rectum contenait peu ou pas de matières fécales chez 93,6 % des vaches. Les principales anomalies des analyses de laboratoire étaient l'hypocalcémie (74,1 %), l'hypokaliémie (73,8 %), l'azotémie (62,8 %), l'hypermagnésémie (61,6 %) et l'hémoconcentration (60,0 %). Les principaux résultats échographiques étaient une dilatation de l'intestin grêle (87,1 %) et une motilité intestinale réduite ou absente (85,2 %). Quarante et une des 47 vaches ont subi une laparotomie du flanc droit et le SIV a été corrigé chez 21 vaches. En comparant les résultats cliniques et biologiques de 18 vaches survivantes et de 29 vaches non survivantes, les groupes différaient significativement en ce qui concerne l'état général sévèrement anormal (16,7 contre 37,9 %), la stase du rumen (22,2 contre 79,3 %), l'atonie intestinale (16,7 contre 48,3 %), la concentration sérique d'urée (6,5 contre 9,8 mmol/L) et la concentration sérique de magnésium (0,98 contre 1,30 mmol/L). En résumé, 38,3 % des vaches ont reçu leur congé et 61,7 % ont été euthanasiées avant, pendant ou après l'intervention chirurgicale. Conclusion et pertinence clinique: Une évolution aiguë de la maladie, peu ou pas de selles dans le rectum et un intestin grêle dilaté étaient caractéristiques du SIV dans cette population étudiée.(Traduit par Dr Serge Messier).

Dilated small and large intestines combined with a severely abnormal demeanor are characteristic of mesenteric torsion in cattle.

OBJECTIVE: To describe the clinical, laboratory, and ultrasonographic findings; treatment; and outcome of cattle with mesenteric torsion (MT). ANIMALS: 61 cattle with MT between November 1, 1986, and December 31, 2019. METHODS: Medical records were retrospectively reviewed. Results were compared for cattle that survived versus did not survive to hospital discharge. RESULTS: All cattle had abnormal demeanor. The most common clinical signs were tachycardia (80.3% [49/61]), tachypnea (65.0% [39/60]), and lower rectal temperature (59.3% [35/59]). Signs of colic occurred in 65.6% (40/61). The most common gastrointestinal findings were an empty or almost empty rectum (100% [59/59]), reduced or absent motility of the small intestines (96.6% [57/59]) or rumen (93.2% [55/59]), positive ballottement and/or percussion and simultaneous auscultation on the right side (91.7% [55/60]), and dilated small (49.2% [29/59]) and large intestines (spiral colon and/or cecum, 44.1% [26/59]) detected during transrectal examination. The most common laboratory findings were acidosis (82.6%, [38/46]) hypermagnesemia (74.5% [35/47]). Ultrasonographic findings included reduced or absent small intestinal motility (86.7% [26/30]) and dilated small intestines (83.8% [31/37]). The spiral colon was dilated in 32.4% (12/37) of the cattle. Eighty-two percent (50/61) of the cattle underwent right flank laparotomy and the MT could be reduced in 34.4% (21/61). Twenty-three percent (14/61) of the cattle survived to hospital discharge, and 77.0% (47/61) were euthanized before hospital discharge. CLINICAL RELEVANCE: Dilated small and large intestines (spiral colon, cecum) combined with a severely abnormal demeanor and tachycardia are characteristic findings in cows with MT. Immediate surgical treatment is paramount.

A retrospective review of small intestinal intussusception in 126 cattle in Switzerland.

Background: Intussusception is a form of ileus of the intestines in which an oral intestinal segment slides into the adjacent aboral intestinal segment, causing obstruction of the bowel. Methods: We analysed the medical records of 126 cattle with intussusception of the small intestine. Results: Demeanour and appetite were abnormal in 123 cattle. Non-specific signs of pain occurred in 26.2%, signs of visceral pain in 46.8% and signs of parietal pain in 56.4%. Intestinal motility was decreased or absent in 93.7% of the cattle. The most common findings of transrectal palpation were rumen dilation (37.3%) and dilated small intestines (24.6%). In 96% of the cattle, the rectum was empty or contained little faeces. The principal laboratory findings were hypokalaemia (89.6%), hypocalcaemia (76.5%), base excess (72.9%), hypochloraemia (71.8%), azotaemia (62.1%) and haemoconcentration (61.1%). The main ultrasonographic findings were reduced or absent intestinal motility (98.2%) and dilated small intestines (96.0%). A diagnosis of ileus was made in 87.8% and a diagnosis of ileus attributable to intussusception was made in another 9.8%. Right-flank laparotomy was carried out in 114 cattle. Fifty-six (44.4%) cows were discharged. Conclusions: Clinical findings of intussusception in cattle are often non-specific. Ultrasonography may be required to diagnose ileus.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma.

Background: Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities. The association of PD-1/PD-L1 expression and its impact on patient prognosis with SBA is unclear. Material and methods: Seventy-five consecutive patients who underwent surgery for SBA were retrospectively analyzed and stained for PD-L1 expression in the tumour or the stroma. Analysis of mismatch repair genes was performed to determine microsatellite status. Kaplan-Meier estimate was used to analyze patient survival. Univariate and multivariable Cox regression-analyses were used to assess the impact of PD-L1 expression and microsatellite status on patient survival.Results: PD-L1 was weakly upregulated within the tumour or the stroma and associated with prolonged survival (p = .0071 and p = .0472, respectively). Fifty-one tumours (68%) revealed microsatellite stability (MSS) and 24 tumours (32%) were microsatellite instable (MSI) without correlating with patient survival (p = .611). Neither PD-L1 expression in the tumour nor in the stroma was identified as an independent risk factor influencing survival (p = .572 and p = .3055).Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival.

High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases.

BACKGROUND: Patients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM. METHODS: Transcript levels of hypoxia-adaptive genes (such as PDK isoenzymes) were assessed in the tissue of healthy liver, corresponding CRLM, healthy colon mucosa and corresponding tumour. Uni- and multivariate analyses were performed. Responses to chemotherapy upon up- or down-regulation of PDK4 were studied in vitro. RESULTS: PDK4 expression within healthy liver tissue was associated with increased overall survival and liver function following surgical resection of CRLM. This association was enhanced in patients with NC. PDK4 expression in CRLM tissue did not correlate with overall survival. Up-regulation of PDK4 increased the resistance of hepatocytes and colon cancer cells against chemotherapy-induced toxicity, whereas knockdown of PDK4 enhanced chemotherapy-associated cell damage. CONCLUSION: Our findings suggest that up-regulated PDK4 expression reduces hepatic chemotherapy-induced oxidative stress and is associated with improved postoperative liver function in patients undergoing multimodal treatment and resection of CRLM.

Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model.

OBJECTIVES: Salinomycin is a polyether antibiotic with selective activity against human cancer stem cells. The impact of salinomycin on patient-derived primary human colorectal cancer cells has not been investigated so far. Thus, here we aimed to investigate the activity of salinomycin against tumor initiating cells isolated from patients with colorectal cancer. METHODS: Primary tumor-initiating cells (TIC) isolated from human patients with colorectal liver metastases or from human primary colon carcinoma were exposed to salinomycin and compared to treatment with 5-FU and oxaliplatin. TICs were injected subcutaneously into NOD/SCID mice to induce a patient-derived mouse xenograft model of colorectal cancer. Animals were treated either with salinomycin, FOLFOX regimen, or salinomycin and FOLFOX. Human colorectal cancer cells were used to delineate an underlying molecular mechanism of salinomycin in this tumor entity. RESULTS: Applying TICs isolated from human patients with colorectal liver metastases or from human primary colon carcinoma, we demonstrated that salinomycin exerts increased antiproliferative activity compared to 5-fluorouracil and oxaliplatin treatment. Consistently, salinomycin alone or in combination with FOLFOX exerts superior antitumor activity compared to FOLFOX therapy in a patient-derived mouse xenograft model of colorectal cancer. Salinomycin induces apoptosis of human colorectal cancer cells, accompanied by accumulation of dysfunctional mitochondria and reactive oxygen species. These effects are associated with expressional down-regulation of superoxide dismutase-1 (SOD1) in response to salinomycin treatment. CONCLUSION: Collectively, the results of this pre-clinical study indicate that salinomycin alone or in combination with 5-fluorouracil and oxaliplatin exerts increased antitumoral activity compared to common chemotherapy.

A Nomogram to Predict Anastomotic Leakage in Open Rectal Surgery-Hope or Hype?

BACKGROUND: Anastomotic leakage is the most dreaded complication after rectal resection and total mesorectal excision, leading to increased morbidity and mortality. Formation of a diverting ileostomy is generally performed to protect anastomotic healing. Identification of variables predicting anastomotic leakage might help to select patients who are under increased risk for the development of anastomotic leakage prior to surgery. The objective of this study was to assess the applicability of a nomogram as prognostic model for the occurrence of anastomotic leakage after rectal resection in a cohort of rectal cancer patients. METHODS: Nine hundred seventy-two consecutive patients who underwent surgery for rectal cancer were retrospectively analyzed. Univariate and multivariable Cox regression analyses were used to determine independent risk factors associated with anastomotic leakage. Receiver operating characteristics (ROC) curve analysis was performed to calculate the sensitivity, specificity, and overall model correctness of a recently published nomogram and an adopted risk score based on the variables identified in this study as a predictive model. RESULTS: Male sex (p = 0.042), obesity (p = 0.017), smoking (p = 0.012), postoperative bleeding (p = 0.024), and total protein level ≤ 5.6 g/dl (p = 0.007) were identified as independent risk factors for anastomotic leakage. The investigated nomogram and the adopted risk score failed to reach relevant areas under the ROC curve greater than 0.700 for the prediction of anastomotic leakage. CONCLUSIONS: The proposed nomogram and the adopted risk score failed to reliably predict the occurrence of anastomotic leakage after rectal resection. Risk scores as prognostic models for the prediction of anastomotic leakage, independently of the study population, still need to be identified.

Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin.

Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/ß-catenin signaling in CD133+ human colorectal cancer cells.

BACKGROUND: The polyether antibiotic Salinomycin (Sal) is regarded as an inhibitor of cancer stem cells. Its effectiveness on human colorectal cancer (CRC) cells in vitro has been demonstrated before. The aim of this study was to establish a murine model to investigate the effectiveness of Sal in vivo. Furthermore, we investigated the impact of Sal on Wnt/ß-catenin signaling in human CD133+ CRC cells. METHODS: The two murine CRC cell lines MC38 and CT26 were used to analyze the impact of Sal on tumor cell proliferation, viability, migration, cell cycle progression and cell death in vitro. For in vivo studies, CT26 cells were injected into syngeneic BALB/c mice to initiate (i) subcutaneous, (ii) orthotopic, or (iii) metastatic CRC growth. Sal was administered daily, 5-Fluoruracil served as a control. For mechanistic studies, the CD133+and CD133- subpopulations of human CRC cells were separated by flow cytometry and separately exposed to increasing concentrations of Sal. The impact on Wnt/ß-catenin signaling was determined by Western blotting and quantitative PCR. RESULTS: Sal markedly impaired tumor cell viability, proliferation and migration, and induced necrotic cell death in vitro. CRC growth in vivo was likewise inhibited upon Sal treatment. Interference with Wnt signaling and reduced expression of the Wnt target genes Fibronectin and Lgr5 indicates a novel molecular mechanism, mediating anti-tumoral effects of Sal in CRC. CONCLUSION: Sal effectively impairs CRC growth in vivo. Furthermore, Sal acts as an inhibitor of Wnt/ß-catenin signaling. Thus, Salinomycin represents a promising candidate for clinical CRC treatment.