Pre- and Postoperative Levels of Carcinoembryonic Antigen in Microsatellite Stable Versus Instable Colon Cancer: a Retrospective Analysis.

PURPOSE: The prognosis of microsatellite stable (MSS) versus instable (MSI) tumors is an ongoing matter of debate, with differences in expression of carcinoembryonic antigen (CEA) in these two tumor subsets being inconsistently reported to date. The aim of this study was to investigate CEA expression in the context of clinical parameters in MSS and MSI tumors. METHODS: Clinical, pathological, and biochemical parameters of colon cancer patients who underwent curative surgery were documented in a database and compared between MSS and MSI cases. The pre- to postoperative trend of CEA was analyzed. Survival was assessed using the Kaplan-Meier (log rank) test. RESULTS: One hundred sixty-nine patients were included in the study. Compared to those with MSS tumors, there was a higher proportion of preoperatively elevated CEA among those with MSI tumors (p = 0.067). Median CEA values decreased over the pre- to postoperative course with MSS (p = 0.01) but not MSI (p = 0.093) tumors. The distribution of N classification differed between MSS and MSI tumors (p = 0.014). Patients with MSI tumors had superior survival. CONCLUSION: Despite the better prognosis, MSI tumors are associated with increases in CEA. Our findings shed light on discrepancies related to the prognostic evaluation of MSI tumors. Furthermore, in follow-up of colorectal cancers, CEA measurements should be interpreted differently for MSI and MSS tumors.

Gastrointestinal Complications After Pancreatoduodenectomy With Epidural vs Patient-Controlled Intravenous Analgesia: A Randomized Clinical Trial.

Importance: Morbidity is still high in pancreatic surgery, driven mainly by gastrointestinal complications such as pancreatic fistula. Perioperative thoracic epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) are frequently used for pain control after pancreatic surgery. Evidence from a post hoc analysis suggests that PCIA is associated with fewer gastrointestinal complications. Objective: To determine whether postoperative PCIA decreases the occurrence of gastrointestinal complications after pancreatic surgery compared with EDA. Design, Setting, and Participants: In this adaptive, pragmatic, international, multicenter, superiority randomized clinical trial conducted from June 30, 2015, to October 1, 2017, 371 patients at 9 European pancreatic surgery centers who were scheduled for elective pancreatoduodenectomy were randomized to receive PCIA (n = 185) or EDA (n = 186); 248 patients (124 in each group) were analyzed. Data were analyzed from February 22 to April 25, 2019, using modified intention to treat and per protocol. Interventions: Patients in the PCIA group received general anesthesia and postoperative PCIA with intravenous opioids with the help of a patient-controlled analgesia device. In the EDA group, patients received general anesthesia and intraoperative and postoperative EDA. Main Outcomes and Measures: The primary end point was a composite of pancreatic fistula, bile leakage, delayed gastric emptying, gastrointestinal bleeding, or postoperative ileus within 30 days after surgery. Secondary end points included 30-day mortality, other complications, postoperative pain levels, intraoperative or postoperative use of vasopressor therapy, and fluid substitution. Results: Among the 248 patients analyzed (147 men; mean [SD] age, 64.9 [10.7] years), the primary composite end point did not differ between the PCIA group (61 [49.2%]) and EDA group (57 [46.0%]) (odds ratio, 1.17; 95% CI, 0.71-1.95 P = .54). Neither individual components of the primary end point nor 30-day mortality, postoperative pain levels, or intraoperative and postoperative substitution of fluids differed significantly between groups. Patients receiving EDA gained more weight by postoperative day 4 than patients receiving PCIA (mean [SD], 4.6 [3.8] vs 3.4 [3.6] kg; P = .03) and received more vasopressors (46 [37.1%] vs 31 [25.0%]; P = .04). Failure of EDA occurred in 23 patients (18.5%). Conclusions and Relevance: This study found that the choice between PCIA and EDA for pain control after pancreatic surgery should not be based on concerns regarding gastrointestinal complications because the 2 procedures are comparable with regard to effectiveness and safety. However, EDA was associated with several shortcomings. Trial Registration: German Clinical Trials Register: DRKS00007784.

Antitumor Activity of Larotrectinib in Esophageal Carcinoma with NTRK Gene Amplification.

BACKGROUND: Increasing knowledge about the genomic changes underpinning cancer development and growth has led to a rapidly expanding number of individualized therapies that specifically target these changes in a patient's tumor. Here we present a case report of a patient with metastatic esophageal carcinoma whose tumor harbored NTRK1 gene amplification and who received targeted systemic therapy with larotrectinib. At initial diagnosis, the patient presented with tumor obstruction of the middle esophagus, simultaneous liver and lung metastases, UICC IV and WHO performance status 3. MATERIALS AND METHODS: The solid tumor genomic profiling test FoundationOne CDx (F1CDx) was used to detect clinically relevant genomic alterations that, in turn, might identify a targeted therapeutic approach if suggested by the findings. The patient was then treated with larotrectinib and had subsequent follow-up biopsies. RESULTS: Simultaneous biopsies of the primary tumor and liver lesions identified a metastatic squamous cell esophageal carcinoma. Comprehensive genomic profiling obtained from liver metastases identified numerous genomic alterations including amplification of NTRK1. Owing to the reduced performance status of the patient, chemotherapy could not be applied and was denied. Although larotrectinib is only approved for the treatment of cancers with NTRK gene fusions, treatment was started and led to a shrinkage of the primary tumor as well as the liver and lung metastases within 6 weeks according to RECIST criteria accompanied by tumor marker decrease. The NTRK1 gene amplification was below the limit of detection in a subsequent liver biopsy. CONCLUSION: The use of comprehensive genomic profiling, specifically F1CDx, enabled the selection of a targeted therapy that led to a rapid reduction of the tumor and its metastases according to RECIST criteria. This case suggests that larotrectinib is not only effective in NTRK fusions but may be efficacious in cases with gene amplification. KEY POINTS: Advances in precision medicine have revolutionized the treatment of cancer and have allowed oncologists to perform more individualized therapy. This case shows that larotrectinib could also be effective in cases of NTRK amplification of cancer. Today, there is only limited knowledge about NTRK alterations in squamous epithelial carcinoma of the esophagus. Longitudinal tumor sequencing during the course of the disease may allow for the detection of a molecular genetic cause once the tumor progresses. Additional actionable gene alterations may then be identified, which may provide the rationale for a therapy switch.

Longitudinal evaluation of efficacy, safety and nutritional status during one-year treatment with the duodenal-jejunal bypass liner.

BACKGROUND: The endoscopic duodenal-jejunal bypass liner (DJBL) represents a novel temporary endoscopic approach for treatment of obesity-associated type 2 diabetes. Recent results from the German DJBL registry confirmed substantial positive metabolic effects of the DJBL in type 2 diabetes. However, the last Food and Drug Administration trial was stopped due to a high occurrence of hepatic abscesses (3.5%). OBJECTIVES: Here, we analyzed time courses of development of co-morbidities, nutritive changes, and occurrence of adverse events during the 1-year treatment phase with the DJBL in the German DJBL registry. METHODS: Sixty-six patients from the registry were analyzed for efficacy, safety, and nutritional status. Patient data sets were analyzed at implantation, 3 and 6 months after implantation, and at explantation visits. RESULTS: Weight, body mass index, glycated hemoglobin, and low-density lipoprotein cholesterol primarily declined during the first 3 months after implantation, whereas systolic and diastolic blood pressure were predominantly reduced during the second half of the treatment phase. Severe DJBL-associated side effects were mainly documented at the explantation visit (intestinal obstruction [1.7%], dislocation [1.7%], and liver abscess [1.7%]). Measurements of serum concentrations of ferritin, albumin, vitamin B12, folic acid, 25-hydroxyvitamin D3 (25 OH-Vit-D3), and calcium provided suggestive evidence of a possible decrease of nutritional absorption of vitamins and trace elements by the DJBL. CONCLUSIONS: The DJBL demonstrates high efficacy with substantial improvement of all parameters of the metabolic syndrome and the potential for reduction of comedications in overweight patients with type 2 diabetes. These registry results are important to optimize recommendations for adaptation of concomitant medication, surveillance of adverse events, nutritional status and supplementation, and adaptation of the implantation period of the DJBL.

Trends in BMI, Glycemic Control and Obesity-Associated Comorbidities After Explantation of the Duodenal-Jejunal Bypass Liner (DJBL).

BACKGROUND: A novel-approach for treatment of obesity and diabetes mellitus type 2 (T2DM) is represented by the endoscopic duodenal-jejunal bypass liner (DJBL). Recent data from the German DJBL registry provide evidence for substantial efficacy of the DJBL during the implantation period in obese patients with T2DM. However, little is known about the trends of glycemic control, BMI, and comorbidities after explantation of the DJBL, which have been investigated in the registry in this report. METHODS: Patients were selected from the registry if they had a dataset at implantation, explantation, and at least one time point after explantation of the DJBL (n = 77). We also investigated a subgroup of patients with available data at least 1 year (-2 weeks) after explantation of the DJBL (n = 32). RESULTS: For a mean BMI at implantation and a mean follow-up period, an increase of BMI of 2.1 kg/m2 (CI 0.8-3.2; p = 0.013) had to be expected (for HbA1c 0.3% (CI - 0.0-0.7; p = n.s.), respectively). In the subgroup analysis, HbA1c and BMI increased after explantation of the DJBL but stayed significantly below baseline levels. Meanwhile, the mean number of antidiabetic drugs slightly increased. There was deterioration seen for blood pressure and LDL cholesterol over the postexplantation period to approximately baseline levels (or higher). CONCLUSION: With this data, we show that improvement of HbA1c and BMI can be partly maintained over a time of nearly 1-year postexplantation of the DJBL. However, for HbA1c, this may be biased by intensified medical treatment and effects deteriorated with time after explantation. These results suggest that implantation of the DJBL needs to be integrated in a long-term weight management program as most of other interventions in obese patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02731859.

Comparative efficacy and safety of the duodenal-jejunal bypass liner in obese patients with type 2 diabetes mellitus: A case control study.

AIMS: The duodenal-jejunal bypass liner (DJBL) is an endoscopic device mimicking surgical duodenal-jejunal bypass, and is indicated for the treatment of obesity-associated type 2 diabetes mellitus. This analysis was conducted to evaluate the efficacy and safety of the DJBL in comparison to lifestyle changes and antidiabetic drugs. MATERIALS AND METHODS: To determine the efficacy and long-term safety of the DJBL, data concerning 235 obese patients with type 2 diabetes mellitus from the German DJBL registry were analysed. For comparison with standard treatment, propensity-score-matching with patients from the German DPV registry, including the matching parameters sex, age, diabetes duration, baseline BMI and baseline HbA1c, was applied. The final matched cohort consisted of 111 patients in the DJBL group and 222 matched control DPV patients. RESULTS: Mean treatment time with the DJBL was 47.5 ± 12.2 weeks, mean BMI reduction was 5.0 kg/m2 (P < .001) and mean HbA1c reduction was 1.3% (11.9 mmol/mol) (P < .001). Reduction of antidiabetic medications and improvements in other metabolic and cardiovascular risk parameters was observed. In comparison to the matched control group, mean reductions in HbA1c (-1.37% vs -0.51% [12.6 vs 3.2 mmol/mol]; P < .0001) and BMI (-3.02 kg/m2 vs -0.39 kg/m2 ; P < .0001) were significantly higher. Total cholesterol, LDL cholesterol and blood pressure were also significantly better. CONCLUSION: This study provides the largest, so far, hypothesis-generating evidence for a putative positive risk/benefit ratio for treatment of obese patients with type 2 diabetes mellitus with the DJBL as an alternative treatment option for this patient population.

Diverting ileostomy versus no diversion after low anterior resection for rectal cancer: A prospective, randomized, multicenter trial.

BACKGROUND: This study sought to determine whether a protective diverting ileostomy improves short-term outcomes in patients with rectal resection and colonic J-pouch reconstruction for low anastomoses. Criteria for the use of a proximal stoma in rectal resections with colonic J-pouch reconstruction have not been defined sufficiently. METHODS: In a multicenter prospective study, rectal cancer patients with anastomoses below 8 cm treated with low anterior resection and colonic J-pouch were randomized to a defunctioning loop ileostomy or no ileostomy. The primary study endpoint was the rate of anastomotic leakage, and the secondary endpoints were surgical complications related to primary surgery, stoma, or stoma closure. RESULTS: From 2004 to 2014, a total of 166 patients were randomized to 1 of the 2 study groups. In the intention-to-treat analysis, the overall leakage rate was 5.8% in the stoma group and 16.3% in the no stoma group (P = .0441). However, some patients were not treated according to randomization and only 70% of our patients with low anastomoses received a pouch. Therefore, we performed a second analysis as to actual treatment. In this analysis, as well, leakage rates (P = .044) and reoperation rates for leakage (P = .021) were significantly higher in patients without a stoma. In multivariate analysis, male gender (P = .0267) and the absence of a stoma (P = .0092) were significantly associated with anastomotic leakage. CONCLUSION: Defunctioning loop ileostomy should be fashioned in rectal cancer patients with anastomoses below 6 cm, particularly in male patients, even if reconstruction was done with a J-pouch.

Impact of postoperative complications on long-term survival after resection for rectal cancer.

BACKGROUND: The relevance of type and severity of postoperative complications after curative resection for rectal cancer on survival and recurrence rates is a matter of controversy. OBJECTIVE: The aim of this study was to investigate the impact of postoperative complications on long-term outcome after resection for rectal cancer. DESIGN: This study is a retrospective analysis of prospectively collected data. SETTINGS: The study was conducted at a university teaching hospital by a specialized colorectal team. PATIENTS: Between January 1984 and October 2008, 811 patients with rectal cancer underwent curative resection. Patients who experienced postoperative complications were divided into a minor complication group (grades I and II) and a major complications group (grades III and IV) according to the Clavien classification. MAIN OUTCOME MEASURES: The influence of several pathological and clinical factors, including complications in terms of overall and disease-free survival, was tested and compared in univariate and multivariate analyses. RESULTS: Curative resection was performed in 811 patients; median age was 65 years. The Kaplan-Meier estimates (± SE) for 5- and 10-year overall cumulative survival were 70.3% ± 1.8% and 54.5% ± 2.4%; Kaplan-Meier estimates for 5- and 10-year disease-free survival were 64.0% ± 1.8% and 50.9% ± 2.3%. One hundred sixty-five patients (20.3%) had minor complications, and 103 patients (12.7%) had major complications. Twelve patients (1.48%) died within 30 days after surgery. There was no significant difference between patients with no complications, patients with minor complications, and patients with major complications in terms of overall (p = 0.41) or disease-free survival (p = 0.32). LIMITATIONS: A possible limitation of our study is that the data represent a cohort study from a single center. CONCLUSION: Following resection for rectal cancer, the severity of postoperative complications (minor or major) according to a standardized classification system does not demonstrate a statistically significant effect on either overall or disease-free survival.

Influence of body mass index on postoperative complications after rectal resection for carcinoma.

OBJECTIVES: The influence of obesity on postoperative complications after various surgical interventions remains controversial. The aim of this study was to evaluate the impact of overweight and obesity on the occurrence of postoperative complications for patients undergoing elective resection for rectal carcinoma. METHODS: We conducted a retrospective data analysis of 676 patients undergoing surgical treatment for rectal carcinoma. Depending on their body mass index (BMI), patients were grouped as follows: group I, patients up to BMI 24.9 kg/m; group II patients, with a BMI between 25 and 29.9 kg/m; and group III, all patients with a BMI >30 kg/m. Complications were classified as minor and major with regard to severity grades (1-5). Statistical analysis was performed to evaluate the difference in complication rates between the different BMI groups. RESULTS: A total of 444 patients were included for analysis. Overall, 300 (67.6%) of the 444 patients did not develop postoperative complications, 82 (18.4%) patients had minor complications (grade 1 + 2), and 56 patients (12.6%) had major (grade 3 + 4) complications. Six (1.4%) patients died (grade 5). The Fisher exact test indicated no statistically significant difference of complication rates between the different BMI groups (P = 0.3716). CONCLUSIONS: Compared with nonobese or normal-weight patients, obese patients do not have a statistically significant higher risk of developing postoperative complications after rectal resection for carcinoma.

Heterotopic pancreatic tissue in the cystic duct: complicating factor or coexisting pathology.

The case of a 75-year-old female suffering from recurrent abdominal pain and nausea is presented. Ultrasound showed gallstones without inflammation of the gallbladder. The patient underwent laparoscopic cholecystectomy and her symptoms resolved. Histological examination of the operation specimen disclosed heterotopic pancreatic tissue within the cystic duct. An accurate clinical diagnosis of pancreatic heterotopia is difficult. The deep submucosal or intramural location of the lesion may hamper retrieval of representative biopsy material. Indications for surgery or endoscopic resection include symptomatic lesions as well as cases of unclear histological examination in order to distinguish pancreatic heterotopia from other tumors.

Solitary giant splenic metastasis in a patient with metachronous gastric cancers.

Splenic metastases from solid tumors are uncommon. They may be observed in a context of multivisceral dissemination or as a solitary lesion. We report the case of an 80-year-old woman with a history of two metachronous gastric cancers treated with distal gastrectomy and resection of the gastric remnant within a period of 15 years, who presented with a huge splenic tumor mass three years after the second operation. Splenectomy was performed. The resection specimens showed a well-circumscribed solid lesion measuring 15 cm in the largest diameter. Histology revealed metastatic gastric cancer. The differential diagnosis and clinical significance of this rare condition is discussed.

Ileocecal intussusception caused by lung cancer metastasis.

Intussusception is a rare clinical finding in adults. Most cases occur in the distal small bowel or large intestine. We report the case of a 65-year-old woman with known non-small-cell lung cancer (NSCLC) who presented with acute abdomen and ileus-like symptoms. Abdominal computed tomography suggested ileocecal intussusception. The patient underwent right hemicolectomy and the histopathological workup showed ileal NSCLC metastasis as the lead lesion of intussusception. The classic triad of cramping abdominal pain, bloody diarrhea and a palpable tender mass, which is present in the majority of pediatric patients, is only infrequently observed in adults. Thus, symptoms are often nonspecific and the clinical presentation may be inconspicuous. Because of the large proportion of structural anomalies, adult intussusception requires definitive treatment, of which surgical resection is the treatment of choice. In patients with colocolonic or ileocolonic intussusception, malignancy should be considered and therefore en bloc resection rather than reduction is the recommended surgical technique, whereas cases of enteric intussusceptions may be reduced by limited resection of the small intestine.

Risk factors for anastomotic leakage after resection for rectal cancer.

BACKGROUND: Controversy still exists concerning the impact of patient and tumor characteristics on anastomotic dehiscence after resection for rectal cancer. METHODS: Between January 1986 and July 2006, 472 patients underwent curative rectal resection. Patient and tumor characteristics, details of treatment, and postoperative results were recorded prospectively. Univariate and multivariate analysis were applied to identify risk factors for anastomotic leakage. RESULTS: In our patients, the anastomotic leak rate was 10.4% (49 of 472 patients), and mortality was 2.2% (1 of 49 patients). In univariate analysis, tumor diameter and absence of a protective stoma were associated with increased anastomotic leak rate, whereas American Society of Anesthesiologists (ASA) score and tumor localization showed borderline significance. In multivariate analysis, tumor diameter, tumor localization, and absence of a protective stoma were significantly associated with anastomotic leakage. CONCLUSIONS: Patients with large and low lying rectal tumors are at high risk for anastomotic leakage. A protective stoma significantly decreases the rate of clinical leaks and subsequent reoperation after low anterior resection.