Introduction

In patients with chronic pancreatitis (CP), pancreatic exocrine insufficiency (PEI) and poor nutritional intake may cause nutritional deficiencies. Guidelines advise monitoring key nutrients and supplementing is case of deficiency to prevent malnutrition-related complications. However, adherence remains low, possibly due to limited evidence on the clinical relevance of single nutrient deficiencies and the benefit of targeted supplementation. The aim of this study is to evaluate the prevalence of nutritional deficiencies in patients with CP and to identify predictors of those at highest risk. Secondary, we seek to explore association between nutritional deficiencies and malnutrition-related complications, and to provide insight into the natural course of nutritional deficiencies.

Aims & Methods

We analyzed data from the COMBO-trial, a nationwide stepped-wedged cluster randomized trial to evaluate the effect of an evidence-based algorithm for the management of CP. Measurements of fat-soluble vitamins, minerals, and albumin conducted in the outpatient clinic during the 35-month study period were included. PEI was defined as fecal elastase-1 concentration <200 µg/g or the use of pancreatic enzyme replacement therapy (PERT). The Pancreatic Exocrine Insufficiency Questionnaire (PEI-Q), designed to evaluate the severity of PEI symptoms, was administered at four distinct time points throughout the study. Supplement use was collected from health records and patient questionnaires. Multivariate logistic regression analysis was performed for the presence of multiple deficiencies. Potential predictors included patient and disease characteristics at baseline and the mean score of the PEI-Q during follow-up.

Results

In total 409 patients were included in this study. At baseline 327 (80.0%) had PEI and PERT was used by 297 (72.6%). Nutritional deficiencies were present in 195 patients (47.7%) of which 81 (19.8%) had multiple deficiencies. The prevalence of deficiencies included vitamin A in 13/172 (7.6%) patients, vitamin D 111/289 (38.4%), vitamin E 15/168 (8.9%), vitamin K 52/88 (59.1%), iron 44/137 (32.1%) calcium 4/198 (2.0%), magnesium 24/132 (18.2%) zinc 13/67 (19.4%), selenium 4/42 (9.5%), and albumin in 41/288 (14.2%) patients. No abnormal coagulation was observed in the 20 patients with vitamin K deficiency and available INR measurements. Osteopenia was diagnosed in 110/236 (46.6%) and osteoporosis in 56/236 (23.7%). Deficiencies in vitamin K and vitamin D, micronutrients critical to bone metabolism, were not associated with osteopenia or osteoporosis. Of 44 patients with an iron deficiency, 22 (50%) were anemic. Deficiency resolved without single nutrient supplementation in 71.4% (vitamin A), 75.0% (vitamin D), 50.0% (vitamin E) , 33.3% (vitamin K), 63.6% (iron), 100% (magnesium), 80.0% (zinc) of cases. Independent predictors for multiple deficiencies were more severe PEI symptoms (OR 1.86, 1.09 – 3.17) and daily alcohol consumption (OR 2.80, 1.27 – 6.18).

Conclusion

Nutritional deficiencies are present in approximately half of the patients with CP. Most nutritional deficiencies resolve without single nutrient supplementation. Predictors for multiple nutritional deficiencies were severity of PEI symptoms and daily alcohol consumption. Therefore, nutritional deficiencies should be considered a marker of malnutrition, with treatment focused on addressing the underlying cause rather than isolated correction through single nutrient supplementation.

Introduction

Lynch syndrome (LS) represents the most prevalent hereditary colorectal cancer (CRC) syndrome, with approximately one in 279 individuals in the general population believed to carry a pathogenic variant. This autosomal dominant condition results from germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). In addition to colorectal cancer, LS encompasses various extracolonic malignancies, such as gastric carcinoma (lifetime risk of 13%) and small bowel cancer (lifetime risk of 8%). Both German and current NCCN guidelines advise upper GI screening using esophagogastroduodenoscopy (EGD) every 2-4 years. However, standard EGD screening often misses lesions in the jejunum, where up to one third of small bowel cancers occur. Consequently, we sought to determine the frequency of jejunal lesion detection with push enteroscopy employing a colonoscope and whether this method maintains the overall diagnostic quality.

Aims & Methods

Patients with a proven pathogenic mutation in a DNA mismatch repair gene were included in a surveillance program at our National Center of Hereditary Tumor Syndromes, where all patients are followed prospectively after signing an informed consent. We assessed endoscopic findings using standard esophagogastroduodenoscopy (EGD) compared to push enteroscopy using a pediatric colonoscope at our center. We implemented the routine use of push enteroscopy in August 2022. The same endoscope was used for the following colonoscopy. Results of endoscopy, histopathology, affected gene were compared.

Results

Between April 2013 and July 2022, a total number of 445 EGDs were performed in 187 patients (range 1-7; 108 (58%) female; median age at endoscopy 48 years), all carrying a pathogenic MMR gene variant (66 MLH1 (35.5%); 86 MSH2 (46%); 25 MSH6 (13%); 9 PMS2 (5%); 1 Epcam (0.05%)).
Between August 2023 and April 2023, a total number of 103 push enteroscopies using a colonoscope were performed in 103 carriers of a pathogenic MMR gene variant (54 (52%) female; median age at endoscopy 48 years; 38 MLH1 (37%); 46 MSH2 (45%); 11 MSH6 (11%); 4 PMS2 (4%); 1 Epcam (1%); 3 MLH1 and MSH2 (3%)).
Using standard EGD, Barrett esophagus was detected in 23 (5%) patients, with three patients exhibiting high-grade dysplasia, whereas push enteroscopy identified Barrett's esophagus in 4 (4%) patients and revealed one case of eosinophilic esophagitis. Helicobacter pylori infection was found in 21 (5%) and 4 (4%) cases, respectively. Intestinal metaplasia was detected in 49 (11%) patients with standard EGD and 23 (22%) patients with push enteroscopy, both revealing one case (MLH1) with dysplasia. Neoplastic and preneoplastic lesions observed included gastric cancer (5; 1%), gastric adenomas (7; 1.6%), duodenal cancer (3 duodenal, 2 ampullary cancers; 1%), and duodenal adenomas (8; 1.8%) with standard EGD, while no neoplastic lesions were found using push enteroscopy. However, push enteroscopy enabled the detection of three jejunal adenomas, including two advanced adenomas.

Conclusion

This prospective endoscopic study demonstrates that monitoring the upper gastrointestinal (GI) tract in Lynch syndrome (LS) patients yields clinically significant findings for a considerable proportion of individuals. The application of push enteroscopy does not impede the identification of pertinent lesions. Notably, we observed an increased detection rate of gastric intestinal metaplasia using this technique.

Introduction

Cholecystectomy is a common procedure in hepatobiliary surgery, with iatrogenic injury often leading to biliary fistula. Laparoscopic subtotal cholecystectomy (LSC) is employed when achieving a critical view of safety is challenging, but it comes with a high complication rate, including bile leaks. Laparoscopic common bile duct exploration (LCBDE) with laparoscopic cholecystectomy (LC) is utilized for cholecystolithiasis complicated with common bile duct (CBD) stones. Handling the CBD incision during LCBDE involves two approaches: indwelling T-tube drainage and primary suture.

Aims & Methods

Our research explores routine extra-drainage with tip-split drainage tubes (TSDT) for LCBDE+LC and LSC to reduce postoperative biliary fistulas. Early inspection of the cystohepatic triangle determines the feasibility of achieving a critical view of safety. If unattainable, LSC is considered, with attempts at standard laparoscopic cholecystectomy. TSDT drainage is decided based on the identification of bile flow from the cystic duct orifice. For cases without bile flow, TSDT drainage alone is used. If bile flow is identified, a purse-string suture of the cystic duct is performed, followed by TSDT placement. The LCBDE approach involves a longitudinal incision matching the stone's diameter. Choledochoscope exploration is completed with absorbable sutures or T-tube placement based on inflammation or the likelihood of residual stones. The TSDT is then placed.

Results

Our study, spanning 350 cases over five years, showed a high TSDT success rate, with no postoperative ERCP or PTCD interventions required. A learning curve of 1 to 2 cases was observed. Out of 350 patients, 30 underwent LSC and 320 LCBDE, resulting in 17 postoperative biliary fistula cases. Twelve were Grade A with no change in clinical management, and five were Grade B requiring minimal adjustments. All Grade A cases resolved within a week, while Grade B cases lasted over a week. Follow-up continued until bile leakage disappeared before catheter removal, with no progression to Grade C or relaparotomy requirements.

Conclusion

Our innovative TSDT technique effectively reduces postoperative bile leaks after LSC and LCBDE. Although not previously reported, TSDT appears superior to routine extra-drainage, being less technically demanding and less risky. General surgeons can likely adopt TSDT widely for improved hepatobiliary surgery outcomes.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) remains a challenge in oncology with an overall survival rate remaining about 10%. Surgery and adjuvant chemotherapy stands as only curative treatment options. Only a minority of patients are diagnosed with resectable disease. While traditional diagnostic modalities show limitations in detecting and monitoring pancreatic cancer, liquid biopsies is a relatively new, non-invasive and promising diagnostic method for early detection, molecular profiling, and observation. Despite previous published or ongoing research projects and studies, liquid biopsies and specifically cell-free DNA (cfDNA) alterations role in management of pancreatic cancer remains unverified.

Aims & Methods

The aim of our study was to evaluate the diagnostic value of liquid biopsies and alterations in cfDNA levels in patients with pancreatic cancer. This study was approved by the Kaunas Regional Bioethics Committee (Approval ID: BE-2-31). Patients with newly diagnosed and histologically confirmed pancreatic cancer and patients with chronic pancreatitis, admitted to the Department of Surgery at Lithuanian University of Health Sciences Hospital, Kaunas Clinics, between September 2022 and December 2023, and healthy volunteers (control group) were included. Blood samples were obtained from the patients before any treatment procedures commenced. cfDNA was extracted from the collected blood using the QIAmp Circulating Nucleic Acid Kit (Qiagen). The concentration and quality of the extracted cfDNA were determined using the Qubit™ 1X dsDNA High Sensitivity (HS) and Broad Range (BR) Assay Kits (ThermoFisher Scientific, Inc., Waltham, MA, USA). Mann-Whitney U-test and Kruskal-Wallis H-test were used to determine the differences in quantitative traits between the comparison groups, with results being presented in median (min – max). The predictive capability (diagnostic performance) of cfDNA to distinguish PDAC and chronic pancreatitis/healthy controls was investigated by means of the area under the ROC (Receiver-Operating Characteristics) curve (AUC).

Results

Sixty-five patients were included (47 patients with PDAC, 10 patients with chronic pancreatitis and 8 healthy controls). Levels of cfDNA were statistically significantly higher in PDAC patients (46.5 (4 - 768) ng/ml) compared to patients with chronic pancreatitis (23.4 (8.56 - 138.4) ng/ml) (p = 0.032) and healthy controls (19.75 (17.6 - 22.8) ng/ml) (p < 0.001). The cfDNA cut-off value distinguishing PDAC from chronic pancreatitis and healthy controls were determined to be 23,65 ng/ml (AUC = 0.716) and 22.9 ng/ml (AUC = 0.915), respectively. There were no differences in cfDNA levels concerning tumor localization, size, differentiation, spread, or survival rates (all p > 0.05).

Conclusion

Liquid biopsies and cfDNA level alterations offer promising opportunities for distinguishing pancreatic cancer from benign inflammatory diseases, such as chronic pancreatitis. However, additional experiments and studies are necessary for more comprehensive validation and clinical use.

Disclosure

This study was partially funded by Lithuanian University of Health Sciences Scientific fund and Lithuanian Future Biomedicine foundation.

Introduction

Diabetes mellitus (DM) is a substantial risk factor for pancreatic cancer (PC). Concurrently, aspirin has been implicated to have chemopreventive effect against cancer of digestive system. However, studies regarding the effect of aspirin on mitigating PC risk among DM populations remain scant.

Aims & Methods

We aimed to examine whether regular use of aspirin was associated with a reduced risk of PC after adjusting for known risk factors among type 2 diabetes (T2D) patients.

This was a territory-wide, retrospective cohort study of newly diagnosed T2D patients between 2001 and 2015 in Hong Kong. Exclusion criteria included <18 years old, history of PC, pancreatic neuroendocrine tumor, serous cystadenoma, chronic or acute pancreatitis, and pancreatic cyst. The outcome of interest was pancreatic cancer. Adjusted hazard ratios (aHRs) for outcomes associated with aspirin use were calculated using multivariable Cox regression models. Aspirin use was treated as a time-varying covariates (≥180 days use at each yearly interval) in the analysis to address and minimize immortal-time bias.

Results

We identified 342,920 T2D patients (52.2% male, mean age: 58.8±11.6 years), including 43,634 (12.7%) aspirin users. During a mean follow-up of 11.1±4.2 years, 1,114 (0.3%) patients developed PC, with an incidence rate of 2.92 per 10,000 person-years. Aspirin use was associated with a reduced PC risk (HR 0.55, 95%CI 0.46-0.66). When compared with the reference group (never use), a lower risk was observed with increasing frequency, with the exception of daily use. In addition, longer durations of aspirin use were associated with a progressively lower PC risks (HR 0.83, 95%CI 0.71-0.96, for less than five years of use; HR 0.56, 95%CI 0.45-0.69, for five to ten years of use; and HR 0.27, 95%CI 0.20-0.36, for ten or more years of use. Both frequency and duration of aspirin use demonstrated statistically significant trends (P_trend <0.001) (Table 1).

Table 1. HRs and 95% CIs for the association between frequency and duration of aspirin use and risk of pancreatic cancer

Aspirin use	No. of patients (n=342,920)	No. of PC (n=1,114)	HR (95% CI)	P*	Ptrend*
Frequency Never user	219,674	736	ref	-	<0.001
<Monthly use	13,809	52	0.66 (0.50-0.88)	0.004
Monthly to <weekly use	13.274	44	0.59 (0.43-0.80)	<0.001
Weekly to <daily use	73,232	201	0.54 (0.46-0.63)	<0.001
Daily use	22,931	81	0.90 (0.69-1.16)	0.401
Duration (years) Never user	219,674	736	ref	-	<0.001
<5	54,029	223	0.83 (0.71-0.96)	0.015
5 - <10	40,003	99	0.56 (0.45-0.69)	<0.001
≥10	29,214	56	0.27 (0.20-0.36)	<0.001

*Cox proportional hazards model was used to calculate the P values. Adjusted covariates included age, sex, lifestyle factors (body mass index, smoking, and alcohol use), metabolic disorders (dyslipidemia and hypertension), time-weighted mean HbA1c, DM complications, cardiovascular diseases, other anti-diabetic medications, non-aspirin non-steroidal anti-inflammatory drugs, and statins.
Abbreviation: CI, confidence interval; HR, hazard ratios; PC, pancreatic cancer; ref, reference

Conclusion

Aspirin use was associated with a reduction in PC risk among T2D patients, which was dependent on both frequency and duration of use. Notably, this trend was observed with increased frequency of use, with the exception of daily use. Further studies are warranted to assess long-term effects and potential risks.