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

Chronic pancreatitis (CrP) is a fibroinflammatory disease that progresses with the loss of both exocrine and endocrine parenchyma of the pancreas due to fibrosis resulting from chronic inflammation (1). Chronic abdominal pain is the most common clinical feature in CrP, which is a malnutrition syndrome (2). Alcohol is the most common cause of CrP (3).
Sarcopenia is defined as a decrease in total body muscle mass (4). Sarcopenia is associated with adverse outcomes in CrP patients.(5).The prevalence of sarcopenia is increased in CrP patients compared to the normal population(6). In a study by Olesen et al., the frequency of sarcopenia in CrP patients was found to be 17%, and they found that sarcopenia was associated with a decrease in the general health. In this study, PEI, smoking and narcotic analgesic use were defined as risk factors for sarcopenia (7).
Pancreatic exocrine insufficiency (PEI) is one of the most common complications of chronic pancreatitis. In a study by Kempeneers et al., mild and severe PEI in CrP patients were reported %31 and %46, respectively (8).
The prevalence of osteopathy is high in patients with CrP and may increase the risk of fractures. In a meta-analysis of 19 studies by Amanda Koh et al., it was shown that 19% of the patients diagnosed with chronic pancreatitis were osteoporotic and 37% were osteopenic (9).

Aims & Methods

The prevalence of sarcopenia, pancreatic exocrine insufficiency (PEI) and osteopathy is high in chronic pancreatitis (CrP), and these are important complications with adverse consequences. The aim of our research is to evaluate the prevalence and risk factors of sarcopenia, PEI and osteopathy in CrP patients.
83 CrP patients were included in the study.
The surface area of the paravertebral muscles was measured from the third lumbar region of the cross-sectional images; PVMI was used to assess sarcopenia. PFE was used to evaluate PEI, and results were reported as no PEI, mild, or severe. DEXA was used to evaluate osteopathy.
EORTC PAN26 and a semiotic questionnaire were performed. CBC, routine biochemical tests and vitamin/mineral levels were measured at the same time of PFE.

Results

The prevalence of sarcopenia, PEI, and osteoporosis was found to be 19 (22.9%), 56 (67.5%), and 18 (21.7%), respectively.
Male gender (OR:4.9 and p=0.044), severe PEI (OR:4.2 and p=0.043), smoking (OR:4.6 and p=0.040) and zinc deficiency (OR:2.2 and p=0.029) were defined as risk factors for sarcopenia.
Of the 83 patients, 20 were diagnosed with mild and 36 with severe PEI, and PEI was not detected in 27 patients. Severe PEI was determined to be associated with osteoporosis/osteopenia (p=0.010), DM (p=0.001), heavy narcotic analgesic use (p=0.030), sarcopenia (p=0.016) and zinc deficiency (p=0.012).
Osteoporosis was detected in 18 patients and 42 patients had osteopenia. PAN26 scores were higher in individuals with osteoporosis (p=0.029). Female gender (OR:7.8 and p=0.004), severe PEI (OR:8.1 and p=0.003) and sarcopenia (OR:5 and p=0.037) were identified as independent risk factors for osteopathy.

Conclusion

The prevalence of sarcopenia, PEI and osteopathy are increased in CrP. Smoking, zinc deficiency, PEI, and male gender are defined as risk factors for sarcopenia. The prevalence of osteopathy increases in patients with sarcopenia and is associated with decreased quality of life.
PVMI was used for the first time to evaluate sarcopenia in CrP patients.
In studies evaluating sarcopenia using cross-sectional imaging methods, zinc deficiency was identified as a risk factor for sarcopenia for the first time in the literature.

References

1-Etemad, Babak, and David C. Whitcomb. "Chronic pancreatitis: diagnosis, classification, and new genetic developments." Gastroenterology 120.3(2001):682-707.
2-Kleeff, Jorg, et al. "Chronic pancreatitis." Nature reviews Disease primers 3.1(2017):1-18.
3- Hirota, Morihisa, et al. "The seventh nationwide epidemiological survey for chronic pancreatitis in Japan: clinical significance of smoking habit in Japanese patients." Pancreatology 14.6(2014):490-496.
4-Cruz-Jentoft, Alfonso J., et al. "Sarcopenia: revised European consensus on definition and diagnosis." Age and ageing 48.1(2019):16-31.
5- Yuan, Shuai, and Susanna C Larsson. “Epidemiology of sarcopenia: Prevalence, risk factors, and consequences.” Metabolism: clinical and experimental vol. 144(2023):155533.
6- Fasullo, Matthew et al. “Sarcopenia in Chronic Pancreatitis - Prevalence, Diagnosis, Mechanisms and Potential Therapies.” Current gastroenterology reports vol. 24,4(2022):53-63.
6-Dodds, Richard Matthew, et al. "The epidemiology of sarcopenia." Journal of Clinical Densitometry 18.4(2015):461-466.
7-Olesen, Søren S., et al. "Sarcopenia associates with increased hospitalization rates and reduced survival in patients with chronic pancreatitis." Pancreatology 19.2(2019):245-251.
8-Kempeneers, Marinus A et al. “Natural Course and Treatment of Pancreatic Exocrine Insufficiency in a Nationwide Cohort of Chronic Pancreatitis.” Pancreas vol. 49,2(2020):242-248.
9-Koh, Amanda et al. “Risk of osteopaenia, osteoporosis and osteoporotic fractures in patients with chronic pancreatitis: A systematic review and meta-analysis.” Clinical nutrition (Edinburgh, Scotland) vol. 42,7(2023):1086-1094.

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

Pancreatic cancer (PC) are associated with notably poor prognoses.The clinical practice guidelines for PC list several risk factors of PC, including diabetes among them. Diabetic patients, who regularly visit the hospital, present a practical opportunity for pancreatic surveillance. Effective surveillance for PC could be achieved by identifying diabetic patients at high-risk for PC who already require regular hospital visits. Nevertheless, there is a notable lack of research on pancreatic cancer risk factors within the diabetic population.

Aims & Methods

This study aimed to identify risk factors for pancreatic cancer in diabetic patients using a longitudinal cohort from the Shizuoka Kokuho database, spanning April 2012 to September 2021. Diabetic patients were identified and monitored for the onset of pancreatic cancer. Factors analyzed included age, sex, the Elixhauser comorbidity index, and specific comorbidities. Statistical analyses involved univariate and multivariate Cox proportional hazards regression.

Results

The Shizuoka Kokuho database, which comprises 2,654,567 individuals, identified 212,775 as diabetic patients. Of these patients, 1,755 developed pancreatic cancer during the observation period, which had a median duration of 5.1 years and a maximum of 8.5 years. The annual incidence rate of pancreatic cancer in this group was 166.7 cases per 100,000 person-years [95% CI: 158.9–174.5].
Identified candidate risk factors included older age, male sex, coexisting liver disease, cardiac arrhythmias, hypertension, chronic pancreatitis, and pancreatic cystic lesions, each with p-values below 0.05. These variables were subsequently incorporated into a multivariate model.
The multivariable regression results indicated that older age and male gender were associated with an increased risk of pancreatic cancer (HR: 1.267 [95% CI: 1.150–1.395]). Liver disease emerged as a notable risk factor (HR: 1.13 [95% CI: 1.01–1.26]). Significant correlations were found between the onset of PC and both chronic pancreatitis (HR: 1.98 [95% CI: 1.48–2.64]) and pancreatic cystic disease (HR: 4.79 [95% CI: 3.43–6.67]). Neither the type of diabetes nor the presence of diabetic comorbidities was associated with the onset of PC.

Conclusion

This cohort study has identified key risk factors for pancreatic cancer in diabetic patients. Findings indicate that advanced age, male sex, a history of liver disease, chronic pancreatitis, and pancreatic cystic lesions significantly increase the risk of pancreatic cancer in this population. These insights underscore the importance of targeted surveillance for early detection of pancreatic cancer in diabetic patients, particularly those with these risk factors.