Pancreatic metastasis of Merkel cell carcinoma and concomitant insulinoma: Case report and literature review

BACKGROUND: Merkel cell carcinomas are rare neoplasm of neuroendocrine origin, usually observed in elderly people in areas with abundant sunlight, and predominantly located on the head and neck, extremities, and trunk. In many patients, a local recurrence after resection of the primary tumour and even distant metastases can be found. CASE PRESENTATION: We report an unusual occurrence of pancreatic metastases from a previously diagnosed Merkel cell carcinoma with the discovery of a concomitant insulinoma. An 82-year old lady suffered from recurrent attacks of hypoglycemia and presented with an abdominal mass, 2 years prior she had an excision done on her eyebrow that was reported as Merkel cell carcinoma. An extended distal pancreatectomy and splenectomy along with resection of the left flexure of the colon for her abdominal mass was carried out. Final histopathology of the mass was a poorly differentiated endocrine carcinoma in the pancreatic tail, in the peripancreatic tissue and in the surrounding soft tissue consistent with metastatic Merkel cell carcinoma in addition to an insulinoma of the pancreatic body. CONCLUSION: This is the first documented case of a metastatic Merkel cell carcinoma and a concomitant insulinoma, suggesting either a mere coincidence or an unknown neuroendocrine tumor syndrome

Over-the-scope-grasper: A new tool for pancreatic necrosectomy and beyond - first multicenter experience

BACKGROUND Endoscopic treatment of pancreatic necrosis can be challenging and time-consuming because sticky necrotic debris is sometimes difficult to remove. The over-the-scope-grasper, a new tool that has recently become available for this purpose, might also be useful for other indications. However, clinical data on the efficacy and safety of this new device are lacking. AIM To evaluate the technical success and safety of the device in a multicenter setting. METHODS The over-the-scope-grasper was used in nine selected endoscopic centers between November 2020 and October 2021 for appropriate indications. Overall, 56 procedures were included in the study. We retrospectively evaluated procedural parameters of all endoscopic interventions using a predefined questionnaire, with special respect to technical success, indications, duration of intervention, type of sedation, and complications. In the case of pancreatic necrosectomy, the access route, stent type, number of necrosis pieces removed, and clinical handling were also recorded. RESULTS A total of 56 procedures were performed, with an overall technical success rate of 98%. Most of the procedures were endoscopic pancreatic necrosectomies (33 transgastric, 4 transduodenal). In 70% of the procedures, access to the necrotic cavity was established with a lumen apposing metal stent. The technical success of pancreatic necrosectomy was 97%, with a mean of 8 pieces (range, 2-25 pieces) of necrosis removed in a mean procedure time of 59 min (range, 15-120 min). In addition, the device has been used to remove blood clots (n = 6), to clear insufficiency cavities before endoluminal vacuum therapy (n = 5), and to remove foreign bodies from the upper gastrointestinal tract (n = 8). In these cases, the technical success rate was 100%. No moderate or severe/fatal complications were reported in any of the 56 procedures. CONCLUSION These first multicenter data demonstrate that the over-the-scope-grasper is a promising device for endoscopic pancreatic necrosectomy, which is also appropriate for removing foreign bodies and blood clots, or cleaning insufficiency cavities prior to endoluminal vacuum therapy

To whom do the results of the multicenter, randomized, controlled INSECT trial (ISRCTN 24023541) apply? - assessment of external validity

A response to Seiler et al: Interrupted or continuous slowly absorbable sutures for closure of primary elective midline abdominal incisions: a multicenter randomized trial (INSECT: ISRCTN24023541). Ann Surg 2009, 249(4):576-582

Pancreatic cancerrelated cachexia: influence on metabolism and correlation to weight loss and pulmonary function

<p>Abstract</p> <p>Background</p> <p>Dramatic weight loss is an often underestimated symptom in pancreatic cancer patients. Cachexia- defined as an unintended loss of stable weight exceeding 10% – is present in up to 80% of patients with cancer of the upper gastrointestinal tract, and has a significant influence on survival. The aim of the study was to show the multiple systemic effects of cachexia in pancreatic cancer patients, in terms of resection rate, effects on pulmonary function, amount of fat and muscle tissue, as well as changes in laboratory parameters.</p> <p>Methods</p> <p>In patients with pancreatic cancer, clinical appearance was documented, including the amount of weight loss. Laboratory parameters and lung-function tests were evaluated, and the thickness of muscle and fat tissue was measured with computed tomography scans. Statistical analysis, including multivariate analysis, was performed using SPSS software. Survival curves were calculated using Kaplan-Meier analysis and the log-rank test. To test for significant differences between the examined groups we used Student's t-test and the Mann-Whitney U test. Significance was defined as p < 0.05.</p> <p>Results</p> <p>Of 198 patients with a ductal adenocarcinoma of the pancreas, 70% were suffering from weight loss when they presented for operation, and in 40% weight loss exceeded 10% of the stable weight. In patients with cachexia, metastases were diagnosed significantly more often (47% vs. 24%, P < 0.001), leading to a significantly reduced resection rate in these patients. Patients with cachexia had significantly reduced fat tissue amounts. Hence, dramatic weight loss in a patient with pancreatic cancer may be a hint of a more progressed or more aggressive tumour.</p> <p>Conclusion</p> <p>Pancreatic cancer patients with cachexia had a higher rate of more progressed tumour stages and a worse nutritional status. Furthermore, patients with cachexia had an impaired lung function and a reduction in fat tissue. Patients with pancreatic cancer and cachexia had significantly reduced survival. If weight loss exceeded 5% there was a significantly reduced resection rate to detect, but the changes were significantly more substantial if weight loss was 10% or more. We propose that a weight loss of 10% be defined as significant in pancreatic cancer.</p

Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia can findings from animal models be translated to humans?

Background: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. Discussion: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. Summary: More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future

Relevance of results of colposcopic examination and results of molecularbiological findings in benign and dysplastic lesions of the cervix uteri

Die Prävalenz für das Zervixkarzimon beträgt weltweit ca. 15,1 je 100000 Einwohner, das entspricht etwa 525000 Karzinomen der Cervix uteri. Ziel der Untersuchung war herauszufinden, welche kolposkopischen Befunde auf Karzinome aber auch auf Präkanzerosen und benigne Veränderungen hinweisen können und welcher Zusammenhang zu Infektionen mit humanen Papillomaviren besteht. In der vorliegenden Arbeit wurden kolposkopische, molekularbiologische und zytologische Befunde von 540 Patientinnen untersucht, bei denen eine der Diagnosen Zervizitis, Metaplasie, CIN I, CIN II, CIN III oder Karzinom der Cervix uteri histologisch gesichert worden war. Durch den Vergleich kolposkopischer und histologischer Befunde konnten Unterscheidungshilfen für leicht- und schwergradige Läsionen ermittelt werden. Auf histologisch schwergradige Befunde deuten Bereiche hin, die nach Essigsäureapplikation glänzend weiß erscheinen, eine erhabene Oberfläche haben sowie eine scharfe Begrenzung vorweisen. Zusätzlich sind grobe und mittlere Mosaikstrukturen sowie grobe Punktierungen Zeichen einer schwergradigen Läsion. Mittels der Polymerasekettenreaktion (PCR) untersuchten wir Zervix- Abstriche auf die Anwesenheit von DNA von humanen Papillomaviren. Mit zunehmendem histologischen Schweregrad fanden sich bei mehr Patientinnen Infektionen mit humanen Papillomaviren. Bei 60% der Zervizitisfälle, 71% der Metaplasien, 84% der CIN I, 88% der CIN II und 98% der CIN III waren Infektionen mit humanen Papillomaviren feststellbar. Auffallend ist eine recht hohe Rate an HPV- Infektionen bei Patientinnen mit Zervizitis. Dies zeigt, dass auch schon bei leichtgradigen Läsionen bei einem nicht kleinen Anteil Infektionen mit humanen Papillomaviren nachweisbar sind; mit zunehmendem Schweregrad steigt diese Nachweisrate an.Worldwide the prevalence of cervical cancer is about 15.1 per 100000 women, which means around 525000 cases of cervical cancer in the world. The aim of our studies was to find out which colposcopic findings can be detected in cervical cancer, dysplasia or benign alterations of the cervix uteri. We also wanted to find out the coincidence of dysplasia and infections by human papillomavirus. In our studies we compared colposcopic, molecularbiological and cytologic results of 540 patients suffering from cervicitis, metaplasia, cervical intraepithelial neoplasia or cervical cancer. We could show criteria to distinguish between low- grade and high- grade lesions. A lesion which appears after the application of acetic acid in a bright white colour, a raised surface and sharp margins, shows in histological examination high- grade lesions. Also the appearance of mosaic structures with moderately or rough surface and dotting with rough surface predicts in a high percentage of cases high- grade lesions. Using the polymerase- chain- reaction (PCR) we analysed in cervical scrapes the presence of DNA of human papillomavirus. With increasing severity in histological examination we found an increasing number of human papillomavirus infection: in 60% of patients suffering from cervicitis, in 71% of metaplasia, in 84% of CIN I, in 88% of CIN II and 98% of CIN III we found infections human papillomavirus. Striking is the high rate of human papillomavirus infections in patients suffering from cervicitis. This shows that also in low grade lesions in a very high number of cases human papillomavirus infections can be found, with increasing severity this number is increasing

Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia

Abstract Background Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. Experimental design We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Results Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. Conclusions We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.</p