[Show abstract][Hide abstract] ABSTRACT: Risk classification and prediction of prognosis in GIST is still a matter of debate. Data on the impact of age and gender as potential confounding factors are limited. Therefore we comprehensively investigated age and gender as independent risk factors for GIST.
Two independent patient cohorts (cohort I, n = 87 [<50 years]; cohort II, n = 125 [≥50 years]) were extracted from the multicentre Ulmer GIST registry including a total of 659 GIST patients retrospectively collected in 18 collaborative German oncological centers. Based on demographic and clinicopathological parameters and a median follow-up time of 4.3 years (range 0.56; 21.33) disease-specific-survival (DSS), disease-free-survival (DFS) and overall survival (OS) were calculated.
GIST patients older than fifty years showed significantly worse DSS compared to younger patients (p = 0.021; HR = 0.307, 95% CI [0.113; 0.834]). DSS was significantly more favorable in younger female GIST patients compared with elderly females (p = 0.008). Female gender resulted again in better prognosis in younger patients (p = 0.033).
Patient age (<50 years) and female gender were significantly associated with a more favourable prognosis in GIST. Extended studies are warranted to confirm our clinical results and to elucidate underlying pathophysiological mechanisms.
BMC Cancer 12/2015; 15(1):1054. DOI:10.1186/s12885-015-1054-y · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pancreatic tumors comprise benign lesion and malignant lesion, most importantly pancreatic adenocarcinoma, acinar cell carcinoma, neuroendocrine carcinoma or metastasis. Surgical resection provides the only chance for cure for malignant pancreatic tumors. In some cases, surgical resection is performed because a malignant lesion is suspected, however, histopathological examinations eventually reveal a benign lesion. Here, we report the case of a 49-year-old woman, who was initially diagnosed with a neuroendocrine tumor of the pancreas with metastasis to the liver. The patient underwent distal pancreatectomy and atypical liver resection. Surprisingly, however, histopathological examination revealed an intrapancreatic accessory spleen (IPAS) of the pancreatic tail as well as liver hemangioma. This unique case report highlights the impact of extensive preoperative examinations to differentiate benign and malignant pancreatic lesions and, possibly, prevent patients from unnecessary surgery.
International Journal of Surgery Case Reports 11/2015; DOI:10.1016/j.ijscr.2015.10.041
[Show abstract][Hide abstract] ABSTRACT: CK1 protein kinases form a family of serine/threonine kinases which are highly conserved through different species and ubiquitously expressed. CK1 family members can phosphorylate numerous substrates thereby regulating different biological processes including membrane trafficking, cell cycle regulation, circadian rhythm, apoptosis, and signal transduction. Deregulation of CK1 activity and/or expression contributes to the development of neurological diseases and cancer. Therefore, CK1 became an interesting target for drug development and it is relevant to further understand the mechanisms of its regulation. In the present study, Cyclin-dependent kinase 2/Cyclin E (CDK2/E) and Cyclin-dependent kinase 5/p35 (CDK5/p35) were identified as cellular kinases able to modulate CK1δ activity through site-specific phosphorylation of its C-terminal domain. Furthermore, pre-incubation of CK1δ with CDK2/E or CDK5/p35 reduces CK1δ activity in vitro, indicating a functional impact of the interaction between CK1δ and CDK/cyclin complexes. Interestingly, inhibition of Cyclin-dependent kinases by Dinaciclib increases CK1δ activity in pancreatic cancer cells. In summary, these results suggest that CK1δ activity can be modulated by the interplay between CK1δ and CDK2/E or CDK5/p35. These findings extend our knowledge about CK1δ regulation and may be of use for future development of CK1-related therapeutic strategies in the treatment of neurological diseases or cancer.
[Show abstract][Hide abstract] ABSTRACT: Background: Molecular genetic techniques have greatly improved the understanding of pediatric illnesses.
Based on our own experience, the aim of this review is to illustrate the importance of such molecular studies for the
development of the pediatric surgery.
Methods: Various molecular techniques for the investigation of DNA, RNA, Chromosomes, gene sequences,
genomic rearrangements and gene amplifications have been employed to answer the clinical and therapeutic questions.
Suitable statistic methods allowed the comparison of the results between patients and controls whenever possible.
Results: We demonstrated that essential information for diagnostics and therapy of pediatric illnesses can be
obtained through molecular genetic testing, including (but not limited to) translocations and consequent protein
chimera expression in infantile lung tumors, the occurrence of genomic variants associated to neuroblastomas, the
occurrence of microdeletions and insertions in target genes for autonomic diseases, the significantly higher occurrence
of target gene mutations and polymorphisms in hypertrophic pyloric stenosis, the identification of a somatic gonosomal
mosaicism and uniparental disomy in a complex disorder of sex differentiation and finally the simultaneous occurrence
of embryonal tumors as early consequences of genomic instability.
Conclusions: The importance of molecular genetic research for the development of pediatric surgery is evident
from the multiple findings hereby described, demonstrating that the application of molecular genetic techniques and
the development of a “genetically oriented” thinking for diagnostic and therapy strategies may indeed broaden the
expertise and knowledge of pediatric surgeons, ultimately resulting in a better quality of care and higher rate of success
for the pediatric patients.
[Show abstract][Hide abstract] ABSTRACT: Non-alcoholic steatohepatitis (NASH) is an obesity associated common cause of liver inflammation and there are concerns that it may turn out to be the most common cause of liver failure as prevalence of obesity increases. We determined the prevalence of NASH in relation to gender and body mass index (BMI). Furthermore, we assessed the association of NASH with the length of the small bowel.
124 liver samples obtained during routine operations were examined looking for NAFLD Activity Score (nonalcoholic fatty liver disease). The length of small bowel was measured intraoperatively. For evaluation, patients were divided into four groups according to their BMI (group 1: normal weight, group 2: overweight, group 3: grade I/II morbidly obese, and group 4 grade III morbidly obese patients).
BMI showed a strong positive correlation with risk of NASH and a weak positive correlation with small bowel length. No normal weight patient was at risk of NASH, whereas in group 2 14% had uncertain and 32% definite NASH. In group 3 11% had uncertain and 27% definite NASH. In group 4 nearly two-thirds were classified as uncertain or definite NASH. Median length of small bowel in all patients was 450 cm (range 226-860 cm). Within group 4, patients with definite/uncertain NASH had a longer small bowel than patients without NASH.
Prevalence of NASH is high in morbidly obese. Small bowel length could influence the complex etiology of the disease.
BMC Research Notes 07/2015; 8(1):290. DOI:10.1186/s13104-015-1224-7
[Show abstract][Hide abstract] ABSTRACT: Aim: Adjuvant treatment is still controversially discussed for elderly colon cancer (CC) patients. Our aim was to investigate the benefit of adjuvant treatment for younger (<70 years) and elderly (≥70 years) patients. Patients and Methods: The long-term outcome of patients (n=855) enrolled in a randomized controlled trial comparing adjuvant chemotherapy with 5-FU alone, 5-FU plus folinic acid (FA), and 5-FU plus interferon-alpha (IFNa) was compared in younger (<70 years) and elderly (≥70 years) patients using a quotient of each patient's survival time and his expected residual life expectancy (QSL) and a multivariate Cox proportional hazards model. Results: Eightyear overall survival (OS) rates were 58.3% and 57.4% for younger (n=653) and elderly (n=202) patients, respectively. In elderly patients, 8-year OS rates were 51.4%, 61.8%, and 56.3, and median QSL scores were 0.338, 0.371, and 0.343 for 5-FU (n=59), 5-FU plus FA (n=76), and 5-FU plus IFNa (n=67), respectively. In elderly patients treatment with 5-FU plus FA decreased the risk for an event by 1.5-fold compared to 5-FU (HR=0.657, 95%CI=0.495-0.870, p=0.004) and 5- FU plus INFa (HR=0.685, 95%CI=0.515-0.912, p=0.009). Conclusion: Our analysis clearly demonstrates for the first time an additional benefit of FA for adjuvant treatment of elderly CC patients. We conclude that this regimen is very safe and effective for adjuvant treatment of elderly patients.
Anticancer research 07/2015; 35(10). · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to determine if international guidelines differ in their recommendations concerning additive therapy for advanced, but potentially curable, gastric cancer. A systematic search of the English and German literature was conducted in the databases Medline, Cochrane Database, Embase, and PubMed. The search terms used were 'guidelines gastric cancer,' 'guidelines stomach cancer,' and 'Leitlinien Magenkarzinom.' Six different guidelines published after January 1, 2010, in which the tumors were classified according to the seventh edition of the TNM system (2010), were identified. Although the examined guidelines were based on the same study results, their recommendations concerning accompanying therapy for gastric cancer differ considerably. While perioperative chemotherapy is recommended in Germany, Great Britain, and large parts of Europe, postoperative adjuvant radiochemotherapy or perioperative chemotherapy is recommended in the USA and Canada. In Japan, postoperative adjuvant chemotherapy is recommended.The results of identical studies were interpreted differently in different countries. Since considerable effort is required for each country to separately test relevant studies for their validity and suitability, an international cooperation could simplify the creation of a common basis for guidelines and contribute to improved comparability of international guidelines.
Journal of Gastric Cancer 03/2015; 15(1):10-18. DOI:10.5230/jgc.2015.15.1.10
[Show abstract][Hide abstract] ABSTRACT: To elucidate diagnostic criteria, clinicopathological features and clinical outcome in patients with esophageal gastrointestinal stromal tumors (GIST), representing an extremely rare subform of GIST with an estimated incidence of about 0.1 to 0.3 per million people.
Esophageal GIST cases from the Ulmer GIST registry consisting of 1077 cases were pooled with case reports and case series of esophageal GIST extracted from MEDLINE. Data were compared with those from 683 cases with gastric GIST from the Ulmer GIST registry.
In comparison to gastric GIST, esophageal GIST (n = 55) occurred significantly more frequent in men (p = 0.035) as well as in patients younger than 60 at diagnosis (p < 0.001). Primary tumor sizes were significantly larger (p < 0.001), thereby resulting more frequently in a high-risk classification (OR = 4.53, CI 95% 2.41-8.52, p < 0.001). The 5-year rates of disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) were 50.9%, 65.3% and 48.3%, respectively. The prognosis of esophageal GIST was less favorable compared with gastric GIST (DSS: p < 0.001, HR = 0.158, 95% CI: 0.087-0.288; DFS: p = 0.023, HR 0.466, 95% CI: 0.241-0.901; OS p = 0.003, HR = 0.481, 95% CI: 0.294-0.785; univariate Cox model) after a median follow-up time of 28 months (range 1.9 to 202). Mutational analysis for KIT showed more frequently wild-type status in esophageal GIST (OR = 10.13, CI 95% 3.02-33.96, p < 0.001).
Esophageal GIST differ significantly from gastric GIST in respect to clinicopathological features and clinical outcome. To optimize treatment options further prospective data on patients with esophageal GIST are urgently warranted.
American Journal of Cancer Research 01/2015; 5(1):333-43. · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and Objectives: To elucidate diagnostic criteria, clinicopathological features and clinical out-come in patients with esophageal gastrointestinal stromal tumors (GIST), representing an extremely rare subform of GIST with an estimated incidence of about 0.1 to 0.3 per million people. Patients and methods: Esophageal GIST cases from the Ulmer GIST registry consisting of 1077 cases were pooled with case reports and case series of esophageal GIST extracted from MEDLINE. Data were compared with those from 683 cases with gastric GIST from the Ulmer GIST registry. Results: In comparison to gastric GIST, esophageal GIST (n = 55) occurred significantly more frequent in men (p = 0.035) as well as in patients younger than 60 at diagnosis (p < 0.001). Primary tumor sizes were significantly larger (p < 0.001), thereby resulting more frequently in a high-risk classification (OR = 4.53, CI 95% 2.41-8.52, p < 0.001). The 5-year rates of disease-specific survival (DSS), disease-free survival (DFS), and over-all survival (OS) were 50.9%, 65.3% and 48.3%, respectively. The prognosis of esophageal GIST was less favorable compared with gastric GIST (DSS: p < 0.001, HR = 0.158, 95% CI: 0.087-0.288; DFS: p = 0.023, HR 0.466, 95% CI: 0.241-0.901; OS p = 0.003, HR = 0.481, 95% CI: 0.294-0.785; univariate Cox model) after a median follow-up time of 28 months (range 1.9 to 202). Mutational analysis for KIT showed more frequently wild-type status in esophageal GIST (OR = 10.13, CI 95% 3.02-33.96, p < 0.001). Conclusions: Esophageal GIST differ significantly from gastric GIST in respect to clinicopathological features and clinical outcome. To optimize treatment options further prospec-tive data on patients with esophageal GIST are urgently warranted. Introduction Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with an annual incidence of 7 to 20 per million [1-6]. There is substantial evidence that GISTs differentiate parallel to the gut pacemaker cells, the interstitial cells of Cajal suggesting an origin from the Cajal cells or their progenitor cells [7-9]. Despite prognos-tic relevance of metastases at primary stage and tumor rupture, risk stratification in GIST is related to tumor size, mitotic rate and as recent-ly recognized also to tumor location. The major-ity of GISTs are located in the stomach (60-70%) and the small intestine (25-30%), whereas GISTs of the colo-rectum (up to 5%) and extra-gastrointestinal manifestations (< 5%) are less common [10-12]. Esophageal GIST is a very rare entity of GIST and represents < 1% of all cases. Therefore data on clinicopathological characteristics and clinical outcome are limit-ed. The aim of the present study was to eluci-date comprehensively demographic and
American Journal of Cancer Research 01/2015; 5(1):333-343. · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical picture of an acute abdomen is frequently encountered in
emergency medicine. In most cases abdominal pathologies underlie
this condition, however, also extra-abdominal diseases may present or
cause an acute abdomen. The fact that this condition is potentially lifeMathias
threatening highlights the importance of instant action. Here, we report
on the case of a young woman that presented with an acute abdomen Doris Henne-Bruns1
in our clinic. Imaging revealed a massively distended stomach reaching
the lesser pelvis. Initially, the etiology for the gastric dilatation remained
unsolved. On the same day we performed an explorative laparotomy in 1 Clinic of General and Visceral
Surgery, University of Ulm,
which massive amounts of clotted, undigested food was recovered via
a gastrotomy. Postoperatively, upon psychiatric consultation, an eating
disorder with daily eating binges could be revealed as being the cause 2 Department of Diagnostic
and Interventional Radiology,
University of Ulm, Germany
for the acute and dramatic gastric dilatation. The patient fully recovered
from surgery and psychiatric co-treatment was initiated. This unique
case report demonstrates how a psychiatric condition may lead to an
acute abdomen, however, it also emphasizes the importance of prompt
diagnosis and adequate therapy to avoid complications and allowing
for full recovery.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The Peutz-Jeghers syndrome (PJS) is a rare hereditary, autosomal-dominant disorder. It is characterized by a gastrointestinal polyposis and mucocutaneous melanic spots. It has also been reported as a precondition for malignancies with a life-time-hazard for cancer up to 93%, caused by a germline mutation in the STK11 gene.
Presentation of case:
A 21-year-old man presented with nausea and abdominal pain. He had a known history of PJS since the age of 13 when he was treated for intussusception due to a hamartomatous polyp. Preoperative diagnostics revealed a second intussusception and an extensive intestinal polyposis. Intraoperative findings confirmed the suspected diagnoses and desvagination was performed. Nearly 50 polyps were removed from the small intestinum over several longitudinal sections. As the appendix appeared thickened an appendectomy was performed simultaneously. Histology showed hamartomatous polyps and the incidental finding of a pT1 carcinoid of the appendix. The patient recovered well and needed no further treatment for his carcinoid tumor.
The mechanism of carcinogenesis in PJS still remains debatable, although the genetic disorder underlying the syndrome is known. A predisposition for carcinoid tumors also stays questionable. To our knowledge there is no description of an association between carcinoid tumors of the appendix and PJS to date.
Life-expectancy in patients with PJS is reduced. Causes are the development of malignancies and complications from the polyps such as intussusception. Since there is no treatment possible main focus must be aimed at early recognition of malignancies and the prevention of complications.
International Journal of Surgery Case Reports 10/2014; 5(12). DOI:10.1016/j.ijscr.2014.06.024
[Show abstract][Hide abstract] ABSTRACT: About 10% of all cancer patients will develop brain metastases during advanced disease progression. Interestingly, the vast majority of brain metastases occur in only three types of cancer: Melanoma, lung and breast cancer. In this review, we focus on summarizing the prognosis and impact of surgical resection of brain metastases originating from gastrointestinal cancers such as esophageal, gastric, pancreatic and colorectal cancer. The incidence of brain metastases is <1% in pancreatic and gastric cancer and <4% in esophageal and colorectal cancer. Overall, prognosis of these patients is very poor with a median survival in the range of only months. Interestingly, a substantial number of patients who had received surgical resection of brain metastases showed prolonged survival. However, it should be taken into account that all these studies were not randomized and it is likely that patients selected for surgical treatment presented with other important prognostic factors such as solitary brain metastases and exclusion of extra-cranial disease. Nevertheless, other reports have demonstrated long-term survival of patients upon resection of brain metastases originating from gastrointestinal cancers. Thus, it appears to be justified to consider aggressive surgical approaches for these patients.
International Journal of Molecular Sciences 09/2014; 15(9):16816-16830. DOI:10.3390/ijms150916816 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The ubiquitously expressed serine/threonine specific casein kinase 1 (CK1) family plays important roles in the regulation of various physiological processes. Small-molecule inhibitors, such as the CK1δ/ε selectively inhibitor IC261, have been used to antagonize CK1 phosphorylation events in cells in many studies. Here we present data to show that, similarly to the microtubule destabilizing agent nocodazole, IC261 depolymerizes microtubules in interphase cells. IC261 treatment of interphase cells affects the morphology of the TGN and Golgi apparatus as well as the localization of CK1δ, which co-localizes with COPI positive membranes. IC261-induced depolymerization of microtubules is rapid, reversible and can be antagonized by pre-treatment of cells with taxol. At lower concentrations of IC261, mitotic spindle microtubule dynamics are affected; this leads to cell cycle arrest and, depending on the cellular background, to apoptosis in a dose-dependent manner. In addition, FACS analysis revealed that IC261 could induce apoptosis independent of cell cycle arrest. In summary this study provides additional and valuable information about various IC261-induced effects that could be caused by microtubule depolymerization rather than by inhibition of CK1. Data from studies that have used IC261 as an inhibitor of CK1 should be interpreted in light of these observations.
PLoS ONE 06/2014; 9(6):e100090. DOI:10.1371/journal.pone.0100090 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
During the last 15 years, there was tremendous progress in minimally invasive surgery and minimal-access surgery. Many conventional surgical procedures were replaced by these techniques, resulting in a wide range of benefits for the patients. In kidney transplantation, many centers choose an approach to the iliac fossa through an oblique or J-shaped incision. This might have possible disadvantages due to the extent of tissue trauma. Thus, we introduced a minimal-access kidney transplantation technique (MAKT) as a transplantation method in our center. We retrospectively analyzed this technique used for 11 living-donor kidney transplants and report here our experience.
Patients and methods:
From April 2008 to July 2011, 11 living-donor kidney recipients were subjected to the MAKT and were matched (age, sex) with a historical group from our center from 2000 to 2007. To analyze the assumption of noninferiority of the MAKT in comparison to the standard approach, a matched case-control study design was chosen, with creatinine level at 1 year after transplantation as the primary outcome variable. We used a Wilcoxon signed rank test; 1-sided significance level was 2.5%.
Eleven recipients were included. Both groups were almost similar regarding age and body mass index. Characteristics of the procedure were significantly different only for cold ischemic time (114 minutes MAKT vs 77 minutes historical group). In the MAKT group, there were no reinterventions necessary, no wound infections, no incisional hernia, no acute rejection episodes, no graft losses, and 2 lymphoceles occurred. Further, no urinary leakage or ureteral stenosis and no vascular complications were observed. The statistical analysis of the primary endpoint revealed a noninferiority of the MAKT technique (P = .0005).
Considering the fact that this is an initial series and a retrospective analysis, the applied MAKT technique seems to be safe in terms of both graft function after 1 year and surgical complications.
[Show abstract][Hide abstract] ABSTRACT: Aim:
We analyzed survival of patients diagnosed with ampullary cancer (AC) and pancreatic ductal adenocarcinomas (PDAC).
Patients and methods:
Between 1996 and 2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were identified. Overall survival was analyzed according to tumor entity, therapeutic approach and pathological tumor stage.
The 5-year overall survival rate of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts, surgical resection improved survival. Analysis of pathological factors revealed a survival benefit for patients staged with small primary tumors (pT1/2) and exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence of lymph node metastasis substantially improved survival in AC, but not in PDAC.
Overall survival of patients with AC is superior compared to that of patients with PDAC. Therapeutically, adequate regional lymph node dissection seems particularly important for the surgical management of AC.
Anticancer research 06/2014; 34(6):3011-3020. · 1.83 Impact Factor