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Mark Hartel

Publications and source records attributed to Mark Hartel.

13 recordsLinked to original sources
PubMed2005

Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma.

Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P-glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1-MRP9) with MRP1-MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer.

Adult↗
PubMed2005

Effect of antecolic reconstruction on delayed gastric emptying after the pylorus-preserving Whipple procedure.

HYPOTHESIS: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE) after a pylorus-preserving Whipple (ppW) procedure better than retrocolic duodenojejunostomy. DESIGN: A single operation team's experience with antecolic and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database using univariate and multivariate models. SETTING: Tertiary referral center that focuses on pancreatic diseases. PATIENTS AND INTERVENTIONS: One hundred consecutive patients undergoing a ppW procedure with retrocolic reconstruction between January 1, 1996, and December 31, 2001, and 100 consecutive patients undergoing a ppW procedure with antecolic reconstruction between January 1, 2002, and December 31, 2003. Characteristics such as median age, median hospital stay, sex, diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists risk groups, stent implantation, and especially DGE were matched for the comparison groups. MAIN OUTCOME MEASURES: We compared DGE, characteristics, and perioperative variables in patients with antecolic vs retrocolic reconstruction after ppW. RESULTS: The DGE occurred significantly more often in patients with retrocolic reconstruction than in those with antecolic reconstruction (P < .001). The antecolic and retrocolic study groups were comparable in age (P = .25), sex (P = .48), and postoperative surgical (P = .19) and medical (P = .054) complications. The univariate analysis between patients with and without DGE did not show significant differences regarding diagnosis, previous operations, blood loss, surgical and medical complications, American Society of Anesthesiologists classification, or stent implantation. In the multivariate analysis, only the type of reconstruction (P = .006) and sex (P = .04) seemed to affect DGE. CONCLUSION: We recommend antecolic duodenjejunostomy in patients undergoing a ppW procedure regardless of their diagnosis.

Aged↗
PubMed2005

Renal cancer cell metastasis into the pancreas: a single-center experience and overview of the literature.

OBJECTIVES: The pancreas is a rare target for metastasis from other primary cancers, but pancreatic metastasis play a role in the diagnostic workup of patients with pancreatic tumors, especially in patients with a history of renal cell carcinoma (RCC). METHODS: Between October 2001 and June 2004 data from 601 patients undergoing pancreatic resection were entered prospectively in a database and were analyzed for metastasis into the pancreas from RCC. RESULTS: Fifteen patients with metastasis to the pancreas from RCC were identified. One patient showed metastatic disease at time of primary diagnosis. In 8 patients, the pancreas was the only site of metastasis, whereas in 7 patients, other organs, such as the thyroid gland, the lung, or the liver, were targets of metastasis, either metachronous or simultaneous at the time of pancreatic metastasis. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 86 months (range, 0-258). Most patients were asymptomatic and diagnosed during standard tumor follow-up. So far, 14 patients remain alive with a median follow-up of 10 months. CONCLUSION: Pancreatic metastasis from RCC is rare but can occur even more than 20 years after primary tumor manifestation. Our results show that pancreatic resections for metastasis can be performed safely with a low rate of complications. Patients with a history of RCC should undergo a long-term follow-up to detect and evaluate for pancreatic metastases as well for metastasis to other organ sites.

Aged↗
PubMed2005

Carcinoid of the ampulla of Vater.

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.

Ampulla of Vater↗
PubMed2004

The role of extended resection in pancreatic adenocarcinoma: is there good evidence-based justification?

Thus far, there are no studies concerning the radicality of pancreaticoduodenectomy which, in well-performed, randomized-controlled trials employing high standards of evidence-based medicine, show a benefit over extended lymphadenectomy. The results of the only two prospective randomized studies are not comparable and both are underpowered (level of evidence Ib). Therefore, it is still unclear whether extended lymphadenectomy for pancreatic carcinoma improves outcome. Only one study suggests a positive tendency toward increased survival rates in node-positive patients. Extended approaches including additional venous resection can be performed without a rise in the morbidity and mortality rates of patients with pancreatic carcinoma. In the future appropriately powered randomized trials of standard vs. extended resections may show the benefit of extended surgical resections. In addition, well powered trials of postoperative adjuvant therapies or preoperative neoadjuvant strategies together with surgical resections may identify more effective combinations showing a survival benefit in patients with pancreatic carcinoma.

Adenocarcinoma↗
PubMed2004

Desmoplastic reaction influences pancreatic cancer growth behavior.

Connective tissue growth factor (CTGF), which is regulated by transforming growth factor-ss (TGFss), has recently been implicated in the pathogenesis of fibrotic diseases and tumor stroma. Inasmuch as generation of desmoplastic tissue is characteristic for pancreatic cancer, it is not known whether it gives pancreatic cancer cells a growth advantage or is a reaction of the body to inhibit cancer cell progression. In the present study we analyzed the expression and localization of CTGF and evaluated whether it influences the prognosis of pancreas cancer. Tissue samples were obtained from 25 individuals (6 women, 19 men) undergoing pancreatic resection for pancreatic cancer. Tissue samples from 13 previously healthy organ donors (5 women, 8 men) served as controls. Expression of CTGF was studied by Northern blot analysis. In situ hybridization and immunohistochemistry localized the respective mRNA moieties and proteins in the tissue samples. Northern blot analysis revealed that pancreatic cancer tissue samples exhibited a 46-fold increase in CTGF mRNA expression ( p < 0.001) over that of normal controls. In vitro studies confirmed that pancreatic stellate cells are the major source of CTGF mRNA expression and revealed a large variance in basal and TGFss-induced CTGF expression in cultured pancreatic cancer cells. This could also be confirmed by in situ hybridization, indicating that CTGF mRNA signals were located principally in fibroblasts, with only weak signals in the cancer cells. High CTGF mRNA levels in the tissue samples correlated with better tumor differentiation ( p < 0.03). In addition, patients whose tumors exhibited high CTGF mRNA levels (> onefold increase above normal controls) lived significantly longer than those whose tumors expressed low CTGF mRNA levels (none to onefold) ( p < 0.04 multivariate analysis). Our present data indicate that CTGF, as a downstream mediator of TGFss, is overexpressed in connective tissue cells and to a lesser extent in pancreatic cancer cells. Because patients with high CTGF mRNA expression levels have a better prognosis, our findings indicate that the desmoplastic reaction provides a growth disadvantage for pancreatic cancer cells.

Adenocarcinoma↗
PubMed2004

Inflammatory response after abdominal surgery.

Surgical manipulation of the gut elicits an inflammatory cascade within the intestinal muscularis that contributes to postoperative bowel dysmotility. A range of cytokines is sequentially released into the peritoneal fluid following abdominal surgery, their concentrations reflecting the magnitude of surgical trauma. The overproduction of inflammatory mediators might have detrimental effects on organ function and contribute to the enhanced risk of anastomotic leakage in the presence of sepsis. Specific cellular immune functions such as the microbicidal activity of peritoneal phagocytes are depressed after elective surgery, imposing a risk of infectious complications. Laparoscopic surgery decreases the local and systemic production of cytokines and acute-phase reactants, and better preserves peritoneal immunity compared with open surgery. As concluded from animal studies, the gas used for the pneumoperitoneum may possess substantial immunomodulatory activity.

Abdomen↗
PubMed2004

Surgical treatment of oesophageal cancer.

Various reconstructive conduits and routes of reconstruction have an impact on operative morbidity and foregut function in patients undergoing oesophagectomy. Advantages of a fundus rotation gastroplasty are the better blood supply and the greater length of the gastric tube and its possible impact on anastomotic complications. For a subgroup of patients with oesophageal carcinoma limited to the lamina propria vagal-sparing oesophagectomy seems to be a good alternative in terms of quality of life to preserve gastric secretory, motor, and reservoir function. Posterior mediastinal reconstruction is usually preferred when complete resection (R0) has been accomplished. Anterior mediastinal reconstruction may secondary prevent dysphagia after incomplete resections due to tumour recurrence (R0, R1). However, for all presently available surgical approaches in the treatment of oesophageal cancer qualified studies (prospective randomised) are needed. In addition, randomized trials are needed to identify the specific subgroups of patients who benefit from neoadjuvant or adjuvant radiochemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Evidence-based surgery in chronic pancreatitis.

BACKGROUND: In the past two decades our knowledge of the pathophysiology and surgical treatment options in chronic pancreatitis has improved substantially. Surgical treatment in chronic pancreatitis has evolved from extending to organ-preserving procedures. DISCUSSION: The classical Whipple resection is no longer a standard procedure in chronic pancreatitis, and is continuously being replaced by operations such as the duodenum-preserving pancreatic head resection and pylorus-preserving Whipple. These procedures allow the preservation of exocrine and endocrine pancreatic function, provides pain relief in up to 90% of patients, and contributes to an improvement in life quality. CONCLUSIONS: In addition to presently available results from randomized controlled trials, new studies comparing available surgical approaches in chronic pancreatitis are needed to determine which procedure is the most effective in the treating chronic pancreatitis.

Chronic Disease↗
PubMed2003

Up-regulation of p75 neurotrophin receptor (p75NTR) is associated with apoptosis in chronic pancreatitis.

Activation of apoptosis in chronic pancreatitis has been demonstrated. The low-affinity neurotrophin receptor p75 (p75NTR) mediates apoptosis in many cell types in vivo and in vitro. The aim of this study was to examine whether p75NTR is involved in the apoptotic process in chronic pancreatitis. The quantity and localization of the receptor was evaluated using northern blot analysis, in situ hybridization, immunohistochemistry, and western blot analysis. Apoptosis was determined by TUNEL assay. By northern blot analysis, p75NTR mRNA levels were increased 40-fold in chronic pancreatitis compared with normal pancreas (P < 0.01). In situ hybridization revealed weak p75NTR mRNA expression in some ductal cells in the normal pancreas. In contrast in chronic pancreatitis moderate p75NTR expression was present in acinar cells next to fibrosis, ductal cells, and cells of ductular structures as well as in some islet cells. Immunostaining of p75NTR in normal pancreas and chronic pancreatitis tissue samples showed a similar intensity and distribution pattern as found by in situ hybridization. Higher p75NTR protein levels could be confirmed by western blot analysis, which revealed an 8.6-fold increase of p75NTR in chronic pancreatitis. TUNEL staining showed, in chronic pancreatitis samples, positivity in some acinar cells next to fibrosis, some ductal cells, and cells of ductular structures. Also some islet cells were positive by TUNEL staining. The presence of p75NTR immunoreactivity was positively correlated (P < 0.05) with the apoptotic index in the exocrine and endocrine pancreas. In conclusion, p75NTR, the low-affinity receptor of neurotrophins which mediates apoptosis, is up-regulated in CP and is involved in the apoptotic process of the exocrine and endocrine pancreas.

Adolescent↗
PubMed2002

Benefit of venous resection for ductal adenocarcinoma of the pancreatic head.

OBJECTIVE: To find out whether there is any benefit from venous resection during pancreaticoduodenectomy for ductal pancreatic adenocarcinoma. DESIGN: Retrospective study. SETTING: University Hospital Mannheim/Heidelberg, Germany. INTERVENTIONS: 271 patients had resections for ductal adenocarcinoma of the pancreatic head between 1980 and 2001. The outcome of patients who did (n = 68) and who did not (n = 203) have simultaneous resection of major veins (portal vein and/or superior mesenteric vein) were compared. MAIN OUTCOME MEASUREMENT: 5 year survival. RESULTS: The groups differed significantly regarding stage, perineural infiltration, lymphangiosis carcinomatosa, operating time, blood loss, and blood transfusion. However, there was no difference in perioperative morbidity (27% and 22%), mortality (4% and 3%), and long-term survival (at 5 years 23% and 24%). Subgroup analysis of patients with margins free of tumour (R0 resections) showed that those patients who had venous resections in whom histological examination did not show infiltration of tumour had the most favourable outcome. CONCLUSION: There is no reason to exclude patients with suspected venous infiltration from radical pancreaticoduodenectomy including venous resection.

Adult↗
PubMed2002

High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas.

INTRODUCTION AND AIMS: Only curative resection for pancreatic adenocarcinoma is related to a favorable prognosis, but the overall survival after surgery still remains poor, and early recurrence is frequently observed. Because recurrence is the limiting factor and the main cause of death after curative resection, the identification of markers that predict early postoperative recurrence is of paramount importance. Angiogenesis is essential for tumor growth and metastases; therefore, we set out to clarify whether vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) correlate with early recurrence and poor prognosis after curative resection. A second goal was to characterize the VEGF-producing cells and the subcellular distribution. METHODOLOGY: Seventy patients with ductal adenocarcinoma of the pancreas were studied after curative resection with a follow-up of at least 2 years. The MVD quantification was performed immunohistochemically with use of a monoclonal antibody to CD34. The VEGF expression was studied with use of polyclonal antibody. To detect the intracellular localization of specific VEGF mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among VEGF expression and MVD, clinicopathologic parameters, and clinical outcome were then statistically analyzed. RESULTS: The VEGF immunoreactivity was 88.6%, and positive mRNA signals were obtained in the cytoplasm of carcinoma and endothelial cells in 81.4%. Furthermore, we observed tumor-associated macrophages close to infiltrating carcinoma cells. All endothelial cells showed positive immunoreactivity to the anti-CD34 antibody, and a median distribution of 85 vessels/x200 field was observed. A significant correlation (p < 0.05) was found between the MVD and the International Union Against Cancer (UICC) stage. Statistical analysis showed a significant correlation between VEGF expression and the height of MVD (p < 0.05). Kaplan-Meier analyses revealed that VEGF expression and MVD had a statistically significant correlation with survival after curative resection (p < 0.05). Furthermore, multivariate analysis indicated that VEGF expression is an independent prognostic marker for cancer recurrence within 8 months after curative surgery (p = 0.003). CONCLUSION: In pancreatic adenocarcinoma, the VEGF expression and the height of MVD are closely correlated, and both-rather than UICC stage and TNM classification (tumor size and nodal involvement)-are markers of prognostic relevance after curative resection. Furthermore, VEGF is a predictor of early recurrence after curative resection. The current study indicates that VEGF may promote the distribution of metastases, leading to early cancer recurrence and poor outcome.

Antigens, CD34↗