Biomedical subjects

H G Beger

Publications and source records attributed to H G Beger.

At least 145 records · Page 8Linked to original sources

PubMed1999

The surgical management of chronic pancreatitis: duodenum-preserving pancreatectomy.

Duodenum-preserving pancreas resection for chronic pancreatitis results in a subtotal resection of the pancreatic head. Of 488 patients suffering from chronic pancreatitis with an inflammatory mass in the head, 48% had a common bile duct stenosis in the ERCP, 63% had a pancreatic main duct stenosis, 25% had a duodenum stenosis, and 17% showed vascular obstruction--mainly compression or occlusion of the portal vein. Hospital mortality after duodenum-preserving head resection was 0.9%. In the late follow-up, 88% of patients were free of pain and 60% were professionally rehabilitated. The incidence of diabetes mellitus in the late follow-up was 14%; however, 6% of the patients had a lasting improvement of endocrine function. Late mortality after a median follow-up of 6 years (1-22 years after surgical treatment) was 9%. Only 10% of the patients needed further hospitalization due to recurrent attacks of acute pancreatitis. Duodenum-preserving head resection should be the surgical procedure of choice in chronic pancreatitis with an inflammatory mass in the head of the pancreas and in cases with pancreas divisum after failure of medical and interventional treatment. Duodenum-preserving total pancreatectomy is a last-resort surgical treatment after failure of left resection for pain in chronic pancreatitis.

Chronic Disease↗

PubMed1999

Surgery and multimodal treatments in pancreatic cancer--a review on the basis of future multimodal treatment concepts.

BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. In spite of several positive studies, and the fact that multimodality treatment is the standard concept in major centers for pancreatic cancer surgery, a recent trial shed some doubt on the positive effect of adjuvant radiochemotherapy, so that the majority with reservations about multimodal treatment feel confirmed in their opinion that surgical treatment alone is sufficient therapy for resectable pancreatic cancer. The controversy among those for and against adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature on the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. A special view was concentrated on the biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities, to characterize the disease for an optimally targeted treatment in conjunction with surgical removal of the tumor. The results of systemic and regional chemotherapy and radiotherapy either alone or in combination, before, during, and after surgery, were critically analyzed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomized trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy (Bakkevold), the adjuvant treatment achieved a significant prolongation of the median survival time. The 5- and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved vs. surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalizing margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being undecisive or against adjuvant therapy, the participation in trials, e.g., ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested vs. surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.

Adenocarcinoma↗

PubMed1998

Prognostic significance of soluble interleukin-2 receptor-alpha in adenocarcinoma of the pancreas.

Soluble interleukin-2-receptor-alpha (sIL-2Ralpha) serum concentrations were examined in chronic pancreatitis patients, patients with cystadenocarcinoma of the pancreas, patients with adenocarcinoma of the pancreas and healthy blood donors. sIL-2Ralpha serum concentrations in pancreatic cancer patients were significantly higher than those of normal control subjects or chronic pancreatitis patients. In patients with adenocarcinoma of the pancreas no significant differences were found between sIL-2Ralpha and tumor size, grading, resectability and lymph node involvement. In Kaplan-Meier regression analysis patients with adenocarcinoma of the pancreas with low sIL-2Ralpha levels (<500 U/ml) lived significantly shorter than patients with sIL-2Ralpha concentrations above 500 U/ml (P < 0.01), suggesting that determination of sIL-2Ralpha serum concentrations could provide additional important information about prognosis.

Adenocarcinoma↗

PubMed1998

Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer.

Insulin receptor substrate-2 (IRS-2) is a multisite docking protein implicated in mitogenic signaling after activation of the insulin and insulin-like growth factor (IGF)-I receptors. In the present study, we characterized IRS-2 expression and function in human pancreatic cancer. IRS-2 mRNA and protein were expressed in ASPC-1 and COLO-357 human pancreatic cancer cell lines. Insulin, IGF-I, and IGF-II enhanced the growth of both cell lines, stimulated tyrosine phosphorylation of IRS-2, and increased IRS-2-associated phosphatidylinositol (PI) 3-kinase activity. The mitogenic effects of insulin, IGF-I, and IGF-II were markedly attenuated by the PI 3-kinase inhibitor LY 294002. Northern blot analysis of total RNA extracted from normal and cancerous tissues revealed that IRS-2 mRNA levels were increased in the cancer tissues (P = 0.032). In the normal pancreas, IRS-2 immunoreactivity was present at low levels in some ductal and acinar cells and at moderate levels in a heterogeneous pattern in all of the endocrine islets. In the pancreatic cancers, IRS-2 was abundant in the ductal-like cancer cells. These findings indicate that IRS-2 is overexpressed in human pancreatic cancer and suggest that it may contribute to enhanced mitogenic signaling via the PI 3-kinase pathway, thereby leading to excessive growth stimulation in this malignancy.

Colonic Neoplasms↗

PubMed1998

The splice-pattern of CD44 is altered in chronic pancreatitis exhibiting dysplastic changes.

Recent studies have shown that several splice variants of CD44, might be involved in tumor progression. Since chronic pancreatitis is suggested to be a risk factor for pancreatic cancer we investigated the splice pattern of CD44 in chronic pancreatitis to elucidate the role of CD44 in pancreas tumorigenesis. The expression of CD44-isoforms was examined in 40 specimens of chronic pancreatitis and 12 specimens of normal pancreas by immunohistochemistry, Westernblotting and exon specific RT-PCR. Pancreatic cancer tissue from two patients who developed pancreatic cancer 2 and 3 years following surgery for chronic pancreatitis were analyzed. Strong expression of CD44s was found in all cells, whereas the expression of CD44v6 was restricted to ductal cells. Westernblotting revealed an overexpression of CD44v6 in chronic pancreatitis as compared to normal pancreas. Exon specific analysis revealed an altered splice pattern of CD44, similar to that in pancreatic cancer, in 12.5% of the chronic pancreatitis specimens. Both patients who developed pancreatic cancer after chronic pancreatitis exhibited this altered splice pattern in both, chronic pancreatitis and pancreatic cancer. These results suggest that variant forms of CD44-mRNA might be expressed in early dysplastic alterations in chronic pancreatitis.

Blotting, Western↗

PubMed1998

Interleukin 1beta-converting enzyme (caspase-1) is overexpressed in adenocarcinoma of the pancreas.

We investigated the expression of interleukin 1beta-converting enzyme (ICE; caspase-1) in human adenocarcinomas of the pancreas. Immunohistochemistry and Western blot analyses revealed an overexpression of ICE in 71 and 80% of tumor cells, respectively. Also, on a mRNA level, ICE mRNA was overexpressed in 45% of the cases, as compared to normal pancreatic tissue. Interestingly, the overexpression of ICE in tumor cells correlated significantly with the overexpression of cyclin D1, epidermal growth factor, and epidermal growth factor receptor (P < 0.0005, P < 0.05, and P < 0.002, respectively), which are involved in cell cycle progression and proliferation in human pancreatic carcinoma. This is the first report concerning ICE expression in human carcinomas; however, the exact mechanism underlying these close correlations warrant further research.

Adenocarcinoma↗

PubMed1998

Heterotopic intestinal transplantation aggravates the insult of chronic rejection.

BACKGROUND: Intestinal grafts are placed either heterotopically (out of continuity) or orthotopically (in continuity); the latter is believed to be advantageous, as intraluminal nutrients and intestinal secretions might modulate the intestinal immune status and possibly delay rejection. METHODS: This study was designed to delineate the effects of heterotopic versus orthotopic allograft position on the morphology and function of intestinal smooth muscle in our rat model of chronic rejection. Syngeneic orthotopic grafts were evaluated to control for changes due to the transplantation process. RESULTS: Histochemistry of the graft's muscularis externa showed a significant thickening due to hyperplasia and hypertrophy, which was most pronounced in heterotopic grafts (control = 92+/-2.4 microm, syngeneic grafts = 140+/-6.7 microm, orthotopic allografts = 278+/-26.6 microm, heterotopic allografts = 456+/-50 microm). In terms of function, muscle strips from allografts only generated 23% of the total bethanechol-induced contractile force in vitro compared to unoperated controls and syngeneic grafts. The mean resting membrane potential of control and isograft muscle cells was -69 +/- 0.9 mV with a slow-wave amplitude of 20+/-0.5 mV. Chronic rejection hyperpolarized the resting membrane potential of orthotopic allografts (-66 +/- 0.5 mV) and even more so of heterotopic allografts (-58 +/- 3.4 mV). Slow-wave amplitudes were decreased in orthotopic (14+/-0.9 mV) and nearly abolished in heterotopic allografts (2+/-1.2 mV). CONCLUSIONS: Our data indicate that allografts in heterotopic position are most susceptible to the insult of chronic rejection exemplified by increased proliferative and hypertrophic transformation of intestinal smooth muscle and a marked decrease in mechanical and electrical activity.

Animals↗

PubMed1998

Early effect of low-dose endotoxin on rat cecal mucosa ex vivo.

It has been suggested that endotoxin triggers translocation of intestinal bacteria in vivo, either by directly damaging intestinal mucosa or by inducing a systemic inflammatory reaction that leads to mucosal disruption. To address this issue, we examined the immediate effect of extraluminal endotoxin on structure and function of isolated rat cecal mucosa without other inflammatory cells in vitro. The cecal mucosa of 12 male Wistar rats was mounted in modified Ussing chambers filled with Dulbecco's modified Eagle's medium and the ampicillin-resistant Escherichia coli HB101:K12 incubated on the mucosal side. Endotoxin was added to the submucosal side at concentrations of 1 and 10 EU/ml, respectively. Under gassing with carbogene at 37 degreesC, the potential difference across the mucosa was measured continuously. Samples of the mucosal and submucosal solutions were removed at 60, 120, and 180 min and plated out on McConkey ampicillin-agar. After 180 min, the mucosal specimens were retrieved and examined by light and scanning electron microscopy. No significant change in potential difference was observed in control or endotoxin-incubated mucosa within the observation period. Neither light nor scanning electron microscopy showed a significant change in the structure of the epithelium, mucosa, or submucosa. No significant translocation of the E. coli across the mucosa was seen. We concluded that endotoxin alone does not induce immediate structural and functional damage to rat cecal mucosa in vitro. Therefore, it seems unlikely that a short endotoxemia alone directly triggers bacterial translocation by disrupting intestinal mucosa, but rather, entotoxin induces a local and systemic inflammatory reaction that leads to mucosal disruption.

Animals↗

PubMed1998

Resection and radiochemotherapy of pancreatic cancer--the future?

BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.

Adenocarcinoma↗

PubMed1998

Prognostic significance of molecular alterations in human pancreatic carcinoma--an immunohistological study.

BACKGROUND: During the last decade, many molecular alterations have been described for pancreatic carcinomas. However, the clinical and prognostic value of these alterations has been discussed and is controversial. METHODS: An immunohistochemical study was performed in 82 cases of adenocarcinoma of the pancreas. Using specific antibodies, expression of EGF, EGF-receptor, cERB-B2, p53, p21CIP1, cyclin-D1, BCL-2, CD95 and KI67 was evaluated. RESULTS: Overexpression of the different molecules was found in 44-69% of the pancreatic carcinomas. With regard to clinico-pathological features, p53 positivity was more frequently found in advanced and undifferentiated tumours (P<0.05), EGF overexpression was significantly more frequent in advanced tumours (P<0.05) and CD95 overexpression was observed to a greater extent in undifferentiated tumours (P<0.05). Besides cyclin-D1, none of the molecules tested was of prognostic significance. Patients whose tumours expressed cyclin-DI lived significantly shorter than patients with cyclin-D1-negative tumours. However, in subgroup analyses of patients with the same tumour stage or tumour grade, even cyclin-D1. expression had no prognostic significance. CONCLUSION: These results demonstrate that the prognostic significance of the molecules tested here is low. Nevertheless, with regard to tumorigenesis and tumour biology of pancreatic carcinoma, determination of molecular alterations could provide important information about pancreatic cancer.

Adenocarcinoma↗

PubMed1998

[Duodenum-preserving resection of the pancreas head in treatment of benign tumors of the pancreas head].

Benign tumors of the pancreatic head are normally treated by a partial duodenopancreatectomy. This operation has been developed for the treatment of malignant alterations in the pancreatic head and includes resection of the gastric bowel, duodenum and common bile duct. The aim of this study was to evaluate whether the less radical duodenum-preserving pancreatic head resection is a suitable surgical procedure in the treatment of benign pancreatic head tumors. From May 1982 to December 1996, seven patients underwent surgical treatment for benign pancreatic head tumors. Two patients suffered from gastrinoma of the pancreatic head, four exhibited a serous or mucinous cystadenoma, and one patient suffered from an intraductal papillary-mucinous tumor in this region. All patients were treated by duodenum-preserving pancreatic head resection. The operation was easily performed with little blood loss and a low rate of complications. None of the patients had to be reoperated upon due to postoperative surgical complications. After a follow-up period of a median 3 years, six of seven patients were had no recurrence of the disease and were symptom-free. One patient who had initially been operated on for gastrinoma still exhibited high gastrin values postoperatively. The endocrine and exocrine pancreatic function was not impaired in the early and late postoperative phase as compared to the preoperative assessment. From our results, it is concluded that duodenum-preserving pancreatic head resection is an adequately radical, yet organ-preserving procedure for the treatment of benign tumors of the pancreatic head without compromising endocrine and exocrine function.

Cystadenoma, Mucinous↗

PubMed1998

Cystic tumours of the pancreas: diagnostic accuracy, pathologic observations and surgical consequences.

BACKGROUND: Cystic neoplasms of the pancreas account for only 1% of primary pancreatic lesions. However, patients with these tumors are diagnosed more frequently. Up to now, nonsurgical management is still the established form of treatment of benign cystic tumours of the pancreas. METHODS: Between 1987 and 1996 we treated 51 patients with serous and mucinous cystadenoma and their malignant counterparts, serous and mucinous cystadenocarcinoma. RESULTS: Eighty-five percent of the patients presented symptoms. Computed tomography and endoscopic cholangiopancreatography (ERCP) were the most sensitive diagnostic techniques; however, in three patients with serous cystadenoma and in one patient with serous cystadenocarcinoma, ERCP findings were completely normal. The tumour was resected in all but one patient. There was no perioperative mortality. After dismissal from the hospital, all patients in whom benign tumours had been resected are still alive; however, the late mortality of mucinous cystadenocarcinoma was 36% after a median follow-up of 6 years. CONCLUSION: Surgical resection is recommended in all cystic tumours, even in serous cystic tumours, because symptoms may develop and malignant transformation to serous cystadenocarcinoma is possible.

Adult↗

PubMed1998

Ampullectomy for adenoma of the papilla and ampulla of Vater.

INTRODUCTION: The frequency of malignant adenomas of the papilla figures between 15 and 30%. Villous adenoma is considered to be a premalignant lesion. TREATMENT: Resection of the papilla is indicated in large tubular and small tubulovillous adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection should also be performed. Ampullectomy includes extirpation of the ampulla of Vater and reinsertion of the common bile duct and the pancreatic main duct into the duodenal wall. RESULTS: Hospital mortality after ampullectomy is less than 0.4%, and surgical morbidity, e.g., cholangitis, below 10%.

Adenoma↗

PubMed1998

Photochemotherapy of experimental colonic tumours with intra-tumorally applied methylene blue.

INTRODUCTION: Phototoxicity of intra-tumoral injected methylene blue (MB+) was studied in 48 experimental colonic tumours in comparison with photosan-3, Zn-phthalocyanine and tetrasulphanated ClAl-phthalocyanine. METHODS: In mice. xenotransplanted subcutaneous tumours about 1 cm in diameter were treated photodynamically twice, with different sensitisers. The irradiation was performed at the sensitiser-specific wavelength, and a density of 100 mW/cm2 and a dose of 100 J/cm2. RESULTS: Light alone without sensitiser did not induce any effect in mice tumours. Surprisingly, Al-phthalocyanine could only be used for intratumoral injections because of toxic effects after intravenous applications in nude mice. Using MB+ (1%), 75% of the tumours were destroyed by a single photodynamic treatment (PDT). In addition, toxicity of MB+ was most intense when compared with Zn-phthalocyanine and photosan-3. However, after the second PDT, there was no statistically significant difference among these sensitisers. Dark toxicity of MB+ (1%) could be well demonstrated by sufficient sensitiser incorporation without irradiation, which led to a stationary tumour volume up to 3 weeks after injection. CONCLUSION: Intra-tumoral MB+ PDT is a potential treatment for inducing necrosis in vivo. With regard to tumour tissue, the selectivity of MB+ is high and depends on a precise local injection of the dye.

Animals↗

PubMed1998

Clinical research in surgery: questions but few answers.

BACKGROUND: Surgeons must be prepared to be questioned about their understanding, activities, and achievements in basic and clinical research in terms of structural, organizational, and financial support of surgical research. RESULTS: Clinical research today comprises basic research related to accumulation of knowledge about biological systems, disease-related research including experimental research with animals, and in vitro research with biological material and clinical studies with the strongest empirical basis in data derived from controlled clinical trials. Most clinical methods related to diagnosis and treatment have been introduced into the practice of everyday medicine even in university hospitals without passing a prospective evaluation protocol. To test the efficacy of a new drug or a newly developed surgical technique, the controlled prospective clinical trial is the best method; however, fewer than 50% of clinical questions can be answered by controlled clinical studies. In Germany the frequency of controlled clinical trials for answering clinical questions is presently low; this is particularly true for surgery, in comparison with other countries. The concept of evidence-based medicine is based on the principles of data generation from controlled trials and meta-analyses of those studies. Best-evidence synthesis means a reasonable synthesis of evident knowledge, experience and intuition. The challenge of professionalization of clinical research in surgery is linked to the establishment of full time positions for basic scientists and clinical researchers and the establishment of clinical research teams and of research professorships including basic scientists in surgical departments. CONCLUSION: Clinical research can be effective only if there is good cooperation between clinicians and basic scientists, if high grade scientific methods are established in clinical research institutions, if there is sufficient financial and personal supply, and if there are enough laboratories and animal operating facilities. There is an urgent need for structures integrating basic scientists in clinical research groups, for more interdisciplinary research projects and more multidisciplinary research, independent of clinical care in terms of manpower.

Clinical Medicine↗

PubMed1998

Adjuvant radiochemotherapy--what is the patients benefit?

BACKGROUND: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. METHOD/PATIENTS: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. RESULTS: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II-III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11-18%, and survival rates significantly improved by 10-14%. Severe acute toxicities occurred in 50-61% of the patients, compromising compatibility, and caused death in 0-1%. Small-bowel obstruction leading to surgery was noted in 2-6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. CONCLUSION: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.

Chemotherapy, Adjuvant↗

PubMed1998

Overexpression of endothelium-derived nitric oxide synthase isoform 3 in the vasculature of human pancreatic tumor biopsies.

Cellular nitric oxide (NO) synthesis determines whether NO has cytoprotective or cytotoxic effects at anatomic sites; thus it is important to identify potential NO synthase isoforms in tumor tissue and tumor cell lines which might be involved in tumor development or destruction. Incubation of human pancreatic adenocarcinoma cell lines (AsPc-1, BxPc-3, CaPan-2) with cytokines resulted in increased NO formation, indicating the existence of the NOS2 isoform. This was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis. Furthermore, we identified the presence of the endothelium-derived NOS isoform 3 by RT-PCR analysis and immunohistochemistry in normal and pancreatic tumor biopsies. NOS3 was markedly overexpressed in the vasculature of the tumor tissue. RT-PCR analysis of tumor biopsies identified NOS isoform 2 mRNA in 60% of cases, but western blot analysis or immunohistochemistry scored negative for this isoform. It is noteworthy that the NOS enzyme activity in pancreatic tumor cell lines and tumor biopsies was inhibited by EGTA by approximately 30% and 65%, respectively. Our results suggest that increased endothelium-derived NOS isoform 3 expression in pancreatic adenocarcinomas regulates blood flow and is therefore involved in the vascularization and neovascularization of human pancreatic tumors.

Adenocarcinoma↗

PubMed1998

Gastric substitute after total gastrectomy--clinical relevance for reconstruction techniques.

BACKGROUND: More than 60 different methods of reconstruction after total gastrectomy have been described. The different surgical procedures can be reduced essentially to pouch reconstruction, pouch size and maintenance of duodenal passage. METHODS: To clarify the importance of pouch reconstruction and maintenance of duodenal passage, we reviewed all controlled prospectively randomized clinical studies reporting on the various methods of reconstruction after gastrectomy. RESULTS: After reconstruction with a pouch, 6-month postoperative patients have a better food intake, a slower food passage (t50% 12 vs 25 min), fewer postprandial symptoms (4-10% vs 20-60%), less weight loss (7 vs 14 kg), and in tendency, they have a better quality of life. With maintenance of duodenal passage, disturbance of blood sugar regulation (stimulated glucose level 22% lower) and iron deficiency anemia (hemoglobin: 13.9 vs 12.5 g/dl; iron: 18.4 vs 10.2 micromol/l) are prevented. In addition, the patients lose less body weight (8% higher) and they tend to have a better quality of life (life quality score: 84 vs 76 points). Nevertheless, in several studies the number of patients is too small to demonstrate significant differences. CONCLUSIONS: After total gastrectomy, curatively operated patients might benefit from a reconstruction with pouch and maintenance of duodenal passage. Nevertheless, the present study results are partially divergent. For definitive demonstration of the superiority of this technique, further controlled longitudinal studies should be conducted with a larger number of cases and suitable instruments for assessing the quality of life.

Anastomosis, Roux-en-Y↗