[Multiple recurrent retroperitoneal liposarcoma in a 66-year-old man]. / Multipel rezidivierendes retroperitoneales Liposarkom bei einem 66-jährigen Patienten.

In this article, the authors present the case of a 66-year-old man who was diagnosed with the first recurrence of his retroperitoneal liposarcoma 7 years after initial diagnosis. In the following 10 years, he needed a total of eight operations, chemotherapy, and radiotherapy because of another seven recurrences. This is the first report on a patient with eight recurrences of a retroperitoneal liposarcoma being in a relatively good general condition even 17 years after initial diagnosis.

Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP).

BACKGROUND: To investigate whether addition of cetuximab to standard adjuvant chemotherapy with gemcitabine improves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabine alone. PATIENTS AND METHODS: Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabine and cetuximab were administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect. RESULTS: Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9-13.6] months and the DFS rate at month 18 of 27.1% (16.7%-37.6%) was inferior to 35%. Median OS was 22.4 (18.2-27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥ grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P = 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%). CONCLUSION: Addition of cetuximab to adjuvant gemcitabine does not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be confirmed.

[An algorithm for postoperative pain management in visceral and thoracic surgery: an observational study]. / Algorithmus zur postoperativen Schmerztherapie in der Viszeral- und Thoraxchirurgie: Eine Verlaufuntersuchung.

INTRODUCTION: We report the results of an observational study of pain intensity before and after implementation of an algorithm for postoperative pain management. The algorithm included multiple factors for treatment. METHODS: Data of 130 consecutive patients with defined surgical procedures were extracted from charts before and after implementation of the algorithm. Our patients documented pain intensity at rest and on movement on a numerival rating scale (NRS) from 0 (= no pain) to 10 (=  worst pain). A successful pain management was definded as maximum pain intensity at rest ≤ 3 and on movement ≤ 5 on the NRS. For statistical analysis we used the Wilcoxon and the chi squared test. RESULTS: The frequency of a successful pain management increased from 49 % (individual pain management) to 85 % (algorithm) at rest 8 (p < 0.001), on movement the rates were 42 % and 86 %, respectively (p < 0.001). In the total group, we found a reduction of maximum pain intensity at rest (mean ±â€Šsd) from 4.05  ±â€Š 2.54 to 2.18 ±â€Š1.82 (p < 0.001) and with movement from 6.04 ±â€Š2.51 to 3.5 ±â€Š2.08 (p < 0.001). CONCLUSION: Implementing an algorithm for postoperative pain management resulted in a clinically relevant reduction of postoperative pain. Our findings reflect the result of a complex change in pain management, and therefore cannot be attributed to any single factors involved.

Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma differential activity of matrix metalloproteinase-9.

BACKGROUND: Expression and enzymatic activity of gelatinases were examined in biopsy specimens from patients with colon and rectal neoplasms. The objective of this study was to determine whether the activity of these enzymes is altered between tumor areas compared with areas of noninvolved, normal mucosa and between colon and rectal carcinoma. METHODS: Matrix metalloproteinase (MMP) production was analyzed by Western immunoblot analysis and gelatin zymography. mRNA was determined by quantitative, real-time polymerase chain reaction analysis. RESULTS: Patients with colon carcinoma (n = 20 patients) showed a significant increase in levels of MMP-9 (92 kDa and 88 kDa) and MMP-2 (72 kDa and 62 kDa) in tumor areas compared with noninvolved regions. In contrast, patients with rectal carcinoma (n = 10 patients) had revealed the same high activity of MMP-9 in tumor regions and corresponding healthy tissue. Confirming activity measurements, in colon tumors, but not in rectal tumors, there was significant up-regulation of MMP-9 transcription compared with healthy tissue in the same patients. There were no significant changes in the tissue inhibitor of metalloproteinase-1 protein when colon and rectal tumor tissues were compared with the corresponding noninvolved regions. Cell culture experiments revealed fibroblasts as the cellular origin of MMPs. The findings showed that the secretion and activation of gelatinases depend on soluble factors secreted by tumor cells and are influenced by extracellular matrix components. CONCLUSIONS: This is the first report showing differences in MMP-9 activity between rectal carcinoma and colon carcinoma. Previous results indicating an active involvement of stromal cells in the generation of MMPs during tumor invasion are extended. Because the abundance of gelatinases increases in colorectal carcinoma, inhibitors of these proteases may be of therapeutic value.

[Prognostic factors for development of peritoneal carcinosis in stomach carcinoma]. / Prognosefaktoren für das Auftreten einer Peritonealcarcinose beim Magencarcinom.

OBJECTIVE: Several adjuvant therapy concepts have been developed to improve the treatment of gastric cancer patients. Dealing with intraperitoneal chemotherapy, it seems to be useful to determine suitable prognostic factors for the occurrence of peritoneal carcinosis, as it is possible to select patients who may profit from this therapy. METHODS: Between June 1975 and December 1999 resection of gastric cancer was performed in 575 patients. From 1 January 1986 clinical data were recorded prospectively, before that time, retrospectively. The complete data concerning preoperative diagnosis, operation, histology, postoperative course and survival time were documented in an Excel file for statistical analysis. Multivariate analysis was performed using the chi-squared logistic regression test. RESULTS: Significant correlation was found between the occurrence of peritoneal dissemination and tumour stage pT3, pN2, G3, cancer of the whole stomach and cancer at the anastomotic site after partial gastric resection. Lauren classification, signet-ring cell cancer, liver metastasis and tumour localisation in the distal or proximal stomach showed no significant correlation to peritoneal carcinosis in the multivariate analysis. However, only one-third of patients with liver metastasis had simultaneous peritoneal dissemination. CONCLUSION: The results show a clinical correlation of tumour localisation, infiltration of the serosa, lymph node metastasis and grading with peritoneal dissemination. The present data serve as a basis for further histochemical and molecular biological investigations e.g. of the expression of adhesion molecules to determine the risk of peritoneal tumour dissemination after gastric cancer.

Colon interposition for esophageal replacement: isoperistaltic or antiperistaltic? Experimental results.

BACKGROUND: Isoperistaltic colon is preferred to antiperistaltic colon for esophageal replacement, but experimental data do not exist to support this practice. METHODS: In 7 dogs a 20 cm long colon loop was interposed between the skin and the small bowel, isoperistaltically in 3 dogs and antiperistaltically in 4 dogs. Three months later five strain-gauges were implanted and evacuation was investigated by motility testing, barium studies, and scintigraphy. RESULTS: Motility recording showed normal colon motility in the excluded loops. Quiescent states (duration 40.2 +/- 13.6 minutes) were followed by contractile states (duration 7.5 +/- 2.4 minutes, frequency 3.3 +/- 0.6 per minute). The main peristaltic direction of isoperistaltic loops was isoperistaltic, and the main peristaltic direction of antiperistaltic loops was antiperistaltic. Evacuation took place exclusively during the contractile status. Half time emptying was more rapid in isoperistaltic loops (35 +/- 11 vs 69 +/- 16 minutes). The content of antiperistaltic loops was held back by antiperistaltic activity. Application of oatmeal porridge into the loops shortened the quiescent status from 40.2 to 13.2 +/- 4.8 minutes. CONCLUSIONS: The colon graft for esophageal replacement is an active system. Food is stored during the quiescent states and evacuated during the contractile states. The original peristaltic direction is preserved so that retroperistalsis in antiperistaltic loops may lead to patient discomfort and pulmonary complications.

[Concomitant occurrence of angiomyolipoma, focal nodular hyperplasia, bile duct adenoma, and cavernous hemangioma in the liver]. / Gleichzeitiges Auftreten von Angiomyolipom, fokaler nodulärer Hyperplasie, cholangiozellulärem Adenom und Hämangiom in der Leber.

The simultaneous occurrence of different hepatic tumors is rare. We present for the first time a concomitant manifestation of an angiomyolipoma, a focal nodular hyperplasia, a bile duct adenoma, and a cavernous hemangioma in a 63-year-old female patient. The largest of the tumors, preoperatively suspected to be hepatocellular carcinoma, was an angiomyolipoma with monotypic epithelioid histology and positive immunoreactivity for HMB-45, actin, desmin, and pancytokeratin. The significance of immunohistochemistry for the differential diagnosis of hepatic neoplasms is emphasized. Finally, a review of the literature with special regard to etiology and pathogenesis of neoplastic liver disease is given, leading to the assumption that the association of four different benign intrahepatic tumors is rather more fortuitous than pathogenetically related, despite the putative similar pathogenesis of focal nodular hyperplasia and hemangioma.

Endoscopic ultrasonography in the preoperative staging of gastric cancer: accuracy and impact on surgical therapy.

BACKGROUND: Endoscopic ultrasonography (EUS) is a standard procedure in the preoperative staging of patients with gastric carcinomas. Herein we present our experience with EUS and discuss the results and their implications for surgical therapy. METHODS: A total of 116 patients with histologically confirmed gastric adenocarcinoma were referred to EUS and classified prospectively by the TNM system. The results of the preoperative endosonographic staging were compared with the definitive histopathological results after the operation. RESULTS: The overall accuracy of EUS for determination of the T stage was 78%. The accuracy for the T1 and T2 stages was 80% and 63%, respectively. With 20% and 30%, there was a relatively high rate of overstaging in these cases. The accuracy for T3 and T4 tumors was 95% and 83%, respectively. The accuracy of EUS for determination of the N stage was 77%, with a sensitivity of 91% and a specificity of 84%. Resectability was predicted correctly with a sensitivity of 94% and a specificity of 83%. CONCLUSIONS: Generally accepted standards for the therapy of advanced gastric carcinomas do not exist. In cases where the therapeutic strategy is surgical exploration, no preoperative staging is necessary. In cases with differentiated treatment strategies, the accuracy of EUS is not sufficient for the selection of patients for endoscopic resection. Its accuracy for submucosal cancer invasion and for the detection of lymph node metastases needs to be further enhanced. If only multimodal therapy is considered, EUS staging seems to be absolutely mandatory. Patients classified preoperatively as T1 to T3 can be operated on primarily with sufficient security. In patients where radical resection of the tumor seems doubtful, we recommend that a diagnostic laparoscopy be performed to confirm the diagnosis.

Fluorodeoxyglucose positron emission tomography and the prognosis of pancreatic carcinoma.

BACKGROUND: Pancreatic carcinoma is associated with a poor prognosis. The aim of this study was to determine whether glucose metabolism in pancreatic cancer has prognostic significance for patients suffering from this disease. METHODS: The survival data of 52 patients with pancreatic carcinoma was correlated with the standardized uptake value (SUV) as a semiquantitative parameter of glucose metabolism, as determined with fluorodeoxyglucose positron emission tomography (FDG PET). A multivariate analysis, including SUV and accepted factors of prognosis, such as stage at presentation and tumor marker Ca 19-9, was performed to determine the prognostic value of FDG PET. RESULTS: The median survival in 26 patients with low SUV (< 6.1) was 9 months (95% confidence interval 6-12 months) vs. 5 months (95% confidence interval 4-6 months) in 26 patients with high SUV (> or = 6.1). Multivariate analysis revealed SUV and tumor marker Ca 19-9 as independent factors of prognosis in patients with pancreatic carcinoma. CONCLUSION: Glucose metabolism, as determined with FDG PET, provides additional prognostic information in patients with pancreatic carcinoma.

Effects of intraperitoneal mitomycin C adsorbed on activated carbon on adhesion formation and mesothelial cells in vitro.

OBJECTIVE: To investigate the incidence of adhesions after intraperitoneal instillation of mitomycin C adsorbed on activated carbon (MMC-CH). DESIGN: Animal and laboratory studies. SETTING: University hospital, Germany. ANIMALS: 90 Sprague-Dawley rats. INTERVENTIONS: Laparotomy, small bowel anastomosis, and intraperitoneal instillation of saline (controls, n = 27), activated carbon alone (n = 24) or MMC-CH (n = 26). Cultures of monolayers of human mesothelial cells. MAIN OUTCOME MEASURES: Measurements of adhesions by planimetry. Toxicity of mitomycin C alone and charcoal alone in mesothelial cell monolayers as reflected by cell proliferation and measurement of lactate dehydrogenase activity. Concentrations of plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) as measures of the fibrinolytic activity of mesothelial cells. RESULTS: Both activated carbon and MMC-CH caused a significant increase of adhesion formation in rats. Activated carbon also reduced the fibrinolytic activity of mesothelial cells, and mitomycin C caused concentration-dependent cytotoxicity in vitro. CONCLUSIONS: Activated carbon combined with high concentrations of mitomycin C may cause intraperitoneal infective complications by increasing the rate of adhesion formation and reducing the fibrinolytic activity of mesothelial cells. We recommend a new absorbable carrier for intraperitoneal chemotherapy.

[Hepatic ischaemia during Whipple resection: case report of a rarely required revascularisation]. / Hepatische Ischämie bei der Whipple-Operation. Kasuistik einer selten notwendigen Revascularisation.

With the performance of a partial duodenopancreatectomy, the collateral vascular bed between the coeliac trunk and the superior mesenteric artery is reduced. Normally, this does not lead to ischaemia of the upper abdominal organs. However, we present the rare case of a patient in whom a Whipple resection in combination with a hyploplastic coeliac trunk led to hepatic and splenal ischaemia and aorto-hepatic bypass grafting. The indication for preoperative arteriography is in discussion, since variations or alteration of the upper abdominal vessels are known to be common but manifest organ ischaemia during resection is a rare complication. Patients with signs of general arteriosclerosis or those in whom upper abdominal resection has been performed previously may benefit from angiography. In other cases a test occlusion before vessel ligation is considered to be suitable in assessing the need for vascular surgical intervention.

[Combined pH measurement and multiple impedance variation assessments--validation of a new technique for detection of non-acid reflux in the esophagus]. / Kombinierte pH-Metrie und Multiple Impedanzvariometrie--Validierung eines neuen Verfahrens zur Erkennung von nichtsaurem Reflux in der Speiseröhre.

In 10 patients with gastroesophageal reflux disease, defective lower esophageal sphincter and normal motility pH and impedance were measured parallel over 24 hours. All patients had a reflux score > 40 with a total of 736 reflux episodes registered by the pH metry of which 724 (sensitivity: 98.9%) were recognized by impedancemetry and with additional 292 reflux phases registered at a stomach pH > 4 by the impedancemetry of which none was recognized by the pH metry as a reflux of pH > 7. With the multiple impedancemetry a reliable recognition of gastroesophageal reflux is possible, independently of the pH and this makes it possible to recognize gastroesophageal reflux also at a non acid milieu of the stomach, e.g. under acid suppression medication or after stomach resection.

[Results of intraperitoneal active charcoal-mitomycin C therapy of stomach carcinoma with serosa invasion]. / Ergebnisse der intraperitonealen Aktivkohle-Mitomycintherapie des Magenkarzinoms mit Serosainvasion.

Patients with gastric carcinoma and serosal invasion were randomized into a "treatment" or "control" protocol after R0 resection ("prophylactic group", n = 45) or palliative resection without cytoreductive surgery in cases with localized peritoneal seeding ("therapy group", n = 19). The results of a planned interim analysis after 5 years indicate that MMC-CH therapy causes little systemic toxicity but enhances the rate of intraabdominal infections (9/33 vs. 2/31, p < 0.01) and reoperations (5/33 vs 0/31, p < 0.05). The preliminary survival analysis shows a possible prognostic effect following R0 resection after 24 months (p < 0.05) and 36 months (p < 0.07), but no benefit for the palliative procedures, which caused the withdrawal of the "therapy" study arm.

[Interdisciplinary multi-modality therapy of advanced hypopharyngeal and proximal esophageal carcinomas]. / Interdisziplinäre multimodale Therapie fortgeschrittener hypopharynx- und proximaler Oesophaguskarzinome.

A multimodal interdisciplinary concept including an aggressive neoadjuvant radiochemotherapy and a multivisceral resection with esophagolaryngectomy and bilateral modified neck dissection was introduced for the treatment of tumors of the cervical esophagus and hypopharynx. In 75% of the patients a R0-resection was achieved resulting in a 5-year survival rate of 38.5% and good functional results. Free jejunal interposition was the most favorable reconstruction because gastric transposition was followed by an increased rate of anastomotic insufficiencies and stenoses requiring bouginage.

[Results of two-stage thyroidectomy in differentiated thyroid gland carcinoma]. / Ergebnisse der zweizeitigen Thyreoidektomie beim differenzierten Schilddrüsenkarzinom.

This retrospective study (1986-1996) investigated 60 patients after total thyroidectomy indicated by a differentiated thyroid carcinoma. Analyzing the rate of paralysis of the recurrent nerve after secondary thyroidectomy due to the timing of the second operation, we found that only patients with secondary thyroidectomy having their second operation at an interval > 7 days suffered from permanent paralysis of the recurrent nerve. In conclusion, a second radical surgical procedure must be performed as early as possible to minimize complications.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the differential diagnosis of pancreatic carcinoma: a report of 106 cases.

The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET) as a tool for the differential diagnosis of pancreatic carcinoma while taking into account serum glucose level. A group of 106 patients with unclear pancreatic masses were recruited for the study. PET was performed following intravenous administration of an average of 190 MBq [18F]FDG. Focally increased glucose utilisation was used as the criterion of malignancy. In addition, the "standardised uptake value" (SUV) was determined 45 min after injection. Carcinoma of the pancreas was demonstrated histologically in 74 cases, and chronic pancreatitis in 32 cases. Employing visual evaluation, 63 of the 74 (85%) pancreatic carcinomas were identified by PET. In 27 of the 32 cases (84%) of chronic pancreatitis it was possible to exclude malignancy. False-negative results (n=11) were obtained mostly in patients with raised serum glucose levels (10 out of 11), and false-positives (n=5) in patients with inflammatory processes of the pancreas. Thus PET showed an overall sensitivity of 85%, a specificity of 84%, a negative predictive value of 71%, and a positive predictive value of 93%. In a subgroup of patients with normal serum glucose levels (n=72), the results were 98%, 84%, 96% and 93%, respectively. Quantitative assessment yielded a mean SUV of 6.4+/-3.6 for pancreatic carcinoma as against a value of 3.6+/-1.7 for chronic pancreatitis (P<0.001), without increasing the diagnostic accuracy. This shows PET to be of value in assessing unclear pancreatic masses. The diagnostic accuracy of PET examinations is very dependent on serum glucose levels.

[Preoperative staging of stomach carcinoma with endosonography--fact or fancy?]. / Präoperatives Staging des Magenkarzinoms mit der Endosonographie--Fact or Fancy?

From January 1993 till December 1995, a total of 116 consecutive patients with gastric carcinoma were evaluated with endosonography and the results were compared with the histology of the resected specimen. The accuracy rate of the endosonography was 80% for T1 tumors an 83% for T4 tumors, and the sensitivity and specificity in the detection of regional involved lymph nodes were 91% and 84% respectively. Therefore endosonographic staging alone ist not a valuable pretherapeutic procedure to decide about endoscopic therapy in limited and neoadjuvant chemotherapy in extended gastric carcinoma.

[Quality of life parameters in after-care of esophageal carcinoma]. / Lebensqualitätsparameter in der Nachsorge des Osophaguskarzinoms.

Thirty-three patients with a radically resected esophageal carcinoma were included in a prospective follow-up study measuring quality of life parameters under the condition of continuous postoperative out-patient care. None of the perioperatively suspected risk factors, like postoperative complications, preoperative risk and weight course or a performed thoracotomy had a predictive value for the long-term quality of life parameters. Yet endoscopic interventions and conservative treatment of dysphagia and eating restrictions improved the quality of life in 12 out of 16 patients with severe symptoms, making the postoperative follow-up an important factor for the quality of life for resected esophageal cancer patients.