German oncology certification system for colorectal cancer - relative survival rates of a single certified centre vs. national and international registry data.

OBJECTIVES: To evaluate how the certification of specialised Oncology Centres in Germany affects the relative survival of patients with colorectal cancer (CRC) by means of national and international comparison. METHODS: Between 2007 and 2013, 675 patients with colorectal cancer, treated at the Hildesheim Hospital, an academic teaching hospital of the Hannover Medical School (MHH), were included. A follow-up of the entire patient group was performed until 2014. To obtain international data, a SEER-database search was done. The relative survival of 148,957 patients was compared to our data after 12, 36 and 60 months. For national survival data, we compared our rates with 41,988 patients of the Munich Cancer Registry (MCR). RESULTS: Relative survival at our institution tends to be higher in advanced tumour stages compared to national and international cancer registry data. Nationally we found only little variation in survival rates for low stages CRC (UICC I and II), colon, and rectal cancer. There were notable variations regarding relative survival rates for advanced CRC tumour stages (UICC IV). These variations were even more distinct for rectal cancer after 12, 36 and 60 months (Hildesheim Hospital: 89.9, 40.3, 30.1%; Munich Cancer Registry (MCR): 65.4, 28.7, 16.6%). The international comparison of CRC showed significantly higher relative survival rates for patients with advanced tumour stages after 12 months at our institution (77 vs. 54.9% for UICC IV; raw p<0.001). CONCLUSIONS: Our findings suggest that patients with advanced tumour stages of CRC and especially rectal cancer benefit most from a multidisciplinary and guidelines-oriented treatment at Certified Oncology Centres. For a better evaluation of cancer treatment and improved national and international comparison, the creation of a centralised national cancer registry is necessary.

Composition of approximated body-surface-potential-maps by utilizing a common 12-lead-ECG device.

A procedure is introduced that allows approximations of body surface potential maps (BSPM) to be obtained by utilizing commonly available digital 12-lead-electrocardiogram (ECG) systems. These Pseudo-BSPMs contain most of the averaged spatio-temporal information for a single characteristic beat. The underlying signal processing is described in detail. The algorithms including an online method verification may easily be added to the software of commercial 12-lead ECG devices.

Improved hydrodynamics of a new aortic cannula with a novel tip design.

BACKGROUND: Reduction of atheroembolic complications during cardiopulmonary bypass remains a major challenge in cardiac surgery. New cannula tip designs may help to attenuate this problem by improved hydrodynamics. METHODS: Pressure gradients and back pressures of a new aortic cannula tip design were measured and compared with the Medos X-Flow, Sarns Soft-Flow and Argyle THI cannulae at various flow rates in a mock circulation followed by flow visualization. RESULTS: Pressure gradients were the lowest for the new cannula. Back pressures of the new cannula were up to 84% lower than for the Argyle cannula. The back pressure profile and flow visualization of the new cannula showed broad centric flow dispersion with a transcannula increase of flow area from 38 mm2 to 139 mm2. CONCLUSIONS: The new design of an aortic cannula tip provides improved hydrodynamics, with low pressure gradients, low back pressures and a uniform central dispersion of flow, reducing the sandblasting effect.

Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial.

BACKGROUND: Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50% of patients after radical nephrectomy. At present, no effective adjuvant treatment is established. We aimed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2-3b pN0-3 M0 renal-cell carcinoma. METHODS: Between January, 1997, and September, 1998, 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany. Before surgery, all patients were centrally randomised to receive autologous renal tumour cell vaccine (six intradermal applications at 4-week intervals postoperatively; vaccine group) or no adjuvant treatment (control group). The primary endpoint of the trial was to reduce the risk of tumour progression, defined as progression or death. All patients were assessed after standardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years. FINDINGS: By preoperative and postoperative inclusion criteria, 379 patients were assessable for the intention-to-treat analysis. At 5-year and 70-month follow-up, the hazard ratios for tumour progression were 1.58 (95% CI 1.05-2.37) and 1.59 (1.07-2.36), respectively, in favour of the vaccine group (p=0.0204, log-rank test). 5-year and 70-month progression-free survival rates were 77.4% and 72%, respectively, in the vaccine group and 67.8% and 59.3%, respectively, in the control group. The vaccine was well tolerated, with only 12 adverse events associated with the treatment. INTERPRETATION: Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter.

Adjuvant therapy of renal cell carcinoma patients with an autologous tumor cell lysate vaccine: a 5-year follow-up analysis.

BACKGROUND: Non-metastasized renal cell carcinoma (RCC) is associated with postoperative progression in 1 out of 3 patients. However, no adjuvant therapy after radical nephrectomy has been established. We investigated the impact of an adjuvant autologous tumor cell lysate vaccination on the 5-year survival rates of patients with non-metastasized RCC. PATIENTS AND METHODS: Between 1990 and 1995, a total of 360 patients with RCC underwent a radical nephrectomy at the St. Georg Hospital Leipzig, Germany. There were 236 patients with RCC stages T2N0M0 or T3N0M0. Out of this group, 148 consecutive patients received an adjuvant autologous tumor cell lysate vaccine (vaccine group, 72 patients with T2N0M0 and 76 patients with T3N0M0), while the remaining 88 patients had no adjuvant therapy (control group, 52 patients with T2N0M0 and 36 patients with T3N0M0). Both groups were comparable for parameters such as age, sex, tumor localization and size, and Störkel-score (p > 0.05 for each parameter; Chi-Square test and Wilcoxon-Mann-Whitney test). RESULTS: For RCC stage T2N0M0, the 5-year progression-free survival rate in the control group was 65.3% compared to 84.6% in the vaccine group (p = 0.0023, log-rank test). The 5-year overall survival was 71.4% in the control group compared to 86% in the vaccine group (p = 0.0059, log-rank test). Patients with RCC stage T3N0M0 in the vaccine group demonstrated a clear advantage in terms of 5-year overall survival (77.5% vs. 25% in the control group, p < 0.0001, log-rank test) and 5-year progression-free survival (68.2% in the vaccine group vs. 19.4% in the control group, p < 0.0001, log-rank test). CONCLUSION: Adjuvant autologous tumor cell lysate vaccination may improve the outcome of patients with non-metastasized RCC after radical nephrectomy. A prospective randomized and multicenter phase III trial was started in 1997 to confirm these results.

Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience.

The prognosis of patients who undergo resection for pancreatic ductal adenocarcinoma with curative intention is generally poor unless they have early-stage disease. Based on our 25-year experience, the results of 194 patients after a standardized Kausch-Whipple resection for adenocarcinoma of the pancreatic head were analyzed and the prognostic factors were evaluated. Between 1972 and 1998 a total of 221 patients were diagnosed for ductal adenocarcinoma of the pancreatic head, and 194 of them subsequently underwent a standardized Kausch-Whipple resection. Long-term results and prognostic factors were examined by multivariate and univariate analyses. The overall postoperative mortality was 3.09%, and the morbidity was 29.9%. By multivariate analysis only curative resection (R0) was significantly related to a favorable prognosis ( p < 0.0001). Furthermore, in case of a curative resection, the presence of lymph node metastases showed prognostic significance in the multivariate analysis ( p = 0.005). Cumulative survival analysis revealed a 5-year survival rate of 25.4%, a 7-year survival rate of 12.3%, and a 10-year survival rate of 8.2% for patients who underwent curative resection (R0) for adenocarcinoma of the pancreatic head. We demonstrated that the R0 status is the only independent prognostic factor after surgery for adenocarcinoma of the pancreatic head. In the case of a curative resection, the presence of lymph node metastases is of prognostic relevance. In view of considerable surgical morbidity and mortality, resection for cancer of the pancreatic head is the only option if the lesion is resectable. We concluded that surgical treatment is "as good as it gets," as extended techniques have not proved to produce better results.

Prognostic implications of routine, immunohistochemical, and molecular staging in resectable pancreatic adenocarcinoma.

Cure for ductal adenocarcinoma of the pancreas is restricted to resectable tumors, but survival after surgery is still poor. Despite apparently curative resection, these cancers rapidly recur. Thus, the present pathologic examination should be enriched by sensitive methods to detect minimal residual disease. In a prospective setting we studied the frequency of minimal residual disease after curative resection by routine histopathology, immunohistology, and polymerase chain reaction (PCR) for mutated K-ras. Furthermore, the prognostic implication of detecting of MRD was determined. Prospectively, tumor tissue and corresponding paraaortic lymph nodes were obtained from 78 patients, who underwent surgery for pancreatic head tumors between 1999 and 2001. Sixty-nine of 78 cases were diagnosed for ductal adenocarcinoma (study group), whereas nine cases were diagnosed for benign pancreatic tumors (control group). Paraaortic lymph nodes were examined in step sections by routine histopathology (hematoxylin and eosin) and immunohistology using a pan-cytokeratin antibody. DNA of the primary tumor and corresponding paraaortic lymph nodes were analyzed by PCR-based assays with respect to mutated K-ras in codon 12. The recurrence-free survival and overall survival were correlated with the results of the latter methods. In 3 of 69 patients tumor cells were detected in paraaortic lymph nodes by routine histopathology and in 5 of 69 patients by immunohistology. K-ras mutations were detected in 42 of 69 ductal adenocarcinomas (61%), whereas 12 (17%) were positive in paraaortic lymph nodes. All of the latter patients had recurrence after surgery and a significant poorer survival than those without mutated K-ras. Furthermore, paraaortic lymph nodes diagnosed for K-ras mutation were independent prognostic markers in multivariate analysis. In the control group K-ras mutations were detected in one adenoma of Vater's papilla but not in paraaortic lymph nodes. Tumor cell DNA can be detected more sensitively by the described PCR method than with hematoxylin and eosin or immunohistologic staining, leading to a higher sensitivity for detection of micrometastases. The described PCR method clearly determines subgroups of patients after curative resection with early recurrence and poor survival and could therefore enrich the pathologic examination.

Total parathyroidectomy without autotransplantation as a standard procedure in the treatment of secondary hyperparathyroidism.

BACKGROUND: Total parathyroidectomy with autografting of parathyroid tissue and subtotal resection of the parathyroid glands are currently considered as standard surgical procedures for the treatment of severe secondary hyperparathyroidism. However, a considerable recurrence rate following these procedures ranges from 5% to 80%. We present a retrospective analysis of the results of parathyroidectomy with autotransplantation to the forearm versus parathyroidectomy alone. PATIENTS AND METHODS: We analyzed the clinical course of 11 consecutive patients who had undergone parathyroidectomy between 1995 and 1999, and who were not simultaneously autografted. Controls were 11 patients in whom autotransplantation of parathyroid tissue into the forearm had been routinely performed between 1993 and 1996 at our institution. Clinical symptoms and recurrence of hyperparathyroidism were assessed for comparison of the alternative treatment modalities. Recurrence of disease was defined by elevated parathormone (PTH) levels (>7.6 pmol/l) with clinical symptoms and/or need for reoperation. RESULTS: No recurrence of hyperparathyroidism was observed in patients without autotransplantation after a mean follow-up of 23 months (range 1-49). Measurement of intact serum PTH revealed residual PTH secretion even after removal of four glands (mean 2.02 pmol/l). Clinical symptoms improved substantially after surgery. In the historical control group 3 of the 11 autotransplanted patients (27%) required resection of transplanted tissue. Additionally, two patients (18%) presented with increased PTH secretion and clinical symptoms of recurrent hyperparathyroidism during follow-up. Thus, a total of five patients (45%) experienced relapsing hyperparathyroidism caused by the implanted tissue. CONCLUSIONS: Total parathyroidectomy without autotransplantation is a safe procedure with a low rate of recurrent hyperparathyroidism when compared to parathyroidectomy with autotransplantation to the forearm in a historical control. These preliminary results mandates further investigations including a randomized trial.

Resection for cancers of the pancreatic head in patients aged 70 years or over.

OBJECTIVE: To find out if resections of cancers of the head of pancreatic are justified in patients over the age of 70 years. DESIGN: Retrospective study. SETTING: University hospital, Germany. SUBJECTS: 519 patients with cancers of the pancreatic head, 93 (18%) of whom were aged 70 or over. MAIN OUTCOME MEASURES: Comparison of outcomes between those aged 70 or over, and those aged less than 70. RESULTS: There were 247 ductal adenocarcinomas, 134 carcinomas of the papilla of Vater, 79 carcinomas of the distal common bile duct, and 59 miscellaneous tumours. Of all variables compared (age, sex, symptoms, operations, clinical and pathological stage. morbidity, mortality, and long-term survival) the only significant difference between the groups was that leaks from the pancreaticojejunostomy occured more often in the older age group (p = 0.02). However, this did not influence overall morbidity or mortality. CONCLUSION: Patients' age is not a limiting factor in attempts at curative resection of cancers of the head of pancreas. If the tumour is resectable and patient is motivated and well enough, resection is indicated whatever the age.

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.

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.