Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas.

BACKGROUND: Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. METHODS: In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. RESULTS: Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. CONCLUSIONS: Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker.

A reliable risk score for stage IV esophagogastric cancer.

BACKGROUND: The role of surgery for patients with metastatic esophagogastric adenocarcinoma (EGC) is not defined. The purpose of this study was to define selection criteria for patients who may benefit from resection following systemic chemotherapy. METHODS: From 1987 to 2007, 160 patients presenting with synchronous metastatic EGC (cT3/4 cNany cM0/1 finally pM1) were treated with chemotherapy followed by resection of the primary tumor and metastases. Clinical and histopathological data, site and number of metastases were analyzed. A prognostic score was established and validated in a second cohort from another academic center (n = 32). RESULTS: The median survival (MS) in cohort 1 was 13.6 months. Significant prognostic factors were grading (p = 0.046), ypT- (p = 0.001), ypN- (p = 0.011) and R-category (p = 0.015), lymphangiosis (p = 0.021), clinical (p = 0.004) and histopathological response (p = 0.006), but not localization or number of metastases. The addition of grading (G1/2:0 points; G3/4:1 points), clinical response (responder: 0; nonresponder: 1) and R-category (complete:0; R1:1; R2:2) defines two groups of patients with significantly different survival (p = 0.001) [low risk group (Score 0/1), n = 22: MS 35.3 months, 3-year-survival 47.6%); high risk group (Score 2/3/4) n = 126: MS 12.0 months, 3-year-survival 14.2%]. The score showed a strong trend in the validation cohort (p = 0.063) [low risk group (MS not reached, 3-year-survival 57.1%); high risk group (MS 19.9 months, 3-year-survival 6.7%)]. CONCLUSION: We observed long-term survival after resection of metastatic EGC. A simple clinical score may help to identify a subgroup of patients with a high chance of benefit from resection. However, the accurate estimation of achieving a complete resection, which is an integral element of the score, remains challenging.

[The carotid artery as recipient vessel: troubleshooting for free jejunal transfer after esophagectomy in preradiated patients]. / Gefäßanschluss an die A. carotis communis: Problemlösung bei freier Jejunuminterposition nach Ösophagektomie und Bestrahlung.

BACKGROUND: In the treatment of esophageal cancer neoadjuvant radiotherapy often leads to vascular damage of the usual recipient arteries for free jejunal transfer. End-to-side anastomosis to the carotid artery could be a potential alternative. PATIENTS AND METHODS: A total of 70 patients with locally advanced carcinoma of the esophagus underwent esophagectomy after neoadjuvant radiochemotherapy. In all patients reconstruction was carried out with a free jejunal transfer. Smaller vessels could be used for anastomoses in 54 of these patients and in 16 cases the jejunal flap artery was attached to the carotid artery. RESULTS: Out of 54 patients 9 (17%) with microvascular anastomoses to the smaller vessels needed surgical intervention for ischemia. In 16 patients with anastomosis to the carotid artery no significant failure of perfusion occurred. CONCLUSION: The carotid artery as recipient vessel in free jejunal transfer seems to be a safe therapeutic option for intestinal reconstruction of preradiated esophageal cancer with good functional results.

[German general and visceral surgery: positioning within the international scientific community]. / Deutsche Allgemein- und Viszeralchirurgie: Positionierung im internationalen wissenschaftlichen Vergleich

BACKGROUND: Assessment of scientific performance is critical for selection committees and research funding. The present work evaluated the standing of German surgical research within the international community. METHODS: A database analysis was performed in December 2009 using the ISI Web of Science. RESULTS: The highest impact factor of surgical journals is currently 8.460 with a median impact of all journals of 1.369. Leading academic surgeons have an h-index of more than 60. German surgeons are within the top five leading researchers in the fields of surgery for esophageal and pancreatic cancer, thyroid, hernia, and liver/kidney transplantation. Among the 50 institutions with most publications on a particular topic, 4-5 German centers are mostly represented. The top positions are in total decisively occupied by leading universities in the USA. CONCLUSION: On the basis of scientific parameters German surgical research can compete with leading international centers in certain fields, but should aim to increase the overall impact of research by publishing more in journals with above average impact factors.

[Neoadjuvant therapy in the upper gastro-intestinal tract. Modern strategies for Barrett's cancer]. / Neoadjuvante Therapie im oberen Gastrointestinaltrakt. Aktuelle Konzepte beim Barrett-Karzinom.

While primary surgical resection with systematic lymphadenectomy remains the treatment of choice for locoregional Barrett's cancer, neoadjuvant chemotherapy is an increasingly accepted treatment modality for patients with locally advanced tumors and patients with extensive lymphatic spread. In contrast to neoadjuvant radiochemotherapy preoperative chemotherapy alone does not seem to increase peri-operative complications and mortality. Responders to pre-operative treatment clearly have a survival advantage as compared to those who do not respond. The use of positron emission tomography to measure changes in glucose metabolism of the primary tumor can predict response early after initiation of neoadjuvant chemotherapy and thus help to select patients who will or will not benefit from this approach. The best treatment strategy for non-responders to neoadjuvant therapy remains to be defined.

["Practical course for visceral surgery in Warnemünde" 10 years on. Significance and benefits of a surgical training course]. / Zehn Jahre "Praktischer Kurs für Viszeralchirurgie Warnemünde". Bedeutung und Nutzen eines chirurgischen Trainingskurses.

BACKGROUND: Skill courses for surgery offer a good but cost and personnel-intensive possibility to obtain practical and theoretical knowledge by the employment of a close teacher-pupil contact of a large group of surgeons. The goal of the study presented here was to evaluate the satisfaction and benefits of the practical course for visceral surgery in Warnemünde after 10 years of course experience. MATERIAL AND METHODS: All participants in the annual course for visceral surgery were included since 1999. During this 1-week course conventional and laparoscopic exercises are performed under direct guidance of an experienced tutor. The participants are divided into 3 groups based on their surgical experience (e.g. <3 years, 3-5 years, >5 years). All participants received a standardised questionnaire before and after successful course completion for the collection of relevant data (e.g. demography, training, surgical experience and course evaluation). RESULTS: A total of 1,062 participants (435 female, 627 male, mean age 37 years) participated in the course. The average surgical experience of the participants was 5 years. Of the participants 489 came from a hospital of basic medical care, 499 from a hospital of maximum medical care and 74 from a university hospital. Of the participants 96% had no or only little experience with skill courses (1,020 out of 1,065) and 827 participants had no or only few possibilities for training outside of the operation room (78%). The conventional part of the course was evaluated by 77% of the participants as very good and by 50% as very good for the laparoscopic part. Only 8.3% of the participants were willing to finance the costs of the course by themselves. CONCLUSIONS: The practical course for visceral surgery leads to a subjective success in learning. Participation in the course leads to a high satisfaction and offers a cost-intensive possibility for a standardised surgical training. But there are too few experiences with skill courses and possibilities for surgical training outside the operation room so far.

[The relationship between German university hospitals and medical schools. Cooperation model versus integration model]. / Das Verhältnis von Klinikum und Fakultät. Kooperations- versus Integrationsmodell.

The relationship between German university hospitals and medical schools is mainly based on the cooperation model; in a few cases the integration model is applied. Both models bear characteristic advantages and disadvantages; in the cooperation model, e.g., processes might be slowed down by a multitude of regulatory mechanisms. The integration model supports a close connection of the medical school and university hospital. Currently, legislation concerning university medicine in Germany shows a trend to increase the influence of the government and the university president within the balance of power. Therefore, the cooperation model is still favored. In order that university hospitals remain sustainable for the future, especially in terms of research, site-specific solutions have to be developed and legitimated.

Limited resection and free jejunal graft interposition for squamous cell carcinoma of the cervical oesophagus.

BACKGROUND: Therapeutic strategies for cervical oesophageal squamous cell carcinoma (SCC) are controversial. Treatment options range from definitive radiotherapy to multimodal treatment. Outcome after limited resection and reconstruction with a free jejunal graft interposition was evaluated retrospectively. METHODS: Patients with clinical T1-4 Nx M0 tumours treated between 1986 and 2006 were included. RESULTS: Of 109 patients, 94 underwent preoperative chemoradiotherapy and 15 had a primary resection. Complete or partial preservation of the larynx was achieved in 93 patients (85.3 per cent). Minor and major complications occurred in 74.3 per cent, with 44.0 per cent of all patients having more than one complication. Reoperation was necessary in 29.4 per cent. The 30-day mortality rate was 1.8 per cent, and the in-hospital mortality rate 2.8 per cent. The complete R0 resection rate was 72.5 per cent. Median overall survival was 34.3 months; 1-, 3- and 5-year survival rates were 83.8, 47.0 and 47.0 per cent respectively. Survival was not influenced by complications (P = 0.401) or reoperation (P = 0.428). CONCLUSION: Despite high complication and reoperation rates, the mortality rate was low, even after preoperative chemoradiation. This complex surgical strategy is a treatment option for cervical SCC in oncological centres with an infrastructure providing multidisciplinary management.

Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial.

Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.

Expression of prostaglandin E synthase in Barrett's cancer.

Expression of prostaglandin E synthase (PGES) - an enzyme of the prostaglandin biosynthetic pathway with suspected impact on carcinogenesis--was studied in Barrett's cancer to determine its pathogenetic role and prognostic impact in this entity. Expression analysis of PGES was performed on mRNA level (quantitative reverse transcription polymerase chain rection [RT-PCR]) in a large surgical series of 123 primary resected adenocarcinomas of the distal esophagus (Barrett's cancer). Gene expression results were correlated with clinical parameters, overall survival and expression levels of previously analyzed target genes of the cyclooxygenase (COX) pathway (COX-1, COX-2) and mediators of angiogenesis (vascular endothelial growth factor [VEGF]-A) and lymphangiogenesis [VEGF-C]. Expression of PGES was demonstrated in all 123 tumors (100%) on mRNA level (quantitative RT-PCR). Relative mRNA expression levels were highly variable between different cases. Gene expression showed a strong positive correlation with both COX isoforms (COX-1: r = 0.502, P < 0.001; COX-2: r = 0.679, P < 0.001), with the angiogenetic VEGF-A (r = 0.583, P < 0.001) and with the lymphangiogentic VEGF-C (r = 0.465, P < 0.001). PGES mRNA expression showed no significant correlation with clinicopathologic parameters (i.e. pTNM categories, UICC stage, survival). Variable overexpression of PGES seems to be potentially implicated in Barrett's carcinogenesis. Gene expression of PGES is strongly correlated with other mediators of the prostaglandin biosynthetic pathway, that is both COX isoforms (COX-1 and COX-2). However, no impact on patients' outcome in relation to PGES expression was found.