Haben multimodale und perioperative Therapiestrategien das Überleben nach onkologischer Ösophaguschirurgie in den letzten 2 Dekaden verändert? Eine retrospektive Kohortenanalyse über 23 Jahre

Zusammenfassung

Hintergrund Malignome des Ösophagus zählen zu den häufigsten krebsbedingten Todesursachen. Den einzigen kurativen Therapieansatz stellt die radikale Ösophagektomie, eingebettet in ein multimodales Therapiekonzept, dar. Ziel der Untersuchung war die Analyse von Langzeitentwicklungen in der operativen Therapie des Ösophaguskarzinoms und deren Einflüsse auf das kurz- (1-JÜR), mittel- (5-JÜR) und langfristige (10-JÜR) Überleben.

Patienten und Methoden Es wurden retrospektiv 301 Patienten am Universitätsklinikum Bonn untersucht, bei denen zwischen 1989 und 2012 eine Ösophagusresektion durchgeführt wurde. Um mögliche Trends im Management und Veränderungen hinsichtlich der Prognose zu analysieren, wurden 2 Kohorten (Kohorte A: operiert 1989 – 2000, Kohorte B: operiert 2001 – 2012) gebildet und bez. demografischer Daten, Tumorentität, Stadium, Komplikationsrate und Überleben miteinander verglichen.

Ergebnisse In der Kohorte B wurden signifikant ältere Patienten in niedrigeren Tumorstadien mit einer größeren Lymphknotenausbeute operiert, eine Zunahme des Adenokarzinoms (AC) war zu beobachten. Während sich die Gesamtmorbidität nicht signifikant veränderte, konnte eine geringere Rate an Anastomoseninsuffizienzen in Kohorte B (5,5%) verglichen mit Kohorte A (12,3%) bei gleichzeitigem Anstieg der kardialen Ereignisse (A: 3,6% vs. B: 12,3%) nachgewiesen werden. Die 30-Tage-Krankenhausmortalität lag bei insgesamt 2,7% und fiel von 5% (Kohorte A) signifikant (p = 0,05) auf 0,7% (Kohorte B). Das mittlere Überleben betrug in der Kohorte A 46 ± 6,5 Monate. In Kohorte B überlebten Patienten mit 53 ± 7,2 Monaten signifikant länger (p = 0,03). In der univariaten Analyse hatten das lokale Tumorstadium, der Resektionsgrad, die Anzahl der befallenen Lymphknoten (LK), der Lymphknotenquotient (LNR) sowie das Auftreten postoperativer Komplikationen einen Einfluss auf das Überleben, wohingegen in der multivariaten Analyse nur noch T-Stadium, R-Status und LNR als unabhängige Prognosefaktoren galten.

Schlussfolgerung Patienten, die sich einer onkologischen Ösophagusresektion unterziehen, sind heutzutage älter als noch vor einigen Jahren. Die frühzeitigere Tumordiagnose, eine radikalere Operationstechnik mit radikalerer Lymphknotendissektion und weniger Anastomoseninsuffizienzen sowie eine verbesserte perioperative Medizin scheinen diesen demografischen Nachteil zu kompensieren. Die größte prognostische Bedeutung beim Ösophaguskarzinom hat die LNR.

Abstract

Background Esophageal malignoma is among the most frequent causes for cancer-related deaths. The only definite curative therapy is esophagectomy embedded in various multimodal treatment regimens. The aim of this study was to evaluate long-term development after esophageal surgery in the last two decades in order to observe possible trends and their influence on short, medium and long term survival.

Patients and Methods Cases of 301 patients who underwent esophagectomy between 1989 and 2012 were analysed retrospectively. To investigate possible changes in perioperative management and their influence on prognosis patients were divided into two cohorts (A: surgery between 1989 and 2000; B: surgery between 2001 and 2012) and further analyzed with regard to demographics, tumor entity, stage, complications and survival. Statistics were conducted to compare both groups while p ≤ 0.05 was regarded as statistically significant.

Results In cohort B patients were significantly older compared to cohort A and underwent surgery in earlier tumor stages with a higher lymphnode yield. Also an increased incidence of adenocarcinoma was observed. While overall morbidity did not change significantly, a decreased rate of anastomotic leakage was observed in cohort B (5.5%) compared to cohort A (12.3%) accompanied by a simultaneous increase in cardiac events (A: 3.6% vs. B: 12.3%). Overall 30-days-mortality was 2.7% and decreased significantly from 5% in cohort A to 0.7% in cohort B (p = 0.05). Median survival was 46 ± 7 month in cohort A, in cohort B an increase could be observed (53 ± 7 months, p = 0.03). By univariate analysis we could demonstrate that stage, affected lymph nodes, lymphnode ratio (LNR) and incidence of postoperative complications were significant predictors for the survival whereas in multivariate analysis T-stage, R-status and LNR were independent predictors for patients outcome.

Conclusion Patients undergoing esophageal resection for cancer nowadays are older than in the past decades. Earlier cancer diagnosis, more radical surgical techniques with an extended lymphnode dissection, a decrease in anastomotic leakage and an improved perioperative care seem to compensate for this potential demographic disadvantage. The most important independent predictor of outcome after esophageal resection is the LNR.

Schlüsselwörter

Follow-up - Langzeitprognose - postoperative Komplikation - Ösophagusresektion

Key words

follow-up - long term prognosis - postoperative complications - esophageal resection

• Literatur

• 1 Allum WH, Bonavina L, Cassivi SD. et al. Surgical treatments for esophageal cancers. Ann N Y Acad Sci 2014; 1325: 242-268
• 2 Holscher AH, Fetzner UK, Bludau M. et al. [Complications and management of complications in oesophageal surgery]. Zentralbl Chir 2011; 136: 213-223
• 3 Gockel I, Niebisch S, Ahlbrand CJ. et al. Risk and complication management in esophageal cancer surgery: a review of the literature. Thorac Cardiovasc Surg 2015;
• 4 Cunningham D, Allum WH, Stenning SP. et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006; 355: 11-20
• 5 van Hagen P, Hulshof MC, van Lanschot JJ. et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012; 366: 2074-2084
• 6 Gockel I, Sultanov FS, Domeyer M. et al. [Surgical therapy for esophageal carcinoma: a prospective 20-year analysis]. Zentralbl Chir 2008; 133: 260-266
• 7 Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205-213
• 8 Siewert JR, Stein HJ, Feith M. et al. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg 2001; 234: 360-367
• 9 Shewale JB, Correa AM, Baker CM. et al. Impact of a fast-track esophagectomy protocol on esophageal cancer patient outcomes and hospital charges. Ann Surg 2015; 261: 1114-1123
• 10 Ruol A, Castoro C, Portale G. et al. Trends in management and prognosis for esophageal cancer surgery: twenty-five years of experience at a single institution. Arch Surg 2009; 144: 247-254
• 11 Glatz T, Marjanovic G, Zirlik K. et al. [Surgical treatment of esophageal cancer: evolution of management and prognosis over the last 3 decades]. Chirurg 2015; 86: 662-669
• 12 Makowiec F, Baier P, Kulemann B. et al. Improved long-term survival after esophagectomy for esophageal cancer: influence of epidemiologic shift and neoadjuvant therapy. J Gastrointest Surg 2013; 17: 1193-1201
• 13 Gockel I, Sultanov FS, Domeyer M. et al. Developments in esophageal surgery for adenocarcinoma: a comparison of two decades. BMC Cancer 2007; 7: 114
• 14 Hsu PK, Chen HS, Wu SC. et al. Impact of hospital volume on long-term survival after resection for oesophageal cancer: a population-based study in Taiwan. Eur J Cardiothorac Surg 2014; 46: e127-e135
• 15 Xiong YQ, Ma SJ, Zhou JH. et al. A meta-analysis of confocal laser endomicroscopy for the detection of neoplasia in patients with Barrettʼs esophagus. J Gastroenterol Hepatol 2016; 31: 1102-1110 doi:10.1111/jgh.13267
• 16 Lee MH, Buterbaugh K, Richards-Kortum R. et al. Advanced endoscopic imaging for Barrettʼs esophagus: current options and future directions. Curr Gastroenterol Rep 2012; 14: 216-225
• 17 Vilz TO, Funke J, Pantelis D. et al. [Surgical therapy and prognostic factors for carcinoma of Vaterʼs papilla]. Zentralbl Chir 2016; 141: 263-269 doi:10.1055/s-0034-1383412
• 18 Zhang BY, Yuan J, Cui ZS. et al. Evaluation of the prognostic value of the metastatic lymph node ratio for gastric cancer. Am J Surg 2014; 207: 555-565
• 19 Omloo JM, Lagarde SM, Hulscher JB. et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg 2007; 246: 992-1000
• 20 Lindner K, Fritz M, Haane C. et al. Postoperative complications do not affect long-term outcome in esophageal cancer patients. World J Surg 2014; 38: 2652-2661
• 21 Haverkamp L, Ruurda JP, van Leeuwen MS. et al. Systematic review of the surgical strategies of adenocarcinomas of the gastroesophageal junction. Surg Oncol 2014; 23: 222-228
• 22 Klink CD, Binnebosel M, Otto J. et al. Intrathoracic versus cervical anastomosis after resection of esophageal cancer: a matched pair analysis of 72 patients in a single center study. World J Surg Oncol 2012; 10: 159
• 23 Honda M, Kuriyama A, Noma H. et al. Hand-sewn versus mechanical esophagogastric anastomosis after esophagectomy: a systematic review and meta-analysis. Ann Surg 2013; 257: 238-248
• 24 Liu QX, Min JX, Deng XF. et al. Is hand sewing comparable with stapling for anastomotic leakage after esophagectomy? A meta-analysis. World J Gastroenterol 2014; 20: 17218-17226
• 25 Artinyan A, Orcutt ST, Anaya DA. et al. Infectious postoperative complications decrease long-term survival in patients undergoing curative surgery for colorectal cancer: a study of 12,075 patients. Ann Surg 2015; 261: 497-505
• 26 Cho JY, Han HS, Yoon YS. et al. Postoperative complications influence prognosis and recurrence patterns in periampullary cancer. World J Surg 2013; 37: 2234-2241
• 27 Xia BT, Rosato EL, Chojnacki KA. et al. Major perioperative morbidity does not affect long-term survival in patients undergoing esophagectomy for cancer of the esophagus or gastroesophageal junction. World J Surg 2013; 37: 408-415
• 28 Baba Y, Yoshida N, Shigaki H. et al. Prognostic impact of postoperative complications in 502 patients with surgically resected esophageal squamous cell carcinoma: a retrospective single institution study. Ann Surg 2016; 264: 305-311 doi:10.1097/SLA.0000000000001510
• 29 Pera M, Manterola C, Vidal O. et al. Epidemiology of esophageal adenocarcinoma. J Surg Oncol 2005; 92: 151-159
• 30 Gavin AT, Francisci S, Foschi R. et al. Oesophageal cancer survival in Europe: a EUROCARE-4 study. Cancer Epidemiol 2012; 36: 505-512
• 31 Dubecz A, Gall I, Solymosi N. et al. Temporal trends in long-term survival and cure rates in esophageal cancer: a SEER database analysis. J Thorac Oncol 2012; 7: 443-447
• 32 Shapiro J, van Lanschot JJ, Hulshof MC. et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; 16: 1090-1098
• 33 Akutsu Y, Matsubara H. The significance of lymph node status as a prognostic factor for esophageal cancer. Surg Today 2011; 41: 1190-1195