Georges Decker

Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma

Objective:To determine the impact of esophagectomy with 3-field lymphadenectomy on staging, disease-free survival, and 5-year survival in patients with carcinoma of the esophagus and gastroesophageal junction (GEJ). Background:Esophagectomy with 3-field lymphadenectomy is mainly performed in Japan. Data from Western experience with 3-field lymphadenectomy are scarce and dealing with relatively small numbers. As a result, its role in the surgical practice of cancer of the esophagus and GEJ remains controversial. Methods:Between 1991 and 1999, primary surgery with 3-field lymphadenectomy was performed in 192 patients, of whom a cohort of 174 R0 resections was used for further analysis. Results:Hospital mortality of the whole series was 1.2%. Overall morbidity was 58%. Pulmonary complications occurred in 32.8%, cardiac dysrhythmias in 10.9%, and persistent recurrent nerve problems in 2.6%. pTNM staging was as follows: stage 0, 0.6%; stage I, 9.2%; stage II, 27.6%; stage III, 28.7%; and stage IV, 33.9%. Overall 3- and 5-year survival was 51% and 41.9%, respectively. The 3- and 5-year disease-free survival was 51.4% and 46.3%, respectively. Locoregional lymph node recurrence was 5.2%; no patient developed an isolated cervical lymph node recurrence. Five-year survival for node-negative patients was 80.2% versus 24.5% for node-positive patients. Five-year survival by stage was 100% in stages 0 and I, 59.1% in stage II, 36.8% in stage III, and 13.3% in stage IV. Twenty-three percent of the patients with adenocarcinoma (25.8% distal third and 17.6% GEJ) and 25% of the patients with squamous cell carcinoma (26.2% middle third) had positive cervical nodes resulting in a change of pTNM staging specifically related to the unforeseen cervical lymph node involvement in 12%. Cervical lymph node involvement was unforeseen in 75.6% of patients with cervical nodes at pathologic examinations. Five-year survival for patients with positive cervical nodes was 27.7% for middle third squamous cell carcinoma. For distal third adenocarcinomas, 4-year survival was 35.7% and 5-year survival 11.9%. No GEJ adenocarcinoma with positive cervical nodes survived for 5 years. Conclusions:Esophagectomy with 3-field lymph node dissection can be performed with low mortality and acceptable morbidity. The prevalence of involved cervical nodes is high, regardless of the type and location of tumor resulting in a change of final staging specifically related to the cervical field in 12% of this series. Overall 5-year and disease-free survival after R0 resection of 41.9% and 46.3%, respectively, may indicate a real survival benefit. A 5-year survival of 27.2% in patients with positive cervical nodes in middle third carcinomas indicates that these nodes should be considered as regional (N1) rather than distant metastasis (M1b) in middle third carcinomas. These patients seem to benefit from a 3-field lymphadenectomy. The role of 3-field lymphadenectomy in distal third adenocarcinoma remains investigational.

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction : a prospective study based on primary surgery with extensive lymphadenectomy

ObjectiveTo assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. Summary Background DataFDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. MethodsForty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). ResultsThe FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1–2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1–2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. ConclusionsFDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Prospective Comparative Study of Integrated Positron Emission Tomography-Computed Tomography Scan Compared With Remediastinoscopy in the Assessment of Residual Mediastinal Lymph Node Disease After Induction Chemotherapy for Mediastinoscopy-Proven Stage IIIA-N2 Non–Small-Cell Lung Cancer: A Leuven Lung Cancer Group Study

PURPOSE Mediastinal restaging after induction therapy for non-small-cell lung cancer remains a difficult and controversial issue. The goal of this prospective study was to compare the performance of integrated positron emission tomography (PET)--computed tomography (CT) and remediastinoscopy in the evaluation of mediastinal lymph node metastasis after induction chemotherapy. PATIENTS AND METHODS Thirty consecutive stage IIIA-N2 non-small-cell lung cancer patients surgically treated at our institution were entered onto this prospective study. N2 disease was proven by cervical mediastinoscopy, at which a mean number of 3.8 lymph node levels were biopsied. After completion of induction chemotherapy, the mediastinum was reassessed by integrated PET-CT and remediastinoscopy. All patients underwent thoracotomy with attempted complete resection and systematic nodal dissection. RESULTS PET-CT showed no evidence of nodal disease (N0) in 13 patients, Hilar nodal disease (N1) disease in three patients, and residual mediastinal disease (N2) in 14 patients. Remediastinoscopy was positive in only five patients. The preinduction involved lymph node level could be accurately re-evaluated in 18 patients. This was not the case in the other 12 because of extensive fibrosis and adhesions. In 17 patients, persistent N2 disease was found at thoracotomy. The sensitivity, specificity, and accuracy of PET-CT were 77%, 92%, and 83%, respectively. These parameters for remediastinoscopy were 29%, 100%, and 60%, respectively. Sensitivity (P < .0001) and accuracy (P = .012) were significantly better for PET-CT. CONCLUSION After a thorough staging mediastinoscopy, postinduction remediastinoscopy had a disappointing sensitivity because of adhesions and fibrosis. Integrated PET-CT yielded a better result than that obtained in previous studies with side-by-side PET and CT images.

Postoperative complications after transthoracic esophagectomy for cancer of the esophagus and gastroesophageal junction are correlated with early cancer recurrence: role of systematic grading of complications using the modified Clavien classification.

Objectives:To assess the impact of postoperative complications after transthoracic esophagectomy, using the modified Clavien classification, on recurrence and on its timing in patients with cancer of the esophagus or gastroesophageal junction. Background Data:It is hypothesized that complications after esophagectomy for cancer may have a negative effect on recurrence and its timing because of negative interference with the immune system. Methods:Out of 150 consecutive patients operated with curative intent between January 2005 and May 2006, the data of 138 patients with macroscopically complete resection and no synchronous other malignancy were graded according to the modified Clavien classification. Uni- and multivariable analyses were performed to study the impact of postoperative complications on tumor recurrence and its timing. Results:Mean age was 63.1 years, male-female ratio was 4:1; 76.1% of the patients underwent primary surgery, 23.9% received induction therapy, R0-resection rate was 92.8%. Adenocarcinoma was found in 75%. Complication rates according to the modified Clavien classification were grade 0: 29.7%, grade 2: 35.5%, grade 3: 17.4%, grade 4: 15.9%, and grade 5 (postoperative mortality): 1.4%. Ten patients developed recurrence within 6 months, 29 within 12 months, 39 within 18 months, 42 within 24 months, totaling up to 47 at 3 years. Univariable analysis retained complications, LN-status, number of positive nodes, extracapsular lymph node involvement (EC LNI), pStage, pT, and R1-status as factors significantly influencing occurrence of recurrence. In the multivariable model, presence of complications, EC LNI, and R1-status were independent negative factors. Cox-regression analysis also identified these same 3 factors as significant determinators for the timing of recurrence. Conclusions:This study indicates a correlation between complications and early recurrence and its timing. Modified Clavien classification, beside R1-status and EC LNI, appears to be a useful prognostic indicator of early recurrence and its timing. Achieving esophagectomy without postoperative complications is of utmost importance also for oncologic reasons given its negative potential on early oncologic outcome.

Anastomotic complications after esophagectomy.

Anastomotic complications after esophagectomy continue to be a burden jeopardizing the quality of life and of swallowing. However, incidence, mortality and morbidity of anastomotic complications have substantially decreased in recent years. It seems that this is not so much related to the use of a particular conduit, approach or route for reconstruction, but rather related to refinement in anastomotic techniques and perhaps even more to progress in modern perioperative management. Knowledge of surgical anatomy and meticulous technique are of paramount importance and obviously related to individual expertise. As to the management, most leaks can be treated by conservative measures and reintervention surgery today is rather exceptional. Early endoscopy and dilatation seem to decrease the incidence and severity of anastomotic stenosis.

Le traitement chirurgical du cancer bronchique non à petites cellules

Resume Introduction La chirurgie reste la meilleure option therapeutique a visee curative pour les stades precoces de cancer bronchique non-a-petites-cellules (CBNPC). Cet article analyse la situation actuelle et les perspectives de la chirurgie du CBNPC. Etat des connaissances L’intervention chirurgicale debute par stadification peroperatoire qui comprend une dissection systematique des ganglions hilaires et mediastinaux et se poursuit par une resection complete, determinant majeur du pronostic. Perspectives La strategie d’economie du parenchyme pulmonaire explique le developpement de lobectomies souvent elargies avec bronchoplastie ( sleeve ) en remplacement de la pneumonectomie. La thoracoscopie a une place dans la stadification invasive du cancer bronchique et la resection des CBNPC peripheriques T1N0 (lobectomie thoracoscopique video-assistee) avec des resultats en terme de survie pour ces petites tumeurs peripheriques au moins aussi bons qu’ apres chirurgie ouverte. En cas d’atteinte ganglionnaire mediastinale (N2), un traitement systemique d’induction est administre dans la plupart des centres et les repondeurs ont une survie significativement amelioree par rapport aux non-repondeurs. La re-stadification mediastinale apres traitement d’induction reste pour le moment tres imprecise. Pour les tumeurs localement avancees (cT4), de nouvelles techniques et approches chirurgicales rendent realisables des resections carenaires, vertebrales ou de la veine cave avec une morbidite et mortalite acceptable mais des etudes complementaires sont necessaires. Conclusions Une selection rigoureuse des patients, une technique chirurgicale meticuleuse avec une prise en charge per- et postoperatoire adequate ont permis de reduire la morbidite et la mortalite de la chirurgie du CBNPC. L’evolution des techniques chirurgicales et la multidisciplinarite devraient permettre d’ameliorer encore les resultats de ce traitement qui reste associe aux meilleures chances de guerison.

Extracapsular lymph node involvement is a negative prognostic factor in T3 adenocarcinoma of the distal esophagus and gastroesophageal junction.

OBJECTIVE To assess prognosis according to whether lymph node involvement is intracapsular or with extracapsular breakthrough in adenocarcinoma of the distal esophagus and gastroesophageal junction. Materials and methods One hundred ninety-five consecutive patients with T3 adenocarcinoma of the distal esophagus and gastroesophageal junction between 1990 and 1999 were studied. All patients underwent primary R0 esophagectomy. The mean number of resected nodes per patient was 36.9. Survival was analyzed according to intracapsular and extracapsular involvement. RESULTS In N0 patients 5-year survival was 57% and 9-year survival was 38.7%. In patients with positive nodes these figures were 26.2% and 18.1%, respectively (P =.0069). Intracapsular and extracapsular node involvement showed 5- and 10-year survival of 40.9% and 21.7% versus 18% and 15.7%, respectively. There was no significant difference in 5- and 10-year survival between N0 and intracapsular node involvement (P =.43). However, there was a significant difference in survival between N0 and extracapsular node involvement (P =.002) and between intracapsular and extracapsular node involvement (P =.0001). CONCLUSIONS This study shows a significant difference in survival according to whether lymph node involvement was intracapsular or extracapsular. Patients with intracapsular lymph node involvement have similar survival rates as N0 patients. Extracapsular lymph node involvement is a bad prognostic factor, independent of the number of involved lymph nodes. The number of involved lymph nodes has an additive negative effect. These data may have an impact on treatment strategies.

Outcome after esophagectomy for cancer of the esophagus and GEJ in patients aged over 75 years

OBJECTIVE Though the surgical treatment of esophageal cancer is increasingly accepted for elderly people defined as aged over 70 years, less is reported about the results in patients over 75. This study is a single institution retrospective analysis of outcome after esophagectomy for cancer of the esophagus and GEJ in patients aged over 75 years. METHODS All consecutive patients 76 years old and over undergoing curative esophagectomy for cancer in the period 1991-2006 were analyzed as to comorbidities, outcome and long-term survival. All the data had been prospectively collected in a database. Postoperative mortality risk was assessed by P-POSSUM and O-POSSUM score for in-hospital mortality and by the recently published Steyerbergs score system [Steyerberg EW, Neville BA, Koppert LB, Lemmens VEPP, Tilanus HW, Coebergh JWW, Weeks JC, Earle CC. Surgical mortality in patients with esophageal cancer: development and validation of a simple risk score. J Clin Oncol 2006;24:4277-84.] for 30-day mortality. Five-year survival was compared to the standardized survival in the general population. RESULTS One hundred and eight patients fulfilling the abovementioned criteria were found (76 males and 32 females, mean age 79.5 years, mean standardized life-expectancy: 7.36 years). Among them, 69% had esophageal tumors and 31% GEJ tumors. The predominant histology was adenocarcinoma (74%). Eighty-six (79.6%) presented with one or more major comorbidities or a history of previous major upper-GI surgery, potentially affecting the surgical outcome. All underwent resection with curative intent (R(0) 83.3%, R(1) 12%, R(2) 4.6%). The overall postoperative morbidity rate was 51.9%, pulmonary complications (37%) being the most frequent. Postoperative mortality, mainly due to cardiopulmonary complications, was 7.4%, which was consistent with that predicted by P-POSSUM score (7.2%) and lower than that predicted by O-POSSUM score (15.1%). Thirty-day mortality was 5.5%, being consistent with that predicted by the Steyerbergs score (6.8%). Overall 5-year survival was 35.7%, while R(0) overall survival 42% and cancer specific R(0) survival 51.7%. CONCLUSIONS Patients 76 years old and over with esophageal or GEJ cancer should not be denied surgery solely on the basis of age. Outcome and long-term results in the selected elderly are not differing from those reported for younger patients. However, despite thorough preoperative assessment being applied in the selection of the candidates for surgery, a practical and reliable individual risk-analysis stratification is still lacking.

Survival after Trimodality Treatment for Superior Sulcus and Central T4 Non-small Cell Lung Cancer

Introduction: For sulcus superior tumors and central cT4 tumors, low resectability and poor long-term survival rates are obtained with single-modality treatment. Methods: Analysis of all consecutive patients in our prospective database, who had potentially resectable superior sulcus (cT3–T4) and central cT4 tumors and were treated with induction chemoradiotherapy (two courses of cisplatin-etoposide) and concomitant radiotherapy (45 Gy/1.8 Gy) after multidisciplinary discussion. Surgery with attempted complete resection was performed in patients showing response or stable disease on computed tomography. Results: Between April 2002 and February 2008, 32 consecutive patients were enrolled. Two patients did not complete the induction chemoradiotherapy. Thirty patients were reassessed after induction, 28 had response or stable disease by conventional imaging. Twenty-seven patients were surgically explored since one patient became medically inoperable during induction treatment. The overall complete resectability was 78% (25/32). Resection was microscopically incomplete (R1) in two patients. In 11 patients (41%), a pneumonectomy was performed, and in 14 patients (52%), a chest wall resection was necessary. In 74% of the resected patients, there was a complete pathologic response or minimal residual microscopic disease. The mean postoperative hospital stay was 9.2 days with no hospital mortality and no bronchopleural fistula. With a median follow-up of 26.5 months, 5-year survival rates are 74% in the intent-to-treat population (n = 32) and 77% in completely resected patients (n = 25), with no statistically significant difference between sulcus superior tumors and centrally located T4 tumors. Conclusion: In patients with sulcus superior tumors and in selected patients with centrally located T4 tumors, trimodality treatment is feasible with acceptable morbidity and mortality. The complete resectability is high, and long-term survival is promising.

Assessing the relationships between health-related quality of life and postoperative length of hospital stay after oesophagectomy for cancer of the oesophagus and the gastro-oesophageal junction

OBJECTIVES To evaluate baseline health-related quality of life (HRQL) factors that influence short-term outcome after oesophagectomy for cancer of the oesophagus and gastro-oesophageal junction and the effects of postoperative length of hospital stay on postoperative HRQL, as perceived by the patients themselves. METHODS Four hundred and fifty-five patients operated on with curative intent between January 2005 and December 2009 were analysed. HRQL scores were obtained by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ)-C30 and oesophageal-specific symptoms (OES-18) questionnaires at baseline (=day before surgery) and 3-monthly post-surgery for the first year. RESULTS There were 372 males and 83 females, with a mean age of 63.1 years. Hospital mortality was 3.7% (17 patients). When analysing postoperative length of stay (LOS), a median of 10 days was found. In a multivariable analysis, using a binary logistic regression model, independent prognosticators for a longer LOS (>10 days) were: medical [hazard ratio, HR, 6.2 (3.62-10.56); P < 0.0001] and surgical [HR 2.79 (1.70-4.59); P < 0.0001] morbidity, readmittance to intensive care unit [HR 33.82 (4.55-251.21); P = 0.001] and poor physical functioning [HR 1.89 (1.14-3.14); P = 0.014]. Postoperatively, patients with early discharge (LOS <10 days) indicated, at 3 and 12 months postoperatively, significant better HRQL scores in the functional scales (physical, emotional, social and role functioning) and in symptoms scales (fatigue, nausea, dyspnoea appetite loss and dry mouth) when compared with LOS >10 days. Return to the level of the reference population scores was achieved at 1 year in the LOS ≤10 days for almost all the scales, but not in the LOS >10 days group. CONCLUSIONS A better perception of preoperative physical functioning might have a beneficial effect on LOS. Our data, furthermore, suggest that early discharge correlates with improved postoperative HRQL outcomes. A clear decrease of the HRQL is seen at 3 months after the surgery, particularly in the LOS >10 days group. Generally, return to the level of the reference population scores is achieved at 1 year in the LOS ≤10 days, but not in the LOS >10 days group.