Tadashi Nishimaki

Surgery Plus Chemotherapy Compared With Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204

PURPOSEnWe performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery.nnnPATIENTS AND METHODSnPatients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival.nnnRESULTSnOf the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis.nnnCONCLUSIONnPostoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Outcomes of Extended Radical Esophagectomy for Thoracic Esophageal Cancer

BACKGROUNDnGreat controversy exists concerning the adequate extent of esophagectomy for cure in patients with esophageal cancer. Extended radical esophagectomy combined with three-field lymphadenectomy has been performed to improve the cure rates for patients with the disease in Japan. The purposes of this study were to assess the mortality and morbidity rates after extended radical esophagectomy and to determine the oncologic indications for this procedure.nnnSTUDY DESIGNnWe reviewed 190 patients who underwent extended radical esophagectomy for invasive esophageal cancer. The procedures were performed prospectively between 1982 and 1996.nnnRESULTSnThe 30-day mortality, in-hospital mortality, and morbidity rates were 1.6%, 4.7%, and 58.4%, respectively. The most common postoperative complication was vocal-cord paralysis (45.3%), followed by major pulmonary complications (21.6%). The overall survival rate for the 190 patients was 41.5% at 5 years, with a median followup period of 61 months. Some subgroups of patients had an extremely poor prognosis despite extended radical esophagectomy. Survival was < or = 5 years in all patients with five or more positive nodes; all patients with simultaneous metastases to the cervical, mediastinal, and abdominal lymph nodes; and all patients with cervical metastases from a lower esophageal tumor.nnnCONCLUSIONSnExtended radical esophagectomy is potentially associated with high morbidity rates although the mortality rates are acceptable, suggesting the necessity of careful patient selection. This procedure is indicated oncologically only for patients with four or fewer metastatic nodes or with metastases confined to one or two of the three anatomic compartments (neck, mediastinum, and abdomen) from upper or midesophageal tumors.

Clinical Significance of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, and Squamous Cell Carcinoma Antigen Levels in Esophageal Cancer Patients

Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and squamous cell carcinoma (SCC) antigen levels were assessed to determine if their levels are useful for staging esophageal cancer preoperatively and for predicting patient survival after esophagectomy. Hence their seropositivity was investigated for a correlation with resectability, clinicopathologic parameters of tumor progression, and treatment outcomes in patients with unresectable esophageal cancer (n = 63) and those undergoing esophagectomy for resectable disease (n = 267). Abnormal elevation of serum SCC antigen levels showed a significant correlation with resectability (p < 0.0001), depth of tumor invasion (p < 0.0001), lymph node status (p = 0.0015), TNM stage (p < 0.0001), lymphatic invasion (p = 0.0019), blood vessel invasion (p = 0.0079), and poor survival after esophagectomy (p = 0.0061). A significant relation (p = 0.0145) was found between elevated serum CEA levels and distant metastasis, whereas the seropositivity of CA 19-9 showed no association with resectability, tumor progression, or patient survival. These results indicate that abnormal elevation of serum SCC antigen is a useful predictor of advanced esophageal cancer associated with poor survival after esophagectomy.

Tumor spread in superficial esophageal cancer: histopathologic basis for rational surgical treatment.

To formulate a rational approach for the surgical treatment of patients with superficial esophageal cancer (SEC), tumor spread was clinicopathologically studied in 89 patients with SEC. There were 31 mucosal and 58 submucosal tumors. Lymph node metastases were not found in any of those with a mucosal tumor, while one or more lymph nodes were positive for cancer in 41.4% of those with a submucosal tumor. Furthermore, cancer metastasized to extramediastinal nodes, including cervical and abdominal nodes, in 14 patients, accounting for 58.3% of those with nodal metastasis. The 5-year survival rate was 100% and there were no recurrences after esophagectomy in those with a mucosal tumor, whereas the survival rate of those with a submucosal tumor was 64.3% at 5 years (p<0.01). Based on the different biological behavior of mucosal and submucosal esophageal cancer, we conclude that mucosal tumors may be adequately treated by any type of local resection but submucosal tumors require a subtotal esophagectomy with systematic lymphadenectomy involving the cervical, mediastinal, and abdominal nodes for cure.RésuméPour déterminer une attitude thérapeutique rationnelle pour le traitement chirurgical du cancer superficiel de loesophage, on a étudié lextension tumorale chez 89 patients. Trente et un patients avaient une tumeur limitée à la muqueuse, alors que 58 avaient une tumeur sétendant à la sous-muqueuse. Aucun patient navait de métastase lymphatique lorsque la tumeur était limitée à la muqueuse alors quun ou plusieurs ganglions étaient envahis chez 41.4% des patients ayant une tumeur de la sous-muqueuse. Qui plus est, 14 patients avaient une métastase au niveau des ganglions cervicaux et/ou abdominaux (58.3% des patients ayant une métastase). La survie à 5 ans était 100% sans aucune récidive après esophagectomie lorsque la tumeur était limitée à la muqueuse alors que la survie à 5 ans nétait que de 64.3% (p<0.01) lorsquil sagissait dune tumeur étendue à la sous-muqueuse. En se basant sur les différences de comportement tumoral des cancers superficiels de lesophage, soit limité à la muqueuse soit étendus à la sous-muqueuse, nous concluons que les premiers peuvent être traités par pratiquement nimporte quel type de résection alors que les seconds nécessitent une esophagectomie subtotale associée à un curage lymphatique élargj aux ganglions cervicaux et abdominaux.ResumenCon el propósito de formular un enfoque racional para el tratamiento quirúrgico de pacientes con cáncer superficial del esófago (CSE), se hizo el estudio clinicopatológico de la extensión tumoral en 89 pacientes con este tipo de neoplasma; se analizaron 31 tumores mucosos y 58 submucosos. No se encontraton metástasis ganglionares en ninguno de los casos de tumor mucoso, en tanto que se hallaron uno o más ganglios positivos para cáncer en 41.4% de los casos de tumor submucoso; además, el cancer hizo metastasis extramediastinales, incluso a ganglíos cervicales y abdominales, en 14 pacientes, lo cual corresponde a 58.3% de los pacientes con metástasis ganglíonales. La tasa de sobrevida a 5 años fue 100%, y no se registraron recunrrecias después de la esofagectomía en los pacientes con tumores mucosos, en tanto que la sobrevida a 5 años de los tumores submucosos fue del 64.3% (p<0.01). Con fundamento en el diferente comportamiento biológico de los cánceres mucosos y submucosos del esófago, se puede concluir que los tumores mucosos pueden ser adecuadamente tratados mediante cualquier tipo de resección local, pero que los tumores submucosos requieren esofagectomia subtotal con linfadenectomía sistémica que incluya los ganglíos cervicales, mediastinales y adbominales.

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer.

BACKGROUNDnExact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy.nnnMETHODSnThe accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification.nnnRESULTSnFor the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%.nnnCONCLUSIONSnEither the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.

Extended radical esophagectomy for superficially invasive carcinoma of the esophagus

BACKGROUNDnThe purpose of the study was to determine whether extended radical esophagectomy is both clinically and oncologically indicated for patients with superficially invasive esophageal carcinomas.nnnMETHODSnWe reviewed 51 patients with this disease in whom extended radical esophagectomy was performed.nnnRESULTSnMajor morbidity developed in 80% of the patients associated with no mortality after the operation. At surgery lymph node metastases were found in 29 patients (57%). Although the number of positive nodes was 3 or less in 93% of those patients, the tumors metastasized not only to the mediastinal nodes but also to the cervical and abdominal nodes, frequently jumping the first echelon of nodes. The overall 5-year survival rate was 68%. The survival curve of the patients with positive nodes was significantly worse (P < .01) than that of patients with negative nodes: the respective 5-year survival rates were 47% and 93%. However, no significant difference was detected between the survival curves of the patients with cervical metastases and those with noncervical metastases.nnnCONCLUSIONSnExtended radical esophagectomy is needed for complete tumor clearance and may be effective in improving the rate of cure in patients with superficially invasive esophageal carcinoma. However, patients should be selected carefully for the performance of extended radical esophagectomy because this procedure is potentially associated with high morbidity rates.

Tumor spread and outcome of treatment in primary esophageal small cell carcinoma

The most effective treatment for patients with esophageal small cell carcinoma has not yet been established because of the overall extremely poor prognosis regardless of the mode of treatment. The role of esophagectomy has been controversial in the management of patients with this disease.

Intramural Metastases from Thoracic Esophageal Cancer: Local Indicators of Advanced Disease

Abstract. The patterns of tumor spread and long-term survival of patients with (n = 54) and without (n = 270) intramural metastasis from esophageal cancer were investigated after either extended radical (n = 155) or less radical (n = 169) esophagectomy. The purpose was to evaluate whether extended radical esophagectomy has an impact on the long-term survival of patients with intramural metastases from the disease. The patients with intramural metastasis had significantly larger primary tumors (p < 0.01) and more frequent T4 tumors (p < 0.001), stage IV disease (p < 0.05), lymphatic invasion (p < 0.05), and lymph node metastasis (p < 0.01) than did those without intramural metastasis. The survival rates of patients with intramural metastases were significantly worse than those of patients without intramural metastases after resection (p < 0.001). No patient with intramural metastases survived more than 4 years after either extended or less radical esophagectomy, and there was no significant difference between the two survival curves. Therefore intramural metastases should be considered local indicators of advanced esophageal cancer, and radical esophagectomy may not be indicated for patients with intramural metastasis from the disease.

Outcomes of simultaneous resection of synchronous esophageal and extraesophageal carcinomas.

BACKGROUNDnAdequate extent of surgical resection of simultaneous primary esophageal and extraesophageal carcinomas is controversial.nnnSTUDY DESIGNnClinicopathologic records and treatment outcomes of 57 patients undergoing simultaneous resection of both synchronous esophageal and extraesophageal carcinomas (SC group) were reviewed and compared with those of 316 patients receiving esophagectomy for solitary esophageal carcinoma (EC group).nnnRESULTSnMortality and morbidity rates were 3.5% and 45.6% in the SC group, and 3.2% and 44.3% in the EC group, respectively. No significant difference was detected in either of the rates between the two patient groups. The overall 5-year survival rate of the SC group was 40%. Survival of the patients undergoing curative resection of both esophageal and extraesophageal tumors (n = 30) was significantly better than that of the patients receiving palliative resection of at least one of the two tumors in the SC group (n=27)(5-year survival, 54.2% versus 19.9%, respectively)(p < 0.01). Survival of the SC group patients undergoing curative resection of both tumors (n = 30) did not differ from that of the EC group patients receiving curative esophagectomy (n = 182)(5-year survival rates, 54.2% versus 60.0%, respectively).nnnCONCLUSIONSnSimultaneous resection of synchronous esophageal and extraesoprhageal carcinomas can be safely performed, and complete tumor clearance of both tumors is needed for favorable long-term results.

Successful resection of metachronous liver metastasis from α-fetoprotein-producing gastric cancer: Report of a case

We present herein the case of a 68-year-old man in whom metachronous liver metastasis from an α-fetoprotein (AFP)-producing gastric cancer was successfully treated. The patient initially underwent a distal gastrectomy for an AFPproducing gastric cancer on January 30, 1997, following which the serum AFP level which had been 228 ng/ml prior to surgery decreased to 30 ng/ml. However, 7 months after surgery, follow-up examination revealed an abnormal elevation of the serum AFP level up to 301 ng/ml, and a liver tumor was subsequently detected at segment 8 (S8) by abdominal ultrasonography. There was no evidence of hepatitis B or C virus infections. After various investigations, he was diagnosed to have liver metastases in S6 and S8, from the AFP-producing gastric cancer, and a partial hepatectomy of S6 and S8 was performed. His postoperative course was uneventful and he was discharged on postoperative day 26. Thereafter, his serum AFP levels decreased and have remained within normal limits for 12 months since his operation. To the best of our knowledge, this is the first case of successful resection of metachronous liver metastasis from an AFP-producing gastric cancer.