Tomonori Sakaguchi

Recurrent nerve nodal involvement is associated with cervical nodal metastasis in thoracic esophageal carcinoma

BACKGROUND Because three-field dissection for esophageal carcinoma is one of the most invasive operations, this procedure should be selected only when strictly indicated; but there are no useful criteria for it. The goal of this study was to identify the useful clinicopathologic factors for indicating three-field dissection. STUDY DESIGN In this study, we reviewed the survival of patients after three-field dissection and identified factors associated with metastases in cervical nodes (CN), especially internal jugular nodes and supraclavicular nodes. Eighty-six patients who underwent curative esophagectomy with three-field dissection for squamous cell carcinoma of the thoracic esophagus were enrolled in this study. Survival rates were compared with respect to the presence of nodal metastasis. The relationship between recurrent nerve nodal (RNN) involvement and CN metastasis (bilateral internal jugular nodes, supraclavicular nodes, or both) was examined. Clinicopathologic factors possibly influencing CN metastasis were studied by multivariate logistic regression analysis. RESULTS The overall 5-year survival rate was 45.1%. The 5-year survival rate for patients without metastatic nodes was 67.5%, for patients with one to four metastatic nodes it was 53.1%, and for patients with five or more it was 9.1 %. The prognosis of those with five or more metastatic nodes was significantly poorer than those of the other two groups. In the positive-node group, the 5-year survival rate for patients with RNN metastasis was 21.7%, and for patients with negative RNN it was 47.0% (p = 0.2). In the positive-node group, the 5-year survival rate for patients with positive CN was 13.7% and for patients with negative CN it was 45.8% (p = 0.01). Fifty-six (88.9%) of 63 patients without RNN metastasis had no CN metastasis in contrast to 13 of 23 patients (56.5%) with RNN metastasis who had no CN metastasis (p = 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity were 43.5%, 88.8%, 58.8%, and 81.2%, respectively. The number of metastatic nodes (5 or more versus 0-4) (odds ratio: 2.9, 95% Confidence Interval (CI) = 1.6-5.5, p = 0.0008) and RNN involvement (odds ratio: 4.5, 95% CI = 1.3-15.9, p = 0.02) were the significant factors associated with CN metastasis in the multivariate analysis. CONCLUSIONS RNN involvement is associated with CN metastasis as is the number of metastatic nodes and may be an indicator for the selection of three-field dissection in thoracic esophageal carcinoma.

Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma

BACKGROUND Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.

Outcome of histologically node-negative esophageal squamous cell carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pNO in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregionai recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pTl tumors (p=0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.RésuméL’évolution des cancers de lœsophage NO et la signification des micrométastases ganglionnaires resent inconnues. Le but de cette étude rétrospective a été de clarifier ces deux problèmes. Nous avons inclus dans cette étude, 98 patients qui ont eu une résection à visée curative pour un cncer de l’œsophage (pNO selon la classificaton TNM). Nous avons revu les causes de mortalité chez ces patients. Les courbes de survie ont été calculées et comparées après stratification selon les données clinicopathologiques. Les micrométastases ganglionnaires chez les patients récidives ont été déterminées par une coloration immunohistochimique de la cytokératine. L’àge des patients allait de 45 à 83 ans (moyenne: 65.3 ans). Il y avait 83 hommes et 15 femmes. Cinquante-quatre patients étaient en vie et 44 patients étaient décédés. Neuf patients sont décédés d’une récidive de leur cancer le l’œsophage, 33 sont décédés d’autres causes (principalement une infection pulmonaire:n=11, ou un cancer extra-esophagien: n=7) alors que deux patients sont décédés de cause inconnue. Huit patients ont eu une récidive locorégionale et deux, une récidive à distance. La survie globale pour les 98 patients a été de 58.2%. La survie des patients ayant des tumeurs pT2 ou pT3 a été significativement moins bonne que pour les tumeurs pTis ou pT1 (p=0.02, test du log-rank). Les autres facteurs clinicopathologiques n’ont pas affecté le pronostic. Par l’étude immunohistochimique aucune micrométastase n’a été retrouvée parmi 365 ganglions réséqués chez des patients ayant eu une récidive. Seule la profondeur d’invasion tumorale a influené l’évolution de la maladie chez les patients NO. Parmi les patients décédés, 75% étaient sans récidive; les deux causes principales étant des complications pulmonaires et un cancer extra-esophagien. Dans cette série, les micrométastases n’ont jamais été la cause de récidive.ResumenNo están bien establecidos ni la evolución ni el resultado final del carcinoma escamocelular del esófago con ganglios negativos, tampoco el significado pronóstico de las micrometástasis ganglionares. El propósito de este estudio retrospectivo fue aclarar estos interrogantes. Noventa y ocho pacientes sometidos a operación curativa por carcinoma esofágico con ganglios histológicmente negativos (pNO en la clasificación TNM) fueron incorporados en el estudio. Se revisaron las causas de muerte y se calcularon las curvas de supervivencia para compararlas luego de la estratificación según parámetros clínico patológicos. El estudio de los ganglios para determinar micrometástasis fue hecho en los pacientes que desarrollaron recurrencia mediante coloración immunohistológica de queratina. Las edades oscilaron entre 45 y 83 años (promedio: 65.3); hubo 83 hombres y 15 mujeres. Cincuenta y dos pacientes están vivos, 44 murieron. Nueve murieron por carcinoma recurrente, 33 por otras causas (neumonía 11, carcinoma extraesofágico 7, etc.) y dos por causa desconocida. Ocho presentaron recurrencia local-regional y dos metástasis distantes. La tasa global de supervivencia para los 98 pacientes fue 58.2%. La supervivencia en los pacientes con neoplasmas pT2 o pT3 fue significativamente peor que en los pTis o pT1 (p=0.02). Otros factores clínicos y patológicos no demostraron efecto sobre el pronóstico. El estudio immunohistoquímico no reveló micrometástasis ganglionares en 365 ganglios resecados de pacientes con recurrencias. Sólo la profundidad de la invasión tumoral afectó la evolución final en estos carcinomas esofágicos con ganglios negativos. Setenta y cinco por ciento de los pacientes murieron por causas diferentes de la recurrencia tumoral, y las dos causas principales de muerte fueron la complicación pulmonar y el carcinoma extraesofágico en los pacientes libres de recurrencia. La presencia de micrometástasis ganglionares no apareció asociada con recurrencia en esta serie.