Muneaki Shibakita

Expression and prognostic significance of PTEN product protein in patients with esophageal squamous cell carcinoma

PTEN is a candidate tumor‐suppressor gene in a variety of malignant tumors. The prognostic importance of PTEN product protein (PTEN) and its correlation with clinicopathologic characteristics have yet to be delineated in patients with esophageal carcinoma.

Esophageal Resection in Elderly Esophageal Carcinoma Patients: Improvement in Postoperative Complications

BACKGROUND Advanced age is considered to be a relative contraindication for radical esophagectomy with a three-field lymph node dissection. METHODS Preoperative risks, postoperative morbidity and mortality, and long-term survival in 55 elderly patients (> or =70 years) who had undergone extensive esophagectomy for esophageal carcinoma were compared with those of 149 younger patients (<70 years). RESULTS Elderly patients had worse preoperative cardiopulmonary function and had more frequent postoperative cardiopulmonary complications compared with younger patients (p < 0.05). The postoperative death rate was not statistically different between the elderly (10.9%) and younger groups (5.4%). When the study period was divided into an early and a late phase, the postoperative death rate dropped significantly (p < 0.05) in recent years (1.4%) when compared with the previous era (10.0%). The overall survival rates were not different between elderly and younger patients. CONCLUSIONS Preoperative cardiopulmonary risk factors and postoperative complications after esophagectomy were more frequently noticed in elderly patients than in younger patients. A dramatic improvement in postoperative death was noticed in recent years. The long-term survival of elderly patients after extended esophagectomy was almost similar to that in younger patients.

Esophageal Cancer With Cirrhosis of the Liver: Results of Esophagectomy in 18 Consecutive Patients

AbstractBackgrounds: Patients with cirrhosis of the liver sometimes are candidates for esophagectomy with extensive lymphadenectomy. Materials and Methods: Of 271 patients with primary esophageal carcinoma, 19 patients (7.0%) had pathologically proven cirrhosis of the liver. Among those, 18 patients underwent esophagectomy with extensive lymph node dissection. Clinicopathologic characteristics of these 18 patients were retrospectively investigated. Results: Pathological T stages were pT1 in 3 patients, pT2 in 9 patients, pT3 in 2 patients, and pT4 in 4 patients. Hepatitis C virus antibody was positive in 1 patient, and 14 patients were alcoholics. Three patients had cryptogenic cirrhosis. Seven patients were classified as Child- Turcotte B and 11 were Child-Turcotte A. Three patients had ICG-R 15 over 30%. Fifteen patients (83.3%) developed a total of 35 postoperative complications. Three patients currently are alive without recurrence. Fifteen patients have died: 7 from cancer recurrence; 5 of causes unrelated to esophageal cancer; and 3 of operative death (operative mortality: 16.7% in 18 cirrhotic patients vs. 5.7% in 227 non-cirrhotic patients; P 5 .102). The 1- and 3-year survival rates for 18 resected cirrhotic patients were 50% and 21%, respectively, and those for 227 resected non-cirrhotic patients were 67% and 42%, respectively (P 5 .051). When operative deaths were excluded from the analysis, the 1- and 3-year survival rates for 15 cirrhotic patients were 60% and 25%, respectively, whereas those for 214 non-cirrhotic patients were 68% and 43%, respectively (P 5 .271). Conclusion: Although cirrhosis has a high morbidity and mortality rate, Child-Turcotte A and B cirrhosis may not contraindicate curative esophagectomy for esophageal carcinoma. However, these patients need meticulous perioperative care to avoid postoperative complications.

Esophageal cancer with distant lymph node metastasis - Prognostic significance of metastatic lymph node ratio

The cervical and celiac lymph node metastases are defined as distant metastasis (Mlym) from thoracic esophageal carcinoma by TNM (primary tumor, regional lymph nodes, and distant metastasis) classification. The prognostic factors, however, of such distant node metastases are not fully understood. Of 85 patients with node-positive thoracic esophageal carcinoma who were treated with the same modalities of treatment, 31 (37%) had Mlym. Prognostic factors for long-term survival were analyzed by univariate and multivariate analyzes. Three patients are alive and free of cancer, and two patients survived over 5 years. Fifteen patients died of recurrent esophageal cancer and 11 patients succumbed to causes unrelated to esophageal cancer. Two patients with a single Mlym died without recurrence of esophageal cancer at 1.4 years and after more than 5 years, respectively. The 1-, 2-, 3-, and 5-year overall survival rates of all 31 patients were 64.5%, 24.8%, 17.0%, and 12.8%, respectively. The factors influencing survival rate were depth of invasion (pT1,2 vs. pT3,4) and metastatic lymph node ratio (≤0.104 vs. ≥0.105). The survival rates were not influenced by number of lymph node metastasis, number of Mlym, or by metastatic lymph node ratio of Mlym. Among those two significant variables verified by univariate analysis, independent prognostic factor for survival determined by multivariate analysis was the metastatic lymph node ratio (risk ratio = 3.4, p = 0.0345). The results of this study indicate that a significant number of patients can be cured of esophageal carcinoma by extensive resection along with extended lymph node dissection even when the disease metastasizes to distant nodes.

Prognostic Factors after Extended Esophagectomy for Squamous Cell Carcinoma of the Thoracic Esophagus

In Japan, extended esophagectomy with extensive lymphadenectomy has become the standard surgical procedure for carcinoma of the thoracic esophagus. Although mortality and morbidity rates after such extensive esophagectomy have been acceptable, the long‐term outcomes are not necessarily satisfactory.

Prognostic significance of Fas and Fas ligand system-associated apoptosis in gastric cancer.

Background: Previous studies indicate that gastric carcinomas express Fas ligand and downregulate Fas to escape from the host immune attack; however, the prognostic importance of Fas/FasL expression in this tumor is yet to be evaluated.Methods: Specimens from 87 gastric carcinoma patients of different stages treated in a defined period with curative intent were evaluated for apoptosis, Fas, FasL, and CD8 expression using an immunohistochemical method.Results: The percentage of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic cells expressed as apoptotic index (AI) was higher in 43 patients when the cut-off value was set at the median value. There were no significant correlations between AI and clinicopathologic parameters. Thirty-nine patients showed a high number of CD81 cells within cancer nests. Positive FasL and Fas expression was seen in 53 and 72 patients, respectively. CD8 and FasL expressions were related only to patients’ age. Fas expression had significant correlations with tumor invasion and Lauren classification. There were significant direct correlations between AI and number of nest CD81 cells and between AI and grade of Fas expression. Apoptotic index, pT stage, CD8 expression, and Fas expression were identified as independent prognostic factors.Conclusions: Spontaneous apoptosis in gastric carcinoma may be an independent prognosticator for survival and is significantly influenced by tumor Fas expression and number of nest CD81 cells.

Surgical treatment of superficial esophageal cancer

ObjectiveThe worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the systematic surgical outcomes of esophagectomy for SEC.Data sourcesOnly manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The keywords consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I in esophageal cancer were searched.Study selectionThere were no exclusion criteria for published information relevant to the topics. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded.Data extractionsThirty-two manuscripts were finally collected from MEDLINE and eight articles were also added from reference lists of the pertinent literatures. In evaluating the statistical analysis of the complications of the reported literature, collective method was used.Data synthesisThe collected information was organized.ConclusionsThe conclusions drawn from those articles showed that the overall prevalence of SEC accounted around 10% and increased to 25% in the 2000s. The overall incidence of lymph node metastasis of SEC was about 25% and its incidences in mucosal and submucosal cancer were 5 and 35%, respectively. The percentage of the cases of squamous cell carcinoma (SCC) vs adenocarcinoma (AC) widely varied depending on the geographic locations reported; most SCC cases were from the Asian countries and most AC cases were from the European countries. Clinical significance of multimodal treatment for SEC has dramatically developed in the recent era and could provide various potential therapeutic options for SEC. These concepts make it possible to individualize surgical management of SEC as part of various multimodal treatments. The operative approaches for SEC varied from minimally invasive thoracoscopic esophagectomy, limited transabdominal distal esophagectomy, conventional transthoracic esophagectomy, transhiatal esophagectomy without thoracotomy, en bloc esophagectomy, and to extended esophagectomy with a complete three-field lymph node dissection. A 5-year overall survival rate of SEC after esophagectomy was good (46 to 83%) to excellent (71 and 100%) for mucosal SEC, but far from satisfactory (33 and 78%) for submucosal SEC. Early diagnosis, development of multimodal treatment, standardization of the surgical procedure including routine lymph node dissection, and improved perioperative management of patients have led to a better survival for patients with SEC.

Surgical treatment for locally advanced (T4) squamous cell carcinoma of the thoracic esophagus.

It is still difficult to decide on the treatment modalities for advanced esophageal carcinoma when the prognostic factors of T4 esophageal cancer are not fully understood. In this article, we report that among 71 patients with T4 thoracic esophageal cancer, 49 underwent esophagectomy, 9 had curative resection (R0 group), and 40 had palliative resection (R1/2 group). A total of 22 patients had palliative treatments: bypass in 5 (bypass group), gastrostomy or jejunostomy in 6 (stoma group), and radiochemotherapy alone in 11 (nonoperation group). Clinicopathologic characteristics were retrospectively investigated. Treatment-related deaths occurred in 7 (10%): none in R0, 3 (8%) in R1/2, 3 (60%) in bypass, and 1 (17%) in stoma group. Swallowing was improved in 50 (70%) patients: 9 (100%) in R0, 30 (75%) in R1/2, 1 (20%) in bypass, 3 (50%) in stoma, and 7 (64%) in the nonoperation group. One-, two-, and three-year overall survival rates were 56%, 22%, and 22% in the R0 group and 35%, 19% and 6% in the R1/2 group, respectively (p = 0.19). In the bypass, stoma, and nonoperation groups, none survived 1.6 years. The factors influencing the survival rate of the 49 patients undergoing esophagectomy were grade of lymph node metastasis, amount of perioperative blood transfusion, lymph vessel, and blood vessel invasion. Among these, independent prognostic factors for survival were amount of blood transfusion (≤6 units vs. ≥7 units, p < 0.0001) and grade of lymph node metastasis {none- or peritumoral [lymph nodes adjacent to the main tumor or at a nearby location (<3 cm) from the tumor] metastasis vs. more distant metastasis [lymph nodes at a distant location (> 3 cm)], p = 0.016}. Bypass and stoma operation neither prolonged the survival nor improved the difficulty of swallowing compared with radiochemotherapy alone. Esophagectomy can achieve the best improvement of swallowing and the longest survival with an acceptable mortality rate. Esophageal carcinoma patients with T4 disease and distinct metastasis in the lymph nodes at a distant location (>3 cm) from the primary tumor may not benefit from an esophageal resection.

A Tailored Perioperative Blood Transfusion Might Avoid Undue Recurrences in Gastric Carcinoma Patients

In a large retrospective study, the prognostic significance of blood transfusion (BT) and type of blood product transfused were searched in 640 curatively resected gastric carcinoma patients. Out of 640 patients, 222 (34.7%) received BT and the incidence of BT was reduced from 45% in the early period to 21% in the most recent period. The five-year disease-free survival was significantly (P < 0.0001) worse in the transfused group and BT became an independent prognosticator (P = 0.0061) in the multivariate analysis. Patients transfused with only packed red blood cells (PRBC) had significantly (P = 0.0258) better survival than those transfused with other types of blood products. In conclusion, BT was found to be an independent prognosticator in gastric carcinoma patients after curative resection. A tailored transfusion with PRBC, when indicated, might be the choice for better survival than whole blood or other blood products.

Prognosis of Patients with T2N0 Tumors in the Alimentary Tract: Should They Be Considered as Early Cancers?

Background: T1N0 tumor of the alimentary tract has an excellent long-term prognosis, however, the prognosis of T2N0 tumor has not been uniformly elucidated. Material and Methods: Between February 1981 and April 2000, 75, 424 and 327 patients with node-negative esophageal, gastric and colorectal carcinomas, respectively, underwent curative resection and were included in this study. Long-term prognosis of those node-negative patients stratified by the T-stage were evaluated retrospectively. Results: The 5-year survival rates of patients with T1N0 and T2N0 esophageal tumors were 95.7 and 93.3%, respectively, however those with T3N0 tumor was only 47.6% (p < 0.01). Similarly, the 5-year survival rates of gastric cancer patients with T1–2N0 tumors was 100%, however those with T3N0 and T4N0 tumors were 55.6 and 44.4%, respectively (p < 0.01). The 5-year survival rates of colorectal cancer patients with T1N0 and T2N0 tumors were 97.3 and 97.5%, respectively. In contrast, those with T3N0 and T4N0 tumors were 78.6 and 58.3%, respectively (p < 0.05, T1N0, T2N0 vs. T3N0; p < 0.001, vs. T4N0). Conclusion: Patients with T2N0 tumors have an excellent long-term prognosis like T1N0 tumors and both categories could be classified as early cancer in the alimentary tract cancers.