Masahiko Tsurumaru

Radical lymph node dissection for cancer of the thoracic esophagus.

ObjectiveThe authors documented the localization and frequency of lymphatic spread in squamous cell carcinoma of the thoracic esophagus and evaluated the influence of radical systematic lymph node dissection on patient survival. Summary Background DataFrom accumulated surgical experience, it was suggested that some of the patients with lymph nodal involvement from cancer could be cured by its clearance. However, it is only recently that cancer of the esophagus has been evaluated in terms of analyzing lymphatic spread and results of lymphadenectomy. MethodsAmong 1298 patients admitted to the Toranomon Hospital between 1973 and 1993,913 (70.3%) had resections, including curative and palliative procedures. For this study, 717 patients with TNM RO (resection with no residual tumor at operation in TNM classification) were analyzed. Survival was compared between groups of patients with less extensive thoracoabdominal (two-field) dissections and extensive collothoracoabdominal (three-field) dissections. ResultsComparative study revealed that 5-year survival rate for TNM RO patients after three-field dissection (55.0%) was significantly better (log rank test, p = 0.0013) than the rate after two-field dissection (38.3%). The results were particularly significant in subgroups with stage III and IV (because of nodal factor). Overall 5-year survival rate after all resections was 42.4%. ConclusionsThe role of radical lymph node dissection in cancer of the thoracic esophagus was evaluated. Long-term survival was compared between two groups with two-and three-field dissection. It was concluded that survival rate was significantly better in patients with extensive three-field dissection.

Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma

Methods. Eighty‐three patients with hepatocellular carcinoma (HCC) were treated with curative surgical resection during the past 8 years.

Use of the stomach as an esophageal substitute.

Esophagoplasty with isoperistaltic stomach is a useful and satisfactory means of reconstruction of the esophagus. It is simpler and there is no necessity for using a reversed gastric tube. The most essential points of technique for the modelling of the stomach, is taking advantage of the ample intramural vascular network and adequate selection of the highest point of the stomach for the site of the esophago-or pharyngogastrostomy. To utilize the intramural vascular network, sufficient width of the stomach is necessary. This also allows strecthing of the stomach. Esophageal resection and reconstruction using the isoperistaltic stomach above the level of the neck was performed on 130 cases. Among them 40 cases were pharyngogastromies and 90 cases were cervical esophagogastromies. There was one operative death due to alcoholic liver cirrhosis (operative mortality rate 0.8%). If the stomach is properly handled, esophageal replacement by the isoperistaltic stomach gives constant success.

c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma

PURPOSE Esophageal carcinoma is a challenging target for radiotherapy. To improve treatment efficacy, an investigation of a predictive factor is desirable. In this study, we evaluated the significance of apoptosis and immunohistochemical staining for p53, Ki-67, c-erbB-2 (HER-2/neu), Ku (p70/p80), and DNA-PKcs for predictive markers of the responsiveness to chemoradiotherapy in esophageal squamous cell carcinoma. MATERIALS AND METHODS This retrospective analysis consisted of 34 patients with esophageal squamous cell carcinoma in whom tumor biopsy was performed before treatment. They were divided into chemoradiosensitive (n = 13) and chemoradioresistant (n = 21) groups according to the tumor response evaluated at a total radiation dose of 40 Gy. The biopsy samples were examined with immunohistochemical staining for various factors and with an in situ nick end labeling method for apoptosis. The examined data were compared between the two groups. RESULTS The difference in the Ki-67, p53, Ku (p70/p80), DNA-PKcs labeling indexes and the apoptosis index in tumor cells between the chemoradiosensitive and chemoradioresistant groups was not statistically significant. The expression of c-erbB-2 oncoprotein was statistically significant in the chemoradioresistant group (p = 0.02), although it did not correlate with survival. CONCLUSIONS c-erbB-2 immunostaining is useful for the prediction of chemoradioresistance in esophageal squamous cell carcinoma.

Strong interaction between the effects of alcohol consumption and smoking on oesophageal squamous cell carcinoma among individuals with ADH1B and/or ALDH2 risk alleles

Background Oesophageal squamous cell carcinoma (OSCC) is considered a difficult cancer to cure. The detection of environmental and genetic factors is important for prevention on an individual basis. Objective To identify groups at high risk for OSCC by simultaneously analysing both genetic and environmental risk factors. Methods A multistage genome-wide association study of OSCC in Japanese individuals with a total of 1071 cases and 2762 controls was performed. Results Two associated single-nucleotide polymorphisms (SNPs), as well as smoking and alcohol consumption, were evaluated as genetic and environmental risk factors, respectively, and their interactions were also evaluated. Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10−40 and OR=4.13, p=8.4×10−76, respectively). Also, smoking and alcohol consumption were identified as risk factors for OSCC development. By integrating both genetic and environmental risk factors, it was shown that the combination of rs1229984 and rs671 risk alleles with smoking and alcohol consumption was associated with OSCC. Compared with subjects with no more than one environmental or genetic risk factor, the OR reached 146.4 (95% CI 50.5 to 424.5) when both environmental and genetic risk factors were present. Without the genetic risks, alcohol consumption did not correlate with OSCC. In people with one or two genetic risk factors, the combination of alcohol consumption and smoking increased OSCC risk. Conclusions Analysis of ADH1B and ALDH2 variants is valuable for secondary prevention of OSCC in high-risk patients who smoke and drink alcohol. In this study, SNP genotyping demonstrated that the ADH1B and/or ALDH2 risk alleles had an interaction with smoking and, especially, alcohol consumption. These findings, if replicated in other groups, could demonstrate new pathophysiological pathways for the development of OSCC.

The importance of grouping of lymph node stations and rationale of three-field lymphoadenectomy for thoracic esophageal cancer.

Although the three‐field lymphadenectomy has established as a standard operation for esophageal cancer in Japan, criticism remains due to the lack of randomized controlled trials with a high EBM level. This retrospective study aims to clarify the effectiveness of the three‐field lymphadenectomy using the data obtained from 906 consecutive patients with esophageal cancer who underwent R0 esophagectomy with the three‐field lymphadenectomy.

Prognostic factors in adenocarcinoma of the gastric cardia: pathologic stage analysis and multivariate regression analysis.

PURPOSE To clarify the pathologic stages of adenocarcinoma of the gastric cardia in which the prognosis is worse than in adenocarcinoma of the middle or distal part of the stomach, and to determine prognostic factors in these stages by multivariate analysis. PATIENTS AND METHODS We analyzed 2,536 cases of surgically resected gastric adenocarcinoma of all pathologic stages. Four hundred seventy-two cases of gastric carcinoma, in which cumulative survival of gastric cardia was poor, were subjected to Cox regression analysis for prognostic factors, and to logistic regression analysis for factors influencing venous or lymphatic invasion. RESULTS The prognosis of adenocarcinoma of the gastric cardia was inferior when compared with similarly staged carcinomas of the middle or lower part of the stomach when there was invasion of proper muscle layer or subserosal layer, with no lymph node metastasis or with only adjacent (group 1) lymph nodes metastases (T2N0 or T2N1, according to the Japanese classification). In these stages, the prognostic factors were age, histologic type, venous invasion, and location of the tumor in the upper part of the stomach. Tumor location in the upper stomach was also a predictor for the presence of venous invasion. CONCLUSION The prognosis of adenocarcinoma of the gastric cardia is poor in patients with T2 tumors with no or few lymph node metastases. Additional treatment after surgery may be necessary to improve the survival of this population.

Development of surgery for carcinoma of the esophagus.

During the period from October 1972 to January 1983, 462 patients with squamous cell carcinoma of the esophagus were admitted to Toranomon Hospital. Those patients with carcinoma of the hypopharynx, cervical esophagus, or cardia extending to the esophagus were excluded from the study. Resection and reconstruction were carried out in 295 patients with a resectability rate of 63.9 percent and an operative mortality rate of 1.7 percent. The 5 year survival rate for 101 patients who had resection with minimum 5 year follow-up was 34.7 percent. Although the ultimate outcome is largely influenced by the tumor type representing malignancy, it is worthwhile to make all efforts to resect the tumor with a negative surgical margin and to resect concomitant lesions if there are any. Surgeons should not be discouraged by the length or size of a tumor. The extent of positive lymph node is closely related to long-term results. However, systemic lymph node dissection should be carried out because 5 year survival can then be expected, even when positive nodes are dissected from various areas.

Thoracoabdominal approach for carcinoma of the cardia of the stomach

In the surgical treatment of carcinoma of the cardia of the stomach, one of the prime concerns of surgeons is the selection of the most ready approach to the lesion. In recent years, precise determination of the location and proximal extent of tumors of the cardia or esophagogastric junction has been made by fiberoptic esophagoscopy. However, not infrequently, it is enthusiastically discussed whether the chest should be opened to accomplish complete resection. Sometimes resection of the cardia is attempted by the abdominal approach to avoid thoracotomy, resulting in incomplete resection of the proximal esophagus involved by tumor and poor visualization during performance of the anastomosis. The present study reports the advantages of the left thoracoabdominal approach [I] f or surgical treatment of lesions of the esophagogastric junction.

Lymphatic invasion according to D2-40 immunostaining is a strong predictor of nodal metastasis in superficial squamous cell carcinoma of the esophagus: Algorithm for risk of nodal metastasis based on lymphatic invasion

In squamous cell carcinoma (SCC) of the esophagus, D2‐40 immunostaining has recently been used to detect lymphatic invasion, but invasion detected using D2‐40 immunostaining for a predictor of nodal metastasis was controversial. Therefore, the usefulness of detecting lymphatic invasion by D2‐40 immunostaining as a predictor of nodal metastasis was examined in superficial (mucosal and submucosal) SCC of the esophagus. A total of 115 superficial SCC of the esophagus were examined on immunohistochemistry using D2‐40. It was found that lymphatic invasion demonstrated on D2‐40 immunostaining was mainly detected in the lamina propria mucosa. Lymphatic invasion was found in 37 cases and the invasion detected in the entire tumor tissue was statistically correlated with nodal metastasis. Based on the lymphatic invasion according to D2‐40 immunostaining, an algorithm was devised for the risk (low, intermediate and high) of nodal metastases in superficial SCC in the esophagus. In conclusion, the detection of lymphatic invasion on D2‐40 immunostaining in tumor tissue is a strong predictor for nodal metastasis in superficial SCC of the esophagus. Lymphatic invasion was found mainly in the lamia propria mucosa, thus the devised algorithm is useful for determining the optimal treatment strategy after endoscopic mucosal resection for esophageal SCC.