Utility of weekly docetaxel combined with preoperative radiotherapy for locally advanced esophageal cancer from pathological analysis.

Esophageal squamous cell cancer (ESCC) is a high-grade carcinoma that is treated with multidisciplinary approaches, including chemoradiotherapy (CRT) followed by surgery. Despite some success with these therapies, overall survival remains poor. In order to investigate a newer CRT regimen, we designed a comparative study to evaluate preoperative CRT using docetaxel (DOC) or 5-Fluorouracil and cisplatin (FU+CDDP [FP] therapy) for treatment of resectable ESCC. In a retrospective review of patients with resectable, locally advanced ESCC, 95 patients received preoperative CRT between 2001 and 2007. CRT was administered using either FP (n = 40) or DOC (n = 55). Pathological response and clinical outcomes were compared between the two groups. Hazard ratios and time-to-event analyses were used to assess outcomes; the ratios were controlled by multivariate logistic regression analysis of potential prognostic factors, and survival was presented with Kaplan-Meier curves. In the FP group, a significant curative effect was observed on the basis of pathological examination of postoperative lesions. However, the DOC group presented a significantly better prognosis on the basis of cumulative survival rates. Logistic regression analysis revealed that the presence of five or more lymph node metastases was an independent predictor of reduced survival. Patients with lymph node metastasis exhibited a better prognosis in the DOC group than those in the FP group. Preoperative CRT for locally advanced esophageal cancer using DOC results in similar or better long-term outcomes compared with FP-based CRT. Therefore, CRT using DOC is a promising therapy option for esophageal cancer.

Circulating micrometastases of esophageal cancer detected by carcinoembryonic antigen mRNA reverse transcriptase-polymerase chain reaction: clinical implications.

In some patients without distant metastases according to conventional preoperative investigations, relapse occurs in distant organs within a few years after radical resection of esophageal cancer. Various attempts have been made to detect micrometastases that are not found by conventional techniques. A quantitative real-time reverse-transcriptase polymerase chain reaction was used to detect messenger RNA for carcinoembryonic antigen in 147 blood samples from 49 patients scheduled for radical resection of esophageal cancer at Juntendo University Hospital between September 2003 and June 2004. The number of circulating cancer cells was assessed and the clinical significance of detecting such micrometastases was analyzed. Multivariate analysis showed that positivity of this assay was significantly associated with pT1 or pT2 disease and stage III or stage IV disease. Patients with more than 40-50 carcinoembryonic antigen mRNA copies among 10(4) normal cells on quantitative analysis had a higher recurrence rate. The number of tumor cells circulating in the blood may have more influence on the prognosis of esophageal cancer than the presence of tumor cells.

Correlation between loss of Bcl-XL expression and improved prognosis in advanced esophageal cancer treated by preoperative chemoradiotherapy.

We investigated the clinical significance of the apoptosis- related molecule expression of tumor cells in patients with advanced esophageal cancer treated with preoperative chemoradiotherapy (CRT). Preoperative CRT reduced Bcl-X(L) expression in a significant proportion of the group responding to CRT but not in the group resisting CRT, although Bcl-2 expression was reduced in both groups. The mean survival time of the patients with cancers that lost Bcl-X(L) following CRT was significantly longer compared to those with cancers expressing Bcl-X(L). These results suggested that CRT reduced Bcl-X(L) expression, and this decrease closely correlated with the prolonged survival of advanced esophageal cancer patients treated with preoperative CRT.

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.

[Surgery for cancer of the esophagus in elderly patients].

Esophageal cancer has a fulminant biological characteristic, and shows a higher rate of lymph node metastasis than other gastrointestinal malignancies. The distribution of lymphatic spread is wide from cervical to abdominal field, and 3-field lymph node dissection is a standard procedure in esophageal cancer surgery. However, the morbidity and mortality rate following esophageal resection is higher than that of other gastrointestinal or thoracic surgery. The most serious postoperative complication of esophageal surgery in elderly patients is a pulmonary problem. In order to reduce postoperative pulmonary complications, we try to preserve bronchial artery, pulmonary branches of the vagal nerve, in addition to definite preservation of bilateral recurrent laryngeal nerve. Our survival rate and mean survival period in elderly patients with esophageal cancer was fairly good. To achieve a high survival rate and reduce postoperative morbidity and mortality in elderly patients, preoperative assessment of pulmonary function and quality control of surgical procedure is essential.

[Esophageal cancer surgery; importance of surgical quality control].

In esophageal cancer, the rate of lymphatic metastasis is higher than any other gastrointestinal cancer. The morbidity and mortality rate of esophageal surgery is still high. In order to reduce high morbidity and mortality rate, esophageal cancer surgery is recommended to be performed at a high-volume hospital in Europe and United States. In Japan, "3-field lymph nodes dissection surgery" has been established for complete lymphatic clearance, and the overall survival has improved. This surgical procedure is now recognized as a standard surgery for advanced esophageal cancer by "Japan Esophageal Society". However, even in Japan, the morbidity and mortality rate of esophageal cancer surgery is higher than gastric or colonic cancer surgery. For rationale of esophageal cancer surgery, we have to continue to improve our surgical quality such as preserving bronchial artery or pulmonary branches of the vagal nerve.

Kinetic measurement of the interaction between a lysozyme and its immobilized substrate analogue by means of surface plasmon resonance.

A method for evaluating the association and dissociation rate constants of interaction between a lysozyme and its substrate analogue, an immobilized p-aminophenyl-tri-N-acetyl-beta-chitotrioside, by means of surface plasmon resonance has been developed. Site-specific immobilization of p-aminophenyl-tri-N-acetyl-beta-chitotrioside, which is a product of p-nitrophenyl-tri-N-acetyl-beta-chitotrioside, on carboxymethyldextran linked to the surface of the cuvette of the instrument, IAsys, was carried out by catalysis with EDC/NHS. The kinetic parameters of the interaction between hen or human lysozyme and the immobilized substrate analogue indicated that a larger dissociation constant of the human lysozyme-immobilized substrate analogue complex depended on a smaller association rate constant. The kinetic parameters of the interaction between the immobilized substrate analogue and a mutant hen lysozyme, in which Arg14 and His15 are deleted, with higher activity than the wild type hen lysozyme were measured. It was suggested that the higher activity of the mutant lysozyme was due to faster removal of the substrate from the active site cleft and/or the formation of a stabler and better complex as to hydrolysis.

Usefulness of autologous blood transfusion for avoiding allogenic transfusion and infectious complications after esophageal cancer resection.

BACKGROUND: A retrospective investigation was conducted to determine whether autologous blood collection could reduce allogenic transfusion after resection of esophageal cancer and whether allogenic transfusion influenced postoperative infection. METHODS: Patients (n = 100) who met the criteria for hemoglobin, age, body weight, and serum protein donated 800 mL of autologous blood from May 1994 to December 1997. The control group (n = 248) was selected from patients who met the same criteria and did not donate autologous blood over the 10 years before the start of autologous blood collection. RESULTS: Only three patients (3%) from the autologous group required allogenic transfusion versus 84 patients (33.7%) from the control group. Sixteen of the 26 patients who received more than 4 units of allogenic blood contracted postoperative infections compared with 25 of 165 patients who did not (P < .0001). Autologous blood transfusion significantly increased the probability of avoiding allogenic transfusion (odds ratio, 27.58), and allogenic transfusion was significantly related to postoperative infection (odds ratio, 1.19), according to logistic regression analysis. CONCLUSIONS: Autologous blood collection reduces the need for allogenic transfusion in patients undergoing resection of esophageal cancer, and avoidance of allogenic transfusion may reduce the risk of postoperative infection.

Esophagectomy without thoracotomy with vagal preservation.

The techniques of vagal preservation for use in esophagectomy without thoracotomy are presented. The purpose of vagal preservation is to avoid the debilitating postvagotomy syndrome. The technique of preservation varies depending on the mode of esophagectomy, the primary disease and the organ selected to be used for esophageal reconstruction. The postoperative quality of life is improved by the preservation of vagal function.

Relief of jaundice by 5-fluorouracil and folinic acid in patients with recurrent gastric cancer.

The aim of this study was to evaluate the effect of 5-fluorouracil (5-FU) and folinic acid on liver function and bile production in patients with recurrent gastric cancer and jaundice. Thirteen patients were studied for liver function and hyperbilirubinaemia, and six patients were studied for bile production retrospectively, who were treated with 5-FU [700 mg m(-2)] and folinic acid [20 mg m(-2)] for 4 days. Serum total bilirubin, aspartate aminotransferase (AST), gamma-glutamyl transferase (gamma-GT) and alkaline phosphatase (ALP) concentrations all improved with treatment (P<0.0001), and bile production increased significantly (P<0.0001) following treatment. 5-FU and folinic acid can significantly improve jaundice and liver function, and promote bile production. It is possible that 5-FU and folinic acid may become a new method for the relief of jaundice in patients with gastrointestinal tract malignancies.

Metastatic gastrinoma to the liver 20 years after primary resection.

Gastrinoma is a rare endocrine tumor that is frequently associated with liver metastasis. The liver metastasis is usually seen simultaneously or soon after a primary operation. A 47-year-old woman who had had a total gastrectomy 20 years earlier developed liver metastasis. An interval of this length between surgery and metastasis is extremely rare. The total gastrectomy prevented the patient from developing the usual symptoms of hypergastrinemia that would have enabled early diagnosis of the metastasis. Laboratory examinations on admission revealed a high serum gastrin concentration (1500 pg/ml). Computed tomography showed an irregularly enhanced mass lesion with an uneven, low-density central area in the right anterior inferior segment of the liver. An extended right hepatectomy was performed. Intraoperative ultrasonography showed no abnormalities in the remnant pancreas. Examination of the cut surface of the specimen revealed a yellow, firm, elastic tumor, 55 mm in diameter. The interior of the tumor appeared necrotic. Histopathologically, the tumor was composed of cells with hyperchromatic, dysplastic nuclei arranged in a trabecular pattern with nest formation. Gastrin staining was positive. A histologic diagnosis of metastatic gastrinoma was made. The patient's gastrin concentration returned to normal and she was well at 2-year follow-up.

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.

Reduced low-density-lipoprotein cholesterol causing low serum cholesterol levels in gastrointestinal cancer: a case control study.

Several epidemiological studies suggested an inverse relation between serum cholesterol level and cancer mortality. We analyzed the relation between gastrointestinal cancers and serum cholesterol levels. A total of 631 patients were recruited as cancer-bearing cases, comprising 181 esophageal cancers, 251 gastric cancers and 199 colorectal cancers. A case-control analysis was conducted on the serum TC, HDL-C, LDL-C and TG levels. TC and LDL-C were significantly lower in cancer-bearers by approximately 15 mg/dl. Furthermore, analyses by cancer site also showed significantly lower TC and LDL-C levels in cancer-bearers than in controls for all three sites. In this analysis, early stage cancer-bearers showed a significant decrease in TC levels by approximately 11 mg/dl compared with controls, and also a similar decrease in LDL-C levels. These results suggest that low TC levels are not related to cancer stage. Furthermore, findings of no significant differences in HDL-C and TG between cancer-bearing cases and controls in addition to a specific decrease in LDL-C in cancer-bearers suggest that hypocholesterolemia observed in these cases stems from low LDL-C. However, cancer-bearers and controls showed a similar distribution of TC and LDL-C levels. We should be aware that latent cancer bearers may be present among subjects with hypocholesterolemia.

A case of inflammatory breast cancer following augmentation mammoplasty with silicone gel implants.

A 54-year-old-woman who underwent augmentation mammoplasty with silicone gel implants 30 years previously, visited our hospital with complaints of bloody nipple discharge, redness and itching of her right breast. Cancer of the right breast was diagnosed by dynamic magnetic resonance imaging (MRI) examination with Gadolinium (Gd)-DTPA enhancement. Radical mastectomy was subsequently performed. The histopathological findings demonstrated scirrhous and inflammatory breast cancer with invasion of dermal lymphatics.

ELISA determination of serum hyocholic acid concentrations in humans and their possible clinical significance.

BACKGROUND/AIMS: Hyocholic acid (HCA), a bile acid isolated from pigs, has a different structure from the predominant bile acids from humans. METHODOLOGY: We prepared an antiserum to HCA in rabbits and developed an enzyme-linked immunosorbent assay (ELISA), which we used to measure serum HCA in healthy subjects and patients with a variety of gastrointestinal and non-gastrointestinal diseases. RESULTS: Patients with hepatic cirrhosis had a mean HCA concentration that was 120-fold greater than that in healthy subjects. Markedly elevated HCA levels were also present in patients with primary hepatoma or pancreatic cancer but not in patients with cancer of the breast, bile duct, duodenum, or stomach. CONCLUSIONS: If these results are confirmed by further study, HCA measurement may prove clinically useful.

Management of the pancreatic metastases from renal cell carcinoma: report of four resected cases.

The pancreas is an uncommon site for metastasis from renal cell carcinoma. In most cases, pancreatic metastases occur as part of widespread nodal and visceral involvement, and there is thus evidence of metastatic disease elsewhere in the body. We present 4 cases with resectable pancreatic metastases arising from renal cell tumors without involvement of the regional lymph nodes at the operation. Three cases out of 4 were asymptomatic and the pancreatic metastases were detected by routine follow-up examination of renal cell carcinoma. Aggressive surgical treatment for the solitary metastatic lesion is advocated. Spread of renal cell carcinoma to the pancreas is, however, via the hematogenous route, and even solitary pancreatic metastasis may be one of the manifestations of the systemic metastasis of renal cell carcinoma. No pancreatic regional lymph nodes metastases were noted. Pancreatectomy should be undertaken to remove the tumor with adequate resection margins while preserving as much of the gland as possible. The prognosis of pancreatic metastases arising from a renal cell carcinoma is discussed with a review of the literature. Adjuvant chemo- and endocrine therapy should also be considered in these cases.

Delayed post-anoxic encephalopathy without relation to carbon monoxide poisoning.

Delayed post-anoxic encephalopathy (DPE) not related to carbon monoxide has rarely been reported and usually carries a poor prognosis. We describe two surviving patients with such DPE and its neuro-otological characteristics. The DPE was caused by shock due to hemorrhage in a 21-year-old student, and by severe hypoxia and hypotension in a 60-year-old man. Our findings suggest that this type of DPE might not be rare, if the patients who suffered from severe anoxia, marked hypotension or both are carefully observed. Recognition of this DPE is important for appropriate management of such patients.

A new choleretic effect of folinic acid.

BACKGROUND/AIMS: In the chemotherapy of recurrent gastric cancer with 5-fluorouracil and folinic acid, an interesting phenomenon, the reduction of jaundice and improvement of liver function, was observed. The aim of this study was to investigate the mechanism of this phenomenon, and to confirm a choleretic effect of folinic acid. METHODOLOGY: The bile duct of anesthetized rats was catheterized, and bile was collected. Bile volume and total bile acid production following intraperitoneal administration of folinic acid were determined and compared to those of control rats. RESULTS: Both bile volume and total bile acid production increased following intraabdominal administration of folinic acid. CONCLUSIONS: Folinic acid has a newly described pharmacologic effect of stimulating bile acid-dependent choleresis. It is possible that folinic acid may become a new drug for the treatment of jaundice or for the improvement of overall liver function.

Outcomes of extended lymph node dissection for squamous cell carcinoma of the thoracic esophagus.

Patients with thoracic esophageal carcinoma who underwent extended lymph node (LN) dissection were studied to assess the state of LN metastasis and evaluate its outcome in terms of a prognostic benefit. Pertaining to LN metastasis, it was found that depending on the location of a primary tumor, the area of choice, in which metastasis tends to develop predominantly, showed some variation. However, irrespective of the location of the tumor, the predominant growth of positive nodes was found to locate among three fields, namely the neck, mediastinum and abdomen even in patients with a single metastatic node. This suggests that extended LN dissection including the neck, mediastinum and abdomen should be considered mandatory, if a complete removal of the tumors for carcinoma of the thoracic esophagus is to be desired. Multivariate analysis revealed importance of LN dissection as a prognostic factor. A cumulative survival rate in the patients with lymphadenectomy through right thoracotomy was statistically better than that in the patients who underwent blunt extraction of the esophagus without lymphadenectomy. Furthermore, extensiveness of LN dissection could effectively serve as a prognostic factor. Consequently, three-field LN dissection yields a prognostic benefit to improve a long term survival in patients with carcinoma of the thoracic esophagus.

Esophageal stripping with preservation of the vagus nerve.

In the surgical treatment of benign stricture of the esophagus, resection should be considered rather than a simple bypass procedure. For resection, blunt esophagectomy without thoracotomy is sometimes the procedure of choice. To prevent postoperative diarrhea due to truncal vagotomy, a new surgical technique to preserve the celiac and hepatic branches of the vagus nerve has been introduced, in conjunction with blunt esophagectomy.