Toshio Mitomi

Randomized, controlled study on adjuvant immunochemotherapy with PSK® in curatively resected colorectal cancer

A randomized, controlled trial of adjuvant immunochemotherapy with PSK®(Kureha Chemical Industry Co., Tokyo, Japan) in curatively resected colorectal cancer was studied in 35 institutions in the Kanagawa prefecture. From March 1985 to February 1987, 462 patients were registered. Four hundred forty-eight of those patients (97.0 percent) satisfied the eligibility criteria. The control group received mitomycin C intravenously on the day of and the day after surgery, followed by oral 5-fluorouracil (5-FU) administration for over six months. The PSK®group received PSK®orally for over three years, in addition to mitomycin C and 5-FU as in the control group. At the end of February 1990, the median follow-up time for this study was four years (range, three to five years). The disease-free survival curve and the survival curve of the PSK®group were better than those of the control group, and differences between the two groups were statistically significant (disease-free survival,P=0.013; survival,P=0.013). These results indicate that adjuvant immunochemotherapy with PSK®was beneficial for curatively resected colorectal cancer.

Congenital Absence of the Portal Vein

A 14-year-old girl presented at the hospital after discovering an abdominal tumor. CT scan and ultrasonography indicated a hepatic tumor and also revealed the absence of the portal vein. The patient was admitted to excise the hepatic tumor. It was found that the venous blood from the small intestines flowed into the left renal vein and then emptied directly into the inferior vena cava. A tumor extending from the right lobe through the middle portion of the liver was excised. The postoperative course was satisfactory and marked regeneration of the residual hepatic tissue was observed. Also the blood level of ammonia in the superior mesenteric vein was low, approximately 120 micrograms/dl, compared to the normal value of 350 micrograms/dl in the portal vein. This low blood level may indicate the presence of some homeostatic control mechanism.

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

BACKGROUND Exact 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. METHODS The 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. RESULTS For 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%. CONCLUSIONS Either 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.

A study of the extracellular matrix protein as the migration pathway of neural crest cells in the gut: Analysis in human embryos with special reference to the pathogenesis of Hirschsprung's disease

Immunocytochemical studies on the human embryo were made using antineuronal cell antibody and a panel of anti-extracellular matrix protein antibodies such as fibronectin, laminine, collagen type IV, and hyaluronic acid. All the enteric ganglia are shown to be from a single, vagal neural crest source, although the recent dual gradient migration theory of neural-crest-derived cells in the gut can be challenged. Neural-crest-derived cells first appear in the mesenchyme of the developing esophagus at 4 weeks, and then migrate down along the gut in a craniocaudal direction. The observed distribution of fibronectin and hyaluronic acid indicates the presence of these matrices providing a migration pathway for neural-crest-derived cells in the developing gut. The appearance of neural-crest-derived cells in the gut is always preceded by the appearance of these matrices. On the other hand, substrate or laminine and collagen type IV appears to promote outgrowth of neurites from settled neural-crest-derived cells and their maturation. The distribution of these matrices within the pathway seems consistent with their role in navigating the neural-crest-derived cells toward their final destination. Enteric neurogenesis is dependent on these matrices, and their alteration in early embryonal stage may be a significant factor in the pathogenesis of Hirschsprungs disease.

Clinical and Biochemical Aspects of Thiamine Treatment for Metabolic Acidosis During Total Parenteral Nutrition

We encountered six cases of total parenteral nutrition (TPN)-associated lactic acidosis during the 6-y period of 1988-1993. The patients were characterized by severe disease of the digestive organs, minimal food intake before surgery, and postoperative TPN with no food intake and with no vitamin supplements. Within 4 wk of TPN, they developed hypotension (< or = 80/60 mmHg), Kussmauls respiration, and clouding of consciousness, as well as abdominal pain not directly related to the underlying disease. Routine laboratory examinations revealed no acute aggravation in hepatic, renal, or pancreatic functions. Arterial blood gas analysis showed pH < or = 7.134 and base excess < or = -17.5 mmol/L. Additional laboratory examinations revealed serum lactate > or = 10.9 mmol/L, serum pyruvate > or = 159 mumol/L, and lactate/pyruvate ratio > or = 0.029. None of the patients responded to sodium bicarbonate or other conventional emergency treatments for shock and lactic acidosis. After the first case, we suspected that thiamine deficiency might be responsible for this pathologic condition, Serum thiamine was proved to be < or = 196 nmol/L in 5 patients. Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients. This article includes a review of 11 relevant reports published from 1982-1992 and a discussion of the biochemical mechanism of onset of thiamine deficiency-associated lactic acidosis. We emphasize the needs (1) to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; (2) to monitor the patients routinely measuring serum thiamine concentration and erythrocyte transketolase activity during TPN; and (3) to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.

High fluorine-18 labeled deoxyglucose uptake in sarcoidosis.

A 72-year-old man underwent a whole-body fluorine-18 labeled deoxyglucose (FDG) PET study for cancer screening. On the PET images, multiple foci of intense FDG uptake were noted in the mediastinum. CT scan showed enlarged mediastinal nodes. Chest X-ray was normal. Mediastinoscopy and lymph node biopsy were performed. Histology results showed noncaseating granulomas and a diagnosis of sarcoidosis was obtained. The patient was asymptomatic and was observed without medications. Early reports have indicated that high FDG uptake can be observed in sarcoid granulomas. Inflammatory cells, especially macrophages, are characterized as cells with high glucose use. In interpreting multiple increased FDG accumulations in the mediastinum, sarcoidosis needs to be considered as a differential diagnosis.

Gut Bacterial Translocation during Total Parenteral Nutrition in Experimental Rats and Its Countermeasure

BACKGROUND The use of total parenteral nutrition (TPN) is commonly associated with mucosal lining of the intestinal tract, causing degenerative changes within the gut-associated lymphoid tissue (GALT). These phenomena are probably caused by the translocation of indigenous intestinal bacteria into other organs and tissues where they induce infections. METHODS Using TPN model rats, this paper looks at the result of the investigation of the action of PSK (proteoglycan), a biological response modifier, which appears to suppress bacterial translocation and maintain local immunity activity. RESULTS Culture of mesenteric lymph nodes obtained post-TPN demonstrate a bacterial rate as high as 60%. Immunohistochemical examination indicates a reduction in the number of plasma cells and a decrease in S-IgA production and secretion. A similar reduction in S-IgA within bile and portal venous blood was also confirmed. Continuous oral administration of PSK in a daily dose of 1,000 mg/kg had a protective effect against the degeneration of GALT. A staining in immunocytes of Peyers patches using immunohistochemical study was performed after administration of PSK and revealed constant levels of MHC-I, MHC-II, T helper cells, and interleukin-2 producing cells, supporting the protective role of PSK against degeneration of GALT with a subsequent reduction in bacterial translocation. CONCLUSIONS Proteoglycan can restore the impaired local immunity in the intestinal tract to normal levels and suppression of the bacterial translocation to provide an important function for patients receiving TPN treatment.

Quantification of serum-soluble HLA class I antigens in patients with gastric cancer

The amount of sHLA-I in serum was examined in 74 patients with gastric cancer and 15 normal healthy controls. For mAbs, W6/32 specific for HLA-A, -B, -C, and biotin IOT2 specific for HLA class I associated with beta 2 microglobulin, were used to determine the values of sHLA-I using an ELISA. The patients in stage-IV gastric cancer showed lower values of sHLA-I (445.4 +/- 247.1 ng/ml) than those in stage I (725.9 +/- 575.8 ng/ml), stage II (752.8 +/- 255.0 ng/ml), and normal controls (868.9 +/- 715.0 ng/ml) (P < 0.05). In analysis of the patients with HLA-A24, the allele that has been reported to secrete more sHLA-I than other alleles, the results were nearly the same. These results suggest that the secretion of sHLA-I is low in patients with very advanced cancer. However, there was no correlation between the sHLA-I level and the metastasis or prognosis in longitudinal studies in 11 patients.

The diagnosis and treatment of esophageal perforations resulting from nonmalignant causes

Esophageal perforations are extremely difficult to diagnose and treat. We report herein our results of a review of 26 patients with esophageal perforation which were spontaneous in 11, iatrogenic in 11, and caused by a foreign body in 4. Surgical treatment was performed in 7 of the patients with spontaneous rupture, but the remaining 19 patients were treated conservatively. The abnormality was found by plain radiography (X-ray) in 22 (85%) of the 26 patients, and by computed tomography (CT) in all 13 patients who underwent this procedure. The detection rates by esophagography and esophagoscopy were 100%, or all of 25 patients examined, and 60%, or 9 of 15 patients examined, respectively. Of 12 patients with underlying diseases, 4 (33%) died after the perforation, whereas only 1 (7%) of 14 patients without any underlying disease died. Postoperative empyema developed in all of 3 patients treated by intraoperative unfixed intrathoracic drainage (UID), but in none of the 4 treated by fixed intrathoracic drainage (FID). Conservative treatment achieved satisfactory results for spontaneous esophageal ruptures confined to the mediastinum, and for iatrogenic perforations and esophageal perforations caused by foreign bodies, provided there was no serious underlying disease such as advanced cirrhosis. Moreover, intraoperative FID proved useful in helping to prevent postoperative empyema.

Possible Predictive Markers of Immunotherapy in Esophageal Cancer: Retrospective Analysis of a Randomized Study

The aim of this report is to evaluate retrospectively the data from a prospective randomized study of 158 esophageal cancer patients who actually completed therapy with protein-bound polysaccharide P (PSK) and the 5-year survivals with and without raised alpha 1-antichymotrypsin and sialic acid levels to determine the value of these parameters in predicting effectiveness of immunotherapy. There was a significant difference in survival between the patients with and without PSK therapy. The survival of the radiochemotherapy plus PSK group treated for > 3 months was significantly better than that of the radiochemotherapy group. Among the patients with abnormal levels of alpha 1-antichymotrypsin and sialic acid, those who received PSK may have a significantly better survival than those without PSK. These results indicate that the preoperative serum levels of alpha 1-antichymotrypsin and sialic acid may possibly predict the effectiveness of immunotherapy using PSK.