Masatoshi Ohta

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.

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.

Small cell neuroendocrine carcinoma of the rectum

Poorly differentiated small cell neuroendocrine (NE) carcinoma of the colon and rectum is a rare primaty epithelial malignancy at this location. A case of a highly aggressive NE tumor of small cell type, combined with non‐invasive well‐differentiated papillary adenocarcinoma in villous adenoma is reported. The patient died rapidly with massive and progressive liver metastasis. The tumor cells were argyrophilic and diffusely immunoreactive for neuron‐specific enolase and synaptophysin. Ultrastructural analysis disclosed NE‐type cored granules in most of the small tumor cells. NE tumors of the colon and rectum are briefly reviewed.

Comparative efficacy of positron emission tomography and ultrasonography in preoperative evaluation of axillary lymph node metastases in breast cancer

PurposeIn primary breast cancer, axillary nodal status is the most powerful predictive factor of recurrence. However, axillary lymph node dissection may cause surgical complications. If preoperative evaluation of axillary lymph node metastases is possible, unnecessary axillary lymph node dissections can be avoided. The purpose of this study was to evaluate the efficacy of positron emission tomography (PET) on detection of axillary lymph node metastases in breast cancer.MethodsPET scans of the axilla were obtained in 32 patients with primary breast cancer. All patients fasted for at least 4 hours before the examination. After transmission scans for attenuation correction were performed, emission scans after intravenous injection of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) were obtained.ResultsOverall accuracy of PET alone, ultrasonography alone, and in combination in the detection of axillary metastases were 82%, 79%, and 85% respectively.ConclusionThere were no significant differences between PET, ultrasonography, and PET in combination with ultrasonography regarding sensitivity, specificity and accuracy in the detection of axillary metastases.

Clinical and Pathologic Factors Predicting Axillary Lymph Node Involvement in Breast Cancer

The diagnosis of axillary disease remains a challenge in the management of breast cancer and is a subject of controversy. In 1998, the Japanese Breast Cancer Society conducted a study assessing axillary lymph node involvement in breast cancer. The study included (a) clinical assessment by preoperative imaging modalities, (b) histologic assessment for peritumoral lymphatic invasion, (c) biologic assessment by gelatinolytic activity using film in situ zymography, and (d) sentinel lymph node (SLN) biopsy. Clinical assessments by CT, PET, and US as well as biologic assessment were limited in their ability to detect axillary lymph node disease, although these imaging techniques may be useful to exclude node-positive patients from the need for SLN biopsy. Histologic assessment for peritumoral lymphatic invasion was useful, particularly for detecting false-negative cases by SLN biopsy. Never-theless, the utility of SLN biopsy in assessing axillary nodal status was confirmed. Axillary lymph node dissection (ALND) can be avoided in patients with a small tumor and a negative SLN. However, further studies will be required to investigate the value of SLN biopsy for predicting regional control and survival before it can replace routine ALND as the optimal staging procedure for operable breast cancer.

Immunohistochemical evaluation of hormone receptor for routine practice of breast cancer: highly sensitive procedures significantly contribute to the correlation with biochemical assays.

Immunohistochemical evaluation of hormone receptors for breast cancer has been performed parallel to biochemical assays. Recently, immunohistochemistry has tended to substitute the biochemical method in Japan. To clarify the factors concerned and problems to be resolved, we reviewed our evaluation system for hormone receptors by immunohistochemistry from 1990. A total of 861 breast cancer samples were examined by immunohistochemistry and biochemistry. In 3 main periods, phase 1 (1990–1993), phase 2 (1995–1998), and phase 3 (1999–2001), increasing sensitivity of the immunohistochemical method was provided by commercially available staining systems and shown to range from 83.6% (phase 1) to 92.0% (phase 3). The highly sensitive procedures of the antigen retrieval and peroxidase-conjugated polymer method are main contributing factors. The authors examined how these procedures influenced the distribution of positive cell population; concordance rate, including sensitivity and specificity; cutoff points; and evaluation categories. The correlation between biochemistry and immunohistochemistry was extensively studied in the 1980s and 1990s. In reference to the progress achieved in the United States and United Kingdom to control the current situation in Japan, it should be recognized that recently developed, highly sensitive procedures boost the immunoreactivity, which will affect the basic factors for technical validation.

Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin(r)) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Abstract Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2–66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with ≥10 positive axillary lymph nodes was significantly higher (P<0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with ≥10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8–45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

Clinical development of trastuzumab in breast cancer.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized arti-HER-2 monoclonal antibody, trastuzumab (HerceptinTM) is now available for clinical use in the U.S.A. It is also expected to be available in Japan in the near future. In this paper, the details of this novel biologic agent are reviewed in conjunction with a phase I study performed in Japan.

A Humanized Anti-c-erbB-2 Monoclonal Antibody for the Treatment of Breast Cancer.

The c-erbB-2 product is thought to be a unique and useful target for antibody therapy of cancers that overexpress the c-erbB-2 gene. Its overexpression is also speculated to be correlated with chemoresistance to doxorubicin. The in vitro and in vivo anti-tumor effects of a humanized antibody directed against the extracellular domain of the c-erbB-2 gene product, rhu4D5, were examined. Rhu4D5 had direct antiproliferative activity against the SK-BR-3 cell line which overexpresses c-erbB-2. The in vivo treatment, using rhu4D5, of SCID mice carrying xenografts of 4-1ST human gastric carcinoma, which overexpresses c-erbB-2, revealed that the recombinant protein had potent anti-tumor activity. Furthermore, the cytotoxic action of human peripheral blood mononuclear cells against the SK-BR-3 cell line was significantly augmented with the administration of rhu4D5, but not with mu4D5. These results indicate that rhu4D5 might be a more efficacious treatment than previously predicted by preclinical studies.