The critical causative event in chronic myelogenous leukemia (CML) is the fusion of the head of the bcr gene with the body of the abl gene, named bcr/abl gene. This chimeric BCR/ABL molecule transforms primary myeloid cells to leukemic cells and induces a CML-like disease in mice. The mouse CML model expressing the BCR/ABL molecule has provided important new insights into the molecular pathophysiology of CML and has directly answered many questions regarding this disease. Furthermore, numerous clinical studies have demonstrated a correlation between leukemic clinical features and the position of the breakpoint in the BCR gene of the chimeric BCR/ABL gene. Understanding of the molecular pathogenesis of CML has led to the development of several novel therapies.
The BCR/ABL molecule is unique oncogeneiety, having ABL tyrosine kinase activity, making it an ideal target for drug development. Subsequent clinical studies now realize the hypothesis that selective inhibition of the abl tyrosine kinase activity using imatinib mesylate might be useful for the treatment of CML.
This article reviews the history of BCR/ABL molecular biology, including the CML model mouse, clinical molecular studies and the recent findings of imatinib mesylate and more potent tyrosine kinase inhibitors developed for the treatment of CML.

View full abstract

Background: We devised a new endoscopic operation for breast diseases. We report the aesthetic and treatment results of this procedure.
Methods: A 2.5-cm axillary skin incision was made for a single approaching port, and a working space was created by retraction. Under video assistance, we resected the mammary gland partially or totally, and in the case of malignant diseases we also performed a sentinel lymph node biopsy and dissected axillary lymph nodes (levels I and II).
Results: From December 2001 through April 2005, we performed endoscopic video-assisted breast surgery (VABS) in 100 patients with breast diseases. The diseases were benign in 18 patients and malignant in 82 patients. Of the malignant diseases, 80 underwent breast-conserving surgery and 2 underwent skin-sparing mastectomy. There was no significant difference in operation time, blood loss, or blood examinations related with the acute phase reaction between VABS and conventional breast-conserving procedures. All surgical margins were negative on examination of permanent histological preparations. The wounds healed without noticeable scarring. The original shapes of the breast were preserved. All patients expressed their great satisfaction with VABS.
Conclusions: VABS can be considered as a surgical option and can provide aesthetic advantages for patients with breast disease.

View full abstract

To characterize the relationship between angiogenesis factors and alveolar remodeling in interstitial lung diseases, we examined alveolar capillary endothelial cells in the normal lung (n=5) and in lungs with nonspecific interstitial pneumonia (NSIP) (n=4) or usual interstitial pneumonia (UIP) (n=6) using immunofluorescence staining for thrombmodulin and von Willebrand factor (vWF). With three-dimensional images of alveolar capillaries, the diameter of capillary tubes and their branching frequency per unit length were determined to define rearrangement of the capillary meshwork. Alveolar capillary endothelial cells in normal lungs expressed surface thrombomodulin, and those in lungs with cellular NSIP often showed coexpression of surface thrombmodulin and cytoplasmic vWF. In the alveolar septa of fibrotic NSIP and UIP, capillary endothelial cells demonstrated vWF in only the cytoplasm. Capillary branching frequencies in NSIP and UIP were decreased to 45% and 22%, respectively, of the normal level (p<0.002). Compared with normal lungs, in NSIP and UIP lungs alveolar capillaries containing TUNEL-positive endothelial cells (p<0.05) showed increases of 3.6-fold and 4.3-fold, respectively, indicating a close correlation between endothelial cell apoptosis and remodeling of alveolar capillary frameworks. The analysis of mRNA expression of vascular endothelial growth factors (VEGF) and their receptors (VEGFR1 and VEGFR2) showed a significant decrease in each VEGF isoform and in VEGFR2 mRNA in representative alveolar wall tissues microdissected from the normal, NSIP, and UIP lungs. These results suggest that decreased expression of VEGF mRNA is associated with a reduction in the number of capillary tubes via endothelial cell apoptosis that possibly results in alveolar remodeling in NSIP and UIP. However, whether VEGF is related to fibroblastic activation in the interstitial matrix remains unclear.

View full abstract

The purpose of this study was to clarify the safety and value of laparoscopic surgery for gastric cancer. This retrospective study involved 101 patients with gastric cancer treated with laparoscopic surgery at the Nippon Medical School Hospital from February 2001 through July 2005. The following variables were evaluated: age, sex, comorbid conditions, tumor size, location, gross type, histological type, depth of wall invasion, and presence or absence of lymph node metastasis. The surgical variables investigated included operating time, blood loss, postoperative complications, and length of postoperative stay. Mean tumor diameter was 24.1 ± 18.4 mm, and most tumors were located in the lower third of the stomach. Endoscopic examination revealed that 98 of the tumors were early gastric cancers. The mean operation time was 255 ± 74 min, and mean blood loss was 128 ± 162 g. Local gastrectomy without lymphadenectomy was performed in 13 cases, and pylorus-preserving gastrectomy with perigastric lymphadenectomy was performed in 16 cases. Distal gastrectomy with systemic lymphadenectomy was performed in 56 cases. Proximal or total gastrectomy with lymph node dissection for tumors located in the upper half of the stomach was performed in 16 cases. The mean postoperative hospital stay was 13.3 ± 7.6 days. No patients died during the admission. Postoperative surgical complications occurred in 10 patients (10%) and consisted of anastomotic bleeding in 3 patients, pneumohypoderma in 1 patient, and remote infection in 6 patients. The only medical complication was a stroke in 1 patient. We conclude that laparoscopy-assisted gastrectomy is a safe and useful operation for most early gastric cancers. If patients are selected properly, laparoscopy-assisted gastrectomy can be a curative and minimally invasive treatment for gastric cancer.

View full abstract

We report a rare case of bleeding ileal varices successfully treated with emergency enterectomy. A 72-year old woman with hepatic cirrhosis due to hepatitis C was admitted to our hospital because of anemia and hematochezia. An endoscopic examination showed no evidence of bleeding in the upper and lower gastrointestinal tracts. Angiographic studies of portal hemodynamics revealed extravasation from the ileal varices and total occlusion of the portal vein due to portal thrombus. This made it difficult to remove the ileal varices using interventional radiology. Therefore, the patient underwent emergency enterectomy for the ileal varices. No further gastrointestinal bleeding occurred during the 1-year follow-up.

View full abstract

We report two cases of malignant afferent loop obstruction following pancreaticoduodenectomy (PD). Case 1. A 70-year-old woman, who had undergone PD for pancreatic cancer, was referred to our hospital because of fever, jaundice, and abdominal pain. Ultrasonography and abdominal computed tomography demonstrated dilatation of a small bowel loop in the right upper quadrant. Laparotomy confirmed the diagnosis of local recurrent tumor causing occlusion of the afferent limb, and Roux-en-Y bypass was performed. Case 2. A 72-year-old man, who had undergone PD for cancer of the major papilla, was hospitalized with a high-grade fever and epigastric pain. Ultrasonography and abdominal computed tomography revealed a dilated afferent loop and multiple masses in liver. At laparotomy, widespread carcinomatosis was found to have caused afferent loop obstruction, and surgical bypass was performed. In conclusion, the surgical bypass seems to be an effective palliative treatment for afferent loop syndrome after PD.

View full abstract

We report on a 13-year-old girl with a solid cystic tumor of the pancreas. She was referred to our hospital with abdominal pain in the left upper quadrant. Physical examination revealed a firm mass in the abdomen. Ultrasonography showed a clearly demarcated round mass with a mixture of solid and cystic components. Computed tomography confirmed that the mass measured 5 × 5 cm with low density in the cystic region and soft-tissue density in the solid region. Magnetic resonance also showed a clearly demarcated mass with a solid portion of low intensity on T1-weighted images and high intensity on T2-weighted images. We diagnosed a solid and cystic tumor of the pancreas and subsequently performed distal pancreatectomy. A firm, well-encapsulated tumor was found in the pancreas tail. The cut surface of the tumor consisted of a solid area with hemorrhage and a cystic area. Light microscopy of the tumor confirmed small neoplastic cells. Pathological diagnosis was solid pseudopapillary tumor (solid cystic tumor) of the pancreas. Surgery was successful, and the postoperative course was uneventful.

View full abstract

A 69-year-old man presented with obstructive jaundice and dark urine. Contrast-enhanced computed tomography revealed an enlarged pancreas with homogenous enhancement. Endoscopic retrograde pancreatography demonstrated short-segmental, irregular narrowing of the main pancreatic duct. The patient underwent exploratory laparotomy and needle biopsies of the pancreas, which showed marked fibrotic change with lymphocyte infiltration. These clinicopathologic findings suggested autoimmune pancreatitis. Four years later, computed tomography demonstrated marked periaortic soft tissue surrounding a calcified infrarenal abdominal aorta compatible with retroperitoneal fibrosis. We diagnosed retroperitoneal fibrosis with noncontiguous pancreatic fibrosis. This patient responded well to corticosteroid treatment. Autoimmune pancreatitis associated with idiopathic retroperitoneal fibrosis seems to be extremely rare, and to our knowledge, only a few cases have been reported.

View full abstract

We report the case of a 59-year-old man with meningeal carcinomatosis (MC) who presented with peripheral facial palsy and progressive sensorineural deafness. The patient had been operated on for gastric cancer 1 year previously, and no metastases had been detected in the retroperitoneum or thorax at follow-up examination 1 year later. However, he developed headache, deafness, and peripheral facial palsy and was referred to us for further evaluation, as magnetic resonance of the head had shown no abnormalities. Ramsay Hunt syndrome was suspected, but no increase in the cerebrospinal fluid cell count was detected. On the other hand, the balance test suggested a central disorder. In addition, the plasma level of carcinoembryonic antigen suddenly increased, suggesting MC. The cerebrospinal fluid was examined several times; in the end malignant cells and an increase in the cell count were detected, and the diagnosis of MC was established.

View full abstract