A noteworthy case of postoperative liver metastasis from gastric cancer which responded well to UFT therapy

A 66-year-old male underwent partial gastrectomy (resection of the pyloric side of the stomach) at another hospital on the basis of a diagnosis of gastric cancer (Fig. 1). Five months later, his CEA level began to rise. At that time, multiple liver metastases were detected by ultrasonography and CT scans. The patient received oral UFT therapy (400 mg/day) at our hospital. A reduction in CEA was observed 63 days after the start of this therapy. A judgment of CR (complete response) was made after 4 months of the therapy. At present, 2 years and 4 months after UFT was first administered, the patient shows no signs of tumor recurrence. This case is noteworthy since there has been no previous report of a case where UFT showed a high efficacy in treating liver metastasis after surgical resection of gastric cancer.     

Copy number loss of FBXW7 is related to gene expression and poor prognosis in esophageal squamous cell carcinoma

FBXW7 is a tumor suppressor gene that plays a role in cell cycle regulation via Myc degradation. However, the clinical significance of FBXW7 in esophageal squamous cell carcinoma (ESCC) has not been evaluated. The purpose of this study was to assess the clinical significance of FBXW7 for prognosis in human ESCC. Real-time RT-PCR was used to examine the expression of FBXW7 to determine its clinicopathological significance in 75 cases of ESCC. Overall survival rate was calculated using the Kaplan-Meier method, while multivariate survival was analyzed with the Cox hazard model. FBXW7 suppression analysis was performed to examine proliferation potency and Myc expression in the FBXW7 siRNA groups. The relationship between FBXW7 expression and the copy number loss of FBXW7 was examined in clinical samples of ESCC. Finally, FBXW7 copy number loss was linked to prognosis in 42 ESCC patients. FBXW7 expression in cancer was lower compared to non-cancer tissues (P=0.003) and is an independent prognostic factor. The proliferation rates and Myc protein expression were significantly enhanced in FBXW7 siRNA cells compared to the controls. Cases with a loss of FBXW7 copy number had low FBXW7 expression and a poorer prognosis than cases with no loss of copy number. Genetic alterations in esophageal cancer lead to the loss of FBXW7 expression and increased cell proliferation. These genetic alterations of FBXW7 status may provide a prognostic factor for ESCC patients.     

Notch-dependent cell cycle arrest and apoptosis in mouse embryonic fibroblasts lacking Fbxw7

The F-box protein Fbxw7 mediates the ubiquitylation and consequent degradation of proteins that regulate cell cycle progression, including cyclin E, c-Myc, c-Jun and Notch. Moreover, certain human cancer cell lines harbor loss-of-function mutations in FBXW7 that result in excessive accumulation of Fbxw7 substrates, implicating Fbxw7 in tumor suppression. To elucidate the physiological function of Fbxw7, we conditionally ablated Fbxw7 in mouse embryonic fibroblasts (MEFs). Unexpectedly, loss of Fbxw7 induced cell cycle arrest and apoptosis that were accompanied by abnormal accumulation of the intracellular domain of Notch1 (NICD1). Forced expression of NICD1 in wild-type MEFs recapitulated the phenotype of the Fbxw7-deficient (Fbxw7(Delta/Delta)) MEFs. Conversely, deletion of Rbpj normalized the phenotype of Fbxw7(Delta/Delta) MEFs, indicating that this phenotype is dependent on the Notch1-RBP-J signaling pathway. Deletion of the p53 gene prevented cell cycle arrest but not the induction of apoptosis in Fbxw7(Delta/Delta) cells. These observations suggest that Fbxw7 does not function as an oncosuppressor in MEFs. Instead, it promotes cell cycle progression and cell survival through degradation of Notch1, with loss of Fbxw7 resulting in NICD1 accumulation, cell cycle arrest and apoptosis.     

Deformity of the fingers among women workers at a papermaking mill

With regard to deformity of the fingers (chiefly Heberden's nodes) frequently occurring in Japan among workers preparing school lunches, an epidemiological study was carried out with a suspicion that this deformity might be an occupational disease. We studied the deformity of fingers among woman employees of a papermaking mill (262 mill workers in comparison with 108 office workers) who excessively use their fingers on the job like workers preparing school lunches. The results of this study showed that the number of mill workers suffering from deformity of the fingers (chiefly Heberden's nodes) was significantly (p less than 0.01) greater than that of office workers. Genetic factor, aging factor and mechanical factor have been cited as the etiological factors for the development of Heberden's nodes. However, our findings suggest that mechanical factor is a more important rather than the genetic or aging factor. As for mechanical factor, we have proposed for the first time that repetition of strong and precise pinching movement with the use of all fingers of both hands is an important factor.     

Complete agenesis of the dorsal pancreas

Pancreatic anomalies are occasionally reported, but complete agenesis of the dorsal pancreas is extremely rare. We report a 47-year-old woman with complete agenesis of the dorsal pancreas. This patient initially presented with jaundice. Computed tomography did not reveal the pancreatic corpus or tail. Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography did not visualize the dorsal pancreatic duct. Choledochojejunostomy was performed because she had obstructive jaundice. At laparotomy, there was an enlarged pancreatic head, but no distal pancreas was seen. Histological examination of the pancreatic biopsy specimen showed scattered islets of Langerhans in diffuse fibrosis, with destruction of the glandular parenchyma. This case was diagnosed as complete agenesis of the dorsal pancreas.     

Spontaneous rupture of an intrahepatic bile duct with biloma treated by percutaneous drainage and endoscopic sphincterotomy

A case of spontaneous rupture of an intrahepatic bile duct with biloma formation treated by percutaneous drainage and endoscopic sphincterotomy is reported. A 73-yr-old woman was admitted with fever and abdominal pain. There was no past history of abdominal surgery, instrumentation, or trauma. Ultrasound and computed tomography revealed a massive fluid collection in the abdominal cavity. Endoscopic retrograde cholangiography demonstrated extravasation of contrast medium from a distal biliary radicle in the left lobe of the liver. After successful treatment by percutaneous drainage and endoscopic sphincterotomy, the patient did well. Ultrasound and computed tomography showed resolution of the biloma. Nontraumatic bilomas are very rare: in fact, only 24 cases of spontaneous biloma have been reported. Endoscopic treatment for patients with spontaneous bilomas can be safe and effective, and should be considered.     

Reversible primary hypothyroidism and elevated serum iodine level in patients with renal dysfunction.

Recovery of thyroid function in patients with both thyroid and renal dysfunction was studied. Among 245 patients with primary hypothyroidism (serum TSH greater than 10 mU/l), 36 had mild to severe renal dysfunction (serum urea nitrogen greater than 7.1 mmol/l and creatinine greater than 106 mumol/l). Of these 36 patients, recovery of the thyroid function after iodine restriction was observed in 30 (83%), in whom an elevated serum non-hormonal iodine level (median 236, range 67-15,591 micrograms/l, N = 19) and a high thyroidal radioactive iodine uptake (51.5 +/- 29.3% at 24 h, N = 26) were observed. The perchlorate discharge test was positive in 7 of 13 patients examined, suggesting an iodide organification defect rather than an atrophic or destructive change in the thyroid. Antithyroid antibodies were negative in 22 patients (73%) and an almost normal thyroid gland or colloid goitre was confirmed histologically in 8 of them. After a 13.2 mg potassium iodide loading test, 24 h urinary excretion of iodine was about 60% in normal controls, but only 10% in a different group of six euthyroid patients with renal dysfunction. These findings suggest that impaired renal handling of iodine rather than autoimmune mechanism may have a significant role in the pathogenesis of reversible hypothyroidism found in patients with renal dysfunction, probably through a prolonged Wolff-Chaikoff effect.     

Promotive action of acylated ascorbate on cellular DNA synthesis and growth at low doses in contrast to inhibitory action at high doses or upon combination with hyperthermia

Effects of 6-O-palmitoyl ascorbate (ascorbate) developed to increase the antitumour activity of ascorbic acid on DNA synthesis and proliferation of Ehrlich ascites tumour cells were investigated. Treatment of the cells with the acylated ascorbate at 25–50 M for 1 h resulted in no effect on DNA synthesis, assayed by pulse incorporation of [³H]thymidine after a culture period of 20 h, but led to 49%–87% enhanced DNA synthesis after 4 days, suggesting that long-term culture is required for promotion by ascorbate to occur. At a dose as high as 75 M acylated ascorbate, however, cellular DNA synthesis was 64% inhibited after 20 h and 99% after 4 days. The results suggest that acylated ascorbate exhibits a dual action on DNA synthesis: promotion at low doses and inhibition at high doses, both of which are potentiated in a time-dependent manner. In contrast to the above-mentioned results at 37°C, acylated ascorbate at 25–75 M inhibited but did not promote DNA synthesis at 42°C whatever the culture period. Similar results were exhibited when proliferation of cells cultured for a long period was investigated. At 37°C, 50M acylated ascorbate increased the number of the cells to 3.6 times the control values after 8 days and to 1.9 times after 11 days; in contrast, a 75-M dose decreased the cell number considerably. Combination with hyperthermia (42°C) suppressed the increase and cell growth was completely inhibited at 75M.Abbreviation 6 Pam-ascorbate 6-O-palmitoyl ascorbate     

Adult T-cell leukemia/lymphoma in which the pathohistological diagnosis was identical to that of Ki-1 positive anaplastic large cell lymphoma.

A 65-year-old man developed severe lumbago and a loss of appetite two months before presentation. A computerized tomograph at admission revealed soft tissue masses destroying the Th12, L4 and L5 vertebral bones. We diagnosed the lesions to be metastatic bone tumors, but the primary focus could not be determined. Just after the irradiation treatment, abnormal lymphocytes were detected in the peripheral blood cells. Under the suspicion of adult T-cell leukemia/ lymphoma (ATL), we thus performed a lymph node biopsy. The specimens were histologically composed of Ki-1 positive anaplastic large cell lymphoma (ALCL). The lymphoma cells demonstrated a biclonal integration of HTLV-1 proviral DNA. After 6 cycles of chemotherapy, the patient has demonstrated a partial and favorable remission from ATL.