PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]

A 36-year-old man was admitted to a hospital with complaints of fever, polyarthralgia and dyspnea. Erythema was observed on his face, extensor surface of the fingers and extremities, and a chest X-ray revealed massive bilateral pleural effusion. He had no sign of myopathy at this point. Pleural fluid was proved to be exudative and contained extremely high levels of hyaluronic acid. He was also complicated with interstitial pneumonitis and was given a pulse therapy with methyl prednisolone followed by daily administration of 55 mg prednisolone (PSL). Twenty days after the commencement of the therapy, pleural effusion decreased but muscle weakness gradually appeared, accompanied by elevation of myogenic enzymes. Myogenic changes on electromyogram, and irregularity of the muscle fibers with slight inflammatory cell infiltrates in a biopsy specimen were demonstrated. He was transferred to our hospital, and a diagnosis of dermatomyositis was made. Later, pleural effusion waxed and waned depending on the dosage of PSL, but no other causative disorder was demonstrated by extensive examinations. This case indicates that the pleuritis could be one of the vasculitic manifestations of dermatomyositis.     

Leiomyosarcoma originating in Meckel's diverticulum: Report of a case and a review of 59 cases in the English literature

A 49-year-old woman was referred to our hospital with complaints of epigastric colicky pain and high fever. Abdominal computed tomography and ultrasonography showed a solid tumor in the lower abdomen. Laparotomy revealed a neoplastic mass arising in Meckel's diverticulum; therefore, a segment of the ileum, including the tumor-possessing diverticulum, was resected with a lymph node dissection. A histologic examination confirmed the lesion to be leiomyosarcoma. In the English literature, 59 cases of leiomyosarcoma in Meckel's diverticulum were reported from 1941 to 1994. The majority of patients were in their 4th decade of life, with both sexes equally affected. The most frequent symptoms associated with this disease were abdominal pain with nausea, vomiting, and melena. The majority were larger than egg-size. Although Meckel's diverticulum is difficult to diagnose preoperatively, mesenteric arteriography may at times prove useful. The standard management of this particular tumor is wide segmental resection, including the tumor and diverticulum with lymph node dissection.     

Extended Lid-Splitting Surgery of Marginal Eyelid Defects

The technique of extended lid-splitting surgery is described. This procedure was used to repair marginal defects of the lower and upper lid, and provided postoperative results that were excellent both functionally and cosmetically, principally because the technique allowed the anatomical structures to be maintained.     

Enhancing Effects of Harman and Norharman on Induction of Preneoplastic and Neoplastic Kidney Lesions in Rats Initiated with N-Ethyl-N-hydroxyethylnitrosamine

The modifying potential of two nephrotoxic agents, harman and norharman, on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatic carcinogenesis was investigated in male F344/DuCrj rats. Animals were given 0.1% EHEN in their drinking water for the first 2 weeks as an initiator. Subsequently, starting 3 weeks from the commencement, they were fed diet containing these compounds at concentrations of 1000, S00 or 0 ppm until week 26, and then killed for light microscopic examination. The mean numbers of renal tubular cell hyperplasias/cm² and those of tumors/cm² in rats given harman and norharman at 1000 ppm after initiation, but not at 500 ppm, were significantly increased as compared to the control values. However, neither compound modified liver carcinogenesis. It is concluded that harman and norharman show enhancing effects on rat kidney carcinogenesis, when ingested at dose levels which cause renal tubular damage.     

Development of a new wound dressing with antimicrobial delivery capability

A bilaminar wound dressing composed of an outer membrane and an inner three-dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial-impregnated polyurethane membrane. In this study, a gentamycin sulfate-impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full-thickness and split-thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open-label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.     

Clinical results of staged repair with complete unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

OBJECTIVE: Our treatment strategy for pulmonary atresia with ventricular septal defect (VSD) and major aortopulmonary collateral arteries is a staged repair that comprises the first complete unifocalization (UF) with 'unification' of intrapulmonary arteries and then the definitive repair. The purpose of this study is to evaluate the outcome of our staged repair strategy with complete UF and to determine the results of our current management strategy. METHODS: From 1982 to 2004, 113 consecutive patients were treated with staged repair at our institute. We evaluated the risk of definitive repair failure or death in the 3 years after definitive repair using logistic regression. Furthermore, we compared the early group (patients who underwent UF before December 1995) and the late group (patients who underwent UF after January 1996). RESULTS: The mean follow-up interval was 8.8 years (0.8 months to 23.3 years), and Kaplan-Meier-estimated overall survival rates after first UF were 80.9, 73.8, and 69.9% at 5, 10, and 15 years, respectively. Survival in patients with an absent central pulmonary artery (PA) was significantly lower than in those with a central PA (p<0.05), and the factor that was significantly associated with definitive repair failure or death in the 3 years after definitive repair was central PA morphology (p<0.05). Higher mean PA pressure after UF was detected in patients with hypoplastic central PA, compared with those without hypoplastic PA (30.9 mmHg vs 23.3 mmHg, p<0.05). In the late group, age (in years) at first UF (3.9 vs 8.4, p<0.01), second UF (4.3 vs 9.2, p<0.01), and definitive repair (5.8 vs 9.1, p<0.01) was significantly younger than in early group, and the survival rate after first UF in the late group was 96.2 and 91.3% at 3 and 7 years, respectively. Systolic right ventricular pressure and the pressure ratio between the right and the left ventricles after definitive repair in the late group were significantly lower than in the early group (53.6 mmHg vs 75.0 mmHg, p<0.01; 61.7% vs 75.9%, p<0.05). CONCLUSIONS: Hypoplastic central PA was a significant risk factor in this disease. The overall survival was improved by our current management strategy. Improved RV pressure after definitive repair appears to affect the long-term outcome.