A case of Cowden disease with a germline mutation in exon5 of PTEN gene diagnosed based on typical esophageal multiple polypoid lesions observed on a medical checkup

A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy revealed multiple polypoid lesions both in the esophagus and stomach. In addition, colonoscopy showed schwannoma in the rectum. He underwent an operation for adenomatous goiter. At first his typical esophageal multiple polypoid lesion was a diagnostic cue to Cowden disease (CD). Other clinical findings convinced us that he was suffering from CD. He was, then, diagnosed as CD according to the criteria of International Cowden Consortium although he had no family medical history suspicious of CD. Interestingly, genetic testing revealed that the patient had a germline mutation in exon5 of PTEN on chromosome 10. It was a point mutation of C to T transition at codon130, resulting in nonsense mutation (CGA→TGA). A close follow-up, especially cancer surveillance, is necessary for him since CD is associated with a high risk of developing malignant disease. It is noted that the typical esophageal features can be a diagnostic cue to CD, as shown in the present case.     

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)₂D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)₂D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1α-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)₂D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)₂D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.     

Thrombocytosis in asplenia syndrome with congenital heart disease: A previously unrecognized risk factor for thromboembolism

Background

Thrombocytosis and thromboembolic complications occur after splenectomy. However, there is no previous report investigating the presence of thrombocytosis and its association with thromboembolic events in patients having asplenia syndrome with congenital heart disease.

Methods

Enrolled were 161 consecutive patients with functionally single ventricle who underwent cardiac catheterization between 1997 and 2010. They were divided into two groups: patients having asplenia (Group A, n = 46) and patients having no asplenia (Group B, n = 115). Aspirin therapy was employed in all patients after surgical interventions except for pulmonary artery banding. We retrospectively reviewed the platelet counts at each seven stage of cardiac catheterization (for pre- and postoperative evaluation of the first palliation, Glenn operation, and Fontan operation, and for late evaluation after Fontan operation), incidence of thromboembolic events, and other possible risk factors for thromboembolism.

Results

The median platelet counts in Group A were consistently higher than those in Group B at any of the seven stages of cardiac catheterizations (p < 0.002). The incidence of thromboembolic complications was also higher in Group A than that in Group B (28% vs. 10%, p = 0.030). Univariate and multivariate logistic regression analyses showed that a platelet count of more than 550 × 10⁹/L at the first cardiac catheterization was associated with thromboembolic complications (Odds ratio 3.17; p = 0.046).

Conclusions

Persistent thrombocytosis is present in patients with asplenia syndrome. It may greatly contribute to the development of thromboembolism during the management of congenital heart disease than expected.     

Intravenous γ-Globulin for Kawasaki Disease

We studied the effect of γ-globulin (IVGG) and aspirin (ASA) on the development of the coronary artery lesions (CAL) of Kawasaki disease (KD) in three different protocols. Within 29 days of the onset of KD the echocardiographic evidence of CAL had developed in 39–42% of the patients in the ASA group, but only in 13.7–20.8% of the patients treated with IVGG (200 or 400 mgγkgX5). In long-term follow-up observation of CAL of these patients the evidence of CAL in both the ASA and the IVGG group regressed gradually; however, the residual rate of CAL was significantly low in the IVGG group at all times up to 24 months after onset. These facts suggest that when using IVGG for KD, we should select a dose of intact γ-globulin, 1,000 mgγkg or more in total, to prevent the occurrence of CAL. We have demonstrated not only a significant reduction in the occurrence of CAL in patients treated with IVGG but a reduction in the residual rate of CAL for two years as compared with those treated by ASA.     

Efficacy of photodynamic therapy with topical 5‐aminolevulinic acid using intense pulsed light for Bowen’s disease

Photodynamic therapy (PDT) with topical 5‐aminolevulinic acid (ALA) is reported to be an effective and safe treatment for superficial non‐melanoma skin cancers. We have developed an photodynamic therapy with topical δ‐aminolevulinic acid (ALA‐PDT) protocol using intense pulsed light (IPL) for treating Bowen’s disease (BD). Three patients diagnosed with BD by skin biopsy were recruited in this study. They received IPL treatment after 3 h of occlusive dressing with application of ALA. This protocol was repeated every 2 weeks for a total of five sessions. The treated areas did not show any signs of BD for more than 1 year; therefore, it appeared that the affected areas showed improvement in all the patients. No patients withdrew from the study because of side‐effects. ALA‐PDT with IPL as a light source is well tolerated by patients and is beneficial for treating BD.