Revisiting DARPP-32 in postmortem human brain: changes in schizophrenia and bipolar disorder and genetic associations with t-DARPP-32 expression.

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32 or PPP1R1B) has been of interest in schizophrenia owing to its critical function in integrating dopaminergic and glutaminergic signaling. In a previous study, we identified single-nucleotide polymorphisms (SNPs) and a frequent haplotype associated with cognitive and imaging phenotypes that have been linked with schizophrenia, as well as with expression of prefrontal cortical DARPP-32 messenger RNA (mRNA) in a relatively small sample of postmortem brains. In this study, we examined the association of expression of two major DARPP-32 transcripts, full-length (FL-DARPP-32) and truncated (t-DARPP-32), with genetic variants of DARPP-32 in three brain regions receiving dopaminergic input and implicated in schizophrenia (the dorsolateral prefrontal cortex (DLPFC), hippocampus and caudate) in a much larger set of postmortem samples from patients with schizophrenia, bipolar disorder, major depression and normal controls (>700 subjects). We found that the expression of t-DARPP-32 was increased in the DLPFC of patients with schizophrenia and bipolar disorder, and was strongly associated with genotypes at SNPs (rs879606, rs90974 and rs3764352), as well as the previously identified 7-SNP haplotype related to cognitive functioning. The genetic variants that predicted worse cognitive performance were associated with higher t-DARPP-32 expression. Our results suggest that variation in PPP1R1B affects the abundance of the splice variant t-DARPP-32 mRNA and may reflect potential molecular mechanisms implicated in schizophrenia and affective disorders.

[Volume reduction surgery for giant coronary sinus with valvular heart disease; report of a case].

A 64-year-old male with giant left atrium and giant coronary sinus, who had aortic valve regurgitation, prosthesis valve paravalvular leakage in mitral position and prosthesis valve malfunction in tricuspid valve position, was successfully treated with double valve replacement, paravalvular leakage repair and volume reduction of left atrium and coronary sinus. Giant coronary sinus was about 70 mm in diameter and was thought to be induced by persistent left superior vena cava, high right atrium pressure and prosthesis valve malfunction in tricuspid valve position. Lung volume was so much increased by volume reduction of left atrium and coronary sinus and patient's symptoms were much improved.

[Full-thickness resection of the focus site for adolescent idiopathic ventricular tachycardia].

We present a case of a 14-year-old male with incessant idiopathic ventricular tachycardia for which both pharmacological and catheter ablation treatments failed. Curative surgery was performed on this patient. By intraoperative epicardial isochronous mapping, arrhythmogenic focus was identified in the right ventricular infundibulum between the large conus branch and the proximal right ventricular coronary branch. After cryoablation both from the epi- and endo-cardial sides failed to terminate the arrhythmia, subsequent full-thickness resection of the identified focus was performed. There was no postoperative recurrence of tachyarrhythmia In idiopathic ventricular tachycardia, arrhythmogenic focus is not always situated on the endo- or epicardial side. Full-thickness resection of the focus site might be necessary in such patients as we experienced this time.

[Reoperation for postoperative pseudoaneurysm after repair for acute aortic dissection associated with disseminated intravascular coagulation and chronic renal failure].

We report a very high risk case of reoperation for pseudoaneurysm after ascending aortic replacement for acute aortic dissection in a 78-year-old man with chronic renal failure and disseminated intravascular coagulation (DIC). Computed tomography 5 years after the 1st operation showed huge pseudoaneurysm originated from the distal anastomosis and the angiogram showed moderate aortic regurgitation. Hemodialysis and congestive heart failure associated with DIC complicated his general condition. Preoperative DIC score was 7 with D-dimer of 39.8 microg/ml. The patient underwent reoperation through night anterior thoracotomy. At 20 degrees C of urinary bladder temperature, we started re-median sternotomy and ablated the adhesion. When the pseudoaneurysm ruptured, we started hypothermic circulatory arrest with selective cerebral perfusion immediately. And Bentall operation and hemi-arch replacement were performed. Postoperative recovery required long period and he was transferred to another hospital at 3 months after the surgery. Postoperative data showed reduction of DIC score to 3.

[Valve-in-valve replacement of primary tissue valve failure of bovine pericardial valve minor].

A 73-year-old woman who underwent mitral valve replacement with a 31 mm Carpentier Edwards Pericardial Xenograft 19 years ago. She revealed sudden onset of a grade IV/VI a seagull like diastolic murmur at the apex, and severe hematuria. Echocardiography demonstrated severe mitral regurgitation. These findings were consistent with acute primary tissue valve failure. Therefore we performed emergency reoperation. At operation, valve leaflet was torn at the commissural stitch, and bioprosthesis strut was buried in the left posterior ventricular wall. The mitral prosthetic valve replaced with a 25 mm CarboMedics OptiForm using a technique of valve-in-valve replacement. This procedure would be one option for replacement of bioprosthetic mitral valve.

Prognostic factors of gastric cancer tumours of less than 2 cm in diameter: rationale for limited surgery.

BACKGROUND: A recent trend in the surgical treatment of patients with early gastric cancer in Japan has been to limit surgery to an extent that ensures complete cure and improvement in the patient's quality of life. If a gastric cancer tumour can be completely eradicated by laparoscopic surgery, the patient can be cured of cancer without major operative stress. A small gastric cancer tumour of less than 2 cm in diameter is an indication for laparoscopic surgery, but little is known about what protocol of surgical treatment is appropriate for this type of tumour. PATIENTS AND METHODS: The clinicopathological features of 150 patients with gastric cancer tumour of less than 2 cm in diameter were reviewed retrospectively from hospital records between 1985 and 1995. The results of retrospective analysis of clinicopathological data of 24 patients with advanced cancer were compared with those of 126 patients with early cancer. Univariate and multivariate analyses of patients with small gastric cancer tumours were performed to evaluate the prognostic significance of clinicopathological features. RESULTS: A significant difference was seen between the gross tumour appearances in the two groups; Borrmann type-4 tumours were more common in the advanced group. Lymph-node metastasis, lymphatic vessel invasion and vascular invasion were found more frequently in the advanced cancer group than in the early cancer group. Scirrhous type was more common in the advanced cancer group. In univariate analysis, unfavourable prognostic factors included deep cancer invasion, presence of lymph-node metastasis, lymphatic invasion and vascular invasion. Using Cox's proportional hazard regression model, only nodal involvement emerged as an independent statistically significant prognostic parameter associated with long-term survival. CONCLUSION: Laparoscopic surgery should not be performed on tumours that are Borrmann type in macroscopic appearance and scirrhous-type histologically. Lymph-node metastasis is an independent prognostic factor. We recommend laparoscopic surgery involving local resection of the stomach without lymphadenectomy for small, early gastric cancer tumours that satisfy the criteria mentioned above. However, the validity of this recommendation should be tested by a prospective randomized control trial in the future.

Will accident reports filed in hospitals in Japan be used in the future as evidence in malpractice lawsuits?

A major drawback of submission of so-called incident reports for medical institutions is that such reports may be able to be obtained on request by patients and to be used as evidence in malpractice lawsuits. In Japan, there are no established rules concerning the use of accident reports in medical lawsuits. More debate is needed for voluntary report systems to become established in medical institutions throughout Japan.

[Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for gastric cancer--study report of JFMTC Study No. 10].

The purpose of this study was to investigate the correlation between efficacy and dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total of 1,410 patients from 180 institutions were allocated into a low-dose group and a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months. The patients in the high-dose group received MMC at 8 mg/m2 on the day of surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600 mg in tegafur) daily for 6 months. The patients in the high-dose group tended to exhibit higher survival rates than those in the low-dose group, although the difference was not significant. For the n(+)ps(-) patients, however, the survival rates were significantly higher in the high-dose group (p = 0.043). The recurrence-free rates showed a similar tendency. The incidence rates of adverse events were significantly higher in the high-dose group than in the low-dose group. Compliance was poorer in the high-dose group. Although the number of adverse events increases, a better prognosis can be expected with a high dose. These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and UFT.

Probability of lymph node metastasis in small gastric cancer tumor: is it an indication for limited surgery?

The purpose of this study was to determine the factors that are predictive of lymph node metastasis in a small gastric cancer tumor <2 cm in diameter. The clinicopathological features of 17 patients with node-positive small gastric cancer were reviewed from the database of gastric cancer at the Department of Surgery, Sendai National Hospital, Sendai, Japan, and they were compared with those of 131 patients with node-negative cancer. The independent risk factors influencing the lymph node metastasis were determined by multiple logistic regression analysis. Depth of invasion, macroscopic appearance, cancer-stromal relationship, and lymphatic microinvasion were found to be associated with lymph node metastasis. The variables found to be significant risk factors for lymph node metastasis were depth of invasion (P = 0.0250) and lymphatic microinvasion (P = 0.0028). It is possible for even a small gastric cancer tumor to have lymph node metastasis. A surgeon treating a small gastric cancer tumor must consider that although the cure rate is high, >10% of these tumors have lymph node metastases. Because of the possibility of lymph node metastasis, even with accurate knowledge of the depth of cancer invasion, selective performance of local resection or limited surgery with incomplete lymph node dissection is not justified. Accurate preoperative diagnosis and the appropriate decision for surgical indication are important. Large-scale randomized, controlled trials should be performed to show the advantage of limited surgery for gastric cancer.

[A case of total cavopulmonary connection by utilization of coronary sinus as a hepatic venous return].

A 2-year-old boy with polysplenia, double outlet right ventricle after pulmonary banding and unilateral bidirectional shunt was operated on. A modified total cavopulmonary connection was done by utilization of coronary sinus as a retrograde route for the hepatic venous return. Left SVC was transected and its distal end was anastomosed to the left pulmonary artery after PA angioplasty. An equine pericardial patch was placed over the ostia of the hepatic vein and coronary sinus. Two ostia of the coronary veins were excluded from the created route. The proximal end of the left SVC was anastomosed to the inferior side of the left pulmonary artery. Postoperative course was uneventful. The postoperative angiogram showed smooth hepatic venous return through the coronary sinus and no pressure gradient was recorded between hepatic vein and pulmonary artery.

[A case of repeated surgical intervention for pulmonary venous obstruction after repair of total anomalous pulmonary venous connection].

A 3-month-old boy showed pulmonary venous obstruction after repair of total anomalous pulmonary venous connection. He was treated with a novel method of stureless in situ pericardium repair. Six weeks after this operation, he showed recurrence of venous obstruction and the same procedure was performed. Another six weeks after this operation, stenosis of the left pulmonary vein necessitated the same procedure again. Although he suffered from pneumonia and died of sepsis, this procedure revealed effectiveness for at least three months. This report showed clinical course after repeated stureless in situ pericardium repair. More experience will be necessary to evaluate the effectiveness of this procedure.

Lymph-node staining with activated carbon CH40: a new method for axillary lymph-node dissection in breast cancer.

OBJECTIVE: To demonstrate the usefulness of activated carbon particles (CH40) as a vital staining dye for visualizing lymphatic vessels and lymph nodes in breast cancer. DESIGN: A retrospective evaluation. SETTING: Department of Surgery in Sendai National Hospital, Japan, a 716-bed teaching hospital. METHODS: To identify as many lymph nodes as possible in the axillary fat, by which we might decrease the possibility of the presence of undetected metastatic nodes, an emulsion of activated carbon particles (CH40) was injected into the centre of the mammary gland, close to the tumour site, 3 days before radical surgery. MAIN OUTCOME MEASURE: The number of lymph nodes found by the traditional method and by the CH40-injection method were recorded. RESULTS: After injection, the CH40 was readily adsorbed into regional lymphatics and streamed along with the lymph flow to blacken regional lymph nodes. The CH40-guided method increased the mean number of nodes per case found in the axilla from 8.4, by the traditional method, to 14.0 nodes per case. CONCLUSIONS: The use of the CH40 technique has two technical advantages; one is that it allows surgeons to locate the blackened lymph nodes at the time of surgery and the other is that it allows pathologists to look for the nodes in fatty tissue. Lymph-node dissection with the aid of activated carbon particles is inexpensive, easy to perform and enables the smallest lymph nodes to be easily recognized. CH40 is the technique of choice for the detection of axillary lymph nodes in cases where the number of lymph nodes detected by the traditional method is too small for accurate surgery. In conclusion, the present study demonstrates that CH40 could be an appropriate tool for more accurate staging of breast cancer axillary specimens.

[Interim report on JFMTC Study no. 21 on the effectiveness of UFT as an adjuvant therapy for semi-advanced cancer of the stomach].

This interim report, for findings as of May, 1998, covers data on 435 gastrectomized patients with semi-advanced stomach cancer collected from 144 institutions between November, 1993 and March, 1996. The active arm of the study involved CDDP i.p. administration of 70 mg/m2 at the time of resective surgery, followed by UFT oral administration for one year at 3-4 capsules daily. A randomized control involved no adjuvant therapy after CDDP i.p. administered as in the active arm. The results obtained indicated no significant difference between the groups in terms of 3 year survival or disease free survival rates. Reports appearing elsewhere have suggested that 3-4 capsules/day of UFT may be insufficient to reach the threshold of the effective tissue level, and that 6 capsules may be necessary to obtain the expected results. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Significant prognostic factors in patients with early gastric cancer.

BACKGROUND: Early gastric cancer is defined as a gastric carcinoma confined to the mucosa or submucosa regardless of lymph node status, and it has an excellent prognosis with a 5-year survival rate of more than 90%. From 1985 to 1995, we encountered 266 cases of early gastric cancer in our hospital. METHODS: A retrospective analysis of the 266 cases of early gastric cancer was performed to evaluate the prognostic significance of clinicopathological features (age, gender, tumor size, tumor location, depth of invasion, lymph node metastasis, histological type, lymphatic invasion, vascular invasion, histological growth pattern, cancer-stromal relationship and type of operation). RESULTS: The overall survival rate of all the patients with early gastric cancer was 95.7%. In univariate analysis, the statistical significant prognostic factors were regional lymph node metastasis (P = 0.0004), lymphatic invasion (P = 0.0053) and cancer-stromal relationship (P = 0.0016). Absence of lymph node metastasis and lymphatic invasion, and a medullary-type histopathology were associated with improved survival. In multivariate analysis, the statistically significant prognostic factors were lymph node metastasis and cancer-stromal relationship. CONCLUSIONS: Presence of lymph node involvement and a scirrhous type of gastric cancer are associated with poor prognosis. Lymph node dissection with gastric resection is necessary for patients with early gastric cancer who have a high risk of lymph node metastasis. Postoperative chemotherapy is recommended for a scirrhous type of early gastric cancer.

Clinicopathologic prognostic factors in patients with Borrmann type 4 gastric cancer: univariate and multivariate analyses.

BACKGROUND: Advanced gastric cancer is classified into four Borrmann types, types 1 to 4. Type 4 is a relatively undifferentiated carcinoma with little or no gland-forming capability. Despite recent advances in the diagnosis and surgical management of gastric cancer, most tumors of Borrmann type 4 are not detected at an early stage and the prognosis remains poor; the five-year survival rate after gastric resection ranges from 10 to 20 percent. We evaluated the affects of several clinicopathologic variables on the 5-year survival rate after resection of Borrmann type 4 gastric cancer. METHODS: Data on clinical characteristics were obtained from the records of patients who underwent gastric resection between 1985 and 1995 at the Department of Surgery, Sendai National Hospital, and follow-up data were obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. The relationship between clinicopathologic variables and 5-year survival rate was estimated by the Kaplan-Meier survival curve and the logrank test. Multivariate Cox's proportional hazards regression analysis was then performed to determine which variables were independent prognostic factors. RESULTS: Eighty-seven patients with Borrmann type 4 gastric cancer underwent a resection during the study period at our hospital. The overall 5-year survival rate was 14.8%. The relationship between clinicopathologic variables and 5-year survival rate was determined by constructing a Kaplan-Meier survival curve. Tumor location (upper, middle and distal vs whole stomach, p=0.0214), lymph node metastasis, capillary microinvasion, and peritonitis carcinomatosa (absent vs present, p<0.05) significantly influenced survival. When multivariate analysis using Cox's proportional hazards regression of 5-year survival was performed, capillary microinvasion, peritonitis carcinomatosa (absent vs present) and tumor location (distal vs whole stomach) emerged as the statistically significant independent prognostic factors associated with long-term survival. CONCLUSION: Capillary microinvasion and the presence or absence of peritonitis carcinomatosa are more powerful predictors of 5-year survival than is lymph node metastasis. Patients with gastric cancer of the whole stomach have a poorer prognosis than do those with carcinoma in the antrum of the stomach.