Involvement of brown adipose tissue in subcutaneous fat necrosis of the newborn.

BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is a rare condition that manifests within days after birth. The interscapular region, axillae and shoulders are the most commonly affected sites, corresponding to anatomic sites of brown adipose tissue (BAT) in newborns. OBJECTIVE: We postulated a specific involvement of BAT in SCFN and searched for brown adipocytes at affected sites. METHODS: Biopsy specimens were immunostained with antibodies against uncoupling protein 1 (UCP-1) and examined by electron microscopy. We also examined BAT by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography and computed tomography (PET-CT) scanning. RESULTS: A few cells in biopsy specimens from two patients bound antibodies against UCP-1, and brown adipocytes were detected at several stages of degeneration. PET-CT scans revealed lower uptake of (18)F-FDG at major sites of SCFN. CONCLUSION: SCFN and BAT can be found at the same sites, suggesting a pathophysiological connection.

Phase I/II study of irinotecan and UFT for advanced or metastatic colorectal cancer.

UNLABELLED: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study. PATIENTS AND METHODS: Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy. RESULTS: The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients. CONCLUSION: Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.

Induction of osteoclast-like cells derived from the synovial lavage fluids of patients with temporomandibular joint disorders.

OBJECTIVE: Although biochemical studies have examined the synovial fluid (SF) of patients with temporomandibular joint (TMJ) disorders (TMDs), the details of the molecular mechanism of bone destruction and remodeling remain unknown. In this study, we induced and characterized osteoclast-like cells from the SF of patients with TMD and investigated the participation of these cells in the pathogenesis of TMD. METHODS: We collected SF cells from patients with TMD after a pumping procedure, cultured osteoclast-like cells, and examined their characteristics, including osteoclast markers and bone resorption activities. In addition, we obtained fibroblastic cells from the SF of TMD patients by continuous sub-culturing. Using these fibroblastic cells, we examined fibroblast markers using immunocytochemical staining and analyzed the receptor activator of nuclear-factor-kappaB ligand (RANKL) mRNA levels. Detection of soluble form of RANKL (sRANKL) in the SF was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Osteoclast-like cells were induced from the SF cells of patients with TMD by adding recombinant human (rh) macrophage colony stimulating factor (M-CSF) and either 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] or prostaglandin E2 (PGE2). These multinucleated giant cells were positive for tartrate-resistant acid phosphatase (TRAP) and had the ability to absorb bone. The fibroblastic cells from the SF of TMD patients were positive for fibroblast markers and RANKL mRNA was up-regulated. Detection of sRANKL in SF of patient group was significantly higher than control group. CONCLUSION: The results suggest that the joint-infiltrating SF cells from TMD patients play important roles in the pathogenesis of these disorders, which is characterized by progressive bone destruction or remodeling.

Is the mass screening for neuroblastoma ineffective?

Though a recent study (Schilling et al. 2002) concluded that the mass screening for neuroblastoma targeting children age 12 months was ineffective, we pointed out several serious problems and reestimated its effectiveness using their data. They employed the subjects in the "control area" as controls, not the "non-participants" whose biases are fewer because their area is the same as that of the participants. The incidence of neuroblastoma among the subjects in the "control area" was about 25% smaller than that of the "non-participants". This leads to underestimation of the effectiveness of the mass screening. They combined false negatives with true positives to calculate the incidence of the "screened group". But since many spontaneous regression cases are included in the true positives, this method inflates the incidence of the "screened group", leading to underestimation of the effectiveness of the mass screening. When the false negatives are compared with the non-participants, the incidence of the cases in stage 4 among the latter is about 40% of that of the former, and the mortality is less than two-thirds. The percentage of spontaneous regression cases among the true positives is estimated to be about 40%. These results are better than those of the Japanese screening programs (targeting infants age 6 months), supporting the effectiveness of mass screening for neuroblastoma.

Contribution of HPLC mass screening for neuroblastoma to a decrease in mortality.

The aim of this study is the estimation of the contribution of HPLC mass screening for neuroblastoma to the decrease in deaths due to this disease. The mortality rates of malignant neoplasms of the adrenal glands (ICD 9, 1940; ICD 10, C74; virtually all the cases of these codes are neuroblastoma during childhood) at 1-4 years of age in cohorts born in 1979-1984, 1985-1988, and 1989-1992 in the whole of Japan were calculated, using data obtained from the Ministry of Health and Welfare. The numbers of infants screened by HPLC in the cohorts were estimated through the reports of the Ministry of Health and Welfare and the database of the Japanese Society for Mass-screening. The mortality of the cohort born in 1989-1992, in which 77.8% of the live births were screened by HPLC, was 1.73 per 100,000 live births. This is about half of that (3.26) of the cohort born in 1979-1984, in which few infants were screened. On the assumption that cases of the 1985-1988 and 1989-1992 cohorts died according to the mortality rate of the 1979-1984 cohort, the expected numbers of deaths were estimated; that for the 1985-1988 cohort was 178.51 (of them, that for the infants screened by HPLC was 39.65), and that for the 1989-1992 cohort was 159.78 (of them, that for the infants screened by HPLC was 124.33). The observed numbers of deaths were 145 and 85, respectively. Assuming that non-HPLC methods have no effects and using 2 unknown quantities x (contribution of HPLC) and y (other factors), simultaneous equations (1) 178.51 - 39.65x - 178.51y = 145 and (2) 159.78 - 124.33x - 159.78y = 85 were made. Solving them, x = 0.5041 and y = 0.0757 were obtained. In conclusion HPLC screening targeting infants aged 6 months reduces death of adrenal neuroblastomas at 1-4 years of age by about 50%.

Metachronous triple cancers of the sigmoid colon, stomach, and esophagus: report of a case.

We report herein an unusual case of metachronous triple cancers of the sigmoid colon, stomach, and esophagus. A 60-year-old man was initially admitted to our hospital for investigation of occult fecal blood. This was found to be caused by sigmoid colon cancer which was resected in July 1985 (T3, N0, M0; Stage II). A follow-up endoscopy performed in 1990 showed early gastric cancer, and a gastrectomy was performed in August 1990 (Tis, N0, M0; Stage 0). Another endoscopic examination performed as follow-up in 1993 revealed early cancer of the remnant stomach, and all the remnant stomach was surgically resected in March 1993 (Tis, N0, M0; Stage 0). He presented again in December 1996, complaining of discomfort in the chest which was found to be caused by cancer of the middle thoracic esophagus. Although surgery was considered necessary, the patient refused to undergo any further operations. Instead, radiation was administered from January 1997. An endoscopy after the completion of radiotherapy confirmed that the cancer had almost disappeared; however, it started to grow again from the beginning of 1998. He was hospitalized due to esophageal stenosis in April 1998, and died of carcinomatous cachexia in September of the same year.

Benign mediastinal teratoma complicated by cardiac tamponade: report of a case.

We present herein the case of a 48-year-old woman with a benign mediastinal teratoma that had been followed up for 3 years, who developed acute cardiac tamponade. The patient had initially undergone an exploratory sternotomy, at which time the tumor was histologically diagnosed as a benign mature teratoma that could not be resected due to its severe, wide adhesion to the surrounding organs. However, following the development of cardiac tamponade, both sternotomy and right intercostal thoracotomy were employed, and the tumor could be excised with cardiopulmonary bypass standby. High levels of amylase and carbohydrate antigen 19-9 were revealed in the pericardiac effusion fluid. The mRNA expression of inflammatory cytokines including interleukin-1 (IL-1), IL-6, and IL-8 in the tumor tissue was also demonstrated by a reverse transcriptase-polymerase chain reaction analysis. This case illustrates the ultimate natural course of benign mediastinal teratoma and emphasizes the importance of early surgical excision, even when this tumor is asymptomatic.

The relationship between homovanillic/vanillylmandelic acid ratios and prognosis in neuroblastoma.

A total of 44 cases with neuroblastoma cases (excluding true positive cases detected in mass screenings) who were born from 1979 to 1991, and had data concerning the clinical stage and values of vanillylmandelic acid (VMA) and homovanillic acid (HVA) at diagnosis (microg/mg creatinine) were followed up until the end of 1994. Deaths were confirmed using the record of vital statistics of the Hokkaido Government. The 60-month survival rate of those who had an HVA/VMA ratio of 1-2 was 80.0%. Conversely, those with ratios <1 or >2 had respective survival rates of 24.1% and 5.3%. Most of those with a ratio >2 died within 24 months of diagnosis. Many of the cases with a ratio <1 lived over 12 months but died within about 36 months. Many tumors of those cases with a ratio of 1-2 originated in extra-adrenal glands, and had negative n-myc amplification. Most of the patients with a ratio >2 were diagnosed at 1 year of age or older. The HVA/VMA ratio at diagnosis is useful in estimating both the survival period and the prognosis.

Total excision of mesenteric cysts by laparoscopic surgery: report of two cases.

Mesenteric cysts are relatively rare tumors, and most patients present nonspecific abdominal symptoms until developing larger cysts. We report two cases of mesenteric cysts that were totally excised during laparoscopic surgery. The cysts of both patients were located in the mesenterium of the cecum or ascending colon. Under laparoscopy, the cyst was punctured to collect the cystic fluid for cytology and then completely removed without bowel resection. Histological examination revealed cystic lymphangiomas with endothelial cell lining. The postoperative course was uneventful. Laparoscopic treatment of benign abdominal cysts is an alternative safe and less invasive operation.

Deconjugation of bilirubin accelerates coprecipitation of cholesterol, fatty acids, and mucin in human bile--in vitro study.

To examine the initial step of brown pigment gallstone formation, sterile human gallbladder bile samples were incubated with or without beta-glucuronidase in vitro. Enhanced bilirubin deconjugation achieved by adding beta-glucuronidase significantly accelerated the formation of a precipitate that contained bilirubin (28.2 +/- 3.8% of dry weight), cholesterol (14.3 +/- 5.2%), free fatty acids (12.0 +/- 1.3%), and glycoprotein (10.0 +/- 6.7%). Both the composition and scanning electron microscopic appearance of the precipitate were similar to these features in brown pigment gallstones. The cholesterol saturation index and nucleation time in the supernatant did not change with various incubation periods. The weight ratios of bilirubin to cholesterol in the precipitates correlated with those in bile (r = 0.76; P = 0.017). Gel chromatography of the precipitate showed high molecular weight glycoprotein to be the major constituent. Bilirubin, cholesterol, fatty acids, and mucin were found to coprecipitate in accordance with bilirubin deconjugation, which process may play an important role in an early stage of the formation of brown pigment gallstones.

Gallbladder carcinoma in the era of laparoscopic cholecystectomy.

OBJECTIVE: To assess the usefulness of laparoscopic cholecystectomy for unsuspected and suspected gallbladder carcinoma. DESIGN: Retrospective review with a mean follow-up of 27 months, ranging from 1 to 47 months. SETTING: University hospital and 8 affiliated hospitals. PATIENTS: Of 2616 laparoscopic cholecystectomies performed over 4 years, 24 gallbladder carcinomas were treated by laparoscopic cholecystectomy and retrospectively reviewed. RESULTS: The clinical course depended on the histopathologic depth of invasion of gallbladder carcinoma. All 6 cases of pathologic tumor (pT) stage in situ (pTis) gallbladder carcinoma and 2 cases of pT1 gallbladder carcinoma showed no invasion to the lymphatic, venous, or perineural spaces, and these 8 patients were all doing well from 2 to 19 months (mean, 11 months) after laparoscopic cholecystectomy. Sixteen cases of pT2 or pT3 gallbladder carcinoma invaded the subserosal layer or the liver, and 5 of the 16 patients were dead of liver dysfunction, abdominal wound recurrence, or liver metastasis 5 days and 7, 12, 15, and 18 months after operation, although additional resection of the liver bed with lymph node dissection was performed after laparoscopic cholecystectomy in 4 of these 5 patients. Abdominal wall recurrence in the absence of distant metastasis was present in 3 (19%) of the 16 patients with pT2 or pT3 gallbladder carcinoma due to inoculation of cancer cells in the abdominal stab wounds where the gallbladder or laparoscope was removed. CONCLUSIONS: Gallbladder carcinoma at the pTis or pT1 stage removed laparoscopically needs no other treatment. We recommend that the gallbladder be removed by vinyl bag and port sites be excised or washed with normal saline to prevent port site recurrence in patients with laparoscopic cholecystectomy for pT2 or pT3 carcinoma.

Multiseptate gallbladder: biliary manometry and scintigraphy.

A 30-year-old man with multiseptate gallbladder, a very rare congenital anomaly, is presented. His presenting symptom was epigastric pain. A hypoplastic gallbladder with multiple septa was demonstrated by ultrasonography and endoscopic retrograde cholangiography. An injection of cerulein reproduced pain, and simultaneous biliary manometry and scintigraphy showed impairment of gallbladder filling and emptying. Laparoscopic cholecystectomy resulted in complete relief of the pain. Biliary manometry and scintigraphy are useful to determine the operative indication in a symptomatic patient with this entity.

Laparoscopic adrenalectomy: review of 14 cases and comparison with open adrenalectomy.

We reviewed 14 cases of laparoscopic adrenalectomy and compared the results with those of a recent series of 15 consecutive patients undergoing a traditional open adrenalectomy for a benign tumor. The laparoscopic adrenalectomy group included nine patients with primary aldosteronism, three with Cushing's syndrome, one with pheochromocytoma, and one with a nonfunctioning incidentaloma. In the patient with pheochromocytoma, a good operative field was safely obtained by a combination of pneumoperitoneum at less than 6 mm Hg insufflation pressure and the abdominal wall-lift method. In both groups, the tumors were removed successfully in all cases. Laparoscopic adrenalectomy, which required neither a large skin and muscle incision nor any resection of the ribs, offered a lower morbidity and earlier recovery in spite of the longer operation time. The most important complication observed in laparoscopic adrenalectomy was that of pneumothorax secondary to an injury of the diaphragm and pleura during the dissection of the left adrenal gland using electrocautery. However, the injury wound was small, and the pneumothorax was resolved by suturing the tear under laparoscopy. These results suggest that laparoscopic adrenalectomy is a minimally invasive alternative to traditional open adrenalectomy and thus has the potential soon to become a standard procedure for the treatment of benign adrenal tumors.

Carcinoma of the ampulla of Vater synchronously associated with early gastric cancer--a report of two cases.

We report two cases of carcinoma of the ampulla of Vater synchronously associated with early gastric cancers. The gastric lesions were diagnosed pre-operatively in one patient and at the time of examination of the resected specimen following pancreatoduodenectomy in the other. Specific problems in the diagnosis and management of these multiple primary carcinomas are discussed. Careful evaluation of the stomach prior to the surgical treatment for ampullary carcinoma is recommended.

Regulation of bile acid synthesis in the rat: relationship between hepatic cholesterol 7 alpha-hydroxylase activity and portal bile acids.

Bile acid biosynthesis has been believed to be regulated by negative feedback control; however, recent experiments have cast considerable doubts on the concept. The aim of the study was to examine the consensus of the negative feedback regulation of bile acids by clarifying the correlation between the portal bile acids and the rate-limiting enzyme of bile acid biosynthesis, hepatic microsomal cholesterol 7 alpha-hydroxylase. We measured the enzyme activity and the portal bile acids in male Wistar rats that were orally administered three different bile acids or cholestyramine for 2 weeks. The serum level of 7 alpha-hydroxycholesterol was also determined to verify whether it would be a parameter of bile acid synthesis rate in the rat. The activity of cholesterol 7 alpha-hydroxylase increased about threefold in rats treated with cholestyramine when compared with controls. On the other hand, in rats fed ursodeoxycholic, chenodeoxycholic, and deoxycholic acids, the enzyme activities decreased to 40%, 26%, and 28%, respectively. Treatment with cholestyramine had no significant effect on the portal bile acid concentration. Administration of ursodeoxycholic and chenodeoxycholic acids resulted in a significant increase in the concentration of portal bile acids, whereas deoxycholic acid feeding did not significantly affect it. In the control group, conjugated cholic acid constituted a major part of the portal bile acids while the administered bile acid and its metabolites became predominant in each bile acid feeding group. Treatment with ursodeoxycholic acid made the portal bile acids more hydrophilic, but, by contrast, administration of chenodeoxycholic, deoxycholic acids, and cholestyramine made the portal bile acids more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS)

Conditions for solid-phase extraction of urinary bile acids with octadecylsilane-bonded silica.

Fast atom bombardment mass spectrometry was used as a detection method in a study of the extraction of urinary bile acids with octadecylsilane-bonded silica. The procedure commonly used in many laboratories was found to result in significant losses of sulfated taurine-conjugated bile acids. Losses of other double conjugates and of bile acid and bile alcohol glucuronides were also seen. The losses were avoided by addition of an equal volume of 0.5 M triethylamine sulfate to the urine before passing it through the sorbent bed. Quantitative elution was then achieved with methanol. Batch variations were observed with sorbents from two different manufacturers.

Effect of biliary drainage on serum 7 alpha-hydroxycholesterol level in patients with obstructive jaundice.

Percutaneous transhepatic biliary drainage was performed in 15 patients with obstructive jaundice and the serum 7 alpha-hydroxycholesterol level was monitored for 2 weeks by capillary gas-liquid chromatography-mass spectrometry. Before biliary drainage, the serum 7 alpha-hydroxycholesterol level was 130 +/- 52 pmole/ml, which was significantly lower than the normal value (238 +/- 100 pmole/ml). After biliary drainage, the serum 7 alpha-hydroxycholesterol level was decreased to 117 +/- 48 pmole/ml on the first day. There were two groups of patients as classified by the behavior of the serum 7 alpha-hydroxycholesterol level after the third day. In one group of patients (responders), the serum level increased significantly up to 525 +/- 83 pmole/ml at the end of the 2 weeks. In another group (nonresponders), the serum level did not increase and remained 145 +/- 86 pmole/ml. The serum bilirubin level tended to improve faster in the responders (decline index = -0.234 +/- 0.152) than in the nonresponders (decline index = -0.057 +/- 0.067; P < 0.05) and a statistically significant correlation was found between the decline index and the total 7 alpha-hydroxycholesterol level on Days 7 or 14. As the serum 7 alpha-hydroxycholesterol level is considered to reflect hepatic bile acid synthesis, which is one of the important functions of the liver, we conclude that the increased serum 7 alpha-hydroxycholesterol level after biliary drainage in the responders indicates recovered liver function and that the low serum level in the nonresponders suggests more severe hepatocellular damage in patients with obstructive jaundice.

Serum 7 alpha-hydroxycholesterol reflects hepatic bile acid synthesis in patients with obstructive jaundice after external biliary drainage.

To examine the hypothesis that serum levels of 7 alpha-hydroxycholesterol reflect bile acid synthesis in the liver, we analyzed serum 7 alpha-hydroxycholesterol and bile acid output in 13 patients with obstructive jaundice after relief of biliary obstruction. Before biliary drainage, the serum level of 7 alpha-hydroxycholesterol was 92 +/- 12 pmol/ml (mean +/- S.E.M.) and was significantly lower than the control value (226 +/- 26 pmol/ml, p < 0.01). After biliary drainage, serum 7 alpha-hydroxycholesterol level and biliary bile acid outputs began to rise in some patients, indicating reversible liver dysfunction. In other patients, serum 7 alpha-hydroxycholesterol levels and bile acid outputs did not increase, suggesting severe or irreversible liver dysfunction. On and after the third day of biliary decompression, serum 7 alpha-hydroxycholesterol levels correlated well with bile acid excretion (p < 0.01, r = 0.93). Other liver function parameters, such as serum bilirubin, serum bile acids, albumin, and bile flow, also revealed significant correlation with serum 7 alpha-hydroxycholesterol levels. We conclude that the serum 7 alpha-hydroxycholesterol level clearly reflects bile acid synthesis in the liver and that it may serve as a useful parameter for the assessment of hepatic functional recovery in patients with obstructive jaundice after biliary drainage.

Effects of pravastatin and ursodeoxycholic acid on cholesterol and bile acid metabolism in patients with cholesterol gallstones.

To investigate the effects of pravastatin and ursodeoxycholic acid (UDCA) on cholesterol and bile acid metabolism in humans, 41 patients with cholesterol gallstone disease were allocated to four groups and treated with pravastatin (20 mg/day), UDCA (600 mg/day), both pravastatin and UDCA, or neither drug (control) for 1-2 weeks prior to elective cholecystectomy. Cholesterol 7 alpha-hydroxylase activity and serum levels of total 7 alpha-hydroxycholesterol were significantly increased by pravastatin and unaffected by UDCA. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was markedly increased by pravastatin and decreased by UDCA. UDCA significantly decreased biliary cholesterol concentration and the cholesterol saturation index and prolonged the nucleation time; however, pravastatin alone had little effect on biliary lithogenicity. Serum total and low-density lipoprotein (LDL)-cholesterol levels were reduced most by the combined administration of pravastatin and UDCA. In conclusion, at a dose of 20 mg/day, pravastatin increased bile acid synthesis but did not decrease biliary lithogenicity. UDCA had no significant effect on bile acid synthesis, but markedly decreased biliary lithogenicity.

Video-assisted thoracoscopic resection of a mediastinal cyst: report of a case.

Video-assisted endoscopic surgery has recently been expanding its potential, which is shown by our report herein describing the case of a 23-year-old woman for whom successful thoracoscopic resection of a mediastinal cystic lesion was carried out. The patient's postoperative course was uneventful with minimal pain and a prompt recovery. Histological examination confirmed that the lesion was a benign cystic teratoma. We believe that video-assisted thoracoscopic surgery will become the standard procedure for most mediastinal cystic lesions in the future.