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.

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.

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.

Laparoscopic adrenalectomy: comparison with open adrenalectomy.

The results of the first 6 cases of laparoscopic adrenalectomy were compared with the most recent 11 consecutive cases of traditional open adrenalectomy for the treatment of benign adrenal tumor. In both groups, all the tumors were less than 4 cm in diameter and were removed successfully with no significant complications. The weight of the resected specimen and estimated blood loss were not significantly different in the two groups, and none of the patients needed a blood transfusion. Although laparoscopic adrenalectomy required a significantly longer operation time (median 230 min vs. 165 min for an open operation), the postoperative recovery estimated by the duration of restricted oral intake or walking was shorter, and the incidence of patients requiring postoperative parenteral analgesics was also significantly lower in laparoscopic adrenalectomy. Although the number of patients treated with the laparoscopic procedure is still small, these results suggest that laparoscopic adrenalectomy is a minimally invasive alternative to open adrenalectomy and, with further improvement of the operative technique and equipment, may become a more reliable and standard procedure for the treatment of benign adrenal tumor.

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.

Late development of cholangiocarcinoma after the treatment of hepatolithiasis.

Although the association of cholangiocarcinoma with intrahepatic calculi (hepatolithiasis) is well recognized, the late development of cholangiocarcinoma after the treatment of hepatolithiasis has not been reported in detail. Of 109 consecutive patients with hepatolithiasis treated during 19 years, eight patients had cholangiocarcinoma, seven of whom had cholangiocarcinoma two to 14 years, with a mean of eight years, after the treatment of hepatolithiasis. Absence of cholangiocarcinoma was confirmed when stones were removed at the time of the initial treatment. The mean age was 56 years, with a female to male ratio of 2:5. At the time of detecting cholangiocarcinoma, three patients had no gallstones and four had gallstones at the corresponding site to the carcinoma. Cystic dilatation of the intrahepatic bile duct was often observed on the direct cholangiogram. The biles were all infected mainly with Escherichia coli and Klebsiella species. Thus, bile stasis and bacteria infection seems to be the important causative factor, causing cholangiocarcinoma rather than the calculi itself. Because the symptoms only mimic those of cholangitis, the possible presence of cholangiocarcinoma should be considered even after the treatment of hepatolithiasis for early detection and curative resection.

Composite glandular-endocrine cell carcinoma of the extrahepatic bile duct: immunohistochemical study.

A composite glandular-endocrine cell carcinoma of the extrahepatic bile duct in a 64 yr old Japanese man is reported. A nodular polyp measuring 1.9 x 1.1 cm was located in the confluence of the extrahepatic bile duct. Histologically, the tumor was composed of well differentiated tubular adenocarcinoma and small cell neuroendocrine carcinoma with a transition between the 2 components. The 2 areas of the tumor immunohistochemically revealed a clear-cut difference in functional differentiation. Tumor cells in the glandular component were immunoreactive to both carcinoembryonic antigen (CEA) and CAM 5.2, while those in the small cell area were immunoreactive to neuroendocrine markers such as neuron specific enolase (NSE), chromogranin A and serotonin. These results suggest that the tumor arose from a multipotential stem cell capable of differentiation in 2 directions.

Intraoperative endoscopic electrohydraulic lithotripsy of pancreatic stones.

Two male patients with complications associated with chronic pancreatitis are described. In each patient, preoperative examinations revealed a large stone obstructing the main duct in the head of the pancreas. Lateral pancreaticojejunostomy was performed to relieve pain and prevent further attacks of pancreatitis. During each operation, the stone was fragmented under direct visual control with the use of a flexible choledochoscope and a contact electrohydraulic lithotriptor. The stone was removed and ductal flow through the head of the pancreas was reestablished. Our experience shows that endoscopic electrohydraulic lithotripsy facilitates operative removal of pancreatic stones deeply located in the head of the pancreas.

Profiling of eicosanoids in inflamed gall bladder wall by gas chromatography with selected-ion monitoring.

The profiling of eicosanoids, including prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2) and leukotriene B4 (LTB4), in dog and human gall bladders was carried out by a combination of an effective and convenient clean-up procedure and gas chromatography with selected-ion monitoring. The clean-up procedure was based on the stepwise elution of their methyl ester derivatives from a silica gel column with n-hexane-ethyl acetate and ethyl acetate-methanol in various ratios. The LTB4 methyl ester was eluted with an n-hexane-ethyl acetate (2:1, v/v) fraction because LTB4 is more lipophilic than the other eicosanoids. The present method permitted the quantitation of trace amounts of eicosanoids, including LTB4, present in tissues in the order of pg/mg of protein, without interference from other endogenous substances. In experimental acalculous cholecystitis produced in dog, the levels of eicosanoids (except LTB4) were significantly changed. Of these eicosanoids, the level of 6-keto-PGF1 alpha was significantly higher in the seromuscular layer and correlated with the observed severe morphological changes. In human chronic cholecystitis with gallstones, the level of 6-keto-PGF1 alpha in the mucosal layer was significantly higher than that in the seromuscular layer. These data suggest that prostaglandin I2 may play an important pathophysiological role in the course of cholecystitis.

Combined effects of cholecystectomy and lithocholic acid on pancreatic carcinogenesis of N-nitrosobis(2-hydroxypropyl)amine in Syrian golden hamsters.

The effects of cholecystectomy and/or lithocholic acid (LCA) on the composition of biliary bile acid and on pancreatic carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) were examined in male Syrian golden hamsters. Cholecystectomy was performed 1 wk before BHP initiation. BHP (250 mg/kg of body weight) was injected s.c. once a wk for 5 wk. A diet containing 0.5% LCA was begun 1 wk after the final BHP injection. All hamsters were sacrificed 36 wk after cholecystectomy, and the pancreas was examined histologically. Only the LCA treatment but no other treatment influenced the bile acid composition, i.e., the increase in LCA and decrease in cholic acid. The incidence of pancreatic carcinoma was 23 of 30 (76.7%) in hamsters receiving cholecystectomy plus BHP followed by LCA diet. The tumor incidence was five of 18 (27.8%) with BHP followed by basal diet, ten of 18 (55.6%) with cholecystectomy plus BHP followed by basal diet, and six of 18 (33.3%) with BHP followed by LCA diet, respectively. The total number of pancreatic carcinomas in hamsters receiving cholecystectomy and BHP followed by LCA diet also increased significantly. These results indicate that combined treatments of cholecystectomy and dietary LCA enhanced BHP-inducing pancreatic carcinogenesis in hamsters.