Relationship Between Adverse Events and Progression-free Survival in Patients Receiving Cabozantinib for Previously Treated Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Although the adverse events (AEs) of drugs, such as sunitinib and axitinib, have been shown to predict treatment responses, evidence to support cabozantinib-induced AEs as predictors of responses to treatment for metastatic renal cell carcinoma (mRCC) is limited. Therefore, we herein investigated the relationship between AE profiles and progression-free survival (PFS) in patients receiving cabozantinib for previously treated mRCC. PATIENTS AND METHODS: The present study retrospectively analyzed 40 patients receiving cabozantinib for previously treated mRCC between July 2020 and August 2022. PFS was estimated using the Kaplan-Meier method and the impact of several parameters, including cabozantinib-induced AEs, on PFS was investigated by a Cox proportional regression analysis. RESULTS: The median observation period was 15 (2-29) months, during which time 31 patients (77.5%) progressed, with median PFS of 11 months. Thirty-nine patients (97.5%) developed at least one AE. Liver toxicity occurred in 16 patients (40.0%) and hand-foot syndrome, hypertension, and diarrhea in 14 each (17.5%). Only hypertension correlated with longer PFS. A multivariate analysis identified hypertension as an independent prognostic factor for PFS (p=0.049). CONCLUSION: These results suggest the potential of treatment-induced hypertension as a significant predictor of prolonged PFS in patients receiving cabozantinib for mRCC.

Pembrolizumab Versus Combined Chemotherapy With Gemcitabine and Paclitaxel: A Comparative Assessment of Clinical Outcomes in Patients With Platinum-refractory Advanced Urothelial Cancer.

BACKGROUND/AIM: There are limited data on comprehensive assessments of several treatments as second-line therapy against advanced urothelial cancer (UC). The objective of this study was to compare clinical outcomes between advanced UC patients receiving either pembrolizumab (Pem) or combined chemotherapy with gemcitabine and paclitaxel (GP) as second-line therapy. PATIENTS AND METHODS: This study retrospectively analyzed the clinical outcomes of 89 patients with platinum-refractory advanced UC, consisting of 46 and 43 who received Pem and GP therapy, respectively, as second-line treatment. RESULTS: There were no significant differences in major clinicopathological parameters between Pem and GP groups. No significant difference in the objective response rate was noted between the two groups. Progression-free survival (PFS) in the Pem group was significantly longer than that in the GP group; however, there was no significant difference in overall survival (OS) between them. Multivariate analyses identified performance status ≤2 and liver metastasis as independent factors associated with poor outcomes in both PFS and OS. The incidence of adverse events in the GP group was significantly higher than that in the Pem group. CONCLUSION: Pem could be regarded as standard agent for platinum-refractory advanced UC patients.

Genome-Wide Association Study Confirming a Strong Effect of HLA and Identifying Variants in CSAD/lnc-ITGB7-1 on Chromosome 12q13.13 Associated With Susceptibility to Fulminant Type 1 Diabetes.

The first genome-wide association study of fulminant type 1 diabetes was performed in Japanese individuals. As previously reported using a candidate gene approach, a strong association was observed with multiple single nucleotide polymorphisms (SNPs) in the HLA region, and the strongest association was observed with rs9268853 in the class II DR region (P = 1.56 × 10-23, odds ratio [OR] 3.18). In addition, rs11170445 in CSAD/lnc-ITGB7-1 on chromosome 12q13.13 showed an association at a genome-wide significance level (P = 7.58 × 10-9, OR 1.96). Fine mapping of the region revealed that rs3782151 in CSAD/lnc-ITGB7-1 showed the lowest P value (P = 4.60 × 10-9, OR 1.97 [95% CI 1.57-2.48]). The risk allele of rs3782151 is a cis expression quantitative trait locus for ITGB7 that significantly increases the expression of this gene. CSAD/lnc-ITGB7-1 was found to be strongly associated with susceptibility to fulminant, but not classical, autoimmune type 1 diabetes, implicating this locus in the distinct phenotype of fulminant type 1 diabetes.

Contralateral pneumothorax during retroperitoneal laparoscopic donor nephrectomy: A case report.

This report presents a case of a 46-year-old woman in whom contralateral pneumothorax occurred during retroperitoneal laparoscopic donor nephrectomy without any evidence of diaphragmatic injuries. After the start of carbon dioxide-induced pneumoperitoneum, the patient's end-tidal carbon dioxide pressure and heart rate suddenly increased. The surgery was then paused, and a chest X-ray revealed a right pneumothorax accompanied by pneumomediastinum. After a thoracostomy tube was inserted, these symptoms immediately improved. After conversion to an open procedure, the surgery was completed. The thoracostomy tube was removed the next day, and the patient was discharged without any complications. As the pneumothorax occurred on the opposite side to the operative field and there was no evidence of diaphragmatic injury, it is suspected to have been caused by a pneumomediastinum-induced rupture of the barrier between the mediastinum and pleural space. This may have occurred due to the insufflated carbon dioxide gas passing directly into the mediastinum and then the pleural space.

The Effects of Unilateral Nephrectomy on Blood Pressure and Its Circadian Rhythm.

Objective Hypertension and diurnal blood pressure (BP) variation are widely accepted as risk factors for renal damage. However, the effects of unilateral nephrectomy on BP and its circadian rhythm have not yet been clarified in patients with a compromised renal function, including dialysis patients. Methods We investigated 22 unilateral nephrectomized patients (16 men and 6 women, age: 64.5±14.3 years). The function of the circulating renin-angiotensin system (RAS) (plasma renin activity and plasma angiotensin II) and 24-h ambulatory BP monitoring (ABPM) were evaluated before and after nephrectomy. Daytime and nighttime 24-h ABPM values were determined based on sleep and waking times. Results In non-dialysis patients, the estimated glomerular filtration rate after nephrectomy was significantly lower than that before (before, 62.4±23.2 mL/min/1.73 m2 vs. after, 43.7±16.8 mL/min/1.73 m2; p<0.01). No significant differences were noted in the levels of BPs and circulating RAS before and after nephrectomy. However, the night-to-day (N/D) ratio of systolic BP (SBP) was significantly higher after nephrectomy than before (before, 93.3±6.5% vs. after, 98.4±6.9%; p<0.01), and the patterns of circadian BP rhythm also significantly differed before and after nephrectomy (p=0.022). Namely, the rates of dipper patterns decreased and nondipper and riser patterns increased after nephrectomy. In contrast, in dialysis patients, no significant differences were observed in the N/D ratio of SBP or the patterns of circadian BP rhythm before and after nephrectomy. Conclusion Unilateral nephrectomy affects the circadian rhythm of BP but not absolute values of BP.

[Strangulation of the Penis by Four Metallic Washers].

We report here a case of strangulation of the penis. A 69-year-old male visited our hospital suffering from a swollen penis and dysuria after installation of four metallic washers to the penis. He had mischievously put them on his penis four days before and subsequently was unable to remove them. We found erosion on the surface of the penis, reduction in blood flow by ultrasonography, and high C-reactive protein levels. Because we could not remove washers by blood removal from glans penis or ring cutter, we performed percutaneous cystostomy and then cut the washers with an electric grinder under general anesthesia. The operation took 2 hours and 25 minutes. The postoperative course was uneventful. Neither disturbance of blood flow nor urethral stricture was found. He completely recovered without erectile dysfunction or difficult urination 7 months after the operation. Management of this rare condition is discussed.

Effects of insulin degludec and insulin glargine on day-to-day fasting plasma glucose variability in individuals with type 1 diabetes: a multicentre, randomised, crossover study.

AIMS/HYPOTHESIS: We compared the effects of insulin degludec (IDeg; Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin) and insulin glargine (IGlar; A21Gly,B31Arg,B32Arg human insulin) on the day-to-day variability of fasting plasma glucose (FPG) levels in individuals with type 1 diabetes treated with basal-bolus insulin injections. METHODS: The effects of basal-bolus insulin therapy for 4 weeks with either IDeg or IGlar as the basal insulin in adult C-peptide-negative outpatients with type 1 diabetes were investigated in an open-label, multicentre, randomised, crossover trial. Randomisation was conducted using a centralised allocation process. The primary endpoints were the SD and CV of FPG during the final week of each treatment period. Secondary endpoints included serum glycoalbumin level, daily dose of insulin, intraday glycaemic variability and frequency of severe hypoglycaemia. RESULTS: Thirty-six randomised participants (17 in the IDeg/IGlar and 19 in the IGlar/IDeg groups) were recruited, and data for 32 participants who completed the trial were analysed. The mean (7.74 ± 1.76 vs 8.56 ± 2.06 mmol/l; p = 0.04) and SD (2.60 ± 0.97 vs 3.19 ± 1.36 mmol/l; p = 0.03) of FPG were lower during IDeg treatment than during IGlar treatment, whereas the CV did not differ between the two treatments. The dose of IDeg was smaller than that of IGlar (11.0 ± 5.2 vs 11.8 ± 5.6 U/day; p < 0.01), but other secondary endpoints did not differ between the treatments. CONCLUSIONS/INTERPRETATION: IDeg yielded a lower FPG level and smaller day-to-day variability of FPG at a lower daily dose compared with IGlar in participants with type 1 diabetes. IDeg serves as a good option for basal insulin in the treatment of type 1 diabetes. TRIAL REGISTRATION: University Hospital Medical Information Network 000009965. FUNDING: This research recieved no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Primary hyperoxaluria complicated with liver cirrhosis: A case report.

Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The excess oxalate combines with calcium in the kidneys to form deposits of calcium oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1), the most common form of this disease, is caused by a deficiency of the liver-specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation is performed as a definitive therapy for PH to correct the enzyme defect. Usually, liver depositions are limited and liver function is normal without fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28-year-old woman was admitted to our hospital under suspicion of PH1 and the presence of nephrocalcinosis. The patient had suffered from kidney stone recurrences from 17 years of age, and was initiated on hemodialysis due to renal failure at the age of 27 years. The serum level of oxalic acid was high, whereas the AGT level in the liver tissue was decreased. Thus, the patient was definitively diagnosed with PH1. Although she had normal liver function, surface nodularity and splenomegaly were detected by computed tomography, suggesting liver cirrhosis. The native liver showed micronodular cirrhosis and portal fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile oxalate crystals and various portal tracts showed these crystals. Our case suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be considered one of the causes of liver cirrhosis.

A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer.

PURPOSE: Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC). METHODS: We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC. Patients received orteronel orally at doses of 200-400 mg twice daily (BID) with or without oral prednisolone (5 mg BID). Dose-limiting toxicity (DLT) was assessed during Cycle 1 (28 days). Patients could continue study treatment until any of criteria for treatment discontinuation were met. Gonadotropin-releasing hormone therapy was continued in patients without prior orchidectomy. RESULTS: Fifteen patients were enrolled and administered at least one dose of orteronel. No DLTs were reported during Cycle 1 in this study. Adverse events (AEs) were reported in all 15 patients. Most common AEs (>30%) were hyperlipasemia (47%), hyperamylasemia (40%), and constipation (33%). Acute pancreatitis (Grades 2 and 3) and pancreatitis (Grade 1) were complicated in three patients during the study. Dose-dependent increase in plasma orteronel concentrations was indicated over the 200-400 mg BID dose range. Prednisolone coadministered did not alter PK of orteronel. Serum testosterone was rapidly suppressed below the lower limit of quantification across all doses. Of 15 subjects, 13 achieved at least a 50% reduction from baseline in prostate-specific antigen. CONCLUSIONS: Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients. The present results support further evaluation of orteronel with or without prednisolone.

Breast cancer metastatic to the kidney with renal vein involvement.

The common sites of breast cancer metastases include bones, lung, brain, and liver. Renal metastasis from the breast is rare. We report a case of breast cancer metastatic to the kidney with extension into the renal vein. A 40-year-old woman had undergone left mastectomy for breast cancer at the age of 38. A gastric tumor, which was later proved to be metastasis from breast cancer, was detected by endoscopy. Computed tomography performed for further examination of the gastric tumor revealed a large left renal tumor with extension into the left renal vein. It mimicked a primary renal tumor. Percutaneous biopsy of the renal tumor confirmed metastasis from breast cancer. Surgical intervention of the stomach and the kidney was avoided, and she was treated with systemic chemotherapy. Breast cancer metastatic to the kidney may present a solitary renal mass with extension into the renal vein, which mimics a primary renal tumor.

The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic ß cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A) may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD) mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C)) was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C). In addition, injection of high-dose poly(I: C) to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C) than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C) treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

Insulin administration may trigger type 1 diabetes in Japanese type 2 diabetes patients with type 1 diabetes high-risk HLA class II and the insulin gene VNTR genotype.

CONTEXT: Insulin administration causes various types of immune responses to insulin. We previously reported three cases of type 1 diabetes mellitus (T1DM) triggered by insulin administration in Japanese type 2 diabetes mellitus patients. OBJECTIVE: The objective of this study was to collect information and characterize insulin-triggered T1DM immunologically and genetically. METHODS: Data for six patients (four men and two women) with insulin-triggered T1DM aged 59.5 ± 12.8 years were collected. Serum or urinary C-peptides, islet-related autoantibodies, insulin antibody, human leukocyte antigen, or the insulin gene variable number of tandem repeat genotype were analyzed. Th1- or Th2-associated responses were evaluated using an Enzyme-Linked ImmunoSpot assay. RESULTS: None of the subjects had received insulin therapy or had an autoantibody to the 65-kDa isoform of glutamic acid decarboxylase before insulin administration. After insulin administration blood glucose control deteriorated acutely without any apparent cause, whereas C-peptide levels rapidly decreased to insulin-deficient levels. The mean duration of insulin administration to the development of T1DM was 7.7 ± 6.1 months. Islet-related autoantibodies became positive, whereas insulin allergy or a high titer of insulin antibody was observed in several cases. All had T1DM high-risk human leukocyte antigen class II (IDDM1) and the insulin gene variable number of tandem repeats genotype (IDDM2). GAD-reactive and insulin peptide-reactive Th1 cells, but not Th2 cells, were identified in two of four cases. CONCLUSIONS: The findings suggest that insulin administration may have triggered TIDM in patients with type 2 diabetes mellitus. IDDM1 and IDDM 2 as well as autoreactive T cells may contribute to the development of T1DM. Developing insulin-triggered T1DM if a patient's blood glucose control acutely deteriorates after insulin administration should be carefully considered.

Diagnostic criteria for acute-onset type 1 diabetes mellitus (2012): Report of the Committee of Japan Diabetes Society on the Research of Fulminant and Acute-onset Type 1 Diabetes Mellitus.

Type 1 diabetes is a disease characterized by destruction of pancreatic ß-cells, which leads to absolute deficiency of insulin secretion. Depending on the manner of onset and progression, it is classified as fulminant, acute-onset or slowly progressive type 1 diabetes. Here, we propose the diagnostic criteria for acute-onset type 1 diabetes mellitus. Among the patients who develop ketosis or diabetic ketoacidosis within 3 months after the onset of hyperglycemic symptoms and require insulin treatment continuously after the diagnosis of diabetes, those with anti-islet autoantibodies are diagnosed with 'acute-onset type 1 diabetes mellitus (autoimmune)'. In contrast, those whose endogenous insulin secretion is exhausted (fasting serum C-peptide immunoreactivity <0.6 ng/mL) without verifiable anti-islet autoantibodies are diagnosed simply with 'acute-onset type 1 diabetes mellitus'. Patients should be reevaluated after certain periods in case their statuses of anti-islet autoantibodies and/or endogenous insulin secretory capacity are unknown.

Chaga mushroom-induced oxalate nephropathy.

Chaga mushrooms have been used in folk and botanical medicine as a remedy for cancer, gastritis, ulcers, and tuberculosis of the bones. A 72-year-old Japanese female had been diagnosed with liver cancer 1 year prior to presenting at our department. She underwent hepatectomy of the left lobe 3 months later. Chaga mushroom powder (4 - 5 teaspoons per day) had been ingested for the past 6 months for liver cancer. Renal function decreased and hemodialysis was initiated. Renal biopsy specimens showed diffuse tubular atrophy and interstitial fibrosis. Oxalate crystals were detected in the tubular lumina and urinary sediment and oxalate nephropathy was diagnosed. Chaga mushrooms contain extremely high oxalate concentrations. This is the first report of a case of oxalate nephropathy associated with ingestion of Chaga mushrooms.

Axitinib controlled metastatic renal cell carcinoma for 5 years.

We present two patients with a long-term response to axitinib for cytokine-refractory metastatic renal cell carcinoma. One patient has had a continuing partial response for 58 months with cytokine-intolerant metastatic renal cell carcinoma and the other patient has had continuing stable disease accompanied by a mixed response for 57 months with cytokine-refractory and intolerant metastatic renal cell carcinoma. The condition of hypertension as an adverse event markedly depended on whether or not axitinib was administered. The patients responded to axitinib with an elevation of diastolic blood pressure to 90 mmHg or higher until 2 weeks after starting axitinib. To get a long-term response to axitinib, it may be important to control well the balance between treatment effect and adverse events while using drug withdrawal.

[Bilateral adrenal hemorrhage due to adrenal metastasis of lung cancer].

A 58-year-old man presented with nausea and left flank pain. The patient was referred to our hospital based on clear detection of anemia and computed tomography findings of bilateral adrenal tumors with hemorrhage and a mass in the apex of the left lung. Right adrenal artery embolization had no effect on enlargement of the right adrenal hematoma or advanced anemia. Right adrenalectomy was then performed in an attempt to control hemorrhaging and make a definitive diagnosis, and the patient's anemia improved following the operation. Histopathological diagnosis suggested adrenal metastasis of lung adenocarcinoma, which was subsequently diagnosed given similarities in transbronchial biopsy findings to those in the right adrenal gland. Adrenal hemorrhage due to metastasis of lung cancer is an extremely rare condition; indeed, to our knowledge, the present case is only the 26th reported worldwide. However, prognosis for this mortal condition may be improved should patients receive adrenalectomy followed by an appropriate treatment regimen.

Silkworm plasmatocytes are more resistant than other hemocyte morphotypes to Bombyx mori nucleopolyhedrovirus infection.

Differences in the viral susceptibility of multiple insect hemocyte morphotypes have not been investigated to date. In this study, a Bombyx mori nucleopolyhedrovirus (BmNPV) derivative possessing a Drosophila hsp70 promoter-driven green fluorescent protein (GFP) gene was used to observe NPV tropism of B. mori larval hemocytes. The experiments clearly revealed that there were fewer GFP-positive plasmatocytes than those observed in other types of hemocytes, such as granulocytes, oenocytoids, and spherulocytes, when infected via the intrahemocoelic or oral route. Our results indicate that silkworm plasmatocytes are more resistant than other hemocyte morphotypes to BmNPV infection.

[Salvage therapy for castration-refractory prostate cancer resistant to docetaxel].

OBJECTIVES: To evaluate the treatment for castration-refractory prostate cancer (CRPC) resistant to docetaxel MATERIALS AND METHODS: Among 45 patients with CRPC treated with docetaxel (70-75 mg/m2) every 3 to 4 weeks at Hamamatsu University Hospital from January 2004 to July 2012, 19 patients underwent salvage treatments. We retrospectively analyzed the medical records of 14 patients except for 5 patients who were enrolled in clinical trials. RESULTS: The median age and serum prostate-specific antigen (PSA) level at starting salvage treatments was 71 years (range 45 to 79) and 241.1 ng/mL (range 3.06 to 1,643.0), respectively. All patients maintained castration status. Salvage treatments include DTX (30 mg/m2) + cisplatin (CDDP) (70 mg/m2)/carboplatin (Area under the curve = 4), etoposide + CDDP, paclitaxel + CDDP, cyclophosphamide, S-l, tegaful-uracil. The reasons why 14 patients moved to salvage treatments after DTX were progressive disease in 12 patients and adverse events in 2. Eight patients had a PSA response, 3 patients>50% and 5 patients<50%. Six patients had a PSA progression. The median overall survival was 10.4 months (range 4.1 to 27.3). All patients died of cancer, 13 patients with prostate cancer and one patient with lung adenocarcinoma. Most adverse events were mild. Transitory grade 3 leukopenia was observed in 2 patients, and grade 3 anemia in 2. No grade 4 toxicities were noted. CONCLUSIONS: All salvage treatments without grade 4 toxicities described in this study may be acceptable in the patients with CRPC progressing after docetaxel although the effect would be limited.

High-grade myxofibrosarcoma presenting at the spermatic cord after radiotherapy for prostate cancer.

A 72-year-old man with a history of prostate cancer presented 7 years postradiotherapy with a painless, egg-sized, rapidly growing nodule on the left groin at the radiation site. He underwent left high orchiectomy under a diagnosis of groin lymph node metastasis of prostate cancer. The tumour had penetrated deep into the internal inguinal ring and was resected as proximally as possible to the internal ring with a positive surgical margin. Macroscopically, the left testis was intact in the resected specimen. Immunohistochemical staining revealed that the tumour consisted of myxofibrosarcoma (MFS) with spindle cells; and was positive for vimentin, cytokeratin (AE1/AE3), MIB-1 and CD68, and negative for α-SMA, S-100, CD34 and myogenin. Thus, the tumour was diagnosed as high-grade MFS of the spermatic cord. Postoperative CT revealed a right renal tumour and adrenal tumour. Right radial nephrectomy was performed and the patient was doing well at 10-month follow-up.

[A clinical study of laparoscopic adrenalectomy for pheochromocytoma--analysis of clinical parameters influencing operative time and intraoperative systolic blood pressure].

PURPOSE: We retrospectively analyzed the preoperative clinical parameters which influence operative time and intraoperative maximum systolic blood pressure in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. MATERIALS AND METHODS: Between January 1992 and September 2010, we performed 28 laparoscopic adrenalectomies for pheochromocytoma at Hamamatsu University School of Medicine. These 28 cases were characterized based on the following parameters: body mass index (BMI), tumor size, history of hypertension, preoperative blood pressure, serum concentration of catecholamine, and 24-h urinary excretion of catecholamine metabolite. We retrospectively analyzed whether or not these parameters influenced operative time or intraoperative maximum systolic blood pressure. RESULTS: All 28 cases of laparoscopic adrenalectomy were performed safely and without intraoperative complications and needed neither blood transfusion nor conversion to laparotomy. The median operative time was 203 minutes, and intraoperative hypertension (systolic blood pressure > 200 mmHg) occurred in 46% (13/28) of cases. Median day of discharge in all patients was post-operative day 5. Significant positive correlation was shown between tumor size and operative time and between intraoperative maximum systolic blood pressure and serum concentration of catecholamine or 24-h urinary excretion of catecholamine metabolite (p < 0.05). CONCLUSION: The lengthened operative time for large tumors and elevated intraoperative blood pressure for tumors with high preoperative catecholamine activity necessitate careful perioperative management in patients receiving laparoscopic adrenalectomy for pheochromocytoma.