Real-world results of immune checkpoint inhibitors from the Taiwan National Health Insurance Registration System.

OBJECTIVE: Immune checkpoint inhibitors (ICIs) are a major advance in cancer treatment, but their payment benefits are unclear, resulting in financial risk. In Taiwan, the National Health Insurance Administration (NHIA) has adapted risk-sharing mechanisms to cover ICIs by collecting and assessing real-world evidence, such as case registration data, to adjust benefit packages for each medication, increase payment benefits of ICIs, and enable national health insurance sustainability. PATIENTS AND METHODS: This nationwide, multicenter, retrospective cohort study assessed the real-world use, effectiveness, and safety of ICIs reimbursed by the NHIA for treating multiple advanced cancers in Taiwan. We obtained data mainly from the NHIA Immune Checkpoint Inhibitor Registry Database. RESULTS: Between April 1, 2019, and March 31, 2020, 1644 patients received at least one dose of ICIs. The overall response rate (RR) was 29.1%. The metastatic urothelial carcinoma of patients ineligible for chemotherapy showed the highest RR. The estimated median progression-free survival (PFS) was 2.8 months (95% confidence interval [CI]=2.7-3 months), and renal cell carcinoma showed the longest PFS. The median PFS was reached in patients with most cancers except classic Hodgkin's lymphoma, which had a small sample size. The estimated survival probability was 50%. CONCLUSIONS: Under the national registration tracking system, Taiwan's high-cost drug policy has enabled access to new medicines and maximized patient benefits.

Luteolin induces apoptosis in oral squamous cancer cells.

Oral squamous cell carcinoma is the most common malignancy of the oral cavity, and treatment approaches are inadequate. Luteolin, a natural flavonoid compound, has been shown to have anti-tumorigenic properties on various types of tumors. Therefore, we hypothesized that luteolin has anti-tumorigenic properties for oral squamous cell carcinoma, and may provide effective chemotherapy. Results revealed that luteolin reduced the viability of SCC-4 cells and induced apoptosis by decreasing the expression of cyclin-dependent kinase (CDKs), cyclins, and phosphor- retinoblastoma (p-Rb) anti-apoptotic protein, but increased the expression of pro-apoptotic proteins and activated caspase 9 and 3, with a concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP). Combination treatment of luteolin with paclitaxel enhanced the cytotoxic effect of paclitaxel in SCC-4 cells, and continuous administration of luteolin suppressed the growth of xenograft tumors in nude mice. These results suggest that luteolin could be an effective chemotherapeutic agent for the treatment of oral squamous cell carcinoma.

Non-life-threatening leukopenia in a renal transplant recipient with acute overdose of mycophenolate mofetil.

Mycophenolate mofetil (MMF) is increasingly used as an immunosuppressant for organ transplantation and for treatment of autoimmune diseases. As yet, the experience with acute overdose of MMF in humans is limited. Herein we have reported a 40-year-old female kidney recipient with moderate leukopenia and lack of gastrointestinal toxicity following ingestion of 25 g MMF, which was confirmed by serum drug levels. We treated the patient with charcoal decontamination and oral cholestyramine. She recovered completely without sequelae.

Possible mechanism by which rapamycin increases cyclosporine nephrotoxicity.

It is well known that the combination of cyclosporine A (CsA) with rapamycin produces serious nephrotoxicity. Herein we suggest a mechanism by which rapamycin increases CsA nephrotoxicity. Previously, we demonstrated that activation of Akt/protein kinase B protects against cyclosporine nephrotoxicity and prevents apoptosis. Recently, it has been shown that Akt phosphorylation activates mammalian target of rapamycin (m-TOR) and inhibits programmed cell death including apoptosis and autophagy. Akt is believed to be an importance factor for cell survival. In theory, blockade of the Akt pathway through inhibition of m-TOR may increase cyclosporine-induced apoptosis. We added cyclosporine and rapamycin to cultures of ER52K proximal renal tubule cells, leading to a significantly decreased survival rate. The nephrotoxicity was associated with increased apoptosis by cleavage of caspase-3 and decreased phosphorylation of m-TOR and AktSer473, findings that support this hypothesis. This nephrotoxic effect may explain the clinical finding that patients treated with rapamycin alone exhibited better renal function than those treated with concomitant cyclosporine therapy.

Early diagnosis of polyomavirus type BK infection in tailoring immunosuppression for kidney transplant patients: screening with urine qualitative polymerase chain reaction assay.

Polyomavirus type BK (BKV) nephropathy is increasingly a significant cause of graft dysfunction and even failure. Early diagnosis followed by reduction of immunosuppression has been associated with an improved prognosis. We screened 250 patients with the urine qualitative polymerase chain reaction (PCR) for BKV DNA. We followed with blood BKV PCR if the urine screen was positive and then reduced immunosuppression in viremic patients. One hundred ninety-nine patients (80%) had no viuria; 43 (17%) viuria; and 8 (3%) both viuria and viremia. Graft biopsy performed in three patients (1%) with viremia and impaired graft function all revealed BKV nephropathy. After 6 months of follow-up, seven out of eight viremic patients (88%) had negative repeat blood PCR and stabilized graft function. An early diagnosis of BKV infection with reduction of immunosuppression may reverse viremia and retard progression of BKV nephropathy. BKV screening by PCR assays should be considered in kidney transplant recipients, especially those with impaired graft function.

A Salmonella infection complicated with suppurative thyroiditis and ruptured aortic mycotic aneurysm in a renal transplant recipient.

We report a renal transplant recipient who presented with fever and chills for 2 days. The blood and stool cultures revealed the growth of Salmonella enteriditis. A whole-body gallium scan played an important role in the subsequent diagnosis of suppurative thyroiditis. To our knowledge, this is the first report of acute S. enteriditis thyroiditis in a renal transplant recipient. Despite vigorous antibiotic use and a partial thyroidectomy, he experienced recurrent S. enteriditis infection, resulting in a ruptured thoracic mycotic aneurysm 1 month later. Finally the patient was successfully cured with aneurysm resection, in situ reconstruction of the thoracic aorta, and prolonged antibiotics.

Predictors of renal function improvement following tacrolimus conversion in cyclosporine-treated kidney transplant recipients.

The objective of this study was to evaluate the relationship between variability of cyclosporine (CsA) absorption and tacrolimus (TAC) conversion seeking factors that predict improvement in allograft function after TAC conversion. We performed a retrospective study of 44 adult kidney transplant recipients undergoing conversion from CsA to TAC-based immunosuppression. Before TAC conversion, patients had complete, consecutive, 6 monthly C2 levels and a follow-up duration beyond 6 months after TAC conversion. The patients were divided into 2 groups: one (n=23) with low variability of CsA absorption and one (n=21) with high variability of CsA absorption. At TAC conversion, the estimated glomerular filtration rate (eGFR) was similar in both patient groups. Six months after TAC conversion, eGFR improved in both groups. Stepwise regression analysis revealed the DeltaSCr6 (change in serum creatinine level at 6 months) to be independently associated with the preconversion serum creatinine (SCr; P<.0001) and the percent coefficient of variation (%CV) of SCr (P=.0034). DeltaSCr6 was inversely associated with posttransplantation years (P=.0033), and 6-month TAC blood levels (P=.0053). The DeltaSCr6 was not associated with variability of oral CsA absorption. The cutoff value of baseline SCr at TAC conversion differentiated an increase in or reduction of SCr to be about 1.0 mg/dL. Our study of CsA-treated kidney transplant recipients who underwent TAC conversion showed that a preconversion SCr>1.0 mg/dL, a high variability of SCr, and early TAC conversion predicted greater short-term benefit on graft function.

Lack of hepatotoxicity upon sirolimus addition to a calcineurin inhibitor-based regimen in hepatitis virus-positive renal transplant recipients.

BACKGROUND: We retrospectively analyzed the impact of sirolimus addition (SRL) with a 25% dosing reduction in calcineurin inhibitors on liver function among patients with or without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. METHODS: Forty-eight renal transplant recipients (HBsAg-positive, n = 5; anti-HCV-positive, n = 7) with allograft dysfunction (serum creatinine: mean 2.7, median 2.0 mg/dL) and normal liver function were enrolled. The duration of the SRL add-on therapy was 8.0 +/- 3.6 months. SRL trough levels were maintained within 6.5 +/- 3.7 ng/mL. The trough levels of tacrolimus and the 2-hour cyclosporine postdose levels were tapered to 4.6 +/- 1.9 ng/mL (24.6% reduction) and 650 +/- 170 ng/mL (24.3% reduction), respectively. SRL-related hepatitis was defined as a rise in liver transferase or alkaline phosphatase or bilirubin over twice the upper limit of normal. Thirty-six HBsAg-negative and anti-HCV-negative patients served as the controls. RESULTS: Hepatotoxicity developed in 6 (12.5%) of the 48 patients and in 3 (8.3%) of 36 control subjects. One (20.0%) of five HBsAg-positive patients (P = .959) and two (28.6%) of seven anti-HCV-positive patients (P = .496) developed hepatotoxicity, respectively. Three (25.0%) of the 12 HBsAg-positive or anti-HCV-positive patients developed hepatotoxicity (P = .420). CONCLUSIONS: Patients with seropositivity of HBsAg or anti-HCV had an insignificantly higher percentage of hepatitis. Use of SRL in the HBV/HCV patients is not contraindicated, but needs monitoring for HBV/HCV activation.

AgSK1, a novel carcinoma associated antigen.

An IgM human monoclonal antibody (HuMAb) SK1 was generated from mesenteric nodal lymphocytes of a colon cancer patient that were fused with a human B-lymphoblastoid cell line SHFP-1. The reactivities of HuMAb SK1 to various human cell lines were screened by cell enzyme linked immunosorbent assay and immunocytochemical staining. The HuMAb SK1 reacted strongly with all 11 human carcinoma cell lines that were tested and had no detectable binding with noncarcinoma cell lines of the following origins: fibroblast; fetal lung; melanoma; soft tissue sarcoma; neuroblastoma; and glioblastoma. Carcinoma preferred reactivity of HuMAb SK1 was further confirmed by immunoperoxidase staining of a large number of frozen tissues, both malignant and benign. The antigen SK1 (AgSK1) in human carcinoma detected by immunoperoxidase staining was also identified biochemically as a sialoglycoprotein that migrated at M(r) 42,000 with an isoelectric point (pI) of approximately 5.9. A preferential staining by HuMAb SK1 was seen among colorectal, gastric, pancreatic, and lung cancers. Competitive inhibition study in solid-phase immunoassay suggested that the HuMAb SK1 did not cross-react with other antibodies specific for CEA, CA 19-9, and TAG 72. The AgSK1 appears to be a novel carcinoma associated antigen which may be a useful tumor marker in cancer diagnosis and treatment.

Expression of Raf kinase inhibitor protein in human hepatoma tissues by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight methods.

PURPOSE: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. To reduce the mortality and improve the effectiveness of therapy, it is important to search for changes in tumor-specific biomarkers whose function may involve in disease progression and which may be useful as potential therapeutic targets. Materials and Mehtods: In this study, we use two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to observe proteome alterations of 12 tissue pairs isolated from HCC patients: Normal and tumorous tissue. Comparing the tissue types with each other, 40 protein spots corresponding to fifteen differentially expressed between normal and cancer part of HCC patients. RESULTS: Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein kinase/extracellular signal-regulated kinase, may play an important role in cancer metastasis and cell proliferation and migration of human hepatoma cells. RKIP may be considered as a marker for HCC, because its expression level changes considerably in HCC compared with normal tissue. In addition, we used the methods of Western blotting and real time-polymerase chain reaction to analysis the protein expression and gene expression of RKIP. The result showed RKIP protein and gene expression in tumor part liver tissues of HCC patient is lower than peritumorous non-neoplastic liver tissue of the corresponding HCC samples. CONCLUSION: These results strongly suggest that RKIP may be considered to be a marker for HCC and RKIP are down-regulated in liver cancer cell.

[The roles of serum free light chain ratio in the diagnosis and prognosis of newly diagnosed multiple myeloma].

OBJECTIVE: The roles of serum free light chain ratio (sFLCR) in the diagnosis and prognosis of newly diagnosed multiple myeloma (NDMM) patients were analyzed. METHODS: The clinical data was retrospectively analyzed for 82 newly diagnosed multiple myeloma (NDMM) patients in the first affiliated hospital of Soochow University from September 28, 2012 to July 18, 2105. The serum free light chain levels were measured and κ/λ ratios were calculated, so we could analyze the roles of sFLCR in the diagnosis and prognosis of newly diagnosed multiple myeloma (NDMM) patients. RESULTS: It was 85.5% (70/82) positive of M protein by serum protein electrophoresis (SFE) and 93.9%(77/82) by serum immunofixation electrophoresis (IFE). Both sFLC and sFLCR abnormalities were 96.3% (79/82). The estimated 40-months overall survival was 87% for the high free light chain ratio group (sFLCR ≥100 or≤0.01) and 61% for the low free light chain ratio group (0.01

[Comparison of allogeneic or autologous hematopoietic stem cell transplant for high-risk peripheral T cell lymphomas].

Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL). Twenty-one patients (21/60) received allo-HSCT, and thirty-nine (39/60) auto-HSCT. Before receiving transplantation, 40/60 patients were in complete remission (CR), 2/60 patients partial remission (PR) and 18/60 patients not remission (NR). In the 40 CR patients before transplant, 10 patients received allo-HSCT and 30 patients auto-HSCT, respectively. In the 20 PR/NR patients before transplant, 11 patients received allo-HSCT and 9 patients auto-HSCT, respectively. After a median follow-up of 39 (range 1-96) months, the K-M analysis showed that the 5-year PFS by auto-HSCT and allo-HSCT were 61% and 60% (P=0.724) , respectively. The 5-year OS by auto-HSCT and allo-HSCT were 62% and 61% (P=0.724) , respectively. There were no statistically significant differences between auto-HSCT and allo-HSCT. And the cumulative TRM of auto-HSCT and allo-HSCT were 22.7% and 41.8% (P=0.250) , respectively within 5-years after transplantation. At the end of the last follow-up, 7 and 2 patients relapsed in auto-HSCT and allo-HSCT groups respectively, the 5-year cumulative recurrence rates of auto-HSCT and allo-HSCT transplantation were 37.2% and 10.1% (P=0.298), respectively. Conclusion: There was no significant difference in the long-term survival between auto-HSCT and allo-HSCT for high risk PTCL patients. Outcome by allo-HSCT may be better for NR patients.

Respective role of polymorphonuclear leukocytes and their integrins (CD-11/18) in the local or systemic toxicity of lipopolysaccharide.

The role of neutrophils (PMNs) and leukocyte integrins was investigated in two models of lipopolysaccharide (LPS)-induced toxicity: the systemic lethality assay in D-galactosamine-sensitized mice and the local reaction elicited by intradermal injection of LPS and tumor necrosis factor (TNF) at 24-h intervals. In the local reaction, depletion of PMNs with an anti-PMN monoclonal antibody (mAb) and mAbs against CD-11a (or LFA1) and CD-11b (or CR3) completely prevented the hemorrhagic necrosis. Evaluation of histological sections and myeloperoxidase levels suggested different mechanism of protection because PMNs were abundant in anti-CD-11- and absent in anti-PMN-treated mice. In the systemic assay, depletion of PMNs ensured 100% survival, whereas after administration of anti-CD-11a or b mAb, the percentages of survivors were 6 and 59%, respectively. One hour after LPS injection, the serum TNF-alpha level was higher in PMN-depleted mice than in controls. These studies provide evidence that neutrophils are essential for the expression of local or systemic LPS-induced injury, whereas the requirement for their leukocytic integrins is obvious only in the local reaction.

Early experience with enteric-coated mycophenolate sodium in de novo kidney transplant recipients.

INTRODUCTION: We sought to evaluate the efficacy of enteric-coated mycophenolate sodium (EC-MPS) and the gastrointestinal (GI) adverse events in de novo kidney transplant recipients. METHODS: This noncontrolled, retrospective review includes 22 de novo kidney transplant recipients. All patients received a standard course of basiliximab and were maintained on triple-drug therapy with EC-MPS, cyclosporine microemulsion (CsA), and prednisolone. The follow-up lasted 7.9 +/- 1.2 months. The incidence of GI adverse effects were compared with those of historical mycophenolate mofetil (MMF) studies. RESULTS: The serum creatinine was maintained within 1.4 +/- 0.7 mg/dL. The 2-hour CsA postdose level was 1080 +/- 327 ng/mL initially and gradually tapered to 851 +/- 435 ng/mL. The daily EC-MPS dose was 1404 +/- 180 mg initially and gradually tapered to 1098 +/- 288 mg. The GI adverse effects at the daily dose of EC-MPS 1422 +/- 126 mg included dyspepsia 27%, acid regurgitation 18.2%, epigastralgia 9%, nausea 9%, vomiting 4.5%, and poor appetite 4.5%. In comparison those from historical MMF 2 g/d studies included dyspepsia 3.1% to 40%, epigastralgia 10%, nausea 3.7% to 34%, and vomiting 0.6% to 10.7%. CONCLUSION: Immunosuppression with CsA, EC-MPS, and steroids maintains stable graft functions. Minimal dose reduction of EC-MPS decreases GI adverse events but without significance. EC-MPC and MMF have respective GI side effects; they can be used alternatively in patients with individual GI intolerance.

Somatic mosaicism for DNA repair capacity in fibroblasts derived from a group A xeroderma pigmentosum patient.

A female Japanese xeroderma pigmentosum (XP) patient with severe skin lesions and various neurologic abnormalities was assigned to complementation group A by conventional cell fusion studies. Ultraviolet (UV)-irradiated skin fibroblasts showed a biphasic survival curve, as measured by colony-forming ability. The surviving fraction decreased rapidly up to 2 J/m2 of UV, with a steep slope of D(O) (mean lethal dose) = 0.95 J/m2. At much higher doses it decreased more slowly, with D(O) = 3.5 J/m2. To èlucidate the cause of this unique survival response, we isolated a large number of independent clones from single colonies and measured their responses to UV. Of 81 clones analyzed, ten showed a marked resistance to killing by UV, which was only slightly more sensitive than normal cells, and these clones had a rate of unscheduled DNA synthesis (UDS) that was about 45% of normal cells. By contrast, the remaining 71 clones were extremely sensitive to UV, typical of XP group A strains, and had a UDS level 1%-3% of normals. Analysis of restriction fragment length polymorphism using seven polymorphic DNA probes indicated that the UV-resistant clones were derived from the same individual as the UV-sensitive clones. These results clearly demonstrate that this patient's fibroblast cells consist of two types with differing responses to UV, and provide direct evidence of somatic mosaicism for DNA repair capacity in an XP patient.

Nonpalpable breast cancer in women aged 40-49 years: a surgeon's view of benefits from screening mammography.

While mammography screening among women aged 50 years or older has proven to reduce breast cancer mortality, screening in younger women has been repeatedly scrutinized. To test the effect of screening among younger women, we examined 84 consecutive patients aged 40-49 at the time of breast cancer diagnosis: 27 (32.1%) were diagnosed solely by mammography, and 57 (67.9%) had a palpable mass. The mean tumor sizes were 1.3 cm and 3.6 cm for the two groups respectively. While 68.8% nonpalpable invasive tumors were classified as Stage I cancer, only 34% of patients with palpable breast cancer had Stage I disease. None of the patients with nonpalpable breast cancer had disease beyond Stage II. In contrast, 28.3% of the patients with palpable invasive breast cancer presented with advanced disease. In addition, 6.3% versus 41.5% of patients with nonpalpable and palpable breast cancer respectively had nodal metastases. The five-year survival rates for the two groups were 100% and 73% respectively, favoring breast cancer detected mammographically. Screening of women aged 40-49 also resulted in more breast-conserving surgery and less chemotherapy. We conclude that screening in this age group should be continued, although individual assessment is needed.

Dietary supplementation with fish oil enhances in vivo synthesis of tumor necrosis factor.

Studies reported here investigate the influence of dietary fat types on cytokine production in response to endotoxin (LPS) challenge. Tumor necrosis factor (TNF) serum levels were markedly higher (by 10-fold) in mice fed chronically a diet rich in fish oil rather than either a diet rich in corn or coconut oil or a low fat diet. This in vivo hyper-responsiveness in LPS-induced TNF production following fish oil consumption concorded with similar exaggerated in vitro TNF release from macrophages exposed to LPS. These data suggest that high consumption of fish oils, by virtue of their high content of omega-3 polyunsaturated fatty acids, can lead to an exaggerated production of mediators of inflammation with potentially adverse consequences on the outcome and severity of infectious diseases.

Reduction in lymphocyte beta-adrenergic receptor density in infants and children with heart failure secondary to congenital heart disease.

To identify changes in catecholamine levels and beta-adrenergic receptor density in children with varying degrees of congestive heart failure, we measured plasma norepinephrine (NE), epinephrine, and beta-adrenergic receptor levels in 91 noncyanotic patients using high-performance liquid chromatography and a radioligand binding assay. Plasma NE levels in 41 patients with heart failure (694 +/- 236 pg/ml) were significantly higher than those in 50 patients without it (274 +/- 68 pg/ml, p < 0.001). In addition, beta-adrenergic receptor density was significantly lower in patients with heart failure (0.81 +/- 0.48 fmol/10(6) cells) than in those without it (2.43 +/- 1.09 fmol/10(6) cells, p < 0.001), but epinephrine levels were not significantly different between the 2 groups. The receptor reduction in heart failure correlated well with elevated plasma NE levels (r = -0.60, p < 0.001). The degree of left to right shunt flow and pulmonary systolic pressure correlated directly with plasma NE levels and inversely with beta-adrenergic receptor density. From the best compromise between sensitivity and specificity, the optimal cutoff point for heart failure was > 390 ng/ml for NE and < 1.30 fmol/10(6) cells for beta-adrenergic receptor density, respectively. A follow-up study in 15 of 30 patients with heart failure after surgery showed a significant decrease in plasma NE and an increase in beta-adrenergic receptor density. Changes in plasma NE levels and beta-adrenergic receptor density occur concurrently with clinical symptoms of heart failure and may be used as indexes for assessing the presence and severity of heart failure in infants and children.

Decreased salivary function in patients with end-stage renal disease requiring hemodialysis.

It has been speculated that impaired salivary flow is common in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD). The aim of this study is to investigate the relation between oral manifestations and salivary function in patients with ESRD undergoing HD. Salivary function was measured by quantitative salivary scintigraphy in 60 patients with ESRD undergoing HD, as well as in 36 age- and sex-matched healthy controls for comparison. The 60 patients with ESRD undergoing HD were separated into two subgroups: group 1, 30 patients with oral manifestations, and group 2, 30 patients without oral manifestations. After an intravenous injection of 5 mCi of technetium 99m pertechnetate, sequential images at 1 minute per frame were acquired for 30 minutes. The 1- and 15-minute uptake ratios were calculated as the tracer uptakes in the four major salivary glands over the background regions of interest. Saliva excretion was stimulated by one 200-mg tablet of ascorbic acid administered orally 15 minutes post-tracer injection, then the maximal excretion ratios of the four major salivary glands were calculated. Our results show significantly poorer salivary function in patients with ESRD with oral manifestations compared with patients with ESRD without oral manifestations and healthy controls by means of objective and quantitative salivary scintigraphy.

Cutaneous blood flow and adrenoceptor response increase in segmental-type vitiligo lesions.

It has been proposed that two types of vitiligo exist from the physiological and clinical points of view. Nonsegmental-type vitiligo is associated with autoimmune diseases while segmental-type vitiligo results from the dysfunction of sympathetic nerves in the affected area. Using laser Doppler flowmetry and iontophoresis for cutaneous microcirculatory assessments, we evaluated these two types of vitiligo in regard to their physiological changes. Ten patients with facial stable stage segmental-type vitiligo and ten stable nonsegmental-type vitiligo patients were selected for this study. Our results revealed that a nearly threefold increase in cutaneous blood flow was noticed in segmental-type vitiligo as compared to contralateral normal skin. In contrast, a 1.4-1.5 times difference was found among nonsegmental-type vitiligo, lesion side clinically normal skin and contralateral normal skin. There was a significant increase in cutaneous alpha- and beta-adrenoceptor response in segmental-type vitiligo lesions. However, no change in plasma catecholamines or adrenoceptor densities on blood cells was noticed. Our findings suggest that a dysfunction of the sympathetic nerves exists in the affected skin and plays a role in the pathogenesis of segmental-type vitiligo.