Investigation of the Effect of Canagliflozin on the Disposition Index, a Marker of Pancreatic Beta Cell Function, in Patients with Type 2 Diabetes.

AIM: Our aim was to investigate the effects of add-on canagliflozin with glimepiride dose adjustment or glimepiride dose adjustment on pancreatic beta cell function in patients with type 2 diabetes mellitus and inadequate glycemic control despite stable triple therapy (metformin, teneligliptin, and glimepiride) plus diet/exercise therapy. METHODS: Forty patients on stable triple therapy were randomized to glimepiride dose adjustment without (glimepiride group) or with add-on canagliflozin 100 mg (canagliflozin group) for 24 weeks. The glimepiride dose was adjusted every 4 weeks based on continuous glucose monitoring over the previous 2 weeks according to a prespecified algorithm. After the 24-week treatment period, the patients returned to the pre-intervention regimen for 1 week (wash-out period). Patients underwent 75 g OGTTs at the start of the run-in period and at the end of the wash-out period. The primary endpoint was the change in disposition index (DI). RESULTS: Thirty-nine patients completed the study (canagliflozin, n = 19; glimepiride, n = 20). The change in DI was +5.1% and -11.0% in the canagliflozin and glimepiride groups, respectively, with a between-group difference ratio of 18.0% (P = 0.330). HbA1c, fasting plasma glucose, body weight, and daily-life continuous glucose monitoring-derived parameters improved in the canagliflozin group. Hypoglycemia occurred in 60% (44 episodes) and 70% (79 episodes) of patients in the canagliflozin and glimepiride groups, respectively. The change in DI was significantly correlated with the changes in glycemic control and variability in overall cohort. CONCLUSION: Adding canagliflozin to the triple therapy improved beta cell function by 18%, but it did not reach statistical significance. This study also demonstrated a correlation between the change in DI and glycemic control. As canagliflozin improved both glucose level and variability with relatively lower risk of hypoglycemia compared with glimepiride dose adjustment, adding canagliflozin to the triple therapy may be clinically beneficial. TRIAL REGISTRATION: UMIN000030208/jRCTs051180036.

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer.

BACKGROUND: Many cancers express heme oxygenase-1 -(HO-1) at a higher frequency than healthy tissues, and this elevated expression is associated with cancer prognosis. Here, we aim to clarify the correlation between HO-1-expressing macrophage numbers and clinicopathological parameters of advanced colorectal cancer. MATERIALS AND METHODS: Formalin-fixed and paraffin-embedded tissues of patients with advanced colorectal cancer were used. To detect HO-1 expression in macrophages, immunohistochemistry was performed. The number of positive cells was measured. Furthermore, HO-1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction. RESULTS: Among the HO-1-negative and HO-1-positive groups, 58.02 and 85.00% of cases, respectively, were positive for lymph node metastasis. The disease-free survival (DFS) time was significantly shorter (p < 0.05) in the -HO-1-positive group (2.44 years) than in the HO-1-negative group (4.09 years). However, according to the Cox proportional-hazards regression model, the HO-1-positive group could not be a risk factor of poor prognosis. HO-1 mRNA expression was confirmed in colorectal normal and cancer tissues. CONCLUSION: In this study, the correlation between HO-1-expressing macrophages and clinicopathological parameters in the tumor microenvironment of colorectal cancer was studied for the first time, and the expression was associated with lymph node metastasis and shortening of DFS.

Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma.

Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B-cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL. Reverse transcription-polymerase chain reaction was performed to detect ERα mRNA in FL. In nonneoplastic germinal centers (GCs) from patients with tonsillitis or reactive lymphadenitis, ERα was expressed in the light zone. ERα-positive cells strongly correlated with the width of GCs (rs  = 0.81, P < 0.01) and the CD21-positive (rs  = 0.69, P < 0.01) and CD23-positive (rs  = 0.83, P < 0.01) FDC meshwork. The axillary lymph nodes had fewer ERα-positive cells, smaller GCs, and a looser CD21- and CD23-positive FDC meshwork with hormone therapy than without hormone therapy (P < 0.01). Neoplastic follicles of G1-2 FL had more ERα-positive cells and a larger CD23+ FDC meshwork than those of G3 FL (P < 0.01). ERα mRNA was detected in both G1-2 FL and G3 FL by reverse transcription-polymerase chain reaction. In conclusion, these results suggested that antiestrogen hormone therapy may decrease the number of ERα-positive FDCs and that the responses mediated by the estrogen-ERα interaction on FDCs may differ between G1-2 FL and G3 FL.

Efficacy and safety of canagliflozin in type 2 diabetes mellitus patients with biopsy-proven nonalcoholic steatohepatitis classified as stage 1-3 fibrosis.

AIM: Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is known to be associated with type 2 diabetes mellitus (T2DM) in high rate. The improvement in hepatic function due to sodium-glucose co-transporter 2 (SGLT2) inhibitors has been reported in T2DM patients with and without NAFLD. However, only a few studies have attempted to evaluate the role of SGLT2 inhibitors in T2DM patients with biopsy-proven NASH, and no detailed prospective studies including the individual hepatic fibrosis stage have been reported. Therefore, we investigated the effect of canagliflozin on hepatic function in T2DM patients with biopsy-confirmed NASH. METHODS: T2DM patients with NASH (hepatic fibrosis stage 1-3 confirmed via liver biopsy, n=10) were enrolled and received canagliflozin (100 mg) once a day for 12 weeks. The primary end point was change in serum alanine aminotransferase (ALT) levels from baseline to week 12. Secondary end points were liver function/fibrosis markers, metabolic parameters, and safety. RESULTS: The change in ALT from baseline to week 12 was -23.9 U/L (95% CI -48.1 to 0.3, P=0.0526). Significant improvements in several hepatic function/fibrosis markers, such as aspartate aminotransferase, fibrosis-4 index, and FM-fibro index, and metabolic parameters including hemoglobin A1c and body weight were found. No serious or liver-related adverse events were reported. Regarding individual patients, different trends in ALT-lowering effects between stage 1 and stage 2/3 subjects were observed; the degree of ALT-lowering effect tended to be greater in the stage 1 group than in the stage 2/3 group. CONCLUSION: Our results suggest that canagliflozin is effective and well-tolerated in patients with T2DM and NASH. Canagliflozin may be useful for the treatment of T2DM patients with NASH, especially those in early stages of NASH.

Effect of Canagliflozin on Urinary Albumin Excretion in Japanese Patients with Type 2 Diabetes Mellitus and Microalbuminuria: A Pilot Study.

BACKGROUND: Albuminuria characterizes the progression of kidney injury. The effect of canagliflozin on the excretion of microalbumin was assessed for investigating its renoprotective potential in Japanese patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: Twenty Japanese patients with T2DM and microalbuminuria were enrolled and administered with 100 mg of canagliflozin once a day for 12 weeks. These subjects were admitted to the clinic at the start and end of the treatment period for 24-h urine collection. The primary endpoint was the percentage change in geometric mean 24-h urinary albumin excretion from baseline to week 12. RESULTS: The urinary albumin level decreased by 42.0% (95% confidence interval: 21.9-57.0; P = 0.0011) after 12 weeks of canagliflozin treatment. A number of blood and urinary parameters also significantly decreased, including hemoglobin A1c, fasting plasma glucose, estimated glomerular filtration rate, and creatinine clearance, while hematocrit was elevated. Among the biomarkers associated with kidney injury and inflammation, the urinary level of the oxidative stress marker 8-hydroxy-2'-deoxyguanosine was also decreased. There were no meaningful correlations noted between changes in urinary albumin excretion and other parameters/biomarkers. No severe adverse events were reported over the 12-week treatment period. CONCLUSIONS: The results of this study indicate that canagliflozin decreases microalbuminuria in Japanese patients with T2DM. Albuminuria could be reduced as a result of changes in various physiological pathways; therefore, it is imperative that future, large-scale, studies attempt to determine the detailed mechanisms involved. Canagliflozin may offer a novel therapeutic option for Japanese patients with T2DM and incipient nephropathy.

Effects of canagliflozin, an SGLT2 inhibitor, on hepatic function in Japanese patients with type 2 diabetes mellitus: pooled and subgroup analyses of clinical trials.

BACKGROUND: We aimed to investigate the efficacy of canagliflozin (based on its effect on liver function and blood glucose levels) and its safety in high alanine aminotransferase (ALT) patients (ALT >30 U/L). METHODS: This post hoc analysis of canagliflozin in type 2 diabetes mellitus (T2DM) patients was divided into Study 1 (pooled analysis of 12- and 24-week placebo-controlled, monotherapy studies) and Study 2 (52-week monotherapy/combination therapy study). The canagliflozin 100 mg group data were compared with placebo or baseline ALT subgroup (baseline ALT >30 or ≤30 U/L) data. The primary endpoint was change in ALT level from baseline. Secondary endpoints were changes in efficacy-related parameters. Adverse events (AEs) were evaluated. RESULTS: The mean ALT change at 12 weeks was -10.3 ± 11.7 and -3.2 ± 17.6 U/L in the canagliflozin vs. placebo group in the high ALT subgroup (P = 0.0206); no significant difference was shown in the low ALT subgroup (Study 1). In both ALT subgroups, glycosylated hemoglobin (HbA1c) and body weight were significantly reduced in the canagliflozin vs. placebo group (all P < 0.0001). The mean change in ALT at 52 weeks was -16.0 ± 18.8 U/L in the high ALT subgroup (P < 0.0001, Study 2). The incidence of AEs or serious AEs in the high ALT subgroup in the canagliflozin group was similar to that in the placebo group (Study 1) or low ALT subgroup (Studies 1 and 2). CONCLUSIONS: In T2DM patients with impaired liver function, canagliflozin may improve liver function, reduce HbA1c and body weight, and be well tolerated.

Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors exhibit diuretic activity, which is a possible mechanism underlying the cardiovascular benefit of these inhibitors. However, the osmotic diuresis-induced increase in urine volume, and the risk of dehydration have been of concern with SGLT2 inhibitor treatment. This study aimed to investigate the mechanism underlying SGLT2 inhibitor canagliflozin-induced diuresis in Japanese type 2 diabetes mellitus (T2DM) patients. METHODS: Thirteen T2DM patients received a daily oral dose of 100 mg canagliflozin before breakfast for 6 days. Blood and urine samples were collected at predetermined time points. The primary endpoint was evaluation of correlations between changes from baseline in urine volume and factors that are known to affect urine volume and between actual urine volume and these factors. RESULTS: Canagliflozin transiently increased urine volume and urinary sodium excretion on Day 1 with a return to baseline levels thereafter. Canagliflozin administration increased urinary glucose excretion, which was sustained during repeated-dose administration. Plasma atrial natriuretic peptide (ANP) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels decreased, while plasma renin activity increased. On Day 1 of treatment, changes in sodium and potassium excretion were closely correlated with changes in urine output. A post hoc multiple regression analysis showed changes in sodium excretion and water intake as factors that affected urine volume change at Day 1. Furthermore, relative to that at baseline, canagliflozin decreased blood glucose throughout the day and increased plasma total GLP-1 after breakfast. CONCLUSION: Canagliflozin induced transient sodium excretion and did not induce water intake at Day 1; hence, natriuresis rather than glucose-induced osmotic diuresis may be a major factor involved in the canagliflozin-induced transient increase in urine output. In addition, canagliflozin decreased plasma ANP and NT-proBNP levels and increased plasma renin activity, which may be a compensatory mechanism for sodium retention, leading to subsequent urine output recovery. CLINICAL TRIAL REGISTRATION: UMIN000019462. FUNDING: Mitsubishi Tanabe Pharma Corporation.

Expression of acetylated and dimethylated histone H3 in colorectal cancer.

AIM: The expression of acetylated and dimethylated histone H3 in colorectal cancer was examined by immunohistochemistry and chromatin immunoprecipitation (ChIP)/Western blot (WB) assay. The correlation between the expression of histone H3 and clinicopathological findings was analyzed. METHODS: Formalin-fixed and paraffin-embedded sections obtained from 80 operated cases of colorectal cancer were immunostained with anti-acetylated histone H3 (H3Ac) antibody and anti-dimethylated histone H3 lysine 4 (H3K4) antibody. Positive immunoreactivity was evaluated using the Allred scoring system. Furthermore, the expression was confirmed by ChIP/WB assay using formalin-fixed and paraffin-embedded sections. RESULTS: There was good correlation between immunostaining and expression on ChIP/WB assay (p = 0.0005). There was a significant difference between the Allred score of H3K4 and the depth of tumor invasion (p = 0.0003) and the pathological stages (p = 0.0065). In overall survival classified by Allred scores of H3Ac (p = 0.0072) and H3K4 (p = 0.0187), the highest scores represented significantly worse prognoses than the other scores. Specifically, in stages II and III, the highest scores represented significantly worse prognoses than the other scores (p < 0.0001 and p = 0.0173, respectively). CONCLUSION: The expression of H3Ac and H3K4 may estimate patient prognosis.

[A case of relapsed colon cancer successfully treated by capecitabine].

We report a case of advanced relapsed colon cancer, which had multiple liver and spleen metastasis, controlled for about two years by capecitabine therapy. A 60-year-old female had been diagnosed with ileus due to sigmoid colon cancer in August, 2005. She received sigmoidectomy and adjuvant chemotherapy (Leucovorin/5-fluorouracil therapy). In postoperative observation, multiple liver and spleen metastasis were detected by computed tomography in February, 2008. Therefore, she was administered twenty courses of FOLFOX therapy. However, a peripheral nerve disturbance appeared. There fore chemotherapy was changed from FOLFOX therapy to FOLFIRI therapy. After 2 courses of FOLFIRI therapy, she had severe nausea, vomiting, appetite loss and diarrhea. Therefore, chemotherapy was changed from FOLFIRI therapy to capecitabine therapy. After capecitabine therapy, her multiple liver and spleen metastasis disappeared, and complete response has continued for about 2 years. She has remained on capecitabine therapy and has a good quality of life.

Observational study on the efficacy and safety of erlotinib in patients with non-small cell lung cancer.

To evaluate the efficacy and safety of erlotinib for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The study involved 307 patients treated with erlotinib at 14 sites (17 departments) in Ibaraki (Japan) between December 2007 and December 2010. The tumor response and disease control rates were 11.1 and 46.3% in all patients, respectively. The median time to treatment failure and survival time were 1.6 months (95% confidence interval, 41-57 days) and 5.3 months (134-181 days) in all patients, respectively. Survival was significantly prolonged in EGFR mutation-positive patients compared with negative patients. EGFR mutation-negative patients who presented with a skin rash had significantly prolonged survival compared with those without a skin rash. The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies. We deduce that erlotinib is effective against NSCLC and is tolerated in clinical practice.

Erlotinib for elderly patients with non-small-cell lung cancer: Subset analysis from a population-based observational study by the Ibaraki Thoracic Integrative (POSITIVE) Research Group.

The incidence and mortality of lung cancer have increased worldwide over the last decades, with an observed increased incidence particularly among elderly populations. It has not yet been determined whether erlotinib therapy exhibits the same efficacy and safety in elderly and younger patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective subgroup analysis of data from a population-based observational study was to assess the efficacy and safety of erlotinib in an elderly (≥75 years, n=74) and a younger group of patients (<75 years, n=233) who received treatment for NSCLC. The time to treatment failure was similar in the elderly [median, 62 days; 95% confidence interval (95% CI): 44-80 days] compared with the younger group (median, 46 days; 95% CI: 35-53 days) (P=0.2475). The overall survival did not differ between the elderly and younger groups (median, 170 days; 95% CI: 142-239 days vs. median, 146 days; 95% CI: 114-185 days, respectively) (P=0.7642). The adverse events did not differ in incidence between the groups and were manageable, regardless of age. Among the NSCLC patients receiving erlotinib treatment, the outcomes of the elderly (≥75 years) and younger (<75 years) groups of patients were similar in our population-based observational study.

Bevacizumab-containing chemotherapy for non-small cell lung cancer patients: a population-based observational study by the Ibaraki thoracic integrative (POSITIVE) research group.

To evaluate the efficacy and safety of bevacizumab-containing chemotherapy for non-small cell lung cancer (NSCLC), we performed a population-based observational study. The efficacy and safety of bevacizumab-containing chemotherapy for NSCLC patients were evaluated at 14 sites (17 hospital departments) in a prefecture of Japan between December 2009 and August 2011. Complete data sets were obtained from 159 patients with NSCLC. The median age was 66 years, and 34.0 % of the patients were 70 years or older. The overall response rate to bevacizumab therapy was 41.6 %, and the disease control rate was 78.5 %. In 88 patients who received bevacizumab-containing chemotherapy as first-line therapy, the response and disease control rates were 55.0 and 78.9 %, respectively. The incidence of clinically significant (grade 3 or more) adverse events was generally low: proteinuria occurred in 2 (1.3 %) patients, hypertension in 2 (1.3 %), hemoptysis in 1 (0.6 %), and interstitial pneumonia in 1 (0.6 %). The time to treatment failure (TTF) in the 159 patients was 169 days, and the median overall survival (OS) was 580 days. In patients who received bevacizumab-containing chemotherapy as first-line therapy, the TTF and OS were 152 and 520 days, respectively. The difference in TTF between patients who received bevacizumab-containing chemotherapy as first-line therapy and those who received it as second-line or later-line therapy was not significant (p = 0.4971). With regard to first-line therapy, the difference in TTF between patients treated with carboplatin + pemetrexed + bevacizumab and those treated with carboplatin + paclitaxel + bevacizumab was not significant (p = 0.9435). We deduced that bevacizumab-containing chemotherapy is effective against NSCLC and also tolerable in clinical practice.

Evaluation of salvage surgery for type 4 gastric cancer.

Patients with type 4 gastric cancer and peritoneal metastasis respond better to chemotherapy than surgery. In particular, patients without gastric stenosis who can consume a meal usually experience better quality of life (QOL). However, some patients with unsuccessful chemotherapy are unable to consume a meal because of gastric stenosis and obstruction. These patients ultimately require salvage surgery to enable them to consume food normally. We evaluated the outcomes of salvage total gastrectomy after chemotherapy in four patients with gastric stenosis. We determined clinical outcomes of four patients who underwent total gastrectomy as salvage surgery. Outcomes were time from chemotherapy to death and QOL, which was assessed using the Support Team Assessment Schedule-Japanese version (STAS-J). Three of the patients received combination chemotherapy [tegafur, gimestat and otastat potassium (TS-1); cisplatin]. Two of these patients underwent salvage chemotherapy after 12 and 4 mo of chemotherapy. Following surgery, they could consume food adequately and their STAS-J scores improved, so their treatments were continued. The third patient underwent salvage surgery after 7 mo of chemotherapy. This patient was unable to consume food adequately after surgery and developed surgical complications. His clinical outcomes at 3 mo were very poor. The fourth patient received combination chemotherapy (TS-1 and irinotecan hydrochloride) for 6 mo and then underwent received salvage surgery. After surgery, he could consume food adequately and his STAS-J score improved, so his treatment was continued. After the surgery, he enjoyed his life for 16 mo. Of four patients who received salvage total gastrectomy after unsuccessful chemotherapy, the QOL improved in three patients, but not in the other patient. Salvage surgery improves QOL in most patients, but some patients develop surgical complications that prevent improvements in QOL. If salvage surgery is indicated, the surgeon and/or oncologist must provide the patient with a clear explanation of the purpose of surgery, as well as the possible risks and benefits to allow the patient to reach an informed decision on whether to consent to the procedure.

G-CSF-producing malignant pleural mesothelioma: an autopsy case report with literature review.

This study reports a 54-year-old man who was a carpenter by occupation. He suffered from left chest and back pain and left pleural effusion. Peripheral blood showed granulocytosis and high serum titers of granulocyte-colony stimulating factor (G-CSF) and CYFRA. He died 20 months later. At autopsy, a pleural tumor located around the left lung and thickening of the pericardium, diaphragm, and esophagus by tumor infiltration was seen. The tumor proliferated in papillary and solid alveolar patterns by neoplastic cells. They were positive for calretinin, D2-40, CK5/6, HBME-1, G-CSF, CK19, and E-cadherin. He was diagnosed with G-CSF-producing epithelioid malignant pleural mesothelioma.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.

Hemostatic action of OC-108, a novel agent for hemorrhoids, is associated with regional blood flow arrest induced by acute inflammation.

Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection of OC-108 in rats decreased blood flow at the injection site within 5 min. Aluminum potassium sulfate, one of the main ingredients of OC-108, reduced the skin blood flow. However, tannic acid, another main ingredient, did not. By perfusion of OC-108 on the mesenteric surface, microcirculatory blood flow was arrested without remarkable change in blood vessel diameter, accompanied by increased vascular permeability and venous hematocrit. These results indicate that OC-108 induces regional blood flow arrest with rapid onset, this effect being attributed to the action of aluminum potassium sulfate, and that hemoconcentration due to increased vascular permeability (plasma extravasation), an acute inflammatory reaction, is involved in the mechanisms of the immediate hemostatic action of OC-108.

Percutaneous CT-guided radiofrequency ablation of pulmonary malignant tumors: preliminary report.

OBJECTIVE: Radiofrequency ablation (RFA) is frequently used for hepatic malignant tumors, but few reports discuss its use for lung tumors. We report our pilot clinical study with RFA for the treatment of pulmonary malignant tumors. PATIENTS AND METHODS: Five patients with histologically-proven malignant primary and three metastatic lung tumors underwent a total of 11 RFA procedures. RFA was performed in two patients as palliative therapy to shrink the tumors and in six as radical therapy. All RFA was performed by the percutaneous CT-guided approach. RESULTS: Three tumors were completely ablated by one procedure. Contrast CT revealed cyst cavity formation or scar formation at these three tumors. Gd contrast-enhanced MRI revealed cystic lesions with ringlike enhancement or scar formation. Partial ablation after the first procedure was noted in six tumors including the two palliative cases. RF ablation was well tolerated in all patients. Intraprocedural complications included six cases of pneumothorax (one patient required chest tube placement), six cases of pleural effusion (two patients required chest tube placement), one case of pneumonia (improved immediately with antibiotics), three cases of bloody sputum (mild), and six cases of chest pain (all cases after the procedure). CONCLUSIONS: This pilot clinical study demonstrates that CT-guided RFA is a relatively safe and effective treatment option for malignant lung tumors. Additional trials are needed to determine the safety, efficacy, and optimal indications of RFA.

[Postoperative intensive care of a patient with Cushing's syndrome accompanied with retroperitoneal abscess and massive subcutaneous emphysema].

A 60-year-old woman with Cushing's syndrome due to right adreno-cortical adenoma was referred to us because retroperitoneal abscess was found during surgical removal of the right adrenal gland. The diagnosis of Cushing's syndrome was made on the basis of elevated serum levels of cortisol. The abscess was accompanied with massive subcutaneous emphysema and pneumomediastinum. After operation the patient was admitted to ICU in the Medical Center for Emergency and Critical Care. PMX-DHP, continuous hemodiafiltration, and drainage were performed, and antibiotics were given. Nine days after the admission the patient recovered generally, and was transfferd to the Department of Urology. It was demonstrated that an opportunistic infection must be always considered in the condition like the present case.