Utility of Transpapillary Biopsy and Endoscopic Ultrasound-Guided Tissue Acquisition for Comprehensive Genome Profiling of Unresectable Biliary Tract Cancer.

Tissue sampling in biliary tract cancer (BTC) is generally performed through transpapillary biopsy (TPB) or endoscopic ultrasound-guided tissue acquisition (EUS-TA). For the first time, we compared the suitability of specimens obtained using TPB and EUS-TA to determine the optimal tissue-sampling method for comprehensive genome profiling (CGP) analysis in patients with unresectable BTC (UR-BTC). Pathology precheck criteria for CGP analysis comprised the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Seventy-eight patients with UR-BTC (35 TPB and 43 EUS-TA) were included. The NCCOP analysis suitability achievement rate was higher in EUS-TA specimens than in TPB specimens (34.9% vs. 8.6%, p = 0.007), whereas that of F1CDx was 0% in both groups. EUS-TA was identified as an independent factor that contributed to the suitability of the NCCOP analysis. The suitability of the NCCOP analysis of EUS-TA specimens showed a tendency to be higher for mass lesions (43.8% vs. 9.1%, p = 0.065), especially for target size ≥ 18.5 mm, and lower for perihilar cholangiocarcinoma (0% vs. 41.7%, p = 0.077). In TPB, papillary-type lesions (66.7% vs. 3.2%, p = 0.016) and peroral cholangioscopy-assisted biopsies (50.0% vs. 3.3%, p = 0.029) showed better potential for successful NCCOP analysis. EUS-TA is suitable for NCCOP analysis in UR-BTC and may be partially complemented by TPB.

Study Protocol for a Prospective Self-Controlled Trial on Success in Meeting Comprehensive Genomic Profiling Analysis Criteria for Specimens Obtained by Endoscopic Ultrasound-Guided Tissue Acquisition Using a 19G Needle from Primary and Metastatic Lesions in Pancreatic Cancer with Metastatic Lesions: The PRIMATE Study.

EUS-TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS-TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS-TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS-TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity of ≥20% and a tissue area of ≥4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Diagnostic performance of EUS-guided tissue acquisition for solid pancreatic lesions ≤10 mm.

Background and Objectives: EUS tissue acquisition (EUS-TA) is the standard diagnostic method for solid pancreatic lesions (SPLs); however, there are few reports on EUS-TA results for SPLs ≤10 mm. Furthermore, given the recent advent of fine-needle biopsy, the current diagnostic accuracy of EUS-TA for SPLs ≤10 mm is unknown. This study aimed to evaluate the diagnostic accuracy and efficacy of EUS-TA for SPLs ≤10 mm. Methods: We retrospectively analyzed the data of 109 patients with SPLs ≤10 mm who underwent EUS-TA. All patients underwent rapid on-site specimen evaluation. Results: The median tumor diameter was 8 mm (range, 2.5-10 mm), and the technical success rate was 99.1% (108/109). Adverse events were observed in 3 patients (2.8%). The diagnostic performance was as follows: sensitivity, 90.1% (64/71); specificity, 97.3% (36/37); accuracy, 92.6% (100/108); positive predictive value, 98.5% (64/65); and negative predictive value, 83.7% (36/43). Multivariate analysis revealed that the number of punctures (odds ratio, 7.03; 95% confidence interval, 1.32-37.5; P = 0.023) and tumor type (odds ratio, 11.90; 95% confidence interval, 1.38-102.0; P = 0.024) were independent risk factors for inaccurate EUS-TA results. The diagnostic accuracy of EUS-TA for pancreatic ductal adenocarcinoma was 87.5% (14/16). No EUS-TA-related needle-tract seeding was observed in patients with pancreatic ductal adenocarcinoma during the observation period. Conclusions: EUS-TA for SPLs ≤10 mm showed adequate diagnostic accuracy and was safe for use with rapid on-site specimen evaluation in all cases.

Comparison of stent patency between EUS-guided hepaticogastrostomy with bridging and endoscopic transpapillary biliary drainage for hilar obstruction.

Background and study aims Endoscopic ultrasound-guided hepaticogastrostomy with bridging between the left and right bile ducts is an alternative to endoscopic transpapillary drainage for malignant hilar biliary obstruction. We aimed to analyze the long-term stent patency of endoscopic ultrasound-guided hepaticogastrostomy with bridging. Patients and methods Patients who underwent endoscopic ultrasound-guided hepaticogastrostomy with bridging between April 2018 and July 2023 were retrospectively analyzed. We retrospectively compared the stent patency of these patients with that of the individuals who underwent endoscopic transpapillary drainage-multi-stenting using unmatched (entire) and propensity score-matched cohorts. Results Endoscopic ultrasound-guided hepaticogastrostomy with bridging had a technical success rate of 90% (18/20). Adverse events were minimal. The number of clinical success cases was 17 and 82 for endoscopic ultrasound-guided hepaticogastrostomy with bridging using metallic stent and endoscopic transpapillary drainage-multi-stenting, respectively. The recurrent biliary obstruction rate was 17.6% and 58.5% for endoscopic ultrasound-guided hepaticogastrostomy with bridging and endoscopic transpapillary drainage-multi-stenting, respectively; the median time to recurrent biliary obstruction (days) was significantly longer for endoscopic ultrasound-guided hepaticogastrostomy with bridging in the entire (not reached vs. 104, P =0.03) and propensity score-matched (183 vs. 79, P =0.05) cohorts. The non-recurrent biliary obstruction rate for endoscopic ultrasound-guided hepaticogastrostomy with bridging was 91.6% at 3 and 6 months and 57% at 12 months. Multivariate analyses revealed that endoscopic ultrasound-guided hepaticogastrostomy with bridging contributed to a lower recurrent biliary obstruction incidence (hazard ratio, 0.31, P =0.05) without significant difference. Conclusions Stent patency was significantly better for endoscopic ultrasound-guided hepaticogastrostomy with bridging. However, future prospective studies are needed.

Feasibility and safety of a novel plastic stent designed specifically for endoscopic ultrasound-guided pancreatic duct drainage.

Background and study aims Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD) is emerging as an effective alternative treatment for obstructive pancreatitis after unsuccessful endoscopic retrograde pancreatography (ERP). However, the high incidence of adverse events associated with EUS-PD (approximately 20%) remains an issue. Recently, we developed a novel plastic stent for EUS-PD, with a radiopaque marker positioned at approximately one-third of the length from the distal end of the stent and side holes positioned exclusively distal to the marker. This study aimed to evaluate the feasibility and safety of using this stent in EUS-PD. Patients and methods We retrospectively reviewed data from 10 patients who underwent EUS-PD with the novel plastic stent at the National Cancer Center Hospital between March 2021 and October 2023. Technical and clinical success, procedure times, adverse events (AEs), recurrent pancreatic duct obstruction (RPO), and time to RPO were assessed. Results Of the 10 patients, five had postoperative benign pancreaticojejunal anastomotic strictures and five had malignant pancreatic duct obstruction. The technical and clinical success rates were both 100% (10/10). An AE (self-limited abdominal pain) occurred in one patient (10.0%). Two patients (20.0%) died of their primary disease during the follow-up period (median, 44 days; range, 25-272 days). The incidence of RPO was 10.0% (1/10), and the 3-month non-RPO rate was 83.3%. Conclusions The novel plastic stent shows potential as a useful and safe tool in EUS-PD.

Immune-related adverse event-associated sclerosing cholangitis due to immune checkpoint inhibitors: imaging findings and treatments.

OBJECTIVES: Immune-related adverse event-sclerosing cholangitis caused by treatment with immune checkpoint inhibitors is rare, and the diagnostic criteria and treatment strategy remain unclear. In this study, we confirmed the clinicopathological features of immune-related adverse event-sclerosing cholangitis and clarified its diagnosis and appropriate management. METHODS: We retrospectively evaluated 10 patients diagnosed with immune-related adverse event-sclerosing cholangitis and identified by electronic database searches. RESULTS: Blood tests revealed liver dysfunction with a predominance of biliary tract enzymes in all patients; however, jaundice was present in only one patient. Contrast-enhanced computed tomography revealed diffuse hypertrophy of the extrahepatic bile duct wall as the most frequent finding; however, endoscopic retrograde cholangiopancreatography showed various imaging features, such as the pruned-tree appearance of intrahepatic bile ducts, in all patients. Transpapillary bile duct biopsy showed inflammatory cell infiltration using immunostaining, with a predominance of cluster of differentiation 8-positive T cells in 63% of the cases. Initial steroid therapy was effective in two cases. Mycophenolate mofetil and tacrolimus were used in steroid-refractory cases. Although six patients showed improvements, all of the remaining patients died owing to immune-related adverse event-sclerosing cholangitis. CONCLUSIONS: Various bile duct imaging findings of immune-related adverse event-sclerosing cholangitis were revealed; transpapillary bile duct biopsy may be useful in the diagnosis of immune-related adverse event-sclerosing cholangitis. Despite the combination of multiple immunosuppressive agents, prognosis of immune-related adverse event-sclerosing cholangitis remains poor. Longer follow-up and larger clinical studies are necessary to establish its treatment strategy.

Incidence and factors associated with stent dysfunction and pancreatitis after gastroduodenal stenting for malignant gastric outlet obstruction.

Background and study aims Endoscopic gastroduodenal stent (GDS) deployment is currently a standard treatment for malignant gastric outlet obstruction (mGOO) in patients with limited life expectancy; however, stent dysfunction (SD) and complicated pancreatitis often occur after GDS deployment. We investigated incidence and contributing factors of SD and complicated pancreatitis. Patients and methods We retrospectively reviewed 203 patients who underwent initial GDS deployment for palliation of mGOO symptoms between October 2017 and July 2022, including 109 who underwent GDS deployment across the duodenal papilla (sub-cohort). Results SDs, including tumor ingrowth (n = 26), kinking (n = 14), and migration (n = 13), occurred in 68 patients (33.5%). Cumulative SD incidence was 41.1% (95% confidence interval, 32.6-49.4%). SD incidence increased to 0.4%, 0.16%, and 0.06% per day at < 8, 8-16, and>16 weeks, respectively. On multivariate analysis, Niti-S pyloric/duodenal stent deployment (sub-distribution hazard ratio [sHR] 0.26, P = 0.01) and survival length ≥ 90 days (sHR 2.5, P = 0.01) were respectively identified as favorable and risk factors significantly associated with SD. Pancreatitis developed in 14 patients (12.8%) in the sub-cohort, which had significantly higher parenchymal diameter ( P < 0.01) and lower main pancreatic duct (MPD) caliber ( P < 0.01) than the non-pancreatitis cohort. On multivariate analysis, MPD caliber < 3 mm independently predicted pancreatitis (odds ratio 6.8, P = 0.03). Conclusions Deployment of the Niti-S pyloric/duodenal stent, with conformability even for angulated strictures, significantly reduced the incidence of SD. Stent selection, life expectancy, and MPD caliber should be taken into consideration during decision-making for GDS deployment for mGOO.

Study protocol for a prospective, multicentre, phase II trial on endoscopic treatment using two fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy.

INTRODUCTION: The current endoscopic treatment for postoperative benign hepaticojejunostomy anastomotic stricture (HJAS) has a high technical success rate and is highly effective in the short term. However, long-term results have shown a high rate of stenosis recurrence, which indicates an insufficient response to treatment. Three prospective studies on fully covered self-expandable metallic stent (FC-SEMS) treatment for benign HJAS used the stenosis resolution rate as the primary endpoint, and no study has yet used the long-term non-stenosis rate (at 12 months) as the primary endpoint. METHODS AND ANALYSIS: We launched the 'saddle-cross study', which will be conducted as a multicentre, prospective intervention of endoscopic treatment using two modified FC-SEMSs (BONASTENT️ M-Intraductal) that have been improved for benign stenosis in patients with benign HJAS, with the long-term non-restenosis rate (at 12 months) as the primary endpoint. This study aims to evaluate the long-term non-restenosis rate (at 12 months) and safety of the saddle-cross technique for benign HJAS. We plan to enrol 50 participants. ETHICS AND DISSEMINATION: This study has been approved by the Certified Review Board of the National Cancer Center, Japan (CRB3180009). The results will be reported at various conferences and published in international peer-reviewed journals.

Efficacy of endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions 20 mm or less in diameter suspected as neuroendocrine tumors or requiring differentiation.

BACKGROUND: For non-functioning pancreatic neuroendocrine tumors (pNETs) ≤ 20 mm, most guidelines consider follow-up observations as an option; however, the various treatment strategies are defined by size alone, even though the Ki-67 index is important for malignancy grading. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the standard for the histopathological diagnosis of solid pancreatic lesions; however, recent results for small lesions remain unclear. Therefore, we examined the efficacy of EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation and the non-increase rate in tumor size in follow-up cases. METHODS: We retrospectively analyzed data of 111 patients (median age = 58 years) with lesions ≤ 20 mm suspected as pNETs or requiring differentiation who underwent EUS-TA. All patients underwent specimen evaluation by rapid onsite evaluation (ROSE). RESULTS: EUS-TA led to a diagnosis of pNETs in 77 patients (69.4%) and tumors other than pNETs in 22 patients (19.8%). The histopathological diagnostic accuracy of EUS-TA was 89.2% (99/111) overall, 94.3% (50/53) for 10-20 mm lesions, and 84.5% (49/58) for ≤ 10 mm lesions, with no significant difference in diagnostic accuracy (p = 0.13). The Ki-67 index was measurable in all patients with a histopathological diagnosis of pNETs. Among 49 patients with a diagnosis of pNETs who were followed up, one patient (2.0%) showed tumor enlargement. CONCLUSIONS: EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation is safe and has adequate histopathological diagnostic accuracy, suggesting that follow-up observations of pNETs with a histological pathologic diagnosis are acceptable in the short term.

Diagnostic Ability of Endoscopic Ultrasound-Guided Tissue Acquisition Using 19-Gauge Fine-Needle Biopsy Needle for Abdominal Lesions.

Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.

Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

Changes in the whole/intact parathyroid hormone ratio and their clinical implications in patients with chronic kidney disease.

BACKGROUND: Although a previous study has reported the relationship between intact parathyroid hormone (iPTH) and whole parathyroid hormone (wPTH) levels in patients undergoing dialysis, the w/i PTH ratio (whole/intact PTH ratio) among predialysis chronic kidney disease (CKD) patients remains unclear. The present study therefore aimed to examine the relationship between w/i PTH ratio and kidney function and determine other factors affecting the w/i PTH ratio. METHODS: An observational study including 773 predialysis CKD patients was conducted. The correlation between w/i PTH ratio and kidney function, as well as clinical factors at different CKD stages, were assessed using univariate and multivariate analyses. In addition, the relationship between w/i PTH ratio and composite renal outcome [kidney transplantation, dialysis, and 30% decline in estimated glomerular filtration rate (eGFR)] was examined. RESULTS: The w/i PTH ratio decreased as the CKD stage progressed. Patients in each CKD stage (1/2, 3, 4, and 5) had a w/i PTH ratio of 0.85, 0.81, 0.78, and 0.59, respectively. The inflection point in the correlation lines between eGFR and w/i PTH ratio was 24.1 mL/min/1.73 m2. In multivariate analysis, the w/i PTH ratio was significantly correlated with serum calcium levels only in the CKD5 group and with eGFR in the CKD3, CKD4 and CKD5 group. Furthermore, w/i PTH ratio, eGFR, serum phosphate levels, and urinary protein/creatinine ratio were determined to be significant independent predictors for composite renal outcome. CONCLUSIONS: Our study demonstrated that changes in the w/i PTH ratio were associated with kidney function, abnormal mineral metabolism, and renal outcome.

A Case of Acquired Haemophilia A in a Patient with Chronic Myelomonocytic Leukaemia.

A 67-year-old male, with a known diagnosis of myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) was admitted to our hospital with a primary complaint of subcutaneous bleeding in his left thigh. Laboratory data showed anaemia and prolongation of activated partial thromboplastin time (85.8 s, normal range 24-39 s) without thrombocytopenia. Coagulation factor VIII (FVIII) activity was less than 1% (normal range 60-150%), and a FVIII inhibitor was identified and quantified at 166 BU/mL to indicate a diagnosis of acquired haemophilia A (AHA). A recent, but sustained circulating monocytosis (>1 × 109/L) was observed, which combined with elevated numbers of neutrophil and monocytic cells in the marrow, suggested evolution of MDS-MLD to chronic myelomonocytic leukaemia (CMML), coinciding with AHA. Further analysis revealed a karyotype of 46, XY, i(14) (q10), which was the same abnormality previously identified in the patient. To treat bleeding caused by AHA, steroid and activated prothrombin complex concentrate were administered. Azacitidine (AZA) was used to treat CMML. During the clinical course, bleeding partially improved; however, subsequent acute myocardial infarction occurred on day 87. Worsening bone marrow failure was observed 4 months after the original admission, despite administration of AZA therapy, and the patient died due to bleeding from AHA. This case suggests that the evolution of MDS to CMML status can be associated with AHA conferring a bleeding tendency.

Effects of a luteinizing hormone-releasing hormone agonist on cognitive, sexual, and hormonal functions in patients with prostate cancer: relationship with testicular and adrenal androgen levels.

PURPOSE: To assess the cognitive and sexual/hormonal functioning of prostate cancer patients treated with a luteinizing hormone-releasing hormone (LH-RH) agonist, and the relationships thereof with adrenal and residual testicular androgen levels. MATERIALS AND METHODS: Previously, we reported the effect of a luteinizing hormone-releasing hormone (LH-RH) agonist on testicular and adrenal androgen production in patients with prostate cancer. A 6-month treatment with an LH-RH agonist significantly reduced testicular androgens by 90-95% and adrenal androgens by 26-40%. This study evaluated the changes in cognitive and sexual/hormonal functions in the same cohort using the Mini-Mental State Evaluation (MMSE) and Expanded Prostate Cancer Index Composite (EPIC) questionnaire, respectively. In addition, the associations of each function with the serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone-sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione (A-dione), and cortisol levels were studied. RESULTS: Cognitive functions did not change significantly during the treatment. Sexual functions were relatively low before treatment and worsened significantly after 6 and 12 months of treatment. Interestingly, sexual bothers were improved with the treatment. The treatment significantly worsened hormonal functions and bothers. Regarding specific items in the hormonal domains, hot flashes and body weight changes were the main effects of worsened hormonal function. Low levels of T and E2 and high levels of A-dione were associated with low MMSE scores at 6 months. Regarding sexual and hormonal functions, A-dione, E2, T, cortisol, and DHEA-S were associated with poorer functioning and bother. Especially, low T levels and high E2 levels were the most significant factors associated with worse sexual and hormonal bothers. CONCLUSION: The LH-RH agonist monotherapy worsened sexual and hormonal functions and hormonal bothers, but not sexual bothers or cognitive functions. The changes in these functions were related to the testicular and adrenal androgens levels.

Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats.

BACKGROUND: Prophylactic use of anticoagulants for septic patients in intensive care unit is a standard therapy for the prevention of venous thrombosis. Moreover, recent studies have demonstrated the anti-inflammatory effects of anticoagulants such as Factor Xa inhibitors and heparins. However, there have been no studies to examine the effects of fondaparinux and enoxaparin when applied in a sepsis model. Therefore, we examined the anti-inflammatory effects and bleeding events when these agents are applied in a lipopolysaccharide challenge model. METHODS: Wistar rats received lipopolysaccharides followed by a bolus infusion of fondaparinux, enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation for endothelial damage and measurement of bleeding area after vascular puncture was performed (n = 6 in each group). In another series, blood samples were taken, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each). RESULTS: Both leukocyte adherence to vascular endothelium and endothelial damage were reduced in fondaparinux and enoxaparin groups. The bleeding area was markedly increased in the fondaparinux group. Coagulation markers were maintained better in the enoxaparin group. Levels of organ damage markers were significantly suppressed in both fondaparinux and enoxaparin groups (p < 0.01, compared with control, each). CONCLUSIONS: Fondaparinux and enoxaparin reduce organ dysfunction by decreasing endothelial damage. However, bleeding was more prominent in the fondaparinux group compared with the enoxaparin group at an equipotent dose for anti-Xa activity. Because the setting of this experiment is different from the clinical use, further study is required for the comparison of both pharmaceuticals.

[Squamous cell carcinoma of the anal canal showing pathological complete response after S-1 plus radiotherapy -a case report].

The patient was a 53-year-old woman who underwent colonoscopy for anal pain and melena. We diagnosed her with Stage I (T2N0M0) anal canal squamous cell carcinoma by biopsy specimen and CT scan. We recommended chemo-radiotherapy because she hoped to keep her anus. For this patient, we planned an S-1 administration at a dose of 120 mg/ body/day for consecutive 14 days followed by 7 days of rest period with whole pelvis and bilateral inguinal radiation (total 45 Gy/25 Fr). Then we added a booster radiation (14 Gy/7 Fr) to a local area for 5 days followed by 2 days of rest period. After 2 weeks of chemo-radiotherapy, we could not detect any tumors by colonoscopy. We diagnosed it as a pathological complete response for biopsy specimen.

[Cholesterol granuloma of the kidney: a case report].

A 58-year-old woman was referred to our outpatient clinic for further examination of a mass detected in the right kidney on follow-up ultrasonography performed for active surveillance of right ovarian cancer. Ultrasonography and computed tomography showed a cyst (diameter, 30 mm) with an irregular wall in the middle of the right kidney. Right nephrectomy was performed since malignancy was suspected. Histological findings of the mass indicated cholesterol granuloma. Although cholesterol granulomas in the middle ear have been frequently reported, those in other organs have been reported in few studies. In this patient, the cholesterol granuloma could be barely distinguished from the cancer by using imaging techniques.

Effect of hemoperfusion using polymyxin B-immobilized fibers on non-shock rat sepsis model.

BACKGROUND: Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) is recognized to be effective for the treatment of septic shock and is widely applied in Japan. However, it is still unknown whether the efficacy is limited to cardiovascular dysfunction. Therefore, the purpose of this study was to examine the effects of PMX-DHP on a non-hypotensive sepsis model. METHODS: Wistar rats were assigned to either a PMX-DHP group, control group, or sham group (n=7 in each group). A sepsis model was made by intravenous infusion of live E. coli. (LD50). The change in systemic blood pressure was less than 20% of the initial level in this model. In the PMX-DHP group, an arteriovenous extracorporeal circuit with a PMX column was applied until 3 h after E. coli injection. The same procedure with a dummy column was applied in the control group. Plasma levels of ALT, LDH, BUN, tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß, IL-6, and IL-10 were measured. The mesenteric microcirculation was observed at 1 and 3 h after E. coli injection. In another series, survival was calculated up to 18 h (n=14 in each group). RESULTS: Organ damage markers were lower in the PMX-DHP group. The levels of pro-inflammatory cytokines were significantly lower in the PMX-DHP group than in the control group. Microcirculation was better maintained in the PMX-DHP group. Survival was significantly better in the PMX-DHP group (93%) compared with that in the control group (57%, P=0.03). CONCLUSIONS: PMX-DHP was effective in a non-hypotensive sepsis model.

[Reiter's syndrome following intravesical instillation of Bacillus Calmette-Guerin].

A 54-year-old man who had received intravesical instillation of bacillus Calmette-Guerin(BCG) after transurethral resection for bladder cancer suffered from multiple arthritis, bilateral conjunctivitis, miction pain and high fever. Under the diagnosis of Reiter's syndrome, a nonsteroidal anti-inflammatory drug, histamine antagonists, anti-tubercular agent and corticosteroid were administered. The symptoms were improved within one month. It is important in early diagnosis and treatment of Reiter's syndrome to observe carefully the complications following intravesical instillation of BCG.

[Refractory thrombotic thrombocytopenic purpura successfully treated with a combination of rituximab and vincristine].

A 26-year-old man was referred to our hospital with vomiting and high fever. He was disoriented and laboratory results showed microangiopathic hemolytic anemia (Hb 7.1 g/dl) and severe thrombocytopenia (15 x 10(3)/microl). The diagnosis of thrombotic thrombocytopenic purpura (TTP) was established. The activity of von Willebrand cleaving protease (ADAMTS13) was found to be remarkably low (<0.5%) and the high activity of the inhibitor (11.0 Bethesda U/ml) was detected, confirming the diagnosis of typical acquired TIP. Although he had been successfully treated with daily plasma exchange and methylprednisolone, he relapsed after a week. To this therapeutic strategy we added four weekly doses of rituximab (375 mg/m2) and two weekly doses of vincristine (1 mg/m2) simultaneously. The response was very rapid and complete, that is, the platelet count recovered to normal seven days after the first rituximab and vincristine treatment. The patient maintains complete remission nine months later under the administration of 17.5 mg prednisolone. Recovery of the plasma ADAMTS13 activity was clearly correlated with the decrease or disappearance of the inhibitor activity. Combination of rituximab and vincristine therapy would appear to be very effective against refractory TTP.