Prospective Study of Vonoprazan-Based First-Line Triple Therapy with Amoxicillin and Metronidazole for Clarithromycin-Resistant Helicobacter pylori.

AIM: This was a prospective, multicenter, single-arm intervention, against historical controls, study of the efficacy of a vonoprazan-based 7-day triple regimen with metronidazole (VPZ-AMPC-MNZ) as a first-line therapy for eradicating clarithromycin-resistant Helicobacter pylori (H. pylori). METHODS: We enrolled 35 patients positive for clarithromycin-resistant H. pylori, as assessed by culture, without a history of eradication. These 35 patients were prospectively eradicated with VPZ-AMPC-MNZ. As historical controls, we also assessed 98 patients with clarithromycin-resistant H. pylori from our prior prospective studies, who achieved H. pylori eradication with a 7-day triple regimen including clarithromycin (VPZ-AMPC-CAM). A preplanned analysis was performed as a superiority study against the historical controls (VPZ-AMPC-MNZ compared to VPZ-AMPC-CAM). In each regimen, vonoprazan was used at 20 mg bid, amoxicillin at 750 mg bid, metronidazole at 250 mg bid, and clarithromycin at 200 mg or 400 mg bid for 7 days. We assessed the outcome of eradication therapy using a 13C-urea breath test or H. pylori stool antigen test. We evaluated safety using patient questionnaires. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of VPZ-AMPC-MNZ were both 100% (95% confidence interval (95% CI) 90.0-100%, n = 35). The eradication rates of VPZ-AMPC-CAM were 76.5% (95% CI 66.9-84.5%, n = 98) in the ITT analysis and 77.3% (95% CI 67.7-85.2%, n = 97) in the PP analysis. The eradication rate of VPZ-AMPC-MNZ was significantly higher than that of VPZ-AMPC-CAM in both the ITT (p = 0.00052) and PP (p = 0.00095) analyses. CONCLUSIONS: The findings suggest that 7-day VPZ-AMPC-MNZ was superior to 7-day VPZ-AMPC-CAM as a first-line regimen for eradicating clarithromycin-resistant H. pylori. We suggest VPZ-AMPC-MNZ as the standard first-line regimen for eradication of clarithromycin-resistant H. pylori in Japan.

Coronavirus Disease 2019 Complicated by Multiple Simultaneous Intracerebral Hemorrhages.

The relationship between coronavirus disease 2019 (COVID-19) and intracerebral hemorrhage remains unclear. We herein report a case of severe COVID-19 pneumonia complicated by multiple simultaneous intracerebral hemorrhages (MSICH). The patient died eight days after the episode of MSICH. No apparent coagulopathy was observed; however, extracorporeal membrane oxygenation and anticoagulation might have caused the occurrence of MSICH. Laboratory findings showed hypercoagulability, suggesting that thrombotic etiologies, such as sinus thrombosis or cerebral infarction, might also have caused MSICH. MSICH can occur as a fatal complication of COVID-19, and this should be considered when providing treatment.

The Use of External-beam Radiotherapy for Muscle-invasive Bladder Cancer in Elderly or Medically-fragile Patients.

AIM: To evaluate the clinical results of external-beam radiotherapy (EBRT) for muscle-invasive bladder cancer (MIBC) in elderly or medically-fragile patients. PATIENTS AND METHODS: Twenty-five consecutive patients with MIBC (cT2-4N0-1M0) receiving EBRT were retrospectively analyzed. Their median age was 82 years. Radiotherapy median dose was 60 Gy administered in 30 fractions. RESULTS: Median follow-up period was 14.7 months. Median overall survival (OS) and progression-free survival (PFS) were 14.7 months and 7.8 months, respectively. The OS, cause-specific survival (CSS), and PFS rates at 1-year were 56.0%, 68.5%, and 40.0%, respectively. The local progression-free rates (LPFR) at 6 months and 1 year were 89.3% and 59.5%, respectively. Performance status 3 was a significantly unfavorable factor for OS, CSS, and progression-free survival; clinical N stage was a significantly unfavorable factor for progression-free survival; and lower irradiation dose (≤50.4 Gy) was a significantly unfavorable factor for LPFR. CONCLUSION: EBRT for elderly or medically-fragile patients is feasible, and achieves acceptable local progression-free status.

The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on Helicobacter pylori Eradication.

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.

[A CASE OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE COMPLICATED WITH HENOCH-SCHÖNLEIN PURPURA NEPHRITIS].

Purpura nephritis and autosomal dominant polycystic kidney disease are relatively rare kidney disorders. We present a case complicated by these two diseases. A 68 year-old man with polycystic kidney disease was referred to our hospital with a high fever lasting 3 days and pyuria. Pyelonephritis was suspected based on computed tomography findings of bilateral swelling of the kidney. Inflammation subsided gradually after the initiation of antimicrobial therapy. However, approximately 3 weeks later, the patient developed a fever and skin purpura on the extremities, stomach colic pain, gross hematuria, and increased proteinuria was evident. Therefore, we diagnosed Henoch-Schönlein purpura complicated with nephritis based on biopsies of the skin and the kidney. Immunosuppressant therapy was administered; every symptom was relieved and proteinuria decreased for approximately 20 months.

[A Case Report : Spontaneous Rupture of Chromophobe Renal Cell Carcinoma].

A 31-year-old man presented with sudden right flank pain. We found a right renal tumor with a perirenal hematoma on enhanced abdominal computed tomography (CT), which suggested spontaneous rupture of the renal tumor. The tumor was located at the upper pole of the right kidney, and was not enhanced. Magnetic resonance imaging (MRI) showed slightly enhanced renal tumor, and positron emission tomography (PET) showed a hot spot in the renal mass. His anemia was getting worse, and we assumed that the renal mass was malignant. Therefore, we performed a right nephrectomy with a transperitoneal approach. On pathological examination, the tumor was found to be chromophobe renal cell carcinoma. The tumor contained a significant amount of necrotic tissue and a hematoma.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

OBJECTIVES: No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). METHODS: We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. RESULTS: Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. CONCLUSIONS: Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

Diagnosis of complex renal cystic masses and solid renal lesions using PET imaging: comparison of 11C-acetate and 18F-FDG PET imaging.

PURPOSE: The study aims to assess the usefulness of PET with C-acetate and F-FDG to differentiate renal cell carcinoma (RCC) from complicated renal cysts. METHODS: Thirty-one patients were enrolled, 14 patients with complicated renal cysts (12 with Bosniak III and 2 with Bosniak IV) and 17 patients with 19 solid renal tumors. The patients underwent both C-acetate PET and FDG PET. Nephrectomy or partial nephrectomy was performed after the PET scans. RESULTS: In 29 patients, 32 renal lesions were diagnosed as RCC. Twenty-three of the 32 RCCs (72%) had positive C-acetate PET findings, whereas only 7 FDG PET studies were positive (22%). Considering the relationship between tumor size measured by macroscopic appearance of resected tumors and PET results, 22 of 25 (88%) tumors more than 1.5 cm showed positive C-acetate PET findings. In 12 patients with Bosniak III renal cysts, 10 renal lesions were diagnosed as RCC. In this subgroup, 5 of the 10 RCCs (50%) had positive C-acetate PET findings, whereas 2 RCCs (20%) had positive FDG PET findings. None of the cases with benign findings had positive C-acetate PET or FDG PET scans. CONCLUSIONS: C-acetate PET demonstrates a pronounced increase in tracer uptake in RCC, especially in renal tumors more than 1.5 cm, and displays a higher sensitivity than FDG PET. These preliminary data show that C-acetate may be a useful PET tracer to exclude RCC in complex renal cysts.

Visceral obesity as a risk factor for left-sided diverticulitis in Japan: a multicenter retrospective study.

BACKGROUND/AIMS: Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan. METHODS: Right-sided diverticulitis and left-sided diverticulitis patients (total of 215) were compared with respect to background, particularly obesity-related factors to identify risk factors for diverticulitis. RESULTS: There were 166 (77.2%) right-sided diverticulitis patients and 49 (22.8%) left-sided diverticulitis patients. The proportions of obese patients (body mass index ≥25 kg/m(2), p=0.0349), viscerally obese patients (visceral fat area ≥100 cm(2), p=0.0019), patients of mean age (p=0.0003), and elderly patients (age ≥65 years, p=0.0177) were significantly higher in the left-sided-diverticulitis group than in the right-sided-diverticulitis group. The proportion of viscerally obese patients was significantly higher in the left-sided-diverticulitis group than in the left-sided-diverticulosis group (p=0.0390). CONCLUSIONS: This study showed that obesity, particularly visceral obesity, was a risk factor for left-sided diverticulitis in Japan.

[Two cases of IgG4-related systemic disease arising from urinary tract].

Case 1: The patient was a 68-year-old man. Abdominal computed tomography performed during hospitalization for the close observation of a pituitary gland tumor, showed a right renal mass. Percutaneus needle biopsy revealed IgG4-related disease of the kidney. Pituitary gland tumor biopsy also indicated that the lesion was associated with IgG4-related disease. The pancreas did not show abnormalities. The patient was treated with prednisolone, and both renal and pituitary lesions markedly decreased in size. Case 2: the patient was an 80-year-old man. Right hydronephrosis was observed, and computed tomography showed a right pelvic tumor. Right renal pelvic tumor was diagnosed, and the patient underwent right nephroureterectomy. Pathological examination showed that this tumor was also associated with IgG4-related sclerotic disease. IgG4-related disease tends to occur in multiple organs. This condition should be considered when treating patients with multiple sclerotic diseases. However, in some patients, the disease may be localized to a single site. Further studies are required to elucidate the characteristics of IgG4-related disease.

Metastatic ureteral involvement of non-small cell lung cancer.

Metastases from a variety of malignant tumors can involve the ureters, but ureteral involvement by lung cancer is extremely rare and usually described at autopsy. We report a rare case of a 76-year-old man who presented with a three-month history of right flank dullness and was noted to have a nonhomogeneous retroperitoneal mass with hydronephrosis of the right kidney on computed tomography of the abdomen. Computed tomography of the thorax showed a nodule in the lower lobe, measuring 3 × 2 cm, in the right lung. After excluding the presence of other primary tumors and metastases, we reached a final diagnosis of solitary retroperitoneal metastasis of adenocarcinoma of the lung. Although rare, in patients of non-small cell lung cancer, presence of hydronephrosis should alert the physician to the possibility of metastasis.

[Localized amyloidosis of the seminal vesicle: a case report].

Primary amyloidosis of the seminal vesicle is a rare disease entity. We report here a case of localized seminal vesicle amyloidosis with hematospermia. A 66-year-old man visited our hospital with a chief complaint of hematospermia. T2 weighted magnetic resonance imaging (MRI) showed a hypointensity mass in the left seminal vesicle. Needle biopsy revealed amyloidosis of the seminal vesicle. Without any specific treatment, the mass lesion disappeared on MRI, and hematospermia was improved.

Free-to-total prostate-specific antigen (PSA) ratio contributes to an increased rate of prostate cancer detection in a Japanese population screened using a PSA level of 2.1-10.0 ng/ml as a criterion.

BACKGROUND: Although the free-to-total prostate-specific antigen (PSA) ratio (f/t ratio) is low in prostate cancer, its usefulness in mass screening remains unclear. We examined the clinical usefulness of the f/t ratio for screening in a Japanese population. METHODS: Since 2000, we have performed PSA screening in Japanese men aged 55-69 years. From 2000 to 2002, patients with total PSA (tPSA) levels over 2.1 ng/ml were referred to the urological clinic for secondary screening, regardless of the f/t ratio. We analyzed both the tPSA level and the f/t ratio in prostate cancer patients, and since 2003, subjects with tPSA levels ranging from 2.1-10.0 ng/ml and f/t ratios higher than 0.22 have not been referred for secondary screening. Here, we report the results of tPSA screening, comparing findings in the two periods (2000-2002 and 2003-2005). RESULTS: Between 2000 and 2005, we performed the tPSA screening test in 27 730 men, and detected 214 cases of prostate cancer. Sixty patients (28.0%) showed tPSA levels between 2.1 and 4.0 g/ml. There were no differences in cancer detection rates between the two periods in the populations referred for an initial screening. However, the percentage of individuals referred for secondary screening decreased from 17.0% to 13.0% during the later period (P < 0.001). The cancer detection rate in all patients with biopsies rose from 13.5% in the earlier period to 22.7% in the later period for the group with tPSA between 2.1 and 10.0 ng/ml (P < 0.001). CONCLUSION: The f/t ratio may be a useful additional screening parameter for patients showing tPSA levels between 2.1 and 10.0 ng/ml on their initial screening examination.

Effects of opioid subtypes on detrusor overactivity in rats with cerebral infarction.

AIM: In order to determine the influence of different opioid receptor subtypes on detrusor overactivity after left middle cerebral artery (MCA) occlusion, cystometric recordings were obtained in conscious rats. METHODS: Female Sprague-Dawley rats were used in this study. Control cystometrography was followed by left MCA occlusion. The sham-operated (SO) rats underwent the same procedures except for MCA occlusion. [D-Ala(2), Phe(4), Gly(5)]-enkephalin (DAGO; mu-opioid agonist), [D-Pen(2,5)]-enkephalin (DPDPE; delta1-opioid agonist), deltorpin II (delta2-opioid agonist), and U-50488 (kappa-opioid agonist) were administered intracerebroventricularly at graded doses. The bladder capacity, residual volume, micturition threshold pressure, and bladder contraction pressure were determined. Finally, the volume of the infarction was measured. RESULTS: The intracerebroventricular administration of DAGO and DPDPE significantly increased the bladder capacity in the cerebrally infarcted (CI) and SO rats, but differences in the changes in bladder capacity between the CI and SO rats were not significant. Deltorpin II did not produce any changes in the bladder capacity in the CI or SO rats at any dose examined. However, the intracerebroventricular administration of U-50488 significantly increased the bladder capacity in the CI rats but not in the SO rats. None of the drugs affected the residual volume, micturition threshold pressure or bladder contraction pressure at any dosage examined. The mean infarcted volumes were not significantly different from those in the vehicle-treated rats. CONCLUSION: These results suggest that the opioid receptor subtypes, mu and delta1 in the brain, are related to the micturition reflex. Furthermore, the kappa opioid agonist might be useful for the suppression of detrusor overactivity caused by cerebral infarction.

[Matrix stone: a case report].

Here, we report a case of matrix stone in a 32-year-old man with diabetes, gout, and chronic renal failure. The patient complained of pain in the left flank. He had undergone an operation for bilateral vesicoureteral reflex at the age of 17 and matrix stone discharge was repeated. Computed tomography revealed a soft tissue mass in the right hydroureter. Percutaneous ureteral lithotripsy was performed successfully. Analysis of the stone components revealed the stone to be composed entirely of protein. Radiological imaging of matrix stones may be difficult to separate from urothelial cancers.

A case of bilateral testicular calcifications in a bicycle motocross rider accompanied by bulbar urethral injury.

A 21-year-old Japanese man who was a professional bicycle motocross rider injured his perineum during a competition. Chief complaints were gross hematuria, perineal pain, and subcutaneous ecchymosis of the scrotum. Urethrocystography revealed a torn bulbar urethra and extravasation in the same region. Scrotal ultrasonography revealed small calcifications in the bilateral testes. Here, we report a case of bilateral testicular calcifications caused by the continuous shock and vibration of the saddle in an off-road bicycle rider.

Durability of working channel in flexible ureteroscopes when inserting ureteroscopic devices.

PURPOSE: We studied the physical damage to the working channel of flexible ureteroscopes caused by insertion of various accessories. A procedure was developed to avoid channel damage. MATERIALS AND METHODS: An experimental model representing a flexible ureteroscope was prepared, and damage to its working channel was evaluated by inserting instruments through it. Deflection angles of the channel were changed from 0 degrees to 120 degrees, and each device was inserted and removed 100 times for each selected angle of the channel. Any induced pinholes were identified by an air-leak test. Also, the inside of the channel was inspected with an extremely fine fiberscope. RESULTS: Insertions of 3F biopsy forceps or a 2.4F Nitinol stone-retrieval device caused only slight damage to the model channel, even when the deflection angle was 120 degrees. However, the tips of 200- or 250-microm holmium laser fibers shaved the inner surface of the channel at 60 degrees of deflection, and at 120 degrees, the laser fiber either penetrated the channel or could not be advanced because of resistance by the channel wall. When the laser fiber was inserted within a protective tube, the channel was never damaged, even when the deflection angle was 120 degrees. CONCLUSIONS: When devices are inserted into the working channel of a flexible ureteroscope, damage to the wall depends on the kind of device and deflection angle. Harm could be avoided by inserting the devices, especially laser probes, within a protective tube.

Four year clinical statistics of iridium-192 high dose rate brachytherapy.

BACKGROUND: We evaluated the efficacy and complications of high dose rate (HDR) brachytherapy using iridium-192 (192Ir) combined with external beam radiotherapy (EBRT) in patients with prostate cancer. METHODS: Ninety-seven patients underwent 192Ir HDR brachytherapy combined with EBRT at our institution between February 1999 and December 2003. Of these, 84 patients were analysed in the present study. 192Ir was delivered three times over a period of 2 days, 6 Gy per time, for a total dose of 18 Gy. Interstitial application was followed by EBRT at a dose of 44 Gy. Progression was defined as three consecutive prostate-specific antigen (PSA) rises after a nadir according to the American Society for Therapeutic Radiology and Oncology criteria. The results were classified into those for all patients and for patients who did not undergo adjuvant hormone therapy. RESULTS: The 4-year overall survival of all patients, the nonadjuvant hormone therapy group (NAHT) and the adjuvant hormone therapy group (AHT) was 87.2%, 100%, and 70.1%, respectively. The PSA progression-free survival rate of all patients, NAHT, and AHT was 82.6%, 92.0%, and 66.6%, respectively. Of all patients, the 4-year PSA progression-free survival rates of PSA<20 and PSA>or=20 groups were 100%, and 46.8%, respectively. According to the T stage classification, PSA progression-free survival rates of T1c, T2, T3, and T4 were 100%, 82.8%, 100%, and 12.1%, respectively. Prostate-specific antigen progression-free survival rates of groups with Gleason scores (GS)<7 and GS>or=7 were 92.8% and 60.1%, respectively. Of NAHT, PSA progression-free survival of PSA<20 was 100% vs 46.8% for PSA>or=20, that of T1c was 100% vs 75% for T2, and that of GS<7 was 100% vs 75% for GS>or=7. No significant intraoperative or postoperative complications requiring urgent treatment occurred except cerebellum infarction. CONCLUSIONS: 192Ir HDR brachytherapy combined with EBRT was as effective as radical prostatectomy and had few associated complications.

Central muscarinic receptor subtypes regulating voiding in rats.

PURPOSE: Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. RESULTS: In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. CONCLUSIONS: Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.