Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

OBJECTIVE: 18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. METHODS: Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n = 7) and patients with biochemical recurrence (Cohort 2, n = 3). All subjects received a single dose of 3.7 MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87 ± 1.05 (percentage of injected dose [%ID]/ml) at 5 min and then decreased to 1.60 ± 0.78 in 6 h. The systemic radioactivity reached a maximum of 211.05 ± 6.77 (%ID$\times$103) at 5 min and decreased to 7.18 ± 3.91 in 6 h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5 mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60 min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. CONCLUSIONS: Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

[Small intestinal mucormycosis associated with acute myeloid leukemia: a case report].

The patient was a man in his 70s. During the treatment for acute myeloid leukemia, abdominal pain and bloody stools appeared. A diagnosis of small intestinal ileus was made by computed tomography scan. Treatment with an ileus tube did not improve his condition, and enteroscopy revealed the presence of ileal ulcers. Based on histological examination, small intestinal mucormycosis was suspected, and thus, antifungal drugs were administered. However, the patient developed perforated peritonitis and underwent small intestine resection. He was finally diagnosed with small intestinal mucormycosis with the help of the resected specimen. The gastrointestinal form of mucormycosis rarely occurs, and small intestinal lesions are very rare. Enteroscopy was helpful in its diagnosis and treatment.

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study.

BACKGROUND: Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. METHODS: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. RESULTS: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). CONCLUSIONS: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. TRIAL REGISTRATION: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903 , date of registration: June 27, 2016, retrospectively registered.

[A Case of Type 4 Gastric Cancer with Esophageal Invasion That Responded to Neoadjuvant Chemotherapy Containing S-1 and Oxaliplatin followed by Surgery].

We encountered a case of type 4 gastric cancer with esophageal invasion that responded to neoadjuvant chemotherapy containing S-1 and oxaliplatin(SOX)followed by surgery, which could be curative resection. A 46-year-old man was referred to our hospital because of abnormal upper gastrointestinal series findings. He was diagnosed with type 4 advanced gastric cancer with esophageal invasion, cT4b(diaphragm)N2M0, Stage ⅢC, and 3 courses of neoadjuvant SOX therapy were administered. Adverse events were minor. After NAC, the primary lesion and lymph nodes showed marked reductions on CT; total gastrectomy and subtotal thoracic esophagectomy were performed. The pathological response to NAC was evaluated as Grade 2 in the primary tumor and Grade 3 in the lymph node; overall, NAC showed considerable antitumor effects. The final diagnosis was ypT3N0M0P0CY0H0, StageⅡA, and was judged as curatively resected. Currently, we are continuing to administer adjuvant chemotherapy containing S-1.

[Ciliated Muconodular Papillary Tumor of the Lung].

A ciliated muconodular papillary tumor (CMPT) has been reported to be a low-grade malignant tumor or benign tumor, consisting of ciliated columnar cells and goblet cells with basaloid cell proliferation, occur in the peripheral lung. We present a case of CMPT in this report. A 42-year-old male was referred to our department due to a nodule detected in the peripheral left lower lobe of lung. The nodule was resected via wedge resection based on a suspected diagnosis of carcinoma. Intraoperative analysis of the frozen sections was suggestive of mucinous adenocarcinoma. A left lower lobectomy and mediastinal lymph node dissection were performed. The resected specimen was characterized as a papillary tumor with central fibrosis, proliferating along the alveolar walls, surrounded by mucous lakes, and consisting of ciliated columnar cells and goblet cells. Nuclear atypia was mild, and no mitotic activity was observed. Based on these findings, the tumor was finally diagnosed as CMPT. No recurrence has been noted for 24 months after surgery.

[A Study of Patients with Regional Lymph Node Recurrence after Breast Surgery].

Regional lymph node recurrence without distant metastasis after the initial treatment of breast cancer is a relatively rare event. The optimal management for regional lymph node recurrence is poorly understood. We retrospectively evaluated 21 patients who developed regional lymph node recurrence between January 1, 2003 and December 31, 2014. The median interval between regional lymph node recurrence and distant metastasis was 1.0 years(range, 0.4 to 2.5 years). On followup, 15 cases(71.4%)were found to eventually develop distant metastases. Median follow-up time after lymph node recurrence was 1.8 years(range, 0.4 to 20.3 years). The 2-year survival rate after regional lymph node recurrence was 65.5%. The mean distant-disease-free interval was 2.2 years in patients with estrogen receptor(ER)-positive tumor(n=10)and 0.7 years in patients with ER-negative tumor(n=11). The distant-disease-free interval after regional lymph node recurrence was significantly shorter in patients with ER-negative tumor than in patients with ER-positive tumor(p=0.008). The 2-year survival rate after regional lymph node recurrence was significantly lower in patients with ER-negative tumor(33.3%)than in patients with ER-positive tumor(100%, p=0.016). This study revealed that regional lymph node recurrence after initial treatment is associated with an increased risk of distant metastasis and death and ER-negative tumors are indicative of a poor prognosis.

Massive pneumoretroperitoneum arising from emphysematous cholecystitis: a case report and the literature review.

BACKGROUND: Emphysematous cholecystitis is a severe variant of acute cholecystitis caused by anaerobic bacteria. Although intraperitoneal air as a complication has been described in association with emphysematous cholecystitis, pneumoretroperitoneum arising from emphysematous cholecystitis is extremely rare. Herein, we describe a rare case of pneumoretroperitoneum arising from emphysematous cholecystitis that was successfully treated with emergency surgery. CASE PRESENTATION: An 84-year-old male was transported to the Emergency Department of our hospital for acute abdomen. Computed tomography revealed acute cholecystitis accompanied by emphysematous change. Computed tomography also revealed massive pneumoretroperitoneum complicated with pneumobilia and gas in the hepatoduodenal ligament. Clinical findings fulfilled the diagnostic criteria for systemic inflammatory response syndrome and sepsis. Emergency surgery was carried out with a diagnosis of both emphysematous cholecystitis and gastrointestinal perforation. Intraoperative findings revealed acute gangrenous cholecystitis and pneumoretroperitoneum presenting with an odor-free foamy abscess along the loose connective tissue behind the ascending colon and mesocolon. No evidence of gastrointestinal perforation was found during surgery. Therefore, cholecystectomy and lavage drainage were performed. Bacterial culture examination isolated a single species of anaerobe, Klebsiella pneumoniae, which was considered to be the cause of emphysematous cholecystitis, pneumobilia, and pneumoretroperitoneum. CONCLUSIONS: Emphysematous cholecystitis should be considered as a possible cause of pneumoretroperitoneum. The present case is the first report of massive pneumoretroperitoneum extending to the dorsal side of the ascending mesocolon as a complication of emphysematous cholecystitis.

Association of µ-opioid receptor gene (OPRM1) haplotypes with postoperative nausea and vomiting.

Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the µ-opioid receptor gene (OPRM1) might be associated with individual differences in opioid sensitivity, as well as with the incidence and severity of postoperative nausea and vomiting (PONV). The goal of the present study was to determine, in a cohort of Japanese surgical patients, genotypes and haplotypes of several SNPs in the OPRM1 gene, and their association with PONV during the early (first 24 h) postoperative period. We examined the incidence and severity of PONV, during the first 24 h after surgery, in 85 Japanese patients receiving intravenous patient-controlled analgesia fentanyl analgesia for postoperative pain control. Eight tag SNPs of the OPRM1 gene (rs1799971, A/G; rs510769, G/A; rs4870266, G/A; rs3798683, G/A; rs1323042, A/C; rs609623, C/T; rs9397685, A/G; and rs644261, C/G) were selected based on their minor allele frequency (>10%) and linkage disequilibrium strength (<80%), and genotyped for haplotype analysis and determination of associations with PONV. Only one out of eight investigated SNPs, rs9397685, in the intronic part of the OPRM1 gene was associated with differences in the occurrence and severity of PONV. We also found four common haplotypes with a frequency of >10% in the investigated patients, including GGGAACAC (33%), AGGGACAC (19%), GGGAACGC (12%), and AGAGACAC (10%). The severity of PONV in carriers of the GGGAACGC haplotype was significantly lower than in the carriers of the other haplotypes (P < 0.05). One intronic SNP, rs9397685, and haplotypes constructed from eight SNPs within the OPRM1 gene locus might be involved in the severity of PONV associated with general anesthesia and opioid administration. This novel finding, if validated and verified in larger and additional ethnic cohorts, might contribute to better knowledge of the contribution of the OPRM1 gene to PONV.

Sigmoid colon cancer arising in a diverticulum of the colon with involvement of the urinary bladder: a case report and review of the literature.

BACKGROUND: Colon cancer can arise from the mucosa in a colonic diverticulum. Although colon diverticulum is a common disease, few cases have been previously reported on colon cancer associated with a diverticulum. We report a rare case of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder, which presented characteristic radiographic images. CASE PRESENTATION: A 73-year-old man was admitted to our hospital for macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a sigmoid colon tumor that protruded into the urinary bladder lumen. The radiographs showed a tumor with a characteristic dumbbell-shaped appearance. Colonoscopy showed a type 1 cancer and multiple diverticula in the sigmoid colon. A diagnosis of sigmoid colon cancer with involvement of the urinary bladder was made based on the pathological findings of the biopsied specimens. We performed sigmoidectomy and total resection of the urinary bladder with colostomy and urinary tract diversion. Histopathological findings showed the presence of a colovesical fistula due to extramurally growing colon cancer. Around the colon cancer, the normal colon mucosa was depressed sharply with lack of the muscular layer, suggesting that the colon cancer was arising from a colon diverticulum. CONCLUSION: The present case is the first report of sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder. Due to an accurate preoperative radiological diagnosis, we were able to successfully perform a curative resection for sigmoid colon cancer arising in a diverticulum with involvement of the urinary bladder.

Correlation between antibiotic use and antibiotic resistance: A multicenter study using the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system in Hokkaido, Japan.

BACKGROUND: The Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) system aggregates information related to antimicrobial resistance (AMR) measures in participating medical institutions nationwide and is intended to be used for promotion of AMR measures in participating facilities and their communities. This multicenter study aimed to determine the usefulness of the J-SIPHE system for evaluating the correlation between antibiotic use and antibiotic resistance in Hokkaido, Japan. METHODS: Data on antibiotic use and detection rate of major resistant Gram-negative bacteria at 19 hospitals in 2020 were collected from the J-SIPHE system, and data correlations were analyzed using JMP Pro. RESULTS: The detection rate of carbapenem-resistant Pseudomonas aeruginosa was significantly positively correlated with carbapenem use (Spearman's ρ = 0.551; P = .015). There were significant positive correlations between the detection rate of fluoroquinolone-resistant Escherichia coli and the use of piperacillin/tazobactam, carbapenems, and quinolones [ρ = 0.518 (P = .023), ρ = 0.76 (P < .001), and ρ = 0.502 (P = .029), respectively]. CONCLUSIONS: This is the first multicenter study to investigate the correlation between antibiotic use and antibiotic resistance using the J-SIPHE system. The results suggest that using this system may be beneficial for promoting AMR measures.

[Pulmonary arteriovenous fistula with Rendu-Osler-Weber disease].

A 36-year-old man was admitted to our hospital for examination of a nodular shadow in the left lung. Chest 3-dimensional computed tomography (3D-CT) revealed a pulmonary arteriovenous fistula (PAVF) of 21 mm in diameter composed of the feeding artery (A4) and the draining vein (V4) in the left S4. Abdominal enhanced CT revealed multiple hepatic arteriovenous fistula. Brain CT revealed a cavernous hemangioma in right occipital cerebrum. He had a family history, habitual epistaxis, and oral telangiectasia and was diagnosed as Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia:HHT). According to his family history, PAVF was likely to be a risk factor of brain infarction and abscess, and the wedge resection of the lingual lobe was performed to remove PAVF.

[Immunoglobulin G4-related inflammatory pseudotumor of the lung].

A 61-year-old man was pointed out a solitary nodule located in the left lung (S9) measuring 18 × 29 mm in size along with lymphadenopathy by chest computed tomography (CT). Positron emission tomography( PET) scan showed a positive sign corresponding to the nodule[ standardized uptake value (SUV) max 5.8]. No diagnostic material was obtained from the transbronchial tumor biopsy, since it was difficult to rule out malignancy, surgical biopsy was performed with sampling of mediastinal lymph nodes. Histopathological examination showed marked infiltration of inflammatory cells, many of which were demonstrated to be immunoglobulin (Ig) G4-positive plasma cells by immunohistochemical staining. Hence, IgG4-related inflammatory pseudotumor of the lung was diagnosed.

Effect of heterojunction structures on photoelectrochemical properties of ZnTe-based photocathodes for water reduction.

Photoelectrochemical (PEC) properties of ZnTe-based photocathodes with various structures were investigated to clarify the effective structure for the water reduction reaction. Samples with n-ZnO/ZnTe/p-ZnTe and n-ZnS/ZnTe/p-ZnTe heterostructures showed superior PCE properties to the samples without a heterojunction. In particular, the n-ZnS/ZnTe/p-ZnTe sample exhibited a large photocurrent even at a low applied potential in an electrolyte containing Eu3+ ion as an electron scavenger. Appreciable H2 evolution with a constant rate (approximately 87 µmol cm-2 h-1) was also observed over the sample loaded with Pt deposits under visible-light irradiation (>420 nm): faradaic efficiency of almost 100% was obtained, indicating no unfavorable side reaction occurred in the sample.

Hypertrophic Pachymeningitis with Characteristics of Both IgG4-related Disorders and Granulomatosis with Polyangiitis.

We herein report a 73-year-old man with isolated hypertrophic pachymeningitis (HP) showing serological and pathological characteristics of both IgG4-related disorders and granulomatosis with polyangiitis. The patient presented with chronic onset headaches and ophthalmalgia. Brain magnetic resonance imaging (MRI) revealed a hypertrophic enhanced dura mater. Serum IgG4 and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels were elevated. A dura mater biopsy showed infiltration of numerous IgG4-positive plasma cells and granulomatous inflammation without apparent vasculitic lesions, storiform fibrosis, or obstructive phlebitis. Corticosteroid treatments improved his clinical symptoms and MRI findings. There have been reports of MPO-ANCA-positive IgG4-related HP presenting as granulomatous inflammation in the dura mater.

[Syndrome of inappropriate secretion of antidiuretic hormone associated with resection of pulmonary squamous cell carcinoma].

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) shows various symptoms based on hyponatremia and brings catastrophic outcome occasionally. A 75-years-old man was found to have an abnormal shadow of the right lung on chest X-ray. Bronchoscopic examination showed that the abnormal shadow was aterectasis caused by the squamous cell carcinoma of middle lobe bronchus, and middle and lower lobectomy of the right lung was performed. On the postoperative day 2, suddenly the serum sodium concentration decreased to 116 mEq/l and serum osmolarity also decreased to 246 mOsm/l. Inspite of hyponatremia, the urine sodium level elevated to 73 mEq/l. So the urine osmolarity elevated to 752 mOsm/l, too. In addition to these data, edema and dehydration were absent, and both renal and adrenal function were normal. So we diagnosed that this abnormal conditions-hyponatremia with corresponding serum hypoosmolality and an inappropriately high urinary osmolality due to continued sodium excretion was induced by SIADH. Fluid restriction and antibiotics therapy for pneumonia resulted in an appropriate rise in the serum sodium level to 138 mEq/l on the postoperative day 21. To avoid catastrophic outcome in the cases of hyponatremia after surgery, it is important to remember that hyponatremia may be induced by SIADH.

A case of focal confluent hepatic fibrosis in the patient with hepatitis C virus-related liver cirrhosis: a mimic of cholangiolocellular carcinoma.

During routine ultrasound examination, a hyperechoic mass was detected in the anterior segment of the liver in an 80-year-old woman with hepatitis C virus-related cirrhosis. Computed tomography and magnetic resonance imaging findings suggested a malignant tumor with abundant fibrous stroma, similar to cholangiolocellular carcinoma. However, subsequent partial hepatectomy revealed a mass characterized by abundant fibrosis without tumor cells, dilated blood vessels, and marginal ductular reaction. Accordingly, focal confluent fibrosis was diagnosed. Generally, the diagnosis of focal confluent fibrosis is straightforward because of its well-established imaging characteristics. However, its differentiation from a malignant tumor can occasionally be difficult because of variation in presentation depending on the amount of fibrous stroma and the degree of inflammatory cell infiltration. In the present case, diagnosis was difficult because the lesion was more localized than usual, presenting a mass-like shape, and there was obvious hyperintensity on T2-weighted imaging and ring-shaped hyperintensity on diffusion-weighted imaging. Moreover, hepatic capsular retraction was indistinct, which can be one of the key findings of focal confluent fibrosis. When a hepatic mass is associated with a fibrous lesion, focal confluent fibrosis should be considered in the differential diagnosis, even though the lesion is associated with several atypical findings.

[Assessment of total bilirubin or SN-38/SN-38G ratio as a predictor of severe irinotecan toxicity].

SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G mainly by UGT1A1, during detoxification. However, significant interindividual pharmacokinetic variability in SN-38 is caused by factors, including inherited predispositions that may affect the function and expression of UGT1A1. Moreover, these individual differences can contribute to the development of clinical conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is metabolized by a mechanism similar to that of SN-38. This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN-38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known to correlate with leucopenia and diarrhea. However, many blood sampling points are required to calculate these AUCs. Therefore, the daily estimation of the AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical level. Thus, the objectives of this study were as follows: (1) to establish whether or not the total bilirubin level is a useful indicator in predicting the development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN-38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN-38/AUCSN-38G. Based on the result of this investigation, it will be discussed whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G. This study included 14 patients with small cell lung cancer or non-small-cell lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were measured by HPLC. The results demonstrated a significant correlation between the total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN-38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade-3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia. Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr) and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN-38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN-38G, 2 to 4 hours after administration might be used as indicators to predict CPT-11-induced neutropenia. These indicators are likely to contribute to the pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in future, and further studies on this subject are expected.

Spinal Accessory Nerve Meningioma at the Foramen Magnum with Medullar Compression: A Case Report and Literature Review.

BACKGROUND: Meningiomas that arise from the cranial nerve are rare. We present a case with an intradural extramedullary tumor at the foramen magnum originating from the spinal accessory nerve. CASE DESCRIPTION: The patient was a 69-year-old woman with dizziness and pain in the bilateral shoulder for 2 years. Neurologic examination revealed spinal accessory nerve palsy (difficult in raising the shoulder, deficit of 3/5) on the left side without further deficits. Magnetic resonance imaging showed medullar compression because of a left intradural extramedullary foramen magnum lesion dorsolateral to the medulla. Surgical exposure via a midline suboccipital approach with C1 laminectomy revealed that the lesion arises from the left accessory nerve without dural attachment. The tumor was resected without injury to the spinal accessory nerve, and histologic examination revealed that it was a meningothelial meningioma. The spinal accessory nerve palsy improved to 4 of 5 after 3 months after surgery. CONCLUSIONS: To our knowledge, this is the first report of an accessory nerve meningioma at the foramen magnum in which the spinal accessory nerve palsy appeared before operation and improved after tumor resection.

Renal arteriovenous fistula induced by extracorporeal shock wave lithotripsy treated by retroperitoneoscopic nephrectomy.

Renal arteriovenous fistula (AVF) is a rare but potentially severe and life-threatening entity. It can occur after various invasive renal interventions, including resection of a localized renal tumor, renal biopsy, percutaneous renal surgery, and even blunt injury of the kidney. The time of clinical presentation of a renal AVF is variable and may occur decades after the injury originally occurred. Here, we report a case of renal AVF induced by extracorporeal shock wave lithotripsy 11 years earlier in an asymptomatic 72-year-old woman. Given the patient's pre-existing hemodialysis dependence, retroperitoneoscopic nephrectomy was performed. On the basis of patient's clinical history, the location of the renal AVF, and the pathological diagnosis, we suggested that renal AVF was a late consequence of the injury to the intrarenal vessels induced by extracorporeal shock wave lithotripsy.