CT-derived skeletal muscle change before immunotherapy predicts survival of advanced gastric cancer: associations with inflammatory markers and liver lipid metabolism.

BACKGROUND: Skeletal muscle (SM) is a key factor in cancer treatment. However, it is unclear whether pretreatment SM change affects the outcome of immune checkpoint inhibitors (ICIs) therapy in gastric cancer (GC). METHODS: Advanced GCs treated with ICIs were retrospectively investigated. SM evaluated by psoas muscle area at the third lumbar vertebra was measured on CT acquired within 1 month from the start of ICIs therapy (CT-1), and on CT acquired 2.8 ± 0.84 months before CT-1. Monthly change rate of SM (MCR-SM) was defined as the change rate of SMs between those two CTs divided by the period between those CTs (month). Monthly change rate of body weight (MCR-BW) during the same period was also calculated. They were compared with disease-specific survival (DSS) and progression-free survival (PFS). MCR-SM was compared with pretreatment markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), and liver-to-spleen CT attenuation ratio (LSR) as a marker of liver lipid metabolism. RESULTS: This study enrolled eighty-three GC patients. MCR-SM significantly correlated with DSS and PFS (P < 0.0001, 0.001, respectively), whereas MCR-BW did not. Kaplan-Meier analyses demonstrated that higher MCR-SM (MCR-SM ≥ -0.7185%) significantly associated with better DSS and PFS (P = 0.0002, 0.03, respectively). Patients with positive MCR-SM showed significantly lower NLR, MLR, and CRP than those with negative (P = 0.01, 0.006, 0.003, respectively). MCR-SM showed a significant positive correlation with LSR (P = 0.007, R = 0.30). CONCLUSIONS: Pretreatment SM loss, associated with high systemic inflammation and hepatic fat accumulation, related to poor outcome of ICIs therapy in GC.

Risk of infection from glucocorticoid and methotrexate interaction in patients with rheumatoid arthritis using biologics: A retrospective cohort study.

AIMS: This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We used the 2005-2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. RESULTS: A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5-18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. CONCLUSION: Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA.

Platelet count and dose, but not comorbidities, predict severe neutropenia in cabazitaxel-treated prostate cancer patients: A retrospective observational study.

OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/µL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.

Quantification of Structural Heterogeneity Using Fractal Analysis of Contrast-Enhanced CT Image to Predict Survival in Gastric Cancer Patients.

BACKGROUND: Malignant tumor essentially implies structural heterogeneity. Fractal analysis of medical imaging has a potential to quantify this structural heterogeneity in the tumor AIMS: The purpose of this study is to quantify this structural abnormality in the tumor applying fractal analysis to contrast-enhanced computed tomography (CE-CT) image and to evaluate its biomarker value for predicting survival of surgically treated gastric cancer patients. METHODS: A total of 108 gastric cancer patients (77 men and 31 women; mean age: 69.1 years), who received curative surgery without any neoadjuvant therapy, were retrospectively investigated. Portal-phase CE-CT images were analyzed with use of a plug-in tool for ImageJ (NIH, Bethesda, USA), and the fractal dimension (FD) in the tumor was calculated using a differential box-counting method to quantify structural heterogeneity in the tumor. Tumor FD was compared with clinicopathologic features and disease-specific survival (DSS). RESULTS: High FD value of the tumor significantly associated with high T stage and high pathological stage (P = 0.009, 0.007, respectively). In Kaplan-Meier analysis, patients with higher FD tumors (FD > 0.9746) showed a significantly worse DSS (P = 0.009, log rank). Multivariate analysis demonstrated that tumor FD, T stage, and N stage were independent prognostic factors for DSS. In subset analysis of lymph-node positive gastric cancers, only tumor FD was an independent prognostic factor for DSS. CONCLUSION: CT fractal analysis can be a useful biomarker for gastric cancer patients, reflecting survival and clinicopathologic features.

Histogram Analysis of Diffusion-Weighted MR Imaging as a Biomarker to Predict Survival of Surgically Treated Colorectal Cancer Patients.

BACKGROUND: Structural abnormality is a well-recognized feature of malignancy. On the other hand, diffusion-weighted MRI (DWI) has been reported as a tool that can reflect tumor biology. AIMS: The purpose of this study is to apply histogram analysis to DWI to quantify structural abnormality of colorectal cancer, and evaluate its biomarker value. METHODS: This is a retrospective study of 80 (46 men and 34 women; median age: 68.0 years) colorectal cancer patients who underwent DWI followed by curative surgery at the Chiba University Hospital between 2009 and 2011. Median follow-up time was 62.2 months. Histogram parameters including signal intensity of kurtosis and skewness of the tumor were measured on DWI at b = 1000, and mean apparent diffusion coefficient value (ADC) of the tumor was also measured on ADC map generated by DWIs at b = 0 and 1000. Associations of tumor parameters (kurtosis, skewness, and ADC) with pathological features were analyzed, and these parameters were also compared with overall survival (OS) and relapse-free survival (RFS) using Cox regression and Kaplan-Meier analysis. RESULTS: ADC of the tumor did not have significant associations with any pathological factors, but kurtosis and skewness of signal intensity in the tumor was significantly different between tumors with distant metastases and those without (4.23 ± 1.31 vs. 3.24 ± 1.32, p = 0.04; 1.09 ± 0.39 vs. 0.57 ± 0.58, p = 0.03). Kurtosis of the tumor was significantly correlated with OS and RFS (p = 0.04, p = 0.03, respectively), and skewness was significantly correlated with OS (p = 0.03) in Cox regression analysis. Higher kurtosis or higher skewness of the tumor was associated with worse OS in Kaplan-Meier analysis (p = 0.01, p = 0.009, log-rank). In subset analysis, there were 50 patients (32 men and 18 women) of lymph node-negative colorectal cancers (≤ stage II); skewness of signal intensity in the tumor was associated with OS using univariate Cox regression analysis (p = 0.04). CONCLUSIONS: Histogram analysis of DWI can be a prognostic biomarker for colorectal cancer.

Development of imaging biomarker for esophageal cancer using intravoxel incoherent motion MRI.

BACKGROUND: Intravoxel incoherent motion MRI (IVIM-MRI) can quantify micro-perfusion at the capillary level in the tissue. The purpose of this study is to measure tumor perfusion using IVIM-MRI, and evaluate its value as a biomarker to predict prognosis in esophageal squamous cell carcinoma (ESCC) patients. METHODS: 109 ESCC patients (93 men and 16 women; median age: 72) who underwent IVIM-MRI prior to treatment between February 2018 and August 2020 were retrospectively investigated. Both mean apparent diffusion coefficient (ADC) value and mean perfusion-related parameter (PP) value of the primary tumor were measured using three b values of 0, 400, and 1000 s/mm2 based on the IVIM model. We analyzed associations of these parameters with clinical stage and disease-specific survival (DSS). RESULTS: Lower ADC and PP values of the tumor were significantly associated with the higher clinical T stage (p < 0.0001, p < 0.0001, respectively). In Kaplan-Meier analyses, patients with lower PP value tumors (< 18.94, median) had significantly worse DSS (p < 0.0001), while tumor ADC value did not show a significant correlation with DSS. In a multivariate analysis, PP value of the tumor was an independent prognostic factor for DSS (p = 0.0027). CONCLUSIONS: Quantification of tumor perfusion using IVIM-MRI can be a non-invasive prognostic biomarker of ESCC, reflecting clinical stage and survival.

Volumetric Histogram Analysis of Apparent Diffusion Coefficient as a Biomarker to Predict Survival of Esophageal Cancer Patients.

BACKGROUND: The purpose of this study was to investigate whether histogram analysis of an apparent diffusion coefficient (ADC) can serve as a prognostic biomarker for esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study enrolled 116 patients with ESCC who received curative surgery from 2006 to 2015 (including 70 patients who received neoadjuvant chemotherapy). Diffusion-weighted magnetic resonance imaging (DWI) was performed prior to treatment. The ADC maps were generated by DWIs at b = 0 and 1000 (s/mm2), and analyzed to obtain ADC histogram-derived parameters (mean ADC, kurtosis, and skewness) of the primary tumor. Associations of these parameters with pathological features were analyzed, and Cox regression and Kaplan-Meier analyses were performed to compare these parameters with recurrence-free survival (RFS) and disease-specific survival (DSS). RESULTS: Kurtosis was significantly higher in tumors with lymphatic invasion (p = 0.005) with respect to the associations with pathological features. In univariate Cox regression analysis, tumor depth, lymph node status, mean ADC, and kurtosis were significantly correlated with RFS (p = 0.047, p < 0.001, p = 0.037, and p < 0.001, respectively), while lymph node status and kurtosis were also correlated with DSS (p = 0.002 and p = 0.017, respectively). Furthermore, multivariate analysis demonstrated that kurtosis was the independent prognostic factor for both RFS and DSS (p < 0.001 and p = 0.015, respectively). In Kaplan-Meier analysis, patients with higher kurtosis tumors (> 3.24) showed a significantly worse RFS and DFS (p < 0.001 and p = 0.006, respectively). CONCLUSIONS: Histogram analysis of ADC may serve as a useful biomarker for ESCC, reflecting pathological features and prognosis.

Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet
.

OBJECTIVE: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. MATERIALS AND METHODS: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531; p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. CONCLUSION: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.

Voriconazole trough concentration and hepatotoxicity in patients with low serum albumin
.

OBJECTIVE: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. MATERIALS AND METHODS: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. RESULTS: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 - 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 µg/mL. CONCLUSION: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 µg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.

Relationship between the blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplant recipients
.

OBJECTIVE: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients. MATERIALS AND METHODS: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients, orally in 7 patients) were enrolled in the present study. RESULTS: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38; p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43; p = 0.34; y = 7.9x + 719). CONCLUSION: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.

Stage IV and recurrent colorectal cancer cured following multimodal therapy: A case series.

The treatment strategies for colorectal cancer (CRC) with distant metastasis or metastatic recurrence after resection of the primary tumor are controversial. In the present study, four cases of patients with advanced CRC with distant metastasis who achieved disease-free survival (DFS) for >5 years and were deemed potentially cured were reported. Case 1 was that of a 53-year-old male patient with rectal cancer and liver metastases (pT3N2bM1, pStage IV), and case 2 was that of a 58-year-old female patient with descending colon cancer (pT3N1M1, pStage IV) who had lung metastases at surgery and postoperatively. Both patients achieved DFS for >5 years after simultaneous or staged partial hepatectomy or pneumonectomy followed by chemotherapy. Case 3 was that of a 75-year-old male patient with transverse colon cancer (pT3N1M0, pStage IIIB) and case 4 was that of a 73-year-old male patient with sigmoid colon cancer (pT3N0M0, pStage IIA). These cases developed liver metastases after resection of the primary tumour and were subsequently treated with chemotherapy before or after partial hepatectomy. DFS for >5 years was achieved. All four patients were considered cured. The data revealed that even patients with CRC and distant metastases can potentially be cured following multidisciplinary treatment. In the present case report, the factors that enabled these patients to be considered cured were discussed and the aim was to improve the treatment strategy to cure CRC with distant metastasis or recurrence.

Incidence of serious infections in the working-age Japanese adult population with rheumatoid arthritis treated with tumor necrosis factor-α inhibitors and interleukin-6 inhibitors: A nationwide retrospective cohort study.

AIM: This retrospective cohort study aimed to compare the risk of serious infections in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α inhibitors (TNFαi) and interleukin-6 inhibitors (IL-6i), with no prior use of biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: We employed the nationwide insurance claims database encompassing the years 2005 to 2018 in Japan. The inclusion criteria specified patients who were prescribed any type of bDMARDs, including TNFαi and IL-6i. The following exclusion criteria were applied: missing prescription dates, RA not diagnosed, below 16 years of age, bDMARDs prescribed within 6 months of registration, RA diagnosed post-bDMARDs prescription, and incidence of serious infections within 2 weeks before bDMARDs therapy. We applied stabilized inverse probability weights and utilized a Cox regression model to estimate the risk of serious infections associated with TNFαi and IL-6i. RESULTS: The cohort of 2493 patients with RA was categorized into a TNFαi group and an IL-6i group of 2018 and 475 participants, respectively. The median follow-up duration (interquartile range) was 347 (147-820) days in the TNFαi group and 369 (149-838) days in the IL-6i group. In the inverse probability-weighted cohort, the incidence rates (95% confidence interval) of serious infections were 2.13 (1.65-2.71) and 3.25 (2.15-4.69) per 100 person-years for the TNFαi and IL-6i groups, respectively. The hazard ratio (95% confidence interval) comparing the TNFαi group to the IL-6i group was 0.66 (0.36-1.20, p = 0.168). DISCUSSION: The results underscore the lack of evidence to preferentially favor either TNFαi or IL-6i as later-line therapy in the management of bDMARDs-naive RA to mitigate the risk of serious infections.

Evaluation of starch granules based on hydroxypropylcellulose as a substitute for excipient lactose.

BACKGROUND: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose. METHODS: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP). RESULTS: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose. CONCLUSIONS: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications.

Predictors of olaparib discontinuation owing to adverse drug events in patients with ovarian, peritoneal, or fallopian tube cancer: a retrospective observational study.

We investigated predictors of olaparib discontinuation owing to adverse effects. Patients with ovarian, peritoneal, or fallopian tube cancers treated with olaparib at Osaka Medical and Pharmaceutical University Hospital between April 2018 and September 2022 were included in this study. The exclusion criteria were as follows: discontinuation of treatment due to disease progression, use of anaemia medications, and use of cytochrome P450 (CYP3A4) inhibitors. The follow-up period was 90 d. Of the 46 eligible patients, 21 patients discontinued olaparib, including 15 patients with grade 3 or higher anaemia, eight patients with grade 3 or higher neutropenia, and four patients with non-haematological toxicity (including multiple onset). Multivariate logistic regression analysis showed that grade 4 neutropenia and anaemia progression to grades 2-3 due to chemotherapy administered before olaparib administration were predictors of olaparib discontinuation. The severity of neutropenia and anaemia due to chemotherapy before olaparib administration may be a potential marker for its discontinuation.

Intraoperative assessment of blood flow using transabdominal ultrasound during laparoscopic surgery of celiac artery compression syndrome.

Surgical treatment of celiac artery (CA) compression syndrome (CACS) is to release the median arcuate ligament (MAL) by removing the abdominal nerve plexus surrounding CA. In laparoscopic surgery of CACS, objective intraoperative assessment of blood flow in CA is highly desirable. We herein demonstrate a case of laparoscopic surgery of CACS with use of intraoperative transabdominal ultrasound. A 52-year-old woman was presented with epigastric pain and vomiting after eating. Contrast-enhanced computed tomography demonstrated significant stenosis at the origin of CA. Doppler study of CA was also performed, and she was diagnosed as CACS. Laparoscopic surgery was performed, and the MAL was divided. And then, Doppler study using intraoperative transabdominal ultrasound confirmed the successful decompression of CA. This patient was discharged on postoperative day 11, and her symptoms was improved. Intraoperative assessment of blood flow in CA using transabdominal ultrasound was a simple and useful method for laparoscopic surgery of CACS.

Clinical and preclinical evidence that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prevent diabetic peripheral neuropathy.

Given possible involvement of the central and peripheral angiotensin system in pain processing, we conducted clinical and preclinical studies to test whether pharmacological inhibition of the angiotensin system would prevent diabetic peripheral neuropathy (DPN) accompanying type 2 diabetes mellitus (T2DM). In the preclinical study, the nociceptive sensitivity was determined in leptin-deficient ob/ob mice, a T2DM model. A clinical retrospective cohort study was conducted, using the medical records of T2DM patients receiving antihypertensives at three hospitals for nearly a decade. In the ob/ob mice, daily treatment with perindopril, an angiotensin-converting enzyme inhibitor (ACEI), or telmisartan, an angiotensin receptor blocker (ARB), but not amlodipine, an L-type calcium channel blocker (CaB), significantly inhibited DPN development without affecting the hyperglycemia. In the clinical study, the enrolled 7464 patients were divided into three groups receiving ACEIs, ARBs and the others (non-ACEI, non-ARB antihypertensives). Bonferroni's test indicated significantly later DPN development in the ARB and ACEI groups than the others group. The multivariate Cox proportional analysis detected significant negative association of the prescription of ACEIs or ARBs and ß-blockers, but not CaBs or diuretics, with DPN development. Thus, our study suggests that pharmacological inhibition of the angiotensin system is beneficial to prevent DPN accompanying T2DM.

A case of rectal metastasis of prostate cancer mimicking extramural growth-type rectal tumor.

Rectal metastases of prostate cancer are rare and may be difficult to diagnose. In this report, we describe a case in which an extramural growth-type rectal tumor was resected and pathologically diagnosed as prostate cancer metastasis. A 70-year-old man on hormone therapy for prostate cancer with seminal vesicle invasion and pelvic lymph node metastasis was referred to our department after an imaging scan showed an extramural growth-type rectal tumor. Endoscopic ultrasound-guided fine needle aspiration was considered for diagnosis, but the patient preferred an early resection without the exam, so surgery was performed. Histopathological examination revealed that the lesion was in the adventitia of the rectum and metastasis of prostate cancer. Metastatic lesions of prostate cancer are not indicated for resection. A detailed preoperative study with the possibility of prostate cancer metastasis in mind is necessary because it is relevant to choosing the treatment strategy.

Apparent diffusion coefficient by magnetic resonance cholangiopancreatography is useful for grading cholecystitis and surgery planning.

INTRODUCTION: Laparoscopic cholecystectomy is a standard procedure for treating cholescytitis, but severe inflammation may cause complications. Our previous study showed that the apparent diffusion coefficient (ADC) values could predict difficult surgery. In the present study, relevance of ADC values in grading the severity of cholecystitis was pathologically investigated. METHODS: We retrospectively analyzed a total of 50 patients who underwent laparoscopic cholecystectomy or laparotomic cholecystectomy/choledocholithotomy. The degree of inflammation in the neck of the gall bladder was pathologically graded into three tiers (grade 1, mild; grade 2, moderate; grade 3, severe), and ulceration, lymphoid follicle formation, and wall thickness of the gallbladder neck were recorded. All factors were statistically compared with the measured ADC values. RESULTS: The ADC value was significantly lower in the severe inflammation group ( grade 3) than in the weak inflammation group (grades 1 and 2) (1.93 ± 0.22 vs 2.38 ± 0.67, respectively; P = .02). Ulceration and wall thickness in the gallbladder neck were significantly correlated with ADC values (P = .04 and .006, respectively), and lymphoid follicle formation was marginally correlated with ADC values (P = .06). The diagnostic utility of the ADC values decreased as the interval between imaging and cholecystectomy increased. [Correction added on 19 October 2022, after first online publication: [On the first sentence of the Results section, (grades 2 and 3) for weak inflammation group has been changed to (grades 1 and 2).] CONCLUSION: ADC values were inversely associated with the pathologic intensity of cholecystitis. We recommend that the ADC value be measured before surgery, so that the procedure can be accordingly planned.

[Analysis of Factors Affecting Proteinuria Onset Timing in Patients Treated with Bevacizumab].

Bevacizumab (BV) is a recombinant and humanized monoclonal antibody that inhibits vascular endothelial growth factor. BV is used to treat various types of cancer. Proteinuria is a characteristic adverse event that occurs as a result of treatment with BV. However, the onset timing of proteinuria after BV administration remains unclear. In the present study, we examined the risk factors affecting the timing of proteinuria onset upon BV administration. Medical records of 135 patients (62 males and 73 females; mean age: 67.8±10.7 years) treated with BV were reviewed at the Kindai University Nara Hospital from April 2011 to December 2019. Proteinuria was identified in 44.4% (60/135) of the studied patients. The time to the first onset of proteinuria was significantly shorter in the administration of doses of BV (≥10) and history of diabetes mellitus. The median cumulative dose associated with the onset of proteinuria was 30.0 (16.1-58.8) mg/kg. When this cumulative dose was compared with 10 mg/kg, no significant difference was observed (p=0.319). The present study demonstrated that the administration of doses of BV (≥10) and history of diabetes mellitus are one of the main risk factors for early-onset proteinuria. These findings may be useful for the future treatment of early-onset proteinuria in patients treated with BV.