Kansai Medical University Hospital Research Articles

Clinical and pathologic characteristics of inflamed juvenile conjunctival nevus and its treatment with immunosuppressant eye drops.

To clarify the clinical and pathologic findings of 7 patients with inflamed juvenile conjunctival nevus (IJCN) treated with tacrolimus. Retrospective study. The medical records of 7 male patients diagnosed with IJCN between February 2007 and October 2022 at the Kansai Medical University Hospital and Ideta Eye Hospital were retrospectively reviewed. The patients' mean age was 11.3 (8-20) years, and the average follow-up period was 18 months. The patients underwent anterior segment optical coherence tomography (AS-OCT) and anterior segment optical coherence tomography angiography (AS-OCTA). All the patients were treated with steroids or immunosuppressant eye drops, or both. Histopathologic examinations were performed on specimens resected from 2 patients. The clinical characteristics of IJCN were as follows: (1) presence of cysts within a pigmented conjunctival mass, (2) tumor accompanied by feeder vessels, and (3) predominantly found in boys with allergic diseases. AS-OCT and AS-OCTA revealed the presence of a cystic structure with poor vascular signals within it and numerous vessels distributed on the sclera underlying the lesion. Immunosuppressant eye drops relieved the congestion, diminished the inflow vessels, and induced shrinkage of the cysts in all the patients. Histopathologic examinations revealed infiltration of inflammatory cells such as lymphocytes and macrophages and low proliferative activity of melanocytes with no division pattern. This study clarified the clinical and histologic characteristics of IJCN. Noninvasive AS-OCT and AS-OCTA might be useful for diagnosing IJCN. The histopathologic findings of this study indicate that immunosuppressive and antiallergic agents can effectively bring about disease remission.

Feasibility Study of Nivolumab in Combination with Carboplatin Plus Paclitaxel and Concurrent Thoracic Radiation in Patients with Untreated Unresectable Locally Advanced Non-Small Cell Lung Cancer.

Despite advancements in diagnosing and treating non-small cell lung cancer (NSCLC), the prognosis remains poor. Immune checkpoint inhibitors have shown promise in enhancing survival rates. Therefore, this study aimed to investigate the safety of nivolumab administration with concurrent chemoradiation therapy (CCRT) in patients with unresectable locally advanced NSCLC. Twelve patients with unresectable locally advanced NSCLC at Kansai Medical University Hospital and Izumi City General Medical Center were enrolled from May 2018 to September 2020. They received nivolumab (360 mg) tri-weekly twice, weekly carboplatin (AUC 2 min × mg/mL) and paclitaxel (40 mg/m2) for 6 weeks, and thoracic radiotherapy (60 Gy/30 fractions), followed by maintenance nivolumab therapy (360 mg, tri-weekly) for 6 months. The primary endpoint was incidence of dose-limiting toxicities (DLTs), and the secondary endpoints included safety, response rate, progression-free survival (PFS), overall survival (OS), 2-year survival rate, and treatment completion rate. Three patients completed the protocol. Nine discontinued due directly to interstitial pneumonia (three) and pneumonia (one). Ten patients (83.3%) experienced a grade 3 or higher event, of which three (25%) experienced a grade 4 or higher event, and of these, one (8.3%) experienced a grade 5 event. Three patients experienced DLTs. Concurrent nivolumab with CCRT was tolerated in unresectable locally advanced NSCLC, which offers potential treatment benefits.

Trifecta outcomes of robotic partial nephrectomy in obese patients: A comparison of body mass index

We analyzed robotic partial nephrectomy (RPN) outcomes in obese patients based on body mass index (BMI) and trifecta achievement. We retrospectively reviewed 296 patients who underwent RPN at Kansai Medical University Hospital between 2014 and 2022. The preoperative clinical data and perioperative outcomes were evaluated. Trifecta achievement (negative surgical margin, no major complications, and no acute kidney injury on postoperative day three) and its relationship to three BMI groups (<25, 25 to <30, and ≥30) were the primary outcome. The correlation between factors in achieving trifecta and BMI was evaluated. Univariate and multivariate analyses assessed variables for achieving the trifecta with logistic regression analysis. C-statistics quantitatively evaluated the prediction accuracy. Among 296 patients, 264 (89.2%) achieved trifecta (BMI categories were <25 [89.9%], 25 to <30 [89.4%], and ≥30 [82.6%]). There was no significant BMI-related difference (p = 0.566). Intraoperative blood loss increased with the BMI (p = 0.034). Multivariate analyses showed preoperative aspects and dimensions used for anatomic (PADUA) score independently predicted trifecta failure (odds ratio 1.71; 95% confidence interval 1.32-2.20; p < 0.001). The C-statistics of the PADUA score increased with increasing BMI. Higher BMI patients had more intraoperative blood loss during RPN. However, RPN remains safe and has acceptable quality and functional outcomes. Since patients with high PADUA scores combined with a high BMI may be at risk of trifecta failure, this should be explained before RPN.

Pathogenesis of Medication-Related Osteonecrosis of the Jaw: Odontogenic Infection-Preceding Type and Osteonecrosis-Preceding Type.

Introduction Medication-related osteonecrosis of the jaw (MRONJ) develops from odontogenic infection. However, there are also some cases of MRONJ developing from sites with no teeth, no root canal lesions, or no periodontal disease. This study aimed to retrospectively review radiographic images of MRONJ cases and examine the differences in characteristics between MRONJ suspected to be related to dental infection (odontogenic MRONJ) and MRONJ that occurred without dental involvement or of unknown cause (non-odontogenic MRONJ). Materials and methods One hundred and forty-five patients were diagnosed with MRONJat Kansai Medical University Hospital and Kansai Medical University Medical Center. The following variables were investigated: sex, age, primary disease, MRONJ site, body mass index, smoking habit, diabetes, corticosteroids, type of antiresorptive agent, administration period, CT findings (separation of sequestrum, osteolysis, periosteal reaction, and osteosclerosis), trigger, leukocytes, neutrocytes, neutrophil-lymphocyte ratio, serum albumin, and serum creatinine levels. Results In the univariate analysis, significant differences between odontogenic and non-odontogenic MRONJs were found in patients whose primary disease was malignancy, receiving denosumab (DMB), and with short administration period of antiresorptive agent, no osteolysis, periosteal reaction, and serum creatinine level. In multivariate analysis, non-odontogenic MRONJ was significantly more common in patients with no osteolysis and with periosteal reaction. Conclusion Non-odontogenic MRONJ tends to occur more frequently in patients treated with high-dose DMB, and there were significantly more cases of non-osteolytic MRONJ without radiographic evidence of osteolysis or with periosteal reactions.

Abstract 1192: Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients

Abstract Background: Chemoradiotherapy (CRT) followed by Durvalumab consolidation has been the standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients. This study aimed to evaluate how CRT changes TCR repertoire on peripheral CD8+PD-1+ T-cells, and the change affects the clinical outcomes of CRT followed by durvalumab treatment. Methods: This was a prospective cohort study conducted from November 2019 to May 2021 in three institutes (National Cancer Center Hospital, Kansai Medical University Hospital, and Aichi Cancer Center Hospital) in Japan. We revealed the diversity of TCR repertoire (diversity evenness 50 [DE50]) on PD-1+CD8+ T cells, and CD8+ T cell phenotype in PBMCs before and after CRT treatment. Results: A total of 40 patients treated with CRT were included. Of these patients, 32 patients received durvalumab consolidation treatment after CRT (Durva cohort). The diversity and usage of T cell Receptor Beta Variable (TRBV) and T-cell receptor beta joining gene (TRBJ) usage were significantly positively correlated before and after CRT (TRBV usage: r=0.62, p&amp;lt;0.001, TRBJ usage: r=0.55, p&amp;lt;0.001). Regarding the association of TCR repertoire diversity with CD8+ T cell phenotype, DE50 and frequencies of CD8 naive were significantly positively correlated before CRT (p=0.049), while there was no correlation between PD-L1 expression and TCR repertoire before CRT (r=0.03, p=0.89) In Durva cohort, DE50 in patients with non-recurrence was higher than those with recurrence both before and after CRT (Before CRT: 0.0032 vs. 0.0019, p=0.13, After CRT: 0.0026 vs. 0.0014, p=0.06). The progression-free survival (PFS) of patients with DE50High before CRT was significantly greater than those with DE50Low (NR vs. 14.3 months; p=0.01). Moreover, when the patients were exploratory classified based on the PD-L1 expression status and the diversity of TCR repertoire, the PFS of the CRT followed by durvalumab apparently differed (DE50High, PD-L1 TPS≥1%, NR, and DE50Low, PD-L1 TPS&amp;lt;1%, 5.9 (4.6-7.3) months, p=0.001). Conclusions: TCR diversity of peripheral CD8+PD-1+ T-cell predicted the recurrence in unresectable locally advanced NSCLC patients treated with chemoradiotherapy followed by durvalumab maintenance. Additionally, the TCR diversity combined with PD-L1 expression status could more accurately predict the efficacy of the CRT followed by durvalumab. Citation Format: Masayuki Shirasawa, Tatsuya Yoshida, Yuki Takeyasu, Takaji Matsutani, Shigehiro Yagishita, Shigehisa Kitano, Hiroaki Kuroda, Toyoaki Hida, Takayasu Kurata, Yuichiro Ohe. Diversity of TCR repertoire on peripheral CD8+PD-1+ T-cell predicting the PFS of chemoradiotherapy followed by durvalumab maintenance in unresectable locally advanced NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1192.

Evaluation of characteristics and prognosis of COVID-19 patients requiring invasive mechanical ventilation during dominance of nonvariant, alpha, delta, and omicron variants in tertiary hospitals of Japan

BackgroundIn November 2021, the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in South Africa and subsequently rapidly spread around the world. Despite the reduced severity of the omicron variants, many patients become severely ill after infection and undergo invasive mechanical ventilation, but there are few reports on their background and prognosis throughout all variant periods. This study aimed to evaluate risk factors affecting patients requiring invasive mechanical ventilation with each variant of COVID-19 pandemic in Japan from nonvariants to omicron variants.MethodThis retrospective observational study was conducted at the Department of Emergency and Critical Care Medicine, Kansai Medical University Hospital and Kansai Medical University Medical Center, Osaka, Japan, from March 2020 to March 2023. Eligible patients were those who underwent invasive ventilation for COVID-19 pneumonia. We set the primary endpoint as in-hospital mortality. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes.ResultsWe included 377 patients: 118 in the Nonvariant group, 154 in the Alpha group, 42 in the Delta group, and 63 patients in the Omicron group. Mortality rates for each group were 23.7% for the Nonvariant group, 12.3% for the Alpha group, 7.1% for the Delta group, and 30.5% for the Omicron group. Patient age was significantly associated with increased mortality (adjusted odds ratio [AOR]: 1.097; 95% confidence interval [CI]: 1.057–0.138, P < 0.001). Immunodeficiency (AOR: 3.388, 95% CI: 1.377–8.333, P = 0.008), initial SOFA score (AOR: 1.190, 95% CI: 1.056–1.341, P = 0.004), dialysis prior to COVID-19 (AOR: 3.695, 95% CI: 1.117–11.663, P = 0.026), and smoking history (AOR: 2.548, 95% CI: 1.153–5.628, P = 0.021) were significantly associated with increased mortality. Differences in variants were not significant factors associated with high mortality.ConclusionWe compared the background and prognosis of patients with COVID-19 pneumonia requiring invasive mechanical ventilation between SARS-CoV-2 variants. In these patients, differences in variants did not affect prognosis. Hospital mortality in critically ill COVID-19 patients was significantly higher in the older patients with bacterial coinfection, or patients with immunodeficiency, COPD, and chronic renal failure on dialysis.

Efficacy and Safety of Polatuzumab-Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) for Diffuse Large B-Cell Lymphoma in the Real-World Setting: A Single Institute Retrospective Study

Background In the POLARIX study, Pola-R-CHP showed significant improvement in progression free survival (PFS) in previously untreated diffuse large B-cell lymphoma (DLBCL) compared to R-CHOP. Pola-R-CHP was approved in September 2022 in Japan ahead of the the world. However, there are still few reports about the safety and efficacy of Pola-R-CHP in real-world setting, leaving some questions about the optimal patient population for Pola-R-CHP. So, we conducted this single institute retrospective observational study in clinical practice. Methods The Pola-R-CHP group included untreated DLBCL patients who received Pola-R-CHP therapy from September 2022 to January 2023 at Kansai Medical University Hospital. The control group included untreated DLBCL patients treated with R-CHOP or R-THP-COP from January 2020 to June 2022 at our hospital. The primary endpoint was the complete remission rate (CRR) at the end of treatment, and secondary endpoints were 6-month PFS, 6-month overall survival (OS) survival, and severity and frequency of adverse events. Results In the Pola-R-CHP group, 30 patients (median age 74 [range;42-88] years) were enrolled. 8 patients over 80 years old were included. 46.7% (14/30) of the cases were Ann Arbor Stage Ⅲ-Ⅳ, and 73.3% (22/30) of the cases had IPI(International Prognostic Index) of 2 or more points. 60.0% (18/30) of patients were GCB (germinal center B-cell) type and 33.3% (10/30) were non-GCB type, and 36.7% (11/30) of patients were DEL (Double expressor lymphoma).In the control group, 100 patients (median age 75 [range;39-88] years) were enrolled. 23 patients over 80 years old were included. 54% (54/100) of the cases were Stage Ⅲ-Ⅳ, and 74%(74/100) of the cases had IPI of 2 or more points. 44%(44/100) of patients were GCB type and 47% (47/100) were non-GCB type (nine were not classified), and 40% (40/100) of patients were DEL. 65% (65/100) of patients were treated with R-CHOP and 35% (35/100) patients were treated with R-THP-COP. There were no significant differences in the patient backgrounds between the respective groups.In Pola-R-CHP cohort, the median follow-up was 282 days (range, 181-348 days). The median number of Pola-R-CHP cycles performed 6 (range; 2-6), with a 6-cycles completion rate of 86.7% (26/30). In patients over 80 years old, the doses of CHP were reduced to 50%. In the Pola-R-CHP group at end of treatment (EOT), the overall response rate was 93.3% (n=28), CRR was 86.7% (n=26), partial response was 6.7% (n=2), and progressive disease was 6.7% (n=2)(Fig.1). In the control group, CRR at EOT was 76.0% but the difference between each group was not significant (p=0.321). The PFS at 6 months was 93.3% (95% confidence interval (CI),75.9%-98.3%) in the Pola-R-CHP group and 80.0% (95%CI,70.7%-86.6%) in the control group, with significantly improvement in the Pola-R-CHP group (p=0.017). Notably, in patients with IPI of 4 to 5, CRR was 88.9 % in the Pola-R-CHP group and 51.5% in the control group (p=0.060), and the PFS at 6 months was significantly higher in the Pola-R-CHP group (88.9% [95%CI,43.4%-98.4%] vs. 60.6%[95%CI,42.0%-74.9%]; p=0.034) In the patients with high metabolic tumor volume (MTV) measured based on PET-CT (cut off value; 166 cm 3 in the top quartile of MTV), PFS at 6 months was significantly higher in the Pola-R-CHP group than the control group (100% vs 73.7% [95% CI,47.9%-88.1%]; p=0.045). OS at 6 months was 89% (95%CI,81%-93.8%) in the control group, while all patients in the Pola-R-CHP group were alive. The most common AE was hematological toxicity: neutropenia, anemia, and thrombocytopenia at grade 3-4 was observed in 43.3%, 16.7%, and 20.0%, respectively (Fig. 2). 14 cases of infection were observed. Peripheral neuropathy was found in 23.3% of the patients, and one of the patients reached grade 3-4. Many cases were complicated with constipation, but only a few cases were grade 3-4. Diarrhea was present in 20%, but all were mild and transient. No deaths due to AE were observed. One patient had to discontinue treatment due to heart failure. Unexpected adverse events were not observed. Conclusion In this study, Pola-R-CHP showed a treatment response and PFS benefit compared to historical control in patients with previously untreated DLBCL in the real-world setting.The incidence of diarrhea and peripheral neuropathy was lower, while AE profiles were similar to POLARIX study. Pola-R-CHP is well tolerated and the efficacy can be promising compared to R-CHOP.

Retrospective study of an incisional hernia after laparoscopic colectomy for colorectal cancer

PurposeThis study aimed to examine the incidence of incisional hernia (IH) in elective laparoscopic colorectal surgery (LC) using regulated computed tomography (CT) images at intervals every 6 months.MethodsWe retrospectively examined the diagnosis of IH in patients who underwent LC for colorectal cancer at Kansai Medical University Hospital from January 2014 to August 2018. The diagnosis of IH was defined as loss of continuity of the fascia in the axial CT images.Results470 patients were included in the analysis. IH was diagnosed in 47 cases at 1 year after LC. The IH size was 7.8 cm2 [1.3–55.6]. In total, 38 patients with IH underwent CT examination 6 months after LC, and 37 were already diagnosed with IH. The IH size was 4.1 cm2 [0–58.9]. The IH size increased in 17 cases between 6 months and 1 year postoperatively, and in 1 case, a new IH occurred. 47%(18/38) of them continued to grow until 1 year after LC. A multivariate analysis was performed on the risk of IH occurrence. SSI was most significantly associated with IH occurrence (OR:5.28 [2.14–13.05], p = 0.0003).ConclusionIH occurred in 10% and 7.9% at 1 year and 6 months after LC. By examining CT images taken for the postoperative surveillance of colorectal cancer, we were able to investigate the occurrence of IH in detail.

Sulfamethoxazole-trimethoprim for pneumocystis pneumonia prophylaxis, causes of discontinuation and thrombocytopenia observed during administration: A single-center retrospective study

IntroductionThe development of pneumocystis pneumonia (PCP) has recently become a growing concern; thus, its prevention has become increasingly important. Sulfamethoxazole-trimethoprim (ST) is a cost-effective first-line and prophylactic treatment for PCP. However, ST administration criteria for PCP prophylaxis remain unclear and are often discontinued because of adverse events (AEs). In this study, we aimed to investigate the causes of ST discontinuation and the associated AEs using objective data. MethodsWe retrospectively analyzed the data of 162 patients admitted to Kansai Medical University Hospital between January 2018 and December 2020, who received ST for PCP prophylaxis. We compared clinical characteristics, laboratory data, and incidence of AEs between ST non-discontinuation and ST discontinuation groups. Additionally, we divided the patients into non-developing and developing thrombocytopenia (≥ Grade 1) groups based on the investigation results. ResultsNo patients developed PCP while receiving ST. The most common causes of ST discontinuation were thrombocytopenia (37%), liver dysfunction (20%), and rash (18%). Multivariate analysis revealed thrombocytopenia (≥ Grade 1) as a factor significantly associated with ST discontinuation. Furthermore, we identified three factors correlated with thrombocytopenia (≥ Grade 1): age ≥50 years, lymphocyte count <1000/μL, and platelet count <180,000/μL. ConclusionsPatients with the aforementioned factors are at higher risk of developing thrombocytopenia (≥ Grade 1) during ST administration for PCP prophylaxis. Therefore, platelet count monitoring is essential to enhance safety and efficacy of ST treatment. Nonetheless, further research is warranted to explore additional implications and interventions.

Treatment strategy for BVO-ME based on long-term outcomes correlating retinal structure by OCT image and visual acuity

BackgroundIntravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity.MethodsPatients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (< 0.7).ResultsForty-seven eyes from 45 patients were assessed. The mean follow-up period from initial to final visit was 64.38 ± 15.07 (range, 38–100) months. BCVA in Group A (n = 32) was significantly greater than in Group B (n = 15) at all timepoints. The ratio that the number of eyes which the EZ band and the foveal bulge were intact in Group A was higher than in Group B (p = 0.0004 and p = 0.0002, respectively). The ratio that the number of eyes which recurrence SRD was observed by the final visit in Group A was lower than in Group B (p = 0.0485).ConclusionsThe integrity of the EZ band and an intact foveal bulge were significant predictors for visual acuity. In contrast, recurrent SRD led to poor visual acuity in the long term, even if BCVA was good in the short term.

Study of damage control strategy for non-traumatic diseases: a single-center observational study

BackgroundDamage control strategy (DCS) has been introduced not only for trauma but also for acute abdomen, but its indications and usefulness have not been clarified. We examined clinical characteristics of patients who underwent DCS and compared clinical characteristics and results with and without DCS in patients with septic shock.MethodsWe targeted a series of endogenous abdominal diseases in Kansai Medical University Hospital from April 2013 to March 2019. Clinical characteristics of 26 patients who underwent DCS were examined. Then, clinical characteristics and results were compared between the DCS group (n = 26) and non-DCS group (n = 31) in 57 patients with septic shock during the same period.ResultsAll 26 patients who underwent DCS had septic shock, low mean arterial pressure (MAP) before the start of surgery, and required high-dose norepinephrine administration intraoperatively. Their discharge mortality rate was 12%. Among the patients with septic shock, the DCS group had a higher SOFA score (P = 0.008) and MAP was lower preoperatively, but it did not increase even with intraoperative administration of large amounts of fluid replacement and vasoconstrictor. There was no significant difference in 28-day mortality and discharge mortality between the two groups.ConclusionsDCS may be useful in patients with severe septic shock.

Prognostic significance of the expression levels of T-cell immunoglobulin mucin-3 and its ligand galectin-9 for relapse-free survival in triple-negative breast cancer.

T-cell immunoglobulin mucin-3 (TIM-3) expressed at the T-cell surface acts as an immune checkpoint when bound by its ligand galectin-9. Blockade of immunosuppression by the TIM3/galectin-9 signalling pathway may offer novel therapeutic approaches for cancer immunotherapy. Consistent with this, TIM-3 expression is associated with poorer prognosis in several different types of cancer, possibly as a result of suppression of anticancer immunosurveillance. A number of studies have now documented some effectiveness of immune checkpoint blockade even in triple-negative breast cancer (TNBC), which is highly aggressive. However, clinical responses are relatively weak, suggesting that several different pathways may be involved. In this context, the role of the TIM-3/galectin-9 checkpoint in TNBC is not clear. The present study aimed to determine the clinicopathological significance of TIM-3 and galectin-9 expression in this cancer. To this end, 62 patients with TNBC undergoing surgery at Kansai Medical University Hospital (Hirakata, Japan), but not given neoadjuvant chemotherapy, were examined. Tissue microarrays were employed for immunohistochemistry to analyse associations of TIM-3 and galectin-9 expression and their impact on relapse-free survival relative to other poor prognostic risk factors. Galectin-9 expression was detected in 49 of 62 patient samples (79%), and TIM-3 in 30 of them (48.4%). Tumour cell galectin-9 expression was associated with a more favourable prognosis (P=0.027) as was TIM-3 expression on tumour-infiltrating lymphocytes (P=0.007). Multivariate analysis indicated that galectin-9- and TIM-3-double-positivity was significantly associated with a more favourable prognosis compared with galectin-9 and/or TIM-3 negativity (P=0.044). Thus, the TIM-3/galectin-9 signalling pathway may impact anticancer immune reactions in the tumour microenvironment of patients with TNBC. Further investigation will be necessary to determine the molecular mechanisms underlying these relationships.

Relationship between Drug Holidays of Antiresorptive Agents and Surgical Outcomes in Cancer Patients with Medication-Related Osteonecrosis of the Jaw.

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients’ age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients’ surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.

Massive digital gene expression analysis reveals different predictive profiles for immune checkpoint inhibitor therapy between adenocarcinoma and squamous cell carcinoma of advanced lung cancer

BackgroundImmune checkpoint inhibitors prolong the survival of non-small cell lung cancer (NSCLC) patients. Although it has been acknowledged that there is some correlation between the efficacy of anti-programmed cell death-1 (PD-1) antibody therapy and immunohistochemical analysis, this technique is not yet considered foolproof for predicting a favorable outcome of PD-1 antibody therapy. We aimed to predict the efficacy of nivolumab based on a comprehensive analysis of RNA expression at the gene level in advanced NSCLC.MethodsThis was a retrospective study on patients with NSCLC who were administered nivolumab at the Kansai Medical University Hospital. To identify genes associated with response to anti-PD-1 antibodies, we grouped patients into responders (complete and partial response) and non-responders (stable and progressive disease) to nivolumab therapy. Significant genes were then identified for these groups using Welch’s t-test.ResultsAmong 42 analyzed cases (20 adenocarcinomas and 22 squamous cell carcinomas), enhanced expression of MAGE-A4, BBC3, and OTOA genes was observed in responders with adenocarcinoma, and enhanced expression of DAB2, HLA-DPB,1 and CDH2 genes was observed in responders with squamous cell carcinoma.ConclusionsThis study predicted the efficacy of nivolumab based on a comprehensive analysis of mRNA expression at the gene level in advanced NSCLC. We also revealed different gene expression patterns as predictors of the effectiveness of anti PD-1 antibody therapy in adenocarcinoma and squamous cell carcinoma.

High tumor budding predicts a poor prognosis in resected duodenal adenocarcinoma

Tumor budding is a histological characteristic defined as the presence of small clusters of cancer cells at the invasion front. Its significance in duodenal adenocarcinoma (DA) has not been fully described. A single-center, retrospective study was conducted. Patients who underwent curative surgery for histologically diagnosed DA from January 2006 to December 2018 at Kansai Medical University Hospital were included. Tumor budding was counted per 0.785 mm2 and classified as low (0-4 buds), intermediate (5-9 buds), or high (≥ 10 buds). In total, 47 patients were included. The 5-year overall survival and relapse-free survival rates were 77% and 72%, respectively. High tumor budding was seen in 15 patients (32%). Excluding patients with superficial type (pT1) DA (n = 22), high tumor budding [hazard ratio (HR) 13.4, p = 0.028], regional lymph node metastasis (HR 19.9, p = 0.039), and adjuvant chemotherapy (HR 0.056, p = 0.036) were independent factors related to the overall survival in multivariate analyses. Distant metastases occurred significantly more often in patients who had high tumor budding than in others (p = 0.039). The data suggest that high tumor budding is a predictor of a poor prognosis in resected DA.

Real-World Data of Trifluridine/Tipiracil for Patients With Advanced Gastric Cancer: A Multi-Institutional Retrospective Study.

A trial with trifluridine/tipiracil (FTD/TPI) versus placebo in patients with heavily pretreated metastatic gastric cancer showed that FTD/TPI is effective with manageable toxicity in these patients. However, real-world data on the effects of FTD/TPI in patients with advanced gastric cancer (AGC) are limited. We retrospectively collected and analyzed the clinicopathological data of patients with AGC who received FTD/TPI monotherapy at our institutions (Kobe City Medical Center General Hospital, Osaka Red Cross Hospital, Himeji Red Cross Hospital, and Kansai Medical University Hospital) between September 2019 and July 2021. Tumor responses were evaluated based on the Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival (OS) and progression-free survival were estimated using the Kaplan-Meier method. A total of 53 patients were included in the study. The median age was 70 (range, 37-85) years; 39 patients (74%) were men; the numbers of patients with Eastern Cooperative Oncology Group performance status scores of 0, 1, and 2 were 10 (19%), 39 (74%), and 4 (8%), respectively; and 27 patients (51%) had diffuse-type histology. A total of 29 patients (56%) had ascites. Prior nivolumab therapy was administered to 49 patients (92%). The response rate and disease control rate (DCR) were 2% and 35%, respectively. The median progression-free survival was 2.4 months, and OS was 5.8 months. Patients with ascites exhibited significantly shorter OS (8.6 vs 4.7 months, P = .0291) than those without ascites, and DCR (54% vs 18%, P = .0055) was significantly worse in patients with ascites. There was no significant difference in the frequency of adverse events of grade 3 or higher between patients with and without ascites. In a real-world setting, FTD/TPI has similar effectiveness as late-line chemotherapy for patients with AGC, including those who previously had received nivolumab.

PD07-12 PREOPERATIVE FACTORS ASSOCIATED WITH INTRAOPERATIVE MAXIMUM ARTERIAL PRESSURES IN PATIENTS WITH PHEOCHROMOCYTOMA AND PARAGANGLIOMA

You have accessJournal of UrologyAdrenal (PD07)1 Sep 2021PD07-12 PREOPERATIVE FACTORS ASSOCIATED WITH INTRAOPERATIVE MAXIMUM ARTERIAL PRESSURES IN PATIENTS WITH PHEOCHROMOCYTOMA AND PARAGANGLIOMA Haruyuki Ohsugi, Nae Takizawa, Hidefumi Kinoshita, and Tadashi Matsuda Haruyuki OhsugiHaruyuki Ohsugi More articles by this author , Nae TakizawaNae Takizawa More articles by this author , Hidefumi KinoshitaHidefumi Kinoshita More articles by this author , and Tadashi MatsudaTadashi Matsuda More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001975.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Mortality associated with surgery for pheochromocytoma and paraganglioma (PPGL) has dramatically decreased due to improvements in treatment, such as preoperative management. A recent study has shown that intraoperative hypertensive episodes occurred independently of perioperative α-receptor blockades. However, limited data are available about preoperative factors that predict intraoperative blood pressure. Therefore, the aim of this study was to identify preoperative factors associated with maximum arterial pressure during surgery in patients with PPGL. METHODS: We retrospectively reviewed 61 PPGL patients who underwent surgical resection at Kansai Medical University Hospital between 2006 and 2020. The preoperative clinical data (comorbidity, classic triad [palpitations, headache, and sweating], and 24-h urinary-fractionated metanephrine [MN] and normetanephrine [NMN]) were analyzed. The primary outcome was intraoperative maximum arterial pressure as a single index for continuous variables. The normal distribution of the results was confirmed by the Kolmogorov–Smirnov test. A linear regression model was used for statistical analysis. RESULTS: The median intraoperative maximum arterial pressure was 165 mmHg (IQR: 150–180). Although the 24-h urinary-fractionated MN and NMN was not normally distributed, the logarithmic representation (base=10) of these continuous variables showed a normal distribution (p=0.549). Log (24-h urinary-fractionated MN and NMN) was correlated with intraoperative maximum arterial pressure (R=0.481, p <0.001). Multivariate analyses showed that the classic triad (t statistic, 2.484; p=0.016), diabetes mellitus (DM) (t statistic, 2.097; p=0.040), and log (24-h urinary-fractionated MN and NMN) (t statistic, 2.506; p=0.015) were independent factors predictive of intraoperative maximum arterial pressure. CONCLUSIONS: The classic triad, DM, and log (24-h urinary-fractionated MN and NMN) were significant factors for predicting intraoperative maximum arterial pressure. Since PPGL patients who have these predictors may develop intraoperative hypertension regardless of treatment with an α-receptor blockade, clinicians should manage these patients more carefully and effectively. Source of Funding: The authors have no funding to report © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e112-e112 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Haruyuki Ohsugi More articles by this author Nae Takizawa More articles by this author Hidefumi Kinoshita More articles by this author Tadashi Matsuda More articles by this author Expand All Advertisement Loading ...

Relationship between Psoriasis and Prevalence of Cardiovascular Disease in 88 Japanese Patients.

Psoriasis is a systemic inflammatory disease known to affect survival in the presence of cerebral or cardiovascular comorbidities. However, no clear guidelines have been defined regarding the extent of vascular lesion testing that should be performed in patients with psoriasis. We therefore performed coronary computed tomography angiography (CCTA) in 88 Japanese patients with psoriasis who visited Kansai Medical University Hospital between 2015 and 2019 and determined the ankle–brachial pressure index (ABI) for 44 of these patients. CCTA abnormalities were found in 39 of the 88 patients, and a need for treatment was identified in 14 patients. The prevalence of cardiovascular lesions in these patients was 15.9%, significantly higher than that in the healthy Japanese population (6.38% according to the Suita Study). In the 44 patients with results for both ABI and CCTA, the rates of CCTA vascular lesions were significantly higher in cases with ABIs indicating hard vessels or above than in cases with supple, normal, or slightly stiff vessels. This is the first report to show a correlation between CCTA and ABI in psoriasis patients. ABI was considered useful as a preliminary test before CCTA. The univariate analysis of the abnormal and normal CCTA groups showed that the prevalence differed significantly among patients with psoriatic arthritis, erythrodermic psoriasis, older age, pre-existing conditions, drinking, and hypertension. The multivariate analysis showed correlations with arthritic or erythrodermic psoriasis.

Predictors of postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma.

To analyze the effect of patterns of extrarenal tumor extension with other pathological factors on postoperative recurrence in patients with non-metastatic pT3a renal cell carcinoma. We retrospectively reviewed 587 non-metastatic renal cell carcinoma patients who underwent radical surgery between 2006 and 2017 at Kansai Medical University Hospital, Hirakata, Osaka, Japan. We extracted a subset of 114 patients with pT3a of predominant histological types: 93 with clear cell renal cell carcinoma (81.6%), 13 with unclassified renal cell carcinoma (11.4%), six with chromophobe renal cell carcinoma (5.3%) and two with papillary renal cell carcinoma. The primary end-point was recurrence-free survival. The Kaplan-Meier method and Cox proportional hazards model were used for statistical analysis. Of the 114 patients with pT3a renal cell carcinoma, 42 patients (36.8%) experienced recurrence. Multivariate analysis showed that perinephric fat invasion (hazard ratio 2.36, P=0.009), sarcomatoid or rhabdoid component (hazard ratio 2.88, P=0.022) and necrosis (hazard ratio 2.34, P=0.030) were independent factors for recurrence-free survival. The high-risk pT3a group, which had more than two independent predictors, had poor prognosis. Recurrence-free survival of the high-risk pT3a group and the pT3b or greater group were similar (median recurrence-free survival 23.0 and 10.8months, respectively). Perinephric fat invasion, sarcomatoid or rhabdoid component and necrosis are independent predictors of recurrence-free survival in patients with pT3a-predominant renal cell carcinoma. Patients with more than two of these predictors have poor oncological outcomes. These findings will aid in risk stratification for predicting recurrence and provide prognostic information for patient counseling.

Serum Brain-Derived Neurotrophic Factor and Myostatin Levels Are Associated With Skeletal Muscle Mass in Kidney Transplant Recipients

Sarcopenia, or reduced muscle mass, can be an important complication in kidney transplant recipients. The skeletal muscles were recently reported to secrete various myokines, such as brain-derived neurotrophic factor (BDNF) and myostatin, to regulate their mass, function, or both. The aim of the present study was to analyze the interrelationship between myokines (BDNF and myostatin) and skeletal muscle mass in kidney transplant recipients. The study population comprised 40 patients who underwent kidney transplantation at Kansai Medical University Hospital. Twenty patients had low skeletal muscle mass index (SMI) values, as measured on dual-energy x-ray absorptiometry, and were categorized into 2 groups (low SMI and normal). Mean serum BDNF levels were 15.7 ng/mL in the low SMI group and 17.8 ng/mL in the normal group (P=.013). Mean serum myostatin levels were 362 pg/mL in the low SMI and 267 pg/mL in the normal group (P=.024). There was a significant positive correlation among metabolic equivalents and serum BDNF levels (r=0.817; P < .001) and a significant negative correlation among metabolic equivalents and serum myostatin levels (r=-0.541; P < .001). Receiver operating characteristic analysis showed that serum BDNF and level of area under curve was 0.712, and serum myostatin level of area under the curve was 0.690. Serum BDNF and myostatin levels showed no significant difference. These results suggest that BDNF and myostatin are potential biomarkers of reduced muscle mass in kidney transplant recipients.