Current status and future perspectives of the managements of metastatic hormone-sensitive prostate cancer.

PURPOSE: The therapeutic landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically. Here, we provide the current status and future prospective of the management of mHSPC. METHODS: We reviewed recent literature of landmark studies on the managements of mHSPC. RESULTS: Upfront docetaxel or androgen receptor signaling inhibitor (ARSi) in addition to ADT has improved survival in mHSPC patients and has become the new standard of care. Triplet therapy with docetaxel, ARSi and ADT also improved survival. In the future, triplet therapy may become the standard of care. Oligometastatic mHSPC patients could benefit from local therapy. The inclusion of risk factors or the genetic biomarkers will provide the best treatment for individual mHSPC patients. CONCLUSION: Strong systemic therapy in the first-line treatment of mHSPC has been shown to improve survival and quality of life. Currently, several clinical trials are evaluating novel compounds such as PARP inhibitor, AKT inhibitor, and immune checkpoint inhibitor. The therapeutic landscape of mHSPC management will change dramatically.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

Simultaneous analysis of serum α2,3-linked sialylation and core-type fucosylation of prostate-specific antigen for the detection of high-grade prostate cancer.

BACKGROUND: Altered prostate-specific antigen (PSA) glycosylation patterns can be useful biomarkers in detecting high-grade prostate cancer (HGPC). The microfluidic immunoassay system can analyse α2,3-linked sialylated PSA (α2,3-Sia-PSA) and α1,6-linked fucosylated PSA (α1,6-Fuc-PSA) using different lectins, Mackkia amurensis agglutinin and Pholiota squarrosa lectin, respectively. Here, we investigated the diagnostic value of simultaneous analysis of α2,3-Sia-PSA and α1,6-Fuc-PSA for the detection of HGPC. METHODS: Men with serum PSA levels of 4-20 ng/mL who underwent prostate biopsy were included. The model to predict HGPC (Gleason grade ≥2) was constructed by multivariate logistic regression analysis, in combination with α2,3-Sia-PSA and α1,6-Fuc-PSA (SF index). RESULTS: In the development cohort (n = 150), the SF index showed good discrimination for HGPC (area under the receiver-operating curve (AUC) 0.842; 95% confidence interval (CI) 0.782-0.903), compared to the single PSA test (AUC 0.632, 95% CI 0.543-0.721), α2,3-Sia-PSA (AUC 0.711, 95% CI 0.629-0.793) and α1,6-Fuc-PSA (AUC 0.738, 95% CI 0.657-0.819). Decision-curve analysis showed the superior benefit of the SF index. In the validation cohort (n = 57), the SF index showed good discrimination for HGPC (AUC 0.769, 95% CI 0.643-0.895). CONCLUSIONS: The SF index could differentiate HGPC, providing useful information for decision making for prostate biopsy in men with abnormal PSA levels.

Disseminated intravascular coagulation induced by pazopanib following combination therapy of nivolumab plus ipilimumab in a patient with metastatic renal cell carcinoma.

Recently, combination therapy including immune checkpoint inhibition (ICI) has proven to be effective as first-line therapy for patients with metastatic renal cell carcinoma. Although the first-line combination therapies with ICI have shown clinical benefit, a number of patients require second-line treatment. We report a 60-year-old man with metastatic renal cell carcinoma who was treated with pazopanib soon after nivolumab plus ipilimumab combination therapy. He experienced Grade 3 disseminated intravascular coagulation (DIC). We suspect that this was caused by an interaction between pazopanib and nivolumab even though ICI therapy was discontinued. He was treated with thrombomodulin and platelet transfusion and recovered from DIC. Treatment with pazopanib was subsequently restarted. No evidence of DIC was observed thereafter. This severe adverse reaction may have been induced by an interaction between activated proinflammatory immune cells and cytokines from an exacerbated inflammatory state and pazopanib. This report highlights the need to perform careful monitoring of patients who receive molecular targeted therapy after ICI-based immunotherapy.

Predictive factors for the efficacy of abiraterone acetate therapy in high-risk metastatic hormone-sensitive prostate cancer patients.

PURPOSE: There is a discrepancy in the efficacy of abiraterone acetate for overall survival (OS) in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study aimed to identify predictive factors for the efficacy of abiraterone acetate for OS in high-risk mHSPC patients by analyzing them over a longer observation period. METHODS: Five hundred high-risk mHSPC patients were retrospectively identified at our hospital and affiliated hospitals in the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2022. Two hundred patients were treated with abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) combined with androgen deprivation therapy (ADT). A total of 300 patients were treated with bicalutamide (80 mg/day) in combination with ADT. RESULTS: OS was not significantly different between the two treatments in the overall cohort (p = 0.1643). In the subgroup without Gleason pattern 5 at the primary lesion, OS was significantly better in patients treated with abiraterone acetate than in those treated with bicalutamide (p = 0.0192). In the subgroup with Gleason pattern 5 at the primary lesion, no significant difference was found between the two treatments (p = 0.1799). Univariate and multivariate analyses in the subgroup without Gleason pattern 5 at the primary lesion suggested that abiraterone therapy may be an important and independent predictor of OS in high-risk mHSPC patients. CONCLUSION: The presence of Gleason pattern 5 at the primary lesion may be a predictor for high-risk mHSPC patients who could benefit from abiraterone acetate treatment.

A novel prediction model for the completion of six cycles of radium-223 treatment and survival in patients with metastatic castration-resistant prostate cancer.

PURPOSE: We evaluated the predictive factors for completion of all six cycles of radium-223 (Ra-223) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). We also developed a novel prediction model for Ra-223 treatment completion using these predictors. METHODS: We retrospectively reviewed data from 122 patients with mCRPC who were treated with Ra-223. The predictive factors for the completion of six cycles of Ra-223 treatment were evaluated. Statistically significant predictive factors were then used to develop a prediction model for treatment completion. Finally, using this prediction model, we classified the overall survival (OS) of the entire cohort into three groups. RESULTS: We identified three significant variables as the predictive factors for treatment completion: baseline alkaline phosphatase (ALP) level, baseline hemoglobin (Hb) level, and baseline pain. The three groups generated using the prediction model were: group 1 (patients with three predictive factors, i.e., ALP < median, Hb ≥ median, and no pain), group 2 (patients with one to two predictive factors), and group 3 (patients without any predictive factors). The treatment completion rates differed between the three groups significantly. Furthermore, the OS also differed among the groups significantly. CONCLUSION: Our study suggested that the baseline ALP level, baseline Hb level, and baseline pain were the predictive factors of completion of all six cycles of Ra-223 treatment in patients with mCRPC. Our prediction model consisting of these factors could predict not only the completion of Ra-223 treatment, but also the post-treatment survival. This model can thus be useful for selection of patients for Ra-223 treatment.

[Gas-Producing Splenic Abscess after Spleen Metastasis of Left Renal Cell Carcinoma Spleen Metastasis Successfully Treated with Sunitinib].

A 67-year-old man underwent open radical left nephrectomy for left renal cell carcinoma [pT4N0M1 (right lower lobe of lung)] and thoracoscopic partial right lung resection for lung metastasis. The patient subsequently developed a solitary lung metastasis at 10 months and then at 26 months postoperatively. He underwent partial lung resection on each occasion. During the 28 months postoperatively, he was found to have a 12 mm middle mediastinal lymph node metastasis and a 30 mm splenic metastasis, which gradually increased in size. Three months after discovery, sunitinib was initiated at 37.5 mg 2 weeks on/1 week off. Twelve days later, the patient presented with complaints of fever. A gas-producing splenic abscess was diagnosed and he was admitted on the same day. His condition improved with antibiotics and splenic drainage. On day 35 of hospitalization, he underwent laparoscopic splenectomy. The patient's postoperative clinical course was uneventful and he was discharged 7 days after the surgery.

Expression of Nectin-4 and PD-L1 in Upper Tract Urothelial Carcinoma.

Enfortumab vedotin is a novel antibody-drug conjugate targeting Nectin-4, which is highly expressed in urothelial carcinoma. However, the expression status of Nectin-4 in upper tract urothelial carcinoma (UTUC) remains unclear. The relationship between Nectin-4 and Programmed Death Ligand 1 (PD-L1) in UTUC is also ambiguous. We performed immunohistochemical analysis of 99 UTUC tissue microarray to assess the expression of Nectin-4 and PD-L1 in UTUC. Nectin-4-positivity was detected in 65 (65.7%) samples, and PD-L1 was detected in 24 (24.2%) samples. There was no correlation between the expression of Nectin-4 and PD-L1. Patients with strong Nectin-4-expressing tumors had a significantly higher risk of progression (p = 0.031) and cancer-specific mortality (p = 0.036). Strong Nectin-4 expression was also an independent predictor of disease progression in the high-risk group (pT3 ≤ or presence of lymphovascular invasion or lymph node metastasis) (Hazard ratio, 3.32 [95% confidence interval, 1.20-7.98; p = 0.027]). In conclusion, we demonstrated that Nectin-4 expression rate in UTUC was 65.7% and independent of PD-L1 expression. Strong Nectin-4 expression was associated with worse progression-free survival in high-risk UTUC. These findings suggested that enfortumab vedotin may be effective in a broad range of patients with UTUC, regardless of PD-L1 expression.

HOXA10 expression profiling in prostate cancer.

BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.

Impact of pegfilgrastim as primary prophylaxis for metastatic castration-resistant prostate cancer patients undergoing cabazitaxel treatment: an open-label study in Japan.

BACKGROUND: Cabazitaxel is an efficacious treatment for patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel, but febrile neutropenia during the first cycle is a frequent complication. Asian patients are at increased risk of febrile neutropenia. Although primary prophylaxis with granulocyte colony-stimulating factor can reduce the incidence, its efficacy has not been prospectively demonstrated in Japanese patients with cabazitaxel treatment. METHODS: PEGAZUS, a prospective, single-arm study conducted at eight clinical sites in Japan, enrolled 21 heavily pretreated patients with metastatic castration-resistant prostate cancer. Patients received cabazitaxel 25 mg/m2 every 3 weeks, up to 10 cycles. Oral prednisolone 10 mg was taken daily. Pegfilgrastim 3.6 mg was administered at least 24 h after the cabazitaxel infusion. The primary endpoint was the incidence of febrile neutropenia in the first cycle. RESULTS: The median number of treatment cycles was seven. The relative dose intensity of cabazitaxel was 67.4% (range, 53.2-91.3%). Two of 21 patients (9.5%) experienced febrile neutropenia in the first cycle. This rate was lower than the rate (43%) previously observed without prophylactic granulocyte colony-stimulating factor in a similar patient population. Six patients showed a prostate-specific antigen response (28.6%). Three of four patients evaluable for tumor response had stable disease and one had progressive disease. Grade ≥3 diarrhea was not observed. Primary prophylaxis with granulocyte colony-stimulating factor significantly reduced the incidence of febrile neutropenia in this study. CONCLUSIONS: Cabazitaxel plus granulocyte colony-stimulating factor is safe and effective for Japanese patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel. Clinical trial registration: ClinicalTrials.gov (NCT02441894).

Small Hyperintensities in the Area of the Perforating Arteries in Patients with Seizure.

BACKGROUND/AIM: We previously observed spotty hyperintense lesions in the region of the perforating arteries on peri-ictal diffusion-weighted imaging (DWI); however, no report has formally described these findings. The aim of this study was to investigate focal intensities on peri-ictal DWI, and to evaluate the clinical significance of these lesions. METHODS: We conducted a retrospective review of 677 consecutive patients with seizure who completed peri-ictal DWI within 24 h after seizure onset. Patients were grouped according to the presence or absence of diffusion hyperintense lesions (DHLs) in the region of the perforating arteries. We compared clinical and imaging characteristics between these 2 groups. RESULTS: Among 677 patients, 23 patients (3.4%) had DHLs. Analyses of apparent diffusion coefficient values and fluid attenuated inversion recovery images suggested that DHLs were acute or subacute ischemic lesions that had appeared prior to seizure onset. Patients with DHLs were more likely to be older in age, have atrial fibrillation, and coronary artery disease, and have more severe deep white matter hyperintensity or leukoaraiosis compared to patients without DHLs. CONCLUSION: DHLs detected on peri-ictal DWI may represent incidental acute cerebral microinfarcts in the aging brain, especially in patients with small vessel disease.

The Change in Neutrophil Lymphocyte Ratio from the First to the Last Repeat Prostate Biopsy Proposed as a Marker of Carcinogenesis.

INTRODUCTION: We investigated whether the change in the neutrophil lymphocyte ratio (NLR) from the first to the last repeat prostate biopsy (ΔNLR) could be the diagnostic tool or not for prostate cancer (PCa) detection. MATERIALS AND METHODS: We retrospectively evaluated medical records of men who had undergone repeat prostate biopsy. The investigated parameters were white blood cell, neutrophil, lymphocyte counts, NLR at the last prostate biopsy, ΔNLR, prostate-specific antigen (PSA), PSA density (PSAD), and PSA velocity. Exclusion criteria were the presence of cancers other than prostate origin, medication, and diseases which induce the change of NLR. RESULTS: A total of 301 men who had undergone repeat prostate biopsy were selected for this study. After applying exclusion criteria, 223 patients were included. Of these patients, 94 were diagnosed with PCa (Group I) and 129 with no malignancy (Group II). Only a single patient had metastasis. On evaluating the area under the receiver operating characteristic curve of all study parameters, ΔNLR was the most accurate marker, followed by PSAD and then NLR measured at the last biopsy. CONCLUSIONS: ΔNLR was the most accurate marker to improve the total predictive value in repeat prostate biopsy for diagnosing PCa.

Involvement of renin-angiotensin-aldosterone system in calcium oxalate crystal induced activation of NADPH oxidase and renal cell injury.

INTRODUCTION AND OBJECTIVES: Reactive oxygen species (ROS) are produced during the interaction between oxalate/calcium oxalate monohydrate (COM) crystals and renal epithelial cells and are responsible for the various cellular responses through the activation of NADPH oxidase (Nox). Ox and COM also activate the renin-angiotensin-aldosterone system (RAAS). Aldosterone stimulates ROS production through activation of Nox with the involvement of mineralocorticoid receptor (MR), Rac1 and mitogen-activated protein kinases (MAPK). We investigated RAAS pathways in vivo in an animal model of hyperoxaluria and in vitro by exposing renal epithelial cells to COM crystals. METHODS: Hyperoxaluria was induced in male SD rats by administering ethylene glycol. One group of rats was additionally given spironolactone. Total RNA was extracted and subjected to genomic microarrays to obtain global transcriptome data. Normal rat kidney cell line (NRK-52E) was incubated with aldosterone(10(-7) M) and COM(67 µg/cm(2)) with or without spironolactone(10(-5) M), a selective inhibitor of SRC family of kinases; protein phosphatase 2(pp2) (10(-5) M) and Nox inhibitor; diphenylene iodonium (DPI) (10(-5) M). RESULTS: Relative expression of genes encoding for AGT, angiotensin receptors 1b and 2, Renin 1, Cyp11b, HSD11B2, Nr3c2, NOx4 and Rac1 was upregulated in the kidneys of rats with hyperoxaluria. Treatment with spironolactone reversed the effect of hyperoxaluria. Both aldosterone and COM crystals activated Nox and Rac1 expression in NRK52E, while spironolactone inhibited Nox and Rac1 expression. Increased Rac1 expression was significantly attenuated by treatment with PP2 and spironolactone. CONCLUSIONS: Results indicate that hyperoxaluria-induced production of ROS, injury and inflammation are in part associated with the activation of Nox through renin-angiotensin-aldosterone pathway.

Axitinib-induced proteinuria and efficacy in patients with metastatic renal cell carcinoma.

BACKGROUND: No report has evaluated axitinib-induced proteinuria as a biomarker for predicting treatment efficacy and survival of patients with metastatic renal cell carcinoma (mRCC). METHODS: The subjects were patients with mRCC treated with axitinib at Kinki University Hospital from February 2008 to November 2014. Clinical records were retrospectively reviewed including baseline patient characteristics, time-dependent changes of urinary protein status, computed tomography scans of metastatic lesions, treatment duration with axitinib, and survival time. RESULTS: A total of 45 patients were evaluable. Median tumor shrinkage rates were 32.3 and 35.0 % in patients with urinary protein increases ≥+2 and <+2, respectively (p = 0.496). Objective response rates were also similar between the two groups. Median progression-free survival (PFS) times with axitinib were 13.5 months [95 % confidence interval (CI) 0.0-27.5] and 11.0 months (95 % CI 0.0-26.7) in patients with urinary protein increases ≥+2 and <+2, respectively (p = 0.975). The maximum tumor shrinkage rate with axitinib was significantly associated with PFS with axitinib as a result of multivariate analysis (p = 0.002). Median overall survival (OS) times were 39.8 months (95 % CI 12.7-67.0) and 25.4 months (95 % CI 11.2-39.6) in patients with axitinib-induced urinary protein increases ≥+2 and <+2, respectively (p = 0.250). The number of metastatic sites (p = 0.006), the MSKCC risk (p = 0.009), and the maximum tumor shrinkage rate with axitinib (p = 0.019) were significantly associated with OS as a result of multivariate analysis. CONCLUSIONS: The degree of urinary protein increase during axitinib treatment was not associated with objective response, PFS, and OS in mRCC patients treated with axitinib.

Pharmacotherapies for renal cell carcinoma in Japan.

The standard treatment for advanced renal cell carcinoma has changed dramatically in the past decade, from cytokine therapy to targeted therapy. Since sorafenib was approved in April 2008, four tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors have become available in Japan. Most Japanese renal cell carcinoma patients are treated by urologists who are involved in not only kidney surgeries, but also targeted therapy using tyrosine kinase inhibitors, as well as mammalian target of rapamycin inhibitors. Optimal treatment methods are selected from theoretically-based global recommendations, such as the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines; however, real-world clinical practice might be different from that in non-Asian countries. This might be because of different practical conditions; for example, different adverse events and efficacy profiles, different healthcare system, and so on. In the present review, we examine current pharmacotherapy for renal cell carcinoma from evidence-based global data, and compare the reality of Japanese clinical practice to explore the importance of individualized patient therapy.

Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer.

BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3ß and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.

[Cases of Fournier's Gangrene in Kinki University].

The aim of our study was to identify risk factors that may influence outcomes for patients presenting with Fournier gangrene. Twelve patients hospitalized and treated between August 2007 and August 2013 were included in this study. Distinct features were noted after one or two weeks of hospitalization. We did not observe a significant correlation between death risk and the extent of necrosis in this patient set. However, the extent of necrosis tended to correlate with the duration of hospitalization in the survivors. We also compared the results of blood biochemical analyses between the surviving and non-surviving groups. A significant difference was noted in the levels of glucose (Glu) after two weeks. In the non-surviving group, Glu levels were increased. These findings suggest a relationship between glycemic control after the initiation of therapy and death. We also examined the results of blood biochemical analyses according to the duration of hospitalization. The lactate dehydrogenase (LDH) levels at admission and LDH levels after two weeks were significantly higher in the patients with a duration of hospitalization longer than the median duration of 61.5 days. These findings suggest a relationship between the duration of hospitalization and the extent of necrosis at diagnosis.