[Tumor Shrinkage as a Prognostic Factor of Metastatic Renal Cell Carcinoma in the Era of Molecular Targeted Therapy].

We evaluated the impact of tumor shrinkage (TS) induced by molecular targeted therapy as the first-line systemic therapy on the survival of patients with metastatic renal cell carcinoma (mRCC). A total of 67 patients with mRCC who received first-line molecular targeted therapy were included in this study. Sixty patients were evaluable by response evaluation criteria in solid tumors. Patients underwent the first evaluation at 8-12 weeks after the start of the therapy. Twenty patients had TS ≧30%, 32 from 30% to -20%, and 8 ≦-20%. The median overall survival periods of patients who achieved TS ≧30%, from 30% to -20%, and ≦-20% at first evaluation were 41.0, 35.0, and 11.5 months, respectively. Univariate and multivariate analyses showed that TS of≧0%, in addition to negative C-reactive protein and the absence of bone metastasis were good predictors of overall survival. The patients who achieved 0% or more at the initial evaluation had longer survival than those who had no tumor reduction (40.0 months vs 12.0 months, p<0. 001). These findings suggest that early TS affects overall survival in real practice. We should consider alternative therapies for patients who have not achieved tumor reduction at the initial evaluation.

Fatal fulminant hepatitis induced by combined ipilimumab and nivolumab therapy despite favorable histologic response and confirmed by autopsy in a patient with clear cell renal cell carcinoma.

Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.

[A Case of Panperitonitis Caused by Spontaneous Bladder Rupture].

A female septuagenarian had poorly controlled diabetes mellitus for more than 20 years. She had persistent pyuria, but did not seek further examination. In 2019, she was transported to our hospital by ambulance for sudden abdominal pain. Physical examination showed a sign of panperitonitis with sepsis. Computed tomography showed ascites and intraperitoneal free air. In addition, there was also a defect in the bladder wall, suggesting bladder rupture. Blood tests showed a marked increase in serum creatinine in addition to increased inflammatory reactants. Because perforation of gastrointestinal tract could not be excluded, an emergency laparotomy was performed. An intraperitoneal perforation of the posterior wall of the bladder was revealed, though there was no intestinal damage. The bladder wall was repaired and cystostomy was performed followed by irrigation and drainage of the abdominal cavity. After the operation, her abdominal symptom resolved and her general status improved. We speculated that voiding disturbance due to neurogenic bladder associated with diabetes mellitus and chronic infection caused the spontaneous bladder rupture. Most cases of spontaneous bladder rupture are associated with a history of pelvic surgery or irradiation, which suggests that this case is extremely rare. In patients with repeated urinary tract infection and underlying disease affecting bladder function, evaluation and appropriate management of bladder dysfunction should be performed ; otherwise, spontaneous bladder rupture may occur.

[A Case of Adrenal Ganglioneuroma that was Hard to Diagnose].

A 72-year-old man was referred to our hospital for examination of a right adrenal tumor incidentally found by computed tomography for close inspection of lumbago. The computed tomography scan and magnetic resonance imaging showed a 51×54×43 mm solid tumor in the right adrenal region. Endocrinological examinations were within normal limits. Because we could not diagnose his condition due to atypical radiographic findings preoperatively and exclude a malignant tumor, laparoscopic right adrenalectomy was performed. The tumor was histologically diagnosed as ganglioneuroma originating from the right adrenal glands.