Primary biliary cirrhosis and autoimmune hepatitis are the two main immune-mediated liver diseases. They are generally differentiated easily on the basis of clinical, biochemical, serological, and histological findings. Occasionally, the normally distinctive features overlap and classification of a given patient's chronic liver disease is difficult. Series of such patients with Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome were reported. We report a case of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome proven by clinicopathology. The patient showed hepatitic features including easy fatigability, icteric sclera. Markers of hepatitis B and C virus were absent. The liver biopsy showed chronic hepatitis with piecemeal necrosis, infiltration of inflammatory cell surrounding bile duct. The clinical data of high titers of antinuclear antibodies and antimitochondral antibodies, elevated serum IgM, suggest mixed features of primary biliary cirrhosis-autoimmune hepatitis. The patient as given only ursodeoxycholic acid (600 mg/day), then was observed follow-up regularly.
Antibodies ; Antibodies, Antinuclear ; Bile Ducts ; Biopsy ; Classification ; Follow-Up Studies ; Hepatitis ; Hepatitis B ; Hepatitis, Autoimmune* ; Hepatitis, Chronic ; Humans ; Immunoglobulin M ; Liver ; Liver Cirrhosis, Biliary* ; Liver Diseases ; Necrosis ; Sclera ; Ursodeoxycholic Acid

Purpose: We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC). Materials and Methods: We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys. Results: The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA). Conclusion Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

Purpose: The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC). Materials and Methods: In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety. Results: Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates. Conclusion Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Purpose: Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. Materials and Methods: The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. Results: Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). Conclusion The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.