Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study.

BACKGROUND: Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS: We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS: After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS: A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

Clinical Analysis of Early-Stage Pancreatic Cancer and Proposal for a New Diagnostic Algorithm: A Multicenter Observational Study.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging but essential for improving its poor prognosis. We established a multicenter study to clarify the clinicopathological features, and to propose new algorithm for early diagnosis of PDAC. Ninety-six patients with stage 0 and IA PDAC were enrolled from 13 high-volume centers. Overall, 70% of the patients were asymptomatic. The serum pancreatic enzyme levels were abnormal in half of the patients. The sensitivity of endoscopic ultrasonography (EUS) for detecting small PDAC was superior to computed tomography and magnetic resonance imaging (MRI) (82%, 58%, and 38%, respectively). Indirect imaging findings were useful to detect early-stage PDAC; especially, main pancreatic duct stenosis on MRI had the highest positive rate of 86% in stage 0 patients. For preoperative pathological diagnosis, the sensitivity of endoscopic retrograde cholangiopancreatography (ERCP)-associated pancreatic juice cytology was 84%. Among the stage IA patients, EUS-guided fine-needle aspiration revealed adenocarcinoma in 93% patients. For early diagnosis of PDAC, it is essential to identify asymptomatic patients and ensure close examinations of indirect imaging findings and standardization of preoperative pathological diagnosis. Therefore, a new diagnostic algorithm based on tumor size and imaging findings should be developed.

Impact of sclerosing dacryoadenitis/sialadenitis on relapse during steroid therapy in patients with type 1 autoimmune pancreatitis.

OBJECTIVES: Steroids are the first-line drugs for induction of remission in patients with type 1 autoimmune pancreatitis (AIP), and the usefulness of steroid maintenance therapy to prevent relapse has recently been reported. However, even during steroid therapy, a relatively large percentage of patients relapse and the predictive factors for relapse have not yet been elucidated. The aim of this study was to clarify the predictive factors for relapse of AIP patients during steroid therapy. MATERIALS AND METHODS: The medical records of 76 patients with type 1 AIP with continued steroid therapy after induction of remission were analyzed retrospectively. The relapse rate during steroid therapy was evaluated, and the risk factors for relapse were investigated by univariate and multivariate analysis of clinical factors. RESULTS: Relapse occurred in 28.9% (22/76) of the patients. The cumulative relapse rates were 10.5% at 1 year, 25.0% at 3 years, 34.9% at 5 years, and 43.0% at 10 years. In multivariate analysis, presence of sclerosing dacryoadenitis/sialadenitis at the time of initial diagnosis of AIP was an independent risk factor for relapse (HR 3.475, p = .009). The cumulative relapse rates of patients with sclerosing dacryoadenitis/sialadenitis reached 21.4% at 1 year, 56.0% at 3 years, and 78.0% at 5 years. CONCLUSIONS: Sclerosing dacryoadenitis/sialadenitis was a predictive factor for relapse in type 1 AIP during steroid therapy; in such cases, strict follow-up is necessary with relapse in mind.

A case of mediastinal lymph node carcinoma of unknown primary site treated with docetaxel and cisplatin with concurrent thoracic radiation therapy.

Mediastinal lymph node carcinoma of unknown primary site is rare and may have a better prognosis if extensive treatment is performed. Case, A 69-year-old-male presented with a persistent cough. Chest computed tomography (CT) demonstrated a large tumor 9.5 × 8.2 cm, in the mediastinum, compressing the right main bronchus, the right pulmonary artery, and the superior vena cava. Because fiberoptic bronchoscopy was insufficient for diagnosis, mediastinoscopic tumor biopsy under general anesthesia was undertaken. Histological examination revealed adenocarcinoma. Extensive examinations revealed no other neoplastic lesion except in the mediastinum. Mediastinal lymph node carcinoma of unknown primary site was diagnosed. The patient was treated with docetaxel and cisplatin with concurrent thoracic radiation therapy. A month after the start of chemoradiotherapy, the mediastinal tumor regressed markedly. The patient remained free of symptoms without regrowth of the primary site. Exploration of the body showed no further abnormalities 20 months after disease onset.

Expression of multidrug resistance-associated protein 2 is involved in chemotherapy resistance in human pancreatic cancer.

Despite the recent introduction of the new anticancer agents gemcitabine (GEM) and TS-1, as well as combination regimens such as GEM plus cisplatin (CDDP), pancreatic cancer treatment remains relatively ineffective. Both intrinsic and acquired resistance to chemotherapy are major roadblocks to the successful treatment of pancreatic cancer patients. The aims of this study were to examine the expression of multidrug resistance-associated proteins (MRPs) MRP1, MRP2 and MRP3 and to evaluate the correlation between MRP2 expression and CDDP resistance in human pancreatic cancer. Five human pancreatic cancer cell lines and several surgically resected pancreatic cancer tissues were subjected to reverse-transcriptase (RT)-PCR, real-time PCR and immunohistochemical analysis. While MRP1 and MRP2 mRNA was expressed in all cell lines, MRP3 mRNA was only detected in two cell lines. In resected pancreatic cancer tissues, only MRP2 mRNA was expressed and it was overexpressed compared with normal pancreatic tissues. MRP2 protein expression was observed in 77.5% (31/40) of cancer tissues, primarily in the cytoplasm of cancer cells, but was not observed in normal pancreatic tissue. Two CDDP-resistant pancreatic cancer cell line SUIT-2 variants, SUIT-2-CD3 and SUIT-2-CD4, were established by continuously administering 10 nM CDDP to SUIT-2 cell lines for 3 and 4 months, respectively. Incubation of these cells with CDDP in the presence of anti-MRP2 antibody or the MRP2 inhibitor MK-571 in a growth inhibition assay demonstrated that the CDDP-resistant variants were more resistant to CDDP than the parent cell line and this resistance was diminished by either anti-MRP2 antibody or MK-571. Moreover, RT-PCR and real-time PCR revealed that while induction of MRP2 mRNA expression was increased in CDDP-resistant compared with parent cells, MRP1 and MRP3 expression remained unchanged. These observations suggest that MRP2 may correlate to intrinsic and acquired resistance for CDDP in human pancreatic cancer.