Inflammatory Myoglandular Polyps: A Case Series of Four Patients and Review of the Literature

Background. Inflammatory myoglandular polyp (IMGP) is a nonneoplastic colorectal polyp. Only a small number of cases have been reported, and the pathogenesis remains unclear. Methods. We analyzed colonoscopy and histologic findings in 4 patients with IMGP. Histologic confirmation of the inflammatory granulation tissue in the lamina propria, proliferation of smooth muscle, and hyperplastic glands with variable cystic changes formed the criteria for the selection of patients. Results. We treated four cases of IMGP and reviewed the literature on this disease. Three cases were located in the sigmoid colon or descending colon. All 4 polyps were identified as red, pedunculated lesions. All 4 cases had no symptoms. In two cases, endoscopic findings of polyps were necessary to be differentiated from juvenile polyps. Conclusions. Pedunculated lesions are the main pattern of IMGP. An analysis of endoscopic and histologic features in IMGP of the colorectum revealed that colonic IMGPs resembled juvenile polyps. On colonoscopy, IMGP should generally be taken into consideration as a differential diagnosis of peduncular polyp

Magnetization process of the spin-1/2 XXZ models on square and cubic lattices

The magnetization process of the spin-1/2 antiferromagnetic XXZ model with Ising-like anisotropy in the ground state is investigated. We show numerically that the Ising-like XXZ models on square and cubic lattices show a first-order phase transition at some critical magnetic field. We estimate the value of the critical field and the magnetization jump on the basis of the Maxwell construction. The magnetization jump in the Ising-limit is investigated by means of perturbation theory. Based on our numerical results, we briefly discuss the phase diagram of the extended Bose-Hubbard model in the hard-core limit.Comment: 13 pages, RevTex, 7 PostScript figures, to appear in Phys.Rev.

Prompt Resolution of Hypoglycemia by Hepatic Transarterial Embolization for Malignant Insulinoma with Multiple Liver Metastases

A 45-year-old female who presented with loss of consciousness and a cold sweat was found to have a pancreatic tumor and multiple liver metastases. Laboratory studies showed marked hypoglycemia and inappropriately elevated serum insulin, C-peptide, and serum tumor markers. Fine needle aspiration revealed Grade 3 small-cell type primary pancreatic neuroendocrine carcinoma. Consequently, the diagnosis of malignant insulinoma was made. Transarterial embolization (TAE) for hepatic metastases resulted in the reduction of tumor volume and prompt resolution of hypoglycemic attacks, whereas diazoxide and systemic chemotherapy had been ineffective for controlling blood glucose levels, and octreotide was unavailable due to the allergic effect. This case report highlights the potential usefulness of TAE for malignant insulinomas in the management of hypoglycemia

Effectiveness, safety, and factors associated with the clinical success of endoscopic biliary drainage for patients with hepatocellular carcinoma: a retrospective multicenter study

Background Only a few reports have assessed the effectiveness of endoscopic biliary drainage (EBD) in hepatocellular carcinoma (HCC) patients with obstructive jaundice and liver dysfunction. Methods This was a retrospective study based on the clinical databases from the Okayama University Hospital and 10 affiliated hospitals. All patients received EBD for jaundice or liver dysfunction. The indication for EBD was aggravation of jaundice or liver dysfunction with intrahepatic bile duct (IHBD) dilation. The technical and clinical success rate, complications, factors associated with clinical failure, and survival duration were evaluated. Results A total of 107 patients were enrolled in this study. Technical success was achieved in 105 of 107 patients (98.1%). Clinical success was achieved in 85 of 105 patients (81%). Complications related to endoscopic retrograde cholangiography (ERC) occurred in 3 (2.8%) patients. Child–Pugh class C (odds ratio 3.90, 95% confidence interval [CI] 1.47–10.4, p = 0.0046) was the only factor associated with clinical failure, irrespective of successful drainage. The median survival duration was significantly longer in patients with clinical success than in those without clinical success (5.0 months vs. 0.93 months; hazard ratio [HR] 3.2, 95% CI 1.87–5.37). HCC Stage I/II/III (HR 0.57, CI 0.34–0.95, p = 0.032), absence of portal thrombosis (HR 0.52, CI 0.32–0.85, p = 0.0099), and clinical success (HR 0.39, CI 0.21–0.70, p = 0.0018) were significant factors associated with a long survival. Conclusions EBD for obstructive jaundice and liver dysfunction in patients with HCC can be performed safely with a high technical success rate. Clinical success can improve the survival duration, even in patients expected to have a poor prognosis

Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

BACKGROUND & AIMS: Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP. METHODS: In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP. RESULTS: PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate. CONCLUSIONS: In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274

Is the Importance of Achieving Stable Disease Different between Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Cytotoxic Agents in the Second-Line Setting for Advanced Non-small Cell Lung Cancer?

BackgroundIt is controversial whether achieving stable disease leads to a survival benefit and whether the importance of achieving stable disease differs between cytotoxic agents and molecular targeted agents. To examine these questions, the authors retrospectively reviewed phase II and III studies in the second-line setting for advanced non-small cell lung cancer using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic agents separately.MethodsThe authors chose 45 trials for the chemotherapy group and nine for the EGFR TKI group by searching the PubMed database. All nine trials in the EGFR TKI group concern gefitinib and erlotinib.ResultsThe median survival time increased 0.0375 month with each 1% increase in stable disease rate (p = 0.039), and each 1% increase in response rate resulted in 0.0744 (p < 0.001) month of median survival time in the analysis combined with both cytotoxic agents and EGFR TKIs. Main and interaction terms for EGFR TKI treatment were not statistically significant. With respect to time to progression, only response rate showed a statistically significant relationship with survival.ConclusionsTo obtain response seems to be more important than to achieve stable disease for both cytotoxic agents and EGFR TKIs, although achieving stable disease is still valuable. The relationship between survival and response or stable disease appears similar for cytotoxic agents and EGFR TKIs

Secreted Ectodomain of SIGLEC-9 and MCP-1 Synergistically Improve Acute Liver Failure in Rats by Altering Macrophage Polarity

Effective treatments for acute liver failure (ALF) are still lacking. We recently reported that a single intravenous administration of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) into the D-galactosamine (D-Gal)-induced rat ALF model improves the liver injury. However, the specific factors in SHED-CM that are responsible for resolving ALF remain unclear. Here we found that depleting SHED-CM of two anti-inflammatory M2 macrophage inducers—monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acidbinding Ig-like lectin-9 (sSiglec-9)—abolished its ability to resolve rat ALF. Furthermore, treatment with MCP-1/sSiglec-9 alone dramatically improved the survival of ALF rats. This treatment induced anti-inflammatory M2, suppressed hepatocyte apoptosis, and promoted hepatocyte proliferation. Treatment with an M2-depletion reagent (mannosylated clodronate liposomes) suppressed the recovery. In addition, MCP-1 and sSiglec-9 synergistically promoted the M2 differentiation of bone marrow-derived macrophages via CCR2, accompanied by the production of multiple liver-regenerating factors. The conditioned medium from MCP-1/sSiglec-9-activated M2 macrophages, but not from interleukin-4-induced ones, suppressed the D-Gal- and LPS-induced apoptosis of primary hepatocytes and promoted their proliferation in vitro. The unique combination of MCP-1/sSiglec-9 ameliorates rat ALF by inhibiting hepatocellular apoptosis and promoting liver regeneration through the induction of anti-inflammatory/tissue-repairing M2 macrophages

Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden

Introduction The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. Methods Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. Results ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. Conclusions High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy