Longer prolapsed rectum length increases recurrence risk after Delorme's procedure.

PURPOSE: Risk factors for recurrence of rectal prolapse after surgery remain unclear. Delorme's procedure is often selected for relatively small-sized rectal prolapse, but there are few reports discussing the association between prolapsed rectum length and prolapse recurrence after Delorme's procedure. We hypothesized that patients with longer rectal prolapses are at a higher risk of recurrence after Delorme's procedure. METHODS: The study population comprised patients with rectal prolapse who underwent Delorme's procedure between January 2014 and December 2019 at Tokyo Yamate Medical Center. We extracted data on patient age, sex, body mass index, previous history of anal surgery, previous history of surgery for rectal prolapse, and length of prolapse, to identify risk factors for prolapse recurrence. RESULTS: Altogether, 96 patients were eligible for analysis. The median length of the prolapsed rectum was 3.0 cm (range, 1.0-6.6 cm). Twenty-four patients (25.0%) experienced recurrence after Delorme's procedure after a median of 7.5 months (interquartile range, 3.2-20.9 months). Multivariate analysis revealed that longer prolapsed rectum length increased the risk of recurrence after Delorme's procedure (hazard ratio, 6.28; 95% confidence interval, 1.83-21.50; P<0.001). CONCLUSION: The length of the prolapsed rectum should be measured before Delorme's procedure for rectal prolapse, because length is associated with a risk of recurrence after the surgery.

A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma.

OBJECTIVES: Despite improved outcomes associated with immunotherapies for non-small cell lung cancer (NSCLC), many patients do not respond to treatment. Therefore, there is still an unmet need for molecularly targeted therapies in this patient population. Fusions of the RET oncogene have been identified as driver alterations in patients with NSCLC. Lenvatinib is a multityrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, RET, and other targets. This study evaluated the safety and efficacy of lenvatinib in patients with RET fusion-positive lung adenocarcinoma. MATERIALS AND METHODS: In this phase 2, multicenter, open-label study (NCT01877083), patients with RET-positive lung adenocarcinoma received oral lenvatinib 24 mg/day. The primary end point was objective response rate (ORR) by investigator review per Response Evaluation Criteria In Solid Tumors v1.1 criteria. The secondary end points included safety and tolerability, progression-free survival (PFS), and overall survival (OS). RESULTS: Of 536 patients who screened for study inclusion and exclusion, 25 patients with RET translocations (KIF5B-RET [n = 13] and CCDC6-RET [n = 12]) were identified and received lenvatinib. The overall ORR was 16% (95% CI: 4.5%-36.1%). At data cutoff (February 3, 2016), the median PFS was 7.3 months (95% CI: 3.6-10.2) and the median OS was not reached. Duration of response was not estimable at the time of data cutoff. All patients experienced a treatment-emergent adverse event (TEAE); 23 (92%) patients experienced a TEAE of ≥ grade 3, and 6 (24%) patients discontinued lenvatinib due to a TEAE. The most common TEAEs were hypertension (68%), nausea (60%), decreased appetite (52%), diarrhea (52%), and proteinuria (48%). CONCLUSIONS: Lenvatinib demonstrated activity in patients with RET fusion-positive lung adenocarcinomas; although the response rate was relatively low, the median PFS supports the activity of lenvatinib in these patients.

[A case of resectable lung metastasis one year six months after surgery for pancreatic cancer].

The patient was a 68-year-old man who underwent pylorus-preserving pancreaticoduodenectomy for cancer of the pancreatic head in March 2012. Pre-operative chest computed tomography (CT) revealed a scar-like shade approximately 1.5 cm in length in the right middle lobe of the lung, but an active metastasis was not suspected. Adjuvant S-1 was initiated in June the same year at 100 mg/day and reduced to 50 mg/day in October because of neutropenia. The internal structure of the right middle lobe was observed to be uneven on a CT scan obtained in July 2013, and the shading increased to approximately 3 cm in length along with spicula. Brushing and transbronchial lung biopsy(TBLB)were performed. No other distant organ metastases were detected on a whole body search. Diagnosis was between a solitary lung metastasis of pancreatic cancer or cT2N0M0, StageIB primary lung cancer. The right middle lobe of the lung was resected via thoracoscopy along with lymph node dissection in September 2013. Histological examination revealed that the lesion was a well differentiated adenocarcinoma, with negative immunostaining for thyroid transcription factor-1(TTF-1) and Napsin A, and positive staining for cytokeratin (CK)7 and CK20, consistent with a solitary lung metastasis of pancreatic cancer. This report documents a rare case of pancreatic cancer with a solitary, resectable lung metastasis without involvement of other organs.

Determination of phosphorylated amino acid residues of Rab8 from Bombyx mori.

The Rab family of small GTPases are key regulators of membrane trafficking. Partially purified Rab8 from Bombyx mori (BRab8) was phosphorylated by protein kinase C in mammalian cells in vitro. To determine which of the seven serines and four threonines are phosphorylated, we generated deletion and site-directed mutants of BRab8, inserted them in Escherichia coli, partially purified the encoded fusion proteins by affinity chromatography, and examined their phosphorylation by protein kinase C in vitro. We found that Ser-132 of BRab8 was specifically phosphorylated by protein kinase C. In addition, Western blotting using an antiserum against BRab8 and in-gel staining for phosphorylated proteins revealed that BRab8 is phosphorylated in vivo.

Molecular cloning and expression of protein kinase C from Bombyx mori.

Two partial cDNA clones (Protein kinase C alpha and Protein kinase C iota), each of which encoded a different member of PKC-protein family, were isolated using RT-PCR from mRNA of Bombyx mori. The full-length cDNAs were isolated using SMART-RACE. The cDNAs were expressed in HepG2 cells and the recombinant proteins were partially purified using an affinity chromatography. Protein kinase C alpha (BPKC alpha) showed a calcium-dependent kinase activity of histones. Whereas protein kinase C iota (BPKC iota) showed a calcium-independent activity. Bisindolyl maleimide I, a PKC inhibitor, inhibited these kinase activities. Furthermore, in vitro BPKC alpha interacted and phosphorylated two proteins expressed in the brain of Bombyx mori: Rab protein, which plays important roles in the vesicle transport in the brain, and bMBD2/3, which is a methyl DNA-binding protein and regulates transcription. These results suggest that these PKCs phosphorylate various substrate proteins and function in the brain of Bombyx mori.