Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label,single arm,multicenter, phase 2 trial

BackgroundAlthough platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC.MethodsEnrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m² on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival (DFS), and overall survival (OS).ResultsA total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m²; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity (RDI) was 79% for S-1 and 80% for cisplatin. The 2-year DFS rate was 42.1%, and 2-year OS rate was 83.3%.ConclusionsThis study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy.Trial registrationThis study was registered on the UMIN clinical study registration site (protocol ID: UMIN000016191) on December 1, 2015.     

Congenital Achromatopsia and Macular Atrophy Caused by a Novel Recessive PDE6C Mutation (p.E591K)

Purpose: We have previously reported clinical features of two siblings, a sister with complete achromatopsia (ACHM) and a brother with incomplete ACHM, in a consanguineous Japanese family. With the current study, we intended to identify a disease-causing mutation in the siblings and to investigate why the phenotypes of the siblings differed.

Methods: We performed a comprehensive ophthalmic examination for each sibling and parent. Whole-exome and Sanger sequencing were performed on genomic DNA. Molecular modeling was analyzed in an in silico study.

Results: The ophthalmic examination revealed severe macular atrophy in the older female sibling at 30 years of age and mild macular atrophy in the brother at 26 years of age. The genetic analysis identified a novel homozygous PDE6C mutation (p.E591K) as the disease-causing allele in the siblings. Each parent was heterozygous for the mutation. Molecular modeling showed that the mutation could cause a conformational change in the PDE6C protein and result in reduced phosphodiesterase activity. We also identified an OPN1SW mutation (p.G79R), which is associated with congenital tritan deficiencies, in the sister and the father but not in the brother.

Conclusions: A novel homozygous PDE6C mutation was identified as the cause of ACHM. In addition, we identified an OPN1SW mutation in the sibling with complete ACHM, which might explain the difference in phenotype (complete versus incomplete ACHM) between the siblings.     

Histological and immunohistochemical features of gingival enlargement in a patient with AML

Here, we discuss the pathophysiology of leukemia-associated gingival enlargement based on a case of acute myelomonocytic leukemia (AML-M4) with typical gingival enlargement. Uniquely, this patient was well enough to allow full periodontal examination and incisional gingival biopsy to be performed both before and after chemotherapy. The patient was a 39-year-old Japanese woman with AML-M4 showing gingival enlargement. Histological and immunohistochemical features of gingiva and bacterial counts in the periodontal pockets were examined before and after chemotherapy. The results were as follows: (1) infiltration of myelomonocytic blasts in enlarged gingiva; (2) resolution of gingival enlargement with complete remission of AML by anticancer chemotherapy; and (3) the numbers of bacteria in the periodontal pockets were not high and were not altered before or after chemotherapy. In patients with AML-M4, remarkable mucosal enlargement is not generally observed in the body except in the gingiva. We hypothesized that antigens derived from periodontal bacteria, even if they are not present in large numbers, could act as chemoattractants for myelomonocytic leukemic cells.     

Omental packing with continuous suction drainage following abdominoperineal resection

Background/Aims: Primary closure of the perineum along with drainage after abdominoperineal resection for lower rectal cancer is a widely accepted procedure but is associated with non-healing of the perineal wound a major complication. We evaluated the efficacy of omental packing and continuous suction drainage after abdominoperineal resection. Methodology: We retrospectively studied 45 patients with adenocarcinoma of the lower rectum who underwent abdominoperineal resection, either without omental packing (NOP group) or with omental packing and continuous suction drainage (OPCD group). A pedicled omentum supplied by the epiploic arcade was conducted and drawn down through the perineal wound, over the small intestine and into the pelvis. Drains were placed on both sides of the pelvis through the perineal wall and continuous suction was performed. Results: Perineal wound infection was significantly more frequent in the NOP group (32%) than in the OPCD group (5%). Ileus was not observed in the OPCD group. The duration of hospitalization was shorter in the OPCD group (17.8±4.2 days) than in the NOP group (21.0±9.1 days). Conclusions: Omental packing with continuous suction is useful to prevent non-healing of the perineal wound after abdominoperineal resection for lower rectal cancer.