Short- and long-term oncological outcomes of totally laparoscopic gastrectomy versus laparoscopy-assisted gastrectomy for clinical stage I gastric cancer

Gastric Cancer - Totally laparoscopic gastrectomy (TLG), which involves a complete intracorporeal gastric transection and the creation of an anastomosis, has been gradually adopted. However, a...     

Intra-corporeal robot-assisted versus open radical cystectomy: a propensity score-matched analysis comparing perioperative and long-term survival outcomes and recurrence patterns

International Journal of Clinical Oncology - To compare perioperative and long-term oncological outcomes and recurrence patterns between robot-assisted radical cystectomy with intra-corporeal...     

FMS‐like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

FMS‐like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co‐altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co‐alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non‐FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.     

Non-parametric bounds on treatment effects with non-compliance by covariate adjustment

Consider a clinical trial where subjects are randomized to two treatment arms but compliance to the assignment is not perfect. Concerning this problem, this paper derives non-parametric bounds on treatment effects by making use of the observed covariates information. The new bounds are narrower and more informative than the existing ones. In addition, a new non-parametric point estimation approach is proposed based on stratified analysis. Furthermore, to examine the accuracy of estimating the proposed bounds, we provide variance estimators for the proposed approach. The results of this paper can yield credible information on treatment effects, which will be useful for medical research and public health policy analysis.     

The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (V_H) region locus was determined and 43 novel V_H segments were identified. The region contains 123 V_H segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 V_H segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of V_H region was calculated to be ∼6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional V_H segments than in pseudogenes. Phylogenetic analysis of 114 V_H segments clearly showed clustering of the V_H segments of each family. However, an independent branch in the tree contained a single V_H, V4-44.1P, sharing similar levels of homology to human V_H families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region.     

Successful conservative management of an anastomotic airway dehiscence at the left main bronchus following bilateral cadaveric lung transplantation

There is a dearth of data on management of anastomotic airway dehiscence following lung transplantation. Herein we report a case of successful conservative management of an anastomotic airway dehiscence after cadaveric donor lung transplantation. A 41-year-old woman with primary ciliary dyskinesia underwent cadaveric bilateral lung transplantation without cardiopulmonary bypass. On the postoperative day 25, left pneumothorax developed and bronchoscopy demonstrated a localized anastomotic dehiscence at the left main bronchus. The dehiscence was managed with 2 weeks of pleural drainage and was completely covered with regenerated bronchial epithelium at 4 months after transplantation. There is no finding suggestive of significant stenosis at 4 years of follow-up. Our case suggested asymptomatic and localized anastomotic dehiscence does not always require endobronchial stent placement or re-operation. Multiple factors that may contribute to the successful conservative management were discussed in this article.     

Clinical application of postoperative non-invasive positive pressure ventilation after lung cancer surgery

Objective

The purpose of this study was to clarify the clinical efficacy of postoperative non-invasive positive pressure ventilation (PONIV) after pulmonary lobectomy in patients with lung cancer.

Methods

From August 2010 and July 2015, 143 patients with lung cancer who underwent pulmonary lobectomy were retrospectively reviewed. PONIV was used immediately after surgery until the morning of postoperative day (POD) 1. Arterial blood gas was analyzed before and just after surgery (POD0) and on POD1. Oxygenation ability was perioperatively assessed by PaO₂/FiO₂ ratio, alveolar–arterial oxygen difference (A-aDO₂), and respiratory index (A-aDO₂/PaO₂).

Results

112 patients received PONIV. From POD0 to POD1, the PaO₂/FiO₂ ratio significantly improved in all patients who received PONIV (333?±?83 to 359?±?47 mmHg, p?=?0.004). Moreover, A-aDO₂ and respiratory index significantly decreased following PONIV. PONIV significantly improved the PaO₂/FiO₂ ratio in patients with PaO₂/FiO₂ ratio of ≤?300 on POD0, older age (≥?70 years), higher body mass index (≥?25 kg/m²), and longer one-lung ventilation time (≥?180 min). There was no respiratory failure requiring mechanical ventilation and no mortality.

Conclusions

PONIV effectively improved oxygenation in patients undergoing pulmonary lobectomy in patients with poor status, especially in patients with PaO₂/FiO₂ ratio of ≤?300 on POD0. PONIV could be an option of perioperative management for major thoracic surgery.

     

A novel phosphodiesterase type 4 inhibitor, YM976 (4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one), with little emetogenic activity

We synthesized a novel phosphodiesterase type 4 (PDE4) inhibitor, YM976, that is structurally different from the other PDE4 inhibitors like rolipram. In the present study, the pharmacological profile of YM976 was investigated. YM976 exhibited a strong and competitive inhibition against PDE4 purified from human peripheral leukocytes with an IC(50) of 2.2 nM. IC(50) values of rolipram and RP73401 were 820 and 0.43 nM, respectively. Test compounds had no effects on the other PDE isozymes, PDE1, -2, -3, and -5. YM976 potentiated prostaglandin E(2)-induced cAMP accumulation in a human mononuclear cell line, U937, and inhibited tumor necrosis factor-alpha production from human peripheral blood mononuclear cells stimulated by lipopolysaccharide. Anti-inflammatory activities of PDE4 inhibitors were compared in rat carrageenan-induced pleurisy models. YM976, rolipram, and RP73401 inhibited the cell infiltration into the pleural cavity with oral ED(30) values of 9.1, 10, and 7.4 mg/kg, respectively. YM976 produced no emesis up to 10 mg/kg, whereas rolipram and RP73401 induced emesis at oral doses of 3 mg/kg. To evidence the dissociation of anti-inflammatory activity from emesis, the anti-inflammatory effect of YM976 was examined in ferrets. YM976 dose dependently reduced carrageenan-induced leukocyte infiltration at the doses of 1, 3, and 10 mg/kg, p.o. On the other hand, rolipram failed to show obvious inhibition at doses that do not induce emesis. In conclusion, YM976 is a novel and orally active PDE4 inhibitor and possesses a good separation of emetogenicity from anti-inflammatory activity.