Prognostic predictions based on pathological findings of peritoneal dissemination in patients with stage IV colorectal cancer without residual disease (R0 status) Abstract Purpose This study aimed to clarify the prognosis of patients after resection of stage IV colorectal cancer and synchronous peritoneal metastasis (no residual disease: R0 status) based on histopathologic findings. Methods The subjects of this study were 26 patients who underwent radical resection of synchronous peritoneal metastases of stage IV colorectal cancer. Only patients with one synchronous peritoneal metastasis were included in this study. The peritoneal lesions were initially classified into two categories based on the presence or absence of adenocarcinoma on their surface: RM-negative or RM-positive. The lesions were subsequently classified as being of massive or diffuse type and of small (< 6 mm) or large (≥ 6 mm) type according to the maximum metastatic tumor dimension. Results Multivariate analysis revealed that massive type metastatic tumors were associated with a better disease-free survival (DFS; p = 0.047) and overall survival (OS; p = 0.033), than diffuse type tumors. Conclusion A detailed stratification of pathological findings could contribute remarkably to prognostic predictions for patients with synchronous peritoneal metastases.

Short-term outcomes of a self-expandable metallic stent as a bridge to surgery vs. a transanal decompression tube for malignant large-bowel obstruction: a meta-analysis Abstract Purpose Preoperative intestinal decompression, using either a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) or a transanal decompression tube (TDT), provides an alternative to emergency surgery for malignant large-bowel obstruction (MLBO). We conducted this meta-analysis to compare the short-term outcomes of SEMS placement as a BTS vs. TDT placement for MLBO. Methods We conducted a comprehensive electronic search of literature published up to March, 2018, to identify studies comparing the short-term outcomes of BTS vs. TDT. Decompression device-related and surgery-related variables were evaluated and a meta-analysis was performed using random-effects models to calculate odd ratios with 95% confidence intervals. Results We analyzed 14 nonrandomized studies with a collective total of 581 patients: 307 (52.8%) who underwent SEMS placement as a BTS and 274 (47.2%) who underwent TDT placement. The meta-analyses showed that the BTS strategy conferred significantly better technical and clinical success, helped to maintain quality of life by allowing free food intake and temporal discharge, promoted laparoscopic one-stage surgery without stoma creation, and had equivalent morbidity and mortality to TDT placement. Conclusions Although the long-term outcomes are as yet undetermined, the BTS strategy using SEMS placement could be a new standard of care for preoperative decompression to manage MLBO.

A clinical trial of somatic and germline analyses for healthy longevity in a postoperative cancer patient Abstract Purpose Recent developments in molecular-targeted therapies have improved the clinical outcome of cancer patients; however, the issue of adverse effects due to treatments has often gone unconsidered. We herein report the results of a clinical trial of dual genomic analyses for healthy longevity in a postoperative cancer patient. Methods We performed dual genomic analyses for a representative 79-year-old rectal cancer patient who relapsed with liver metastasis. First, we determined single-nucleotide polymorphisms according to the constitution and disease risk in the genomic DNA from the patient’s saliva by referring to the data of 10,000 Japanese patients obtained from Yahoo Japan Corporation. Second, we conducted whole-exome sequencing to detect druggable mutations in the primary tumour. Results Forty of 59 determinable characters related to the constitution were consistent with the clinical phenotype. Several diseases classified as ‘high risk’ diseases actually occurred during the patient’s clinical course. Of the 129 significant mutations, we identified somatic mutations in BRAF, PIK3CA, and SMAD4 as targets. Conclusion The dual genomic examination will improve the follow-up observation system to support primary care doctors in the social community for taking care of postoperative cancer patients.

Development and validation of a nomogram predicting postoperative pneumonia after major abdominal surgery Abstract Purpose Postoperative pneumonia (POP) is a common complication that can adversely affect the outcomes after surgery. This study aimed to devise and validate a model for stratifying the probability of POP in patients undergoing abdominal surgery. Methods We included 1050 patients who underwent major abdominal surgery between 2012 and 2013. A nomogram was devised by evaluating the predictive factors for POP. Results Of the 1050 patients, 56 (5.3%) developed POP. Multivariable logistic regression analysis revealed that the independent predictive factors for POP were age, male sex, history of cerebrovascular disease, Brinkman Index (BI) ≥ 900, and upper midline incision. A nomogram was devised by employing these five significant predictive factors. The prediction model showed a relatively good discrimination performance, with a concordance index of 0.77. Conclusions A nomogram based on age, male sex, history of cerebrovascular disease, BI ≥ 900, and upper midline incision may be useful for identifying patients with a high probability of developing POP after major abdominal surgery.

Surgical outcome of pulmonary artery reconstruction using the expanded polytetrafluoroethylene patch in patients with lung cancer Abstract Purpose Pulmonary artery reconstruction is sometimes utilized as an alternative to pneumonectomy in lung cancer surgery. We herein report our experience of pulmonary artery reconstruction using an expanded polytetrafluoroethylene (ePTFE) patch based on the surgical results and long-term outcome. Methods Clinical records of lung cancer patients who underwent patch plasty were reviewed retrospectively. Results Between 2003 and 2017, pulmonary artery patch plasty were performed in 21 patients [18 males, 3 females; mean age 65 (range 47–79) years]. Induction chemoradiotherapy was performed in three patients. Bronchoplasty was performed in five patients. The pathologic stages were stage I in 3 patients, stage II in 6 and stage III in 12. Pneumonectomy, lobectomy and segmentectomy were performed in 2, 18 and 1 patient, respectively. The left upper lobe was the most frequent origin of lung cancer (15 patients). There was no reconstruction-related morbidity or mortality. The overall survival rate at 5 years was 64.1% with a mean follow-up of 39.5 months, and the survival rates for N0–1 and N2–3 were 80.8% and 28.6%, respectively. Conclusion Patch angioplasty using the ePTFE sheet is a reliable procedure in radical surgery for lung cancer.

Surgical outcomes of pulmonary metastasis from hepatopancreatobiliary carcinomas: a comparison with pulmonary metastasis from colorectal carcinomas Abstract Objectives Surgical indications for pulmonary metastasis from hepatopancreatobiliary (HPB) carcinomas remain controversial. Methods Between 2000 and 2015, 25 patients with pulmonary metastasis from HPB carcinomas and 145 with that from colorectal carcinomas underwent metastasectomies in our institution. The primary diseases were hepatocellular carcinoma (HCC) in 8 patients, pancreatic carcinoma (PC) in 12 and biliary tract carcinoma (BTC) in 5. All patients had a sufficient pulmonary reserve, controlled primary disease and no evidence of other metastatic disease. Perioperative factors were investigated retrospectively to analyze the overall survival (OS), pulmonary metastasis-free survival (PmFS) after pulmonary metastasectomy and disease-free interval between surgery for primary disease and the development of pulmonary metastasis (DFI). Results Complete resection was performed in all patients with lobectomy in 3, segmentectomy in 5 and partial resection in 17. The respective 1-, 2- and 5-year OS rates after metastasectomy were 82.6%, 69.8% and 69.8% in HPB patients and 98.3%, 92.4% and 78.0% in colorectal carcinoma patients (p = 0.351). The 2-year PmFS of HPB patients was 80.0%, versus 60.6% for colorectal carcinoma patients (p = 0.265). The DFI was 41.4 months for HPB patients and 34.5 months for colorectal carcinoma patients (p = 0.273). Conclusions Metastasectomy for pulmonary metastasis from HPB may be performed in carefully selected patients.

Preservation of physiological passage through the remnant stomach prevents postoperative malnutrition after proximal gastrectomy with double tract reconstruction Abstract Purpose Double tract reconstruction (DT) after proximal gastrectomy (PG) is considered beneficial for postoperative nutrition status by preserving the physiological passage of food. We conducted this study to assess postoperative nutrition status based on food passage after this operation. Methods The subjects of this retrospective study were 63 patients who underwent PG with DT. The patients were divided into two groups according to whether they had postoperative malnutrition (PM) 1 year postoperatively (PM group) or not (non-PM group). PM was defined by both weight loss > 10% and a low body mass index of < 20 or < 22 kg/m2 for patients younger and older than 70 years, respectively. We then evaluated the predictors of PM. Results There were 33 patients in the PM group. These patients were predominantly female (p < 0.01) and lacked physiological passage through the remnant stomach (PRS) on postoperative fluoroscopy (defined as non-PRS, p = 0.03). Multivariate logistic regression analysis revealed that female gender and non-PRS status were independent predictors of PM (odds ratio [95% CI]; 7.42 [1.33–41.4]; p = 0.02, 6.77 [1.01–45.4]; p = 0.04, respectively). Conclusion Preservation of the physiological passage of food through the remnant stomach prevents PM after PG with DT.

Intraperitoneal chemotherapy for peritoneal metastases using sustained release formula of cisplatin-incorporated gelatin hydrogel granules Abstract Purpose We previously reported the effectiveness of gelatin microspheres incorporating cisplatin in a mouse model of peritoneal metastases. In this study, we report our new complete sustained-release formula of gelatin hydrogel granules incorporating cisplatin (GHG–CDDP), which exerted a good anti-tumor effect with less toxicity. Methods GHG–CDDP was prepared without organic solvents to enable its future clinical use. The pharmaceutical characterization of GHG–CDDP was performed, and its in vivo degradability was evaluated. The anti-tumor effect was evaluated using a murine peritoneal metastasis model of the human gastric cancer MKN45-Luc cell line. Results Our new manufacturing process dramatically reduced the initial burst of CDDP release to approximately 2% (wt), while the previous product had a 25–30% initial burst. In intraperitoneal degradation tests, approximately 30% of GHG–CDDP remained in the murine abdominal cavity 7 days after intraperitoneal injection and disappeared within 3 weeks. GHG–CDDP significantly suppressed the in vivo tumor growth (p = 0.02) and prolonged the survival time (p = 0.0012) compared with the control. In contrast, free CDDP did not show a significant therapeutic effect at any dose. Weight loss and hematological toxicity were also significantly ameliorated. Conclusions GHG–CDDP is a promising treatment option for peritoneal metastases through the complete sustained-release of CDDP with less systemic toxicity.

The roles played by the MYCN, Trk, and ALK genes in neuroblastoma and neural development Abstract Neuroblastoma is one of the most frequent, yet distinctive and challenging childhood tumors. The uniqueness of this tumor depends on its biological markers, which classify neuroblastomas into favorable and unfavorable, with 5-year survival rates ranging from almost 100–30%. In this review, we focus on some biological factors that play major roles in neuroblastoma: MYCN, Trk, and ALK. The MYCN and Trk family genes have been studied for decades and are known to be crucial for the tumorigenesis and progression of neuroblastoma. ALK gene mutations have been recognized recently to be responsible for familial neuroblastomas. Each factor plays an important role in normal neural development, regulating cell proliferation or differentiation by activating several signaling pathways, and interacting with each other. These factors have been studied not only as prognostic factors, but also as targets of neuroblastoma therapy, and some clinical trials are ongoing. We review the basic aspects of MYCN, Trk, and ALK in both neural development and in neuroblastoma.

Transplantation of a decellularized mitral valve complex in pigs Abstract Purpose Conventional mitral valve replacement is associated with the loss of natural continuity of the mitral valve complex. This study evaluated the morphologic/histological characteristics and function of a decellularized mitral valve used as a transplantable graft. Methods Hearts excised from pigs were decellularized by perfusion using detergent. Grafts with the mitral annulus, valve, chordae, and papillary muscle isolated from the decellularized heart were then transplanted into recipient pigs. After transplantation, the function of the graft was analyzed through echocardiography. A histological analysis was performed to evaluate the postoperative features of the decellularized graft. Results The decellularized graft was successfully transplanted in all cases but one. The remaining grafts maintained their morphology and function. They did not exhibit mitral regurgitation or stenosis. Only one animal survived for 3 weeks, and a histological analysis was able to be performed in this case. The transplanted valve was re-covered with endothelial cells. The microvessels in the papillary muscle were recellularized with vascular endothelial cells, and the papillary muscle was completely attached to the papillary muscle of the recipient. Conclusion The early outcome of decellularized mitral graft transplantation was acceptable. This native organ-derived acellular scaffold is a promising candidate for the replacement of the mitral valve complex.