Shizuoka Cancer Center Hospital Research Articles

Chylothorax after pulmonary resection and lymph node dissection for primary lung cancer; retrospective observational study

BackgroundPulmonary resection with mediastinal lymph node dissection for treating primary lung cancer could sometimes causes chylothorax as a postoperative complication. This study examined the validity of treatments for chylothorax in our hospital.MethodsWe evaluated 2019 patients who underwent lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection for primary lung cancer at Shizuoka Cancer Center Hospital, Shizuoka, Japan, between September 2002 and March 2018. The diagnostic criteria for postoperative chylothorax were that the drainage from the pleural drain was evidently white and turbid, or the pleural effusion contained a triglyceride level of > 110 mg/dL. The clinical courses and treatments were retrospectively reviewed.ResultsPostoperative chylothorax occurred in 37 patients (1.8%), 20 men and 17 women, with a median age of 70 years (33–80). A low-fat diet was instituted to all patients; 35 cases improved with conservative treatment, and 2 cases required reoperation. Nine cases had a drainage volume ≥ 500 mL one day following the low-fat diet commencement, which was resolved with conservative treatment and decreased drainage was observed on the third day of treatment in seven of those cases. Two cases with excessive drainage of ≥ 1000 mL in one day and systemic symptoms associated with chyle loss needed surgery.ConclusionsEven when the daily drainage volume exceeds 500 mL following a low-fat diet, there were many cases that could be cured conservatively. The indication for surgery needs to be carefully considered.

Influence of genetic variants of opioid-related genes on opioid-induced adverse effects in patients with lung cancer: A STROBE-compliant observational study.

Despite the dramatic advancement of cancer chemotherapy and immunotherapy, the insufficient progress has been made in basic or translational research on personalization of opioid therapy. Predicting the effectiveness of opioid analgesic therapy and the risk of adverse effects prior to therapy are expected to enable safer and more appropriate opioid therapy for cancer patients. In this study, we compared the incidence of opioid-induced adverse effects between patients with different variants of the genes related to responsiveness to opioid analgesics.Participants were 88 patients with lung cancer who provided general consent for exome sequencing and were treated with morphine or oxycodone at Shizuoka Cancer Center Hospital between April 2014 and August 2018. Incidence rates for 6 adverse effects of opioid therapy (somnolence, nausea, constipation, delirium, urinary retention, and pruritus) were determined and the influence of single nucleotide polymorphisms in coding regions of the opioid μ receptor 1 (OPRM1) (rs1799971), opioid δ receptor 1 (rs2234918), opioid κ receptor 1 (rs1051660), catechol-O-methyltransferase (COMT) (rs4680), dopamine receptor D2 (rs6275), adenosine triphosphate binding cassette B1 (rs1045642), G-protein regulated inward rectifier potassium channel 2 (rs2070995), and fatty acid amide hydrolase (rs324420) genes on those adverse effects were analyzed.Analysis of OPRM1 gene variant status (Asn133Asp A > G) showed that G/G homozygotes were at significantly lower risk of somnolence compared with A allele carriers (0% vs 28.4%; Fisher exact test, P = .005; OR, 0; 95% CI, 0–0.6), and analysis of COMT gene variant status (Val158Met, G > A) showed that G/G homozygotes were at significantly higher risk of somnolence compared with A allele carriers (35.0% vs 10.4%; Fisher exact test, P = .008; OR, 4.5; 95% CI, 1.4–18.1). No relationship between variant status and adverse effects was found for the other genes.These findings demonstrate that OPRM1 and COMT gene variants influence the risk of somnolence as an adverse effect of opioid analgesic therapy.

Effectiveness and safety of a newly introduced multidisciplinary perioperative enhanced recovery after surgery protocol for thoracic esophageal cancer surgery.

Data are sparse regarding the multidisciplinary perioperative enhanced recovery after surgery protocol (E-P) for thoracic esophageal cancer surgery that was newly used at another institution. Therefore, this study aimed to retrospectively evaluate the effectiveness and safety of the protocol. We enrolled 101 patients who underwent transthoracic esophagectomy for E-P at the Shizuoka Cancer Center Hospital (SCC). The outcomes obtained at the SCC were compared with the outcomes of 140 patients treated with E-P at the Saitama Medical University International Medical Center (SMU). At the SMU, we compared the results before and after the introduction of E-P. The rates of morbidity, pulmonary complications, and postoperative pneumonia were 44%, 31%, and 6.9% at the SCC and 44%, 27%, and 6.5% at the SMU (P = 0.91, 0.55, and 0.88, respectively). The mean time to walk was 1.1 and 1.5days at the SCC and SMU, respectively (P < 0.001). The median length of hospital stay was longer at the SMU than at the SCC (24.0 versus 20.8days; P = 0.004). In the comparative study before and after the introduction of E-P, the rate of postoperative pneumonia was 16% in the conventional management group and 6.5% in the E-P group (P = 0.02). Postoperative pneumonia was reduced before and after introduction of E-P. As similar short-term postoperative outcomes were promising (except for the time to walk and postoperative hospital stay), the same E-P that was safely performed at the SMU can be implemented as a standard practice.

A Retrospective Cohort Study to Investigate the Incidence of Cachexia During Chemotherapy in Patients with Colorectal Cancer.

IntroductionThis retrospective study focused on cancer cachexia in clinical practice. We evaluated the incidence of cancer cachexia and the relationship between cancer cachexia and overall survival (OS) or toxicities in patients with advanced colorectal cancer after undergoing first-line systemic chemotherapy.MethodsWe examined 150 patients with colorectal cancer who underwent first-line systemic chemotherapy between February 1, 2010 and August 31, 2016 at Shizuoka Cancer Center Hospital and Kurume University Hospital. Cancer cachexia was defined as > 5% weight loss or > 2% weight loss with a body mass index of < 20 kg/m2 within the past 6 months according to the European Palliative Care Research Collaborative criteria.ResultsOne hundred patients from Shizuoka Cancer Center and 50 from Kurume University Hospital were registered. Median age and body mass index were 65 years (range 29–85) and 21.7 kg/m2 (14.8–32.5), respectively. Cumulative incidence of cancer cachexia was 50.7% at 24 weeks, and reached 91.3% over the whole study period. OS was significantly different between patients with and without cancer cachexia within 24 weeks after starting first-line treatment, although the onset of cancer cachexia within 24 weeks could not be considered as an independent prognostic factor for OS. Severe appetite loss and fatigue tended to occur more frequently in patients with cancer cachexia within 24 weeks.ConclusionCancer cachexia appears to have an onset in approximately half of patients with advanced colorectal cancer within 24 weeks after starting first-line treatment. Although causal relationships were controversial, the onset of cancer cachexia within 24 weeks tends to be related to worse outcomes. Thus, it would be better to monitor weight loss leading to cachexia in patients with advanced colorectal cancer, especially within 24 weeks after starting first-line chemotherapy.Trial RegistrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN000035002).Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01516-6) contains supplementary material, which is available to authorized users.

Impact of Positive Pleural Lavage Cytology for Each Stage of Non-Small Cell Lung Cancer Patients

Positive preresection pleural lavage cytology (PLC+) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC+ for the different pathologic stages (p-stages) of NSCLC. A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC+ on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC+ was compared using the Kaplan-Meier method with the log-rank test for comparison. PLC+ was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P < .001), a pathologic tumor size larger than 3 cm (P= .033), the presence of pleural invasion (P < .001), and adenocarcinoma (P= .038). In patients with PLC+, the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC-) (P < .001). On multivariate analysis, the PLC+ status was an independent prognostic factor of DFS (hazard ratio 1.70; P= .013). Among the 818 patients with p-stage I NSCLC, PLC+ was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC+ was equal to that in patients with p-stage IIIA NSCLC with PLC- (5-year DFS, 40.4% and 39.0%). PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC+, especially for patients with p stage I.

A retrospective cohort study to investigate the incidence of cancer-related weight loss during chemotherapy in gastric cancer patients

PurposeThis study aimed to evaluate cancer-related weight loss (WL) after the start of first-line chemotherapy as a surrogate marker for cancer cachexia in patients with advanced gastric cancer. We investigated the incidence of WL and the relationship between WL and overall survival (OS) or adverse events.MethodsWe conducted a retrospective cohort study in 131 patients with advanced gastric cancer who received first-line systemic chemotherapy between September 1, 2010, and August 31, 2016, at Kurume University Hospital and Shizuoka Cancer Center Hospital. WL was defined in this study as weight loss of > 5% or weight loss of > 2% with a body mass index of < 20 kg/m2 within the last 6 months after the start of chemotherapy.ResultsMedian age and median Eastern Cooperative Oncology Group performance status of the patients participating in this study were 68 years old and 0, respectively. Incidence of WL was 53% at the first 12 weeks after starting first-line chemotherapy, and increased to 88% after 48 weeks. Overall survival rates were significantly associated with WL at 12, 24, and 48 weeks. Appetite loss and fatigue were more frequent and more severe in patients with WL.ConclusionWL was especially observed in more than half the patients within 12 weeks after starting chemotherapy. WL appeared to relate to adverse events or reduced survival. These results suggest the importance of monitoring WL or providing nutritional support at the beginning of chemotherapy.

Clinical features of Clostridium bacteremia in cancer patients: A case series review

Clostridium bacteremia is a well-known cause of infection in patients with gastrointestinal lesions. However, the clinical characteristics of this infection in cancer patients are unclear. We retrospectively reviewed cases of blood cultures positive for Clostridium species between March 1, 2004 and May 30, 2018 at the Shizuoka Cancer Center Hospital. Medical records of 40 patients who met the study criteria were reviewed for age, gender, underlying disease, history of disease, blood culture results, laboratory test results, and radiographic data. The common sources of Clostridium species in these patients were hepatobiliary tract infection and liver abscess (13/40; 32.5%) and bacteremia/enteritis due to gastrointestinal tumor (13/40; 32.5%). All patients had malignancies, with the most common being colorectal cancer (n = 9) followed by pancreatic cancer (n = 8) and gastric cancer (n = 6). The most common species isolated was C. perfringens followed by C. ramnosum. Twenty-five patients (62.5%) had polymicrobial bacteremia with the following organisms isolated from concurrent blood cultures: Escherichia coli (n = 8) and Klebsiella spp. (n = 7). Of these bacteremia cases, 37 had digestive organ lesions such as gastrointestinal malignancy, peritoneal dissemination, or intestinal infiltration. Seventeen patients died, resulting in an overall mortality rate of 42.5% at 30 days. Common cases of Clostridium bacteremia were derived from gastrointestinal lesions, and because Clostridium bacteremia is observed regardless of species, it should be considered necessary to examine gastrointestinal lesions.

Quantitative computed tomography for predicting cardiopulmonary complications after lobectomy for lung cancer in patients with chronic obstructive pulmonary disease.

In lung cancer resection, chronic obstructive pulmonary disease is a risk factor for post-operative complications. Few studies on post-operative complications of lung cancer resection have considered radiographic emphysematous change as an index. Here, we have examined the relationship between the regional ratio of the emphysematous area in pre-operative computed tomography images and cardiopulmonary complications in patients with chronic obstructive pulmonary disease who underwent lung cancer resection. We retrospectively evaluated 159 patients with chronic obstructive pulmonary disease who underwent lobectomy for lung cancer at Shizuoka Cancer Center Hospital, Shizuoka, Japan, between 2002 and 2011. Pre-operative factors, including the proportion of the emphysematous area measured by computed tomography as a percentage of the low attenuation area (LAA%), as well as intraoperative factors were analyzed. Cardiopulmonary complications, including pyothorax, pneumonia and atelectasis, acute pulmonary injury, indwelling chest tube, long duration of oxygen supply, and arrhythmia, were evaluated. Cardiopulmonary complications were observed among 61 patients (38%). Univariate analysis revealed that patient age, percentage of forced expiratory volume in 1s, LAA%, and volume of blood loss were significantly associated with cardiopulmonary complications. Multivariate analysis indicated patient age and LAA% as being significant independent predictors of cardiopulmonary complications. The regional ratio of the emphysematous area is useful for predicting cardiopulmonary complications in patients with chronic obstructive pulmonary disease who undergo lobectomy for lung cancer. In such patients who are also ≥ 70years of age and exhibit LAA% ≥ 1.0%, careful intra- and post-operative management is warranted.

Preventive Effect of Nutrition Support on Peroneal Neuropathy in Cancer Patients.

Background: The occurrence of peroneal neuropathy was reported to be higher in cancer patients than in non-cancer patients. Cancer patients should have their nutritional intake carefully managed in order to minimize weight loss and avoid the occurrence of peroneal neuropathy. However, the effect of nutrition support on the prevention of peroneal neuropathy is not understood.Aims: The present study aimed to assess epidemiologically the effect of nutrition support on the occurrence of peroneal neuropathy in cancer patients.Methods: We performed a retrospective case-control study in 178,597 cancer patients admitted to Shizuoka Cancer Center Hospital from 2002 to 2017. The rates of peroneal neuropathy were assessed between the 8-year period before nutrition support started and the 7-year period during which nutrition support performed.Results: Twenty-nine and 14 cases of peroneal neuropathy occurred in the periods without and with nutrition support, respectively. Compared with the period without nutrition support, the risk of peroneal neuropathy decreased by 62% during the period with nutrition support (odds ratio, 0.38; 95% confidence interval, 0.18–0.74; P < 0.05).Conclusion: Our study suggests the preventive effects of nutrition support on peroneal neuropathy in cancer patients.

Depth of invasion in superficial oral tongue carcinoma quantified using intraoral ultrasonography.

Depth of invasion (DOI) in oral carcinoma has been integrated into the primary tumor categories in the current tumor-node-metastasis staging (8th edition). However, there is no standard modality to determine DOI preoperatively. The aims of the present study were to evaluate the accuracy of a preoperative measurement of DOI using ultrasonography (US) for superficial oral tongue carcinomas, and to correlate the values obtained with histologically determined DOI measurements. We retrospectively analyzed the records of 56 patients with oral tongue carcinoma who underwent intraoral US preoperatively, followed by curative surgery at the Shizuoka Cancer Center Hospital in Japan. For the measurement of DOI with US, our unique technique (water balloon method) was evaluated. The histologically measured tumor size (maximum diameter) showed a distribution of 7.0 to 40.0 mm (mean, 18.6 mm). The correlation between the US-obtained and histologically obtained DOIs was significant (r = 0.867; P < 0.001). In tumors characterized histologically as superficial (DOI ≤ 5 mm), a significant correlation was observed between US-obtained and histologically obtained DOIs (r = 0.870, P < 0.001). For the entire cohort, the sensitivity and specificity of US assessment of DOI of ≤ 5 mm or > 5 mm were 92.3% and 70.6%, respectively. Intraoral US provides sufficient accuracy for the measurement of tumor DOI in oral tongue carcinoma and is complementary in assessing superficial lesions. 4. Laryngoscope, 128:2778-2782, 2018.

Classification of Clinical Syndromes Associated with Skull-Base Metastasis in the MR Era

Skull-base metastases frequently cause progressive ipsilateral disturbances of cranial nerves or pain, resulting in poor quality of life in patients with cancer. Magnetic resonance(MR)imaging is the method to detect skull-base metastases, which demonstrates focal lesions of low-intensity signal and enhancement on T1-weighted MR images. We reviewed clinical data and MR images from 127 patients with skull-base metastases diagnosed at Shizuoka Cancer Center Hospital between August 2012 and November 2017. The most common primary site was the lung(44 patients), followed by the breast(34), colon(8), and prostate(8). The interval from diagnosis of the primary tumor to skull-base metastasis ranged from 0 to 276 months(median, 9 months). The interval was shortest with lung cancer(median, 0 month), and longest with carcinoma of the liver(median, 81 months). The most commonly affected site was the clivus(74%), followed by the petrous(35%), and the occipital condyle(18%). We classified 55 symptomatic patients into 6 clinical syndromes: orbital(18%), parasellar(7%), middle cranial fossa(24%), jugular foramen(7%), and occipital condyle(15%), described by Greenberg, and a new entity "clivopetrosal" syndrome presenting diplopia due to abducens palsy(20%). Of 47 patients who underwent irradiation, 29 patients(62%)achieved relief of their symptoms. Median overall survival after diagnosis of a skull-base metastasis was 7 months. Male sex and colon cancer were associated with poor prognosis. When a cancer patient presents with new-onset cranial nerve palsies or craniofacial pain, physicians need to identify skull-base metastases for prompt radiotherapy.

Preventive effect of nutrition support on peroneal neuropathy in cancer patients

Background: The occurrence of peroneal neuropathy was reported to be higher in cancer patients than in non-cancer patients. Cancer patients should have their nutritional intake carefully managed in order to minimize weight loss and avoid the occurrence of peroneal neuropathy. However, the effect of nutrition support on the prevention of peroneal neuropathy is not understood. Aims: The present study aimed to assess epidemiologically the effect of nutrition support on the occurrence of peroneal neuropathy in cancer patients. Methods: We performed a retrospective case-control study in 178,597 cancer patients admitted to Shizuoka Cancer Center Hospital from 2002 to 2017. The rates of peroneal neuropathy were assessed between the 8-year period before nutrition support started and the 7-year period during which nutrition support performed. Results: Twenty-nine and 14 cases of peroneal neuropathy occurred in the periods without and with nutrition support, respectively. Compared with the period without nutrition support, the risk of peroneal neuropathy decreased by 62% during the period with nutrition support (odds ratio, 0.38; 95% confidence interval, 0.18-0.74; P < 0.05). Conclusion: Our study suggests the preventive effects of nutrition support on peroneal neuropathy in cancer patients.

Postoperative delirium after pharyngolaryngectomy with esophagectomy: a role for ramelteon and suvorexant

BackgroundPostoperative delirium is common after extensive surgery, and is known to be associated with sleeping medications. In this study, we aimed to investigate the relationships between sleeping medications and postoperative delirium after pharyngolaryngectomy with esophagectomy.MethodsWe performed a retrospective analysis of 65 patients who underwent pharyngolaryngectomy with esophagectomy at Shizuoka Cancer Center Hospital between January 2012 and March 2016. All data were assessed by two psychiatrists, and univariate and multivariate analyses were performed.ResultsPostoperative delirium developed in 9 (13.8%) patients, with most cases (77.8%) occurring between postoperative day (POD) 1 and POD 3. Of the 24 patients taking a minor tranquilizer after surgery, 8 (33.3%) became delirious, but, of the remaining 41 patients taking ramelteon with or without suvorexant, only one (2.4%) became delirious after surgery. Moreover, of the 16 patients taking both ramelteon and suvorexant, no postoperative delirium was observed. Ramelteon with or without suvorexant was significantly associated with a decreased rate of postoperative delirium compared with minor tranquilizer use (p = 0.001). Multivariate analysis confirmed that the use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium (odds ratio 0.060, p = 0.013).ConclusionThe use of ramelteon with or without suvorexant was the only significant preventive factor of postoperative delirium after pharyngolaryngectomy with esophagectomy. However, using minor tranquilizers was associated with postoperative delirium. We recommend ramelteon with or without suvorexant for preventing postoperative delirium after pharyngolaryngectomy with esophagectomy.

Leptomeningeal Dissemination in Patients with Pituitary Metastasis from Breast Cancer

Pituitary metastases are uncommon complications of systemic cancer and account for only 1% of pituitary lesions. Breast cancer is one of the most common tumors to metastasize to the pituitary gland. A multidisciplinary approach that calls for close collaboration among oncologists, neurosurgeons, radiologists, and endocrinologists is mandatory for diagnosis and treatment of pituitary metastasis. From 2002 through 2013, 6 patients with pituitary metastases were treated at Shizuoka Cancer Center Hospital. The patients' age at presentation ranged from 45 to 75 years (average 59 years). Five of 6 patients had symptoms: anterior pituitary insufficiency in 4, diabetes insipidus in 3, and visual deficits in 2 patients. Five patients had other metastases at the time of presentation. Local irradiation to the metastatic lesion was adopted in 4, and whole brain irradiation was in 2 patients. In all cases, local control was achieved after irradiation, however, the pituitary insufficiency did not recover. Two of 4 patients treated with local irradiation suffered from meningeal dissemination within 5 months after treatment, and died at 8 and 11 months after diagnosis of pituitary metastasis, respectively. The patients treated with whole brain irradiation had longer survival periods. Early diagnosis, endocrinological management, and radiation therapy improve the quality of life in patients suffering from pituitary metastasis. Whole brain irradiation may be favorable in order to prevent meningeal dissemination.

Risk factors for complications after pharyngolaryngectomy with total esophagectomy.

BackgroundPharyngolaryngectomy with total esophagectomy (PLTE) is an effective surgical treatment for synchronous or metachronous hypopharyngeal or laryngeal cancer and thoracic esophageal cancer, although it is more invasive than esophagectomy and total pharyngolaryngectomy. The aim of this study was to identify risk factors for complications after PLTE.MethodsFrom November 2002 to December 2014, a total of 8 patients underwent PLTE at the Shizuoka Cancer Center Hospital, Shizuoka, Japan. We investigated the clinicopathological characteristics, surgical procedures, and postoperative complications of these patients.ResultsOf the 8 patients, 5 underwent one-stage PLTE and 3 underwent staged PLTE. There was no mortality in this study. Two cases of tracheal necrosis, two of anastomotic leakage, and one of ileus were observed as postoperative complications. Two patients who underwent one-stage PLTE with standard mediastinal lymph node dissection developed tracheal necrosis and severe anastomotic leakage.ConclusionOne-stage PLTE and standard mediastinal lymph node dissection were identified as the risk factors for severe postoperative complications. Staged PLTE or transhiatal esophagectomy should be considered when PLTE is performed and standard mediastinal lymph node dissection should be avoided when one-stage PLTE is performed with transthoracic esophagectomy.

Establishment and validation of prognostic nomograms including HER2 status in metastatic gastric cancer.

24 Background: It remains unclear whether human epidermal growth factor receptor 2 (HER2) status is an outcome-associated biomarker independent of known prognostic factors for metastatic gastric cancer (MGC). There are few reports on nomograms in MGC, while several studies have been published on nomograms for other cancer types. This retrospective study aimed to develop nomograms that combine HER2 status and other prognostic factors for predicting survival outcome of individual patients with MGC starting first-line treatment. Methods: We used a training set of 838 consecutive patients with MGC starting first-line chemotherapy between 2005 and 2012 in Aichi Cancer Center Hospital (ACC) to establish nomograms that calculate the predicted probability of survival at different time points; overall survival (OS) at 1 and 2 years. The covariates analyzed in this model by Cox proportional hazard models included HER2 status, Eastern Cooperative Oncology Group performance status (PS), history of gastrectomy, serum lactic acid dehydrogenase (LDH), and serum alkaline phosphatase levels (ALP). Nomograms were independently validated using data on 269 consecutive patients with MGC who underwent first-line chemotherapy between 2010 and 2012 in Shizuoka Cancer Center Hospital (SCC). Missing covariate data were estimated using multiple imputation methods. The discriminatory ability and accuracy of the models were assessed using Harrell’s c-index. IHC3+ or IHC2+/ISH+ tumors were defined as HER2-positive. Results: Patient characteristics were as follows: median age, 64 vs. 66 years; ECOG PS 0/1/2, 34%/51%/15% vs. 45%/44%/11%; prior gastrectomy, 42% vs. 39%; 1/ &gt; 1 metastatic sites, 56%/44% vs. 43%/57%; high LDH, 76% vs. 27%; high ALP, 22% vs. 26%; and positive/negative HER2 status, 10%/45% vs. 7%/53%, respectively. At a median follow-up of 12.3 (ACC) and 11.6 (SCC) months, 782 and 248 patients had died, and median OS was 12.5 and 12.4 months (P= 1.00), respectively. The nomograms were capable of predicting an OS with a c-index of 0.68 and 0.58. Conclusions: These nomograms may provide objective and approximate prediction of OS for individual MGC patients in clinical settings.

&lt;b&gt;Optimizing an ion semiconductor sequencing data analysis method to identify somatic mutations in the genomes of cancer cells in clinical tissue &lt;/b&gt;&lt;b&gt;samples &lt;/b&gt;

Identification of causal genomic alterations is an indispensable step in the implementation of personalized cancer medicine. Analytical methods play a central role in identifying such changes because of the vast amount of data produced by next generation sequencer. Most analytical techniques are designed for the Illumina platform and are therefore suboptimal for analyzing datasets generated by whole exome sequencing (WES) using the Ion Proton System. Accurate identification of somatic mutations requires the characterization of platform-dependent error profiles and genomic properties that affect the accuracy of sequence data as well as platform-oriented optimization of the pipeline. Therefore, we used the Ion Proton System to perform WES of DNAs isolated from tumor and matched control tissues of 1,058 patients with cancer who were treated at the Shizuoka Cancer Center Hospital. Among the initially identified candidate somatic single-nucleotide variants (SNVs), 10,279 were validated by manual inspection of the WES data followed by Sanger sequencing. These validated SNVs were used as an objective standard to determine an optimum cutoff value to improve the pipeline. Using this optimized pipeline analysis, 189,381 SNVs were identified in 1,101 samples. The analytical technique presented here is a useful resource for conducting clinical WES, particularly using semiconductor-based sequencing technology.

The Outcomes and Next Landscapes of Project HOPE (High-Tech Omics-Based Patient Evaluation) for Hepatocellular Carcinoma

Introduction: Project HOPE (High-tech Omics-based Patient Evaluation) aims to provide the multiomics data of cancer patients for the promotion of individualized medicine and the practice of prophylaxis. To reveal the relationship between the clinical data and genetic expression, genetic analyses based on the results of project HOPE were performed for 24 patients who underwent hepatectomy for hepatocellular carcinoma (HCC). Methods: Fresh surgical specimens obtained from HCC patients who underwent surgery at the Shizuoka Cancer Center Hospital, were analyzed by whole-exon sequencing (WES, Life Technologies) and gene expression profiling (GEP, Agilent Technologies). As of April 1, 2015, 24 patients have been analyzed, and the aberrant genes were identified from the results of the WES and GEP analyses. Results: The present study included 17 males and 7 females, with a median age of 67 years (range: 42-81 years). Six of the patients were positive for hepatitis B surface antigen, 9 were positive for hepatitis C antibody and 9 patients were negative for hepatitis virus infection. The WES analysis showed that specific single nucleotide variants (SNVs) were identified in the genes of CTNNB1 and TP53 at a frequency of 15% and 11%, respectively. The GEP analysis revealed the upregulation of the HIST1H3B (59%), EZH2 (33%) and MYCN (22%) genes in tumor tissue (in comparison to normal tissue), while the expressions of CDH1 (11%) and SOCS1 (11%) were found to be downregulated in tumor tissue. In the analysis of the association between the clinical data and gene expression, the rate of advanced tumor staging (UICC stage > 2) was significantly higher in the patients with upregulated HIST1H3B expression in tumor tissue than in those with normal HIST1H3B expression (57.1% vs. 10%, P=0.033). Moreover, the relapse-free survival rate of the patients with upregulated HIST1H3B expression of tumor tissue was significantly lower than that of patients with normal HIST1H3B expression (estimated median relapse-free survival time: 5.8 vs. 7.7 months; P=0.009). Conclusion: Our genetic analysis based on the results of Project HOPE revealed HIST1H3B to be novel cancer-related gene and a predictive factor for HCC. In the future, we plan to accumulate the results of 150 HCC patients, and it is hoped that the additional novel cancer-related genes will be identified.

Robotic-assisted lateral lymph node dissection for lower rectal cancer: short-term outcomes in 50 consecutive patients.

The goal of this study was to evaluate the short-term outcomes of robotic-assisted lateral lymph node dissection for patients with advanced lower rectal cancer. Between 2012 and 2013, 50 consecutive patients underwent robotic-assisted lateral lymph node dissection for rectal cancer in Shizuoka Cancer Center Hospital. Perioperative outcomes including operative time, operative blood loss, length of stay, postoperative complications, and histopathological data were collected prospectively. Median patient age was 62years (range 36-74years). Operative procedures included low anterior resections (n=27), intersphincteric resections (n=16), and abdominoperineal resections (n=7). Bilateral lymph node dissection was performed in 44 patients. The median operative time was 476min (range 320-683min), and the median time required for lateral lymph node dissection was 165min (range 85-257min). The median blood loss was 27mL (range 5-690mL). There were no cases of open surgery or laparoscopic conversion. The median duration of postoperative hospital stay was 8days (range 6-13days). Clavien-Dindo classification Grade III-IV complications occurred in only one patient (2.0%). There were no cases of anastomotic leak. There was no perioperative mortality. The median number of harvested lateral lymph nodes was 19 (range 5-47). Robotic-assisted lateral lymph node dissection is a safe, feasible, and useful approach for patients with advanced lower rectal cancer.

Chest Tube Tip Culture as a Predictor of Postoperative Infection in Lung Cancer Operations

Postoperative infection is one of the most frequently observed complications after lung resection and should be addressed in perioperative management. This study evaluated the clinical significance of chest tube tip culture relevant to postoperative infection. From September 2002 to December 2011, 1,438 patients who underwent lung cancer operations in Shizuoka Cancer Center Hospital were evaluated. Postoperative infections, including surgical site infection, postoperative pneumonia, and postoperative empyema without fistula, were defined as those occurring within 30 days of thoracotomy. Postoperative infections developed in 84 of the 1,438 patients (5.8%), including 42 (2.9%) with surgical site infection, 36 (2.5%) with pneumonia, and 13 (0.9%) with empyema. The sensitivity, specificity, and positive predictive value of chest tube tip culture were 23%, 98%, and 41.3%, respectively. Multivariate analysis demonstrated that the independent risk factors associated with the development of postoperative infections were coexisting diabetes mellitus and positive chest tube tip culture. Positive chest tube tip culture was the only independent risk factor associated with surgical site infection. The independent risk factors associated with postoperative pneumonia were age 70 years or older, coexisting diabetes mellitus, and positive chest tube tip culture. Finally, positive chest tube tip culture was the only independent risk factor associated with postoperative empyema. Positive chest tube tip culture strongly predicts postoperative infections in lung cancer surgery and necessitates careful observation in the perioperative period.