Publications by authors named "Keishi Sugimachi"

177 Publications

Health-related quality of life after esophagectomy in patients with esophageal cancer.

Esophagus 2021 Sep 1. Epub 2021 Sep 1.

Department of Hepato-Biliary and Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Esophageal cancer is one of the malignant tumors with the poorest prognosis. Esophagectomy, which is the mainstay of curative-intent treatments, imposes excessive surgical stress on the patients, and postoperative morbidity and mortality rates after esophagectomy remain high. On the other hand, the number of survivors after esophagectomy for esophageal cancer is increasing due to recent improvements in surgical techniques and multidisciplinary treatments for this cancer. However, esophagectomy still has a great influence on the fundamental aspect of patients' lives, that is, the health-related quality of life (HR-QOL), including their physical, emotional, and social functions in the short- and long-term postoperatively. HR-QOL is a multifactorial concept used to assess the symptoms and functional changes caused by the disease itself and treatments from the patients' perspectives. Therefore, assessing the HR-QOL of patients with esophageal cancer after esophagectomy is becoming increasingly important. However, the status of HR-QOL changes after esophagectomy has not been satisfactorily evaluated, and there is no worldwide consensus as to how the postoperative HR-QOL can be improved. This review aimed to raise awareness of healthcare providers, such as surgeons and nurses, on the importance of HR-QOL in patients with esophageal cancer after curative-intent esophagectomy by providing multifaceted information concerning the short- and long-term HR-QOLs, including the status of changes and the determinants of HR-QOL after esophagectomy, and furthermore, essential points for improvement of HR-QOL after esophagectomy.
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http://dx.doi.org/10.1007/s10388-021-00874-6DOI Listing
September 2021

Prognostic significance of preoperative PNI and CA19-9 for pancreatic ductal adenocarcinoma: A multi-institutional retrospective study.

Pancreatology 2021 Aug 18. Epub 2021 Aug 18.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: The aim of this study was to investigate the clinical value of nutritional and immunological prognostic scores as predictors of outcomes and to identify the most promising scoring system for patients with pancreatic ductal adenocarcinoma (PDAC) in a multi-institutional study.

Methods: Data were retrospectively collected for 589 patients who underwent surgical resection for PDAC. Prognostic analyses were performed for overall (OS) and recurrence-free survival (RFS) using tumor and patient-related factors, namely neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), modified GPS, C-reactive protein-to-albumin ratio, Controlling Nutritional Status score, and the Geriatric Nutritional Risk Index.

Results: Compared with PDAC patients with high PNI values (≥46), low PNI (<46) patients showed significantly worse overall survival (OS) (multivariate hazard ratio (HR), 1.432; 95% CI, 1.069-1.918; p = 0.0161) and RFS (multivariate HR, 1.339; 95% CI, 1.032-1.736; p = 0.0277). High carbohydrate antigen 19-9 (CA19-9) values (≥450) were significantly correlated with shorter OS (multivariate HR, 1.520; 95% CI, 1.261-2.080; p = 0.0002) and RFS (multivariate HR, 1.533; 95% CI, 1.199-1.961; p = 0.0007). Stratification according to PNI and CA19-9 was also significantly associated with OS and RFS (log rank, P < 0.0001).

Conclusions: Our large cohort study showed that PNI and CA19-9 were associated with poor clinical outcomes in PDAC patients following surgical resection. Additionally, combining PNI with CA19-9 enabled further classification of patients according to their clinical outcomes.
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http://dx.doi.org/10.1016/j.pan.2021.08.003DOI Listing
August 2021

The Evolving Genomic Landscape of Esophageal Squamous Cell Carcinoma Under Chemoradiotherapy.

Cancer Res 2021 Aug 19. Epub 2021 Aug 19.

Department of Pathology and Tumor biology, Graduate School of Medicine, Kyoto University.

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy (CRT), and the prognosis of ESCC after CRT has not improved over the past few decades. The mutation process in CRT-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 ESCC patients who received radiotherapy combined with 5-fluorouracil/platinum. In multi-region analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under CRT selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of CRT. Single-region analysis of 28 pretreatment tumors indicated that focal copy number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after CRT. MYC gain remained throughout the CRT course and potentially contributes to intrinsic resistance to CRT. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by CRT and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision CRT.
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http://dx.doi.org/10.1158/0008-5472.CAN-21-0653DOI Listing
August 2021

Improved indocyanine green retention after short-term lenvatinib withdrawal in three patients with hepatocellular carcinoma.

Clin J Gastroenterol 2021 Oct 27;14(5):1484-1490. Epub 2021 Jun 27.

Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka City Fukuoka Prefecture, 811-1395, Japan.

Use of lenvatinib, which has a high response rate in advanced hepatocellular carcinoma, sometimes results in tumor shrinkage and resectability of previously unresectable liver cancers. In Asia, including Japan, liver reserve, one of the determinants of resectability, is mainly determined by the indocyanine green (ICG) retention rate. Three patients with advanced liver cancer treated at our institution had very poor ICG retention rates during treatment with lenvatinib. Lenvatinib may reduce blood flow in both cancerous and non-cancerous regions by inhibiting vascular endothelial growth factor. Therefore, accurate determination of liver function likely requires withdrawal of this treatment several days before ICG retention testing.
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http://dx.doi.org/10.1007/s12328-021-01470-yDOI Listing
October 2021

Feasibility of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma: a multi-center experience.

Surg Today 2021 May 25. Epub 2021 May 25.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Purpose: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions.

Methods: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively).

Conclusions: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma.
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http://dx.doi.org/10.1007/s00595-021-02305-6DOI Listing
May 2021

Neutrophil-to-lymphocyte Ratio as a Predictor of Malignancy of Intraductal Papillary Mucinous Neoplasms.

Anticancer Res 2021 Mar;41(3):1663-1669

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background: Intraductal papillary mucinous neoplasm (IPMN) can lead, via the adenoma-carcinoma sequence, to invasive adenocarcinoma, which has a poor prognosis. Most IPMNs do not meet the indications for surgery and instead are monitored regularly, but no biomarkers of malignant transformation during surveillance have been established.

Patients And Methods: A total of 50 patients with IPMN who underwent pancreatectomy were evaluated retrospectively. Clinicopathological parameters during the surveillance period before surgery were assessed to explore biomarkers for predicting malignancy.

Results: The serum level of carbohydrate antigen 19-9 was significantly higher in IPMN-derived invasive adenocarcinoma. The neutrophil-to-lymphocyte ratio was significantly lower in low-grade IPMN than high-grade and Inv-IPMN cases by univariate and multivariate analysis. Disease-free survival was significantly shorter in patients with high-grade and invasive IPMN compared with those with low-grade IPMN. In patients whose preoperative surveillance was performed for more than 12 months, the neutrophil-to-lymphocyte ratio was significantly higher in those with high-grade and invasive IPMNs compared with patients with low-grade IPMN in the year before surgery.

Conclusion: The NLR is a useful biomarker for distinguishing between low-grade and high-grade IPMN and thus should be monitored during surveillance.
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http://dx.doi.org/10.21873/anticanres.14929DOI Listing
March 2021

Impaired tumor immune response in metastatic tumors is a selective pressure for neutral evolution in CRC cases.

PLoS Genet 2021 01 21;17(1):e1009113. Epub 2021 Jan 21.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

A Darwinian evolutionary shift occurs early in the neutral evolution of advanced colorectal carcinoma (CRC), and copy number aberrations (CNA) are essential in the transition from adenoma to carcinoma. In light of this primary evolution, we investigated the evolutionary principles of the genome that foster postoperative recurrence of CRC. CNA and neoantigens (NAG) were compared between early primary tumors with recurrence (CRCR) and early primary tumors without recurrence (precancerous and early; PCRC). We compared CNA, single nucleotide variance (SNV), RNA sequences, and T-cell receptor (TCR) repertoire between 9 primary and 10 metastatic sites from 10 CRCR cases. We found that NAG in primary sites were fewer in CRCR than in PCRC, while the arm level CNA were significantly higher in primary sites in CRCR than in PCRC. Further, a comparison of genomic aberrations of primary and metastatic conditions revealed no significant differences in CNA. The driver mutations in recurrence were the trunk of the evolutionary phylogenic tree from primary sites to recurrence sites. Notably, PD-1 and TIM3, T cell exhaustion-related molecules of the tumor immune response, were abundantly expressed in metastatic sites compared to primary sites along with the increased number of CD8 expressing cells. The postoperative recurrence-free survival period was only significantly associated with the NAG levels and TCR repertoire diversity in metastatic sites. Therefore, CNA with diminished NAG and diverse TCR repertoire in pre-metastatic sites may determine postoperative recurrence of CRC.
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http://dx.doi.org/10.1371/journal.pgen.1009113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864431PMC
January 2021

Adenomyomatous hyperplasia of the extrahepatic bile duct: a systematic review of a rare lesion mimicking bile duct carcinoma.

Clin J Gastroenterol 2021 Apr 5;14(2):393-401. Epub 2021 Jan 5.

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.

Adenomyomatous hyperplasia (AH) is a tumor-like inflammatory hyperplastic lesion. In the biliary system, AH commonly arises in the gallbladder, but AH of the extrahepatic bile duct is extremely rare. AH usually develops and is found with symptoms related to biliary stenosis or obstruction, but there are few disease-specific manifestations. It is difficult to make a definitive diagnosis by imaging or cytopathological examination; thus, surgical resections were performed in all past reported cases. The pathophysiological etiology of AH is unknown, but it is considered to be associated with chronic inflammation. According to the epidemiological findings of cases reported to date, the possibility of malignant transformation is considered to be negative. However, the symptoms and imaging findings of AH are difficult to distinguish from those of early-stage bile duct carcinoma. In the current review, we discuss the epidemiology, pathophysiology, diagnosis, and management of AH of the bile duct.
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http://dx.doi.org/10.1007/s12328-020-01327-wDOI Listing
April 2021

Relationship between surgical R0 resectability and findings of peripancreatic vascular invasion on CT imaging after neoadjuvant S-1 and concurrent radiotherapy in patients with borderline resectable pancreatic cancer.

BMC Cancer 2020 Dec 2;20(1):1184. Epub 2020 Dec 2.

Department of Hepato-Biliary-Pancreatic Surgery, Chiba Cancer Center, Chiba, Japan.

Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC.

Methods: Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group.

Results: There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was - 10.0% [- 31.7-20.4%].

Conclusions: Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT.

Trial Registration: UMIN-CTR, UMIN000009172 . Registered 23 October 2012.
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http://dx.doi.org/10.1186/s12885-020-07698-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709301PMC
December 2020

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-Label Multicenter Prospective Trial (JASPAC05).

Ann Surg 2020 Oct 15. Epub 2020 Oct 15.

Department of Hepato-biliary Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Objective: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in borderline resectable pancreatic cancer (BRPC).

Summary Background Data: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established.

Methods: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a one-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively.

Results: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively.

Conclusions: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC.

Trial Registration: UMIN000009172.
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http://dx.doi.org/10.1097/SLA.0000000000004535DOI Listing
October 2020

Successful hybrid surgery for ileal conduit stomal varices following oxaliplatin-based chemotherapy in a patient with advanced colorectal cancer.

Surg Case Rep 2020 Sep 29;6(1):236. Epub 2020 Sep 29.

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka, 811-1395, Japan.

Background: Ectopic variceal bleeding is a rare but life-threatening complication of portal hypertension (PH). Oxaliplatin-based chemotherapy for colorectal cancer (CRC) is associated with sinusoidal obstruction syndrome of the liver, which can lead to PH.

Case Presentation: Here, we report a successful hybrid surgery that included intraoperative obliteration of ileal conduit stomal varices (ICSVs) for a 66-year-old woman with CRC and liver metastasis that had been treated multimodally during the previous 4 years, including 17 courses of oxaliplatin-based chemotherapy. She was admitted to our hospital for massive hemorrhage from an ileal conduct stoma. Image findings showed ICSVs as a part of portosystemic shunt, which were afferently supplied from the superior mesenteric vein (SMV) and drained by the numerous cutaneous veins connected to the left femoral vein. Obliteration of the stomal varices by interventional radiologic techniques alone was inappropriate because of difficulties of cannulating the efferent cutaneous veins. We, therefore, performed hybrid surgery for the ICSV, which included cannulation into the SMV branch and antegrade obliteration of the varices with a 5% solution of ethanolamine oleate with iopamidol under blocking the SMV flow, using a vascular clip and ligation. Hemorrhage in her ileal conduit stoma disappeared completely.

Conclusion: Customized treatment of ectopic varices should be based on their precise vascular anatomy; hybrid surgery with intraoperative angiography is an alternative treatment for ectopic varices such as ICSV.
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http://dx.doi.org/10.1186/s40792-020-01021-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524906PMC
September 2020

Cardiac tamponade in a long-term survival esophageal cancer patient after esophageal bypass and chemoradiotherapy: a case report.

Clin J Gastroenterol 2020 Dec 31;13(6):1041-1045. Epub 2020 Aug 31.

Dept. of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan.

Esophageal bypass surgery is an effective treatment strategy for esophageal cancer with esophago-tracheobronchial fistula. We herein report an esophageal cancer patient with esophago-pulmonary fistula who achieved a long-term survival but died suddenly because of cardiac tamponade. A 70-year-old male patient with esophago-pulmonary fistula due to esophageal tumor invasion underwent definitive chemoradiotherapy as the initial treatment. Esophageal bypass surgery followed by additional chemotherapy was performed, and the patient survived for a long time. Four years and six months later, a small abscess in an esophago-pulmonary fistula was visualized on computed tomography. One month later, he suffered suddenly severe dyspnea and died. An autopsy suggested that the direct cause of death had been cardiac tamponade due to atrio-pericardial fistula. Definitive therapy for esophageal cancer with fistula after esophageal bypass is an effective treatment, but close special attention must be paid to the possibility of irradiation-related late toxicity.
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http://dx.doi.org/10.1007/s12328-020-01222-4DOI Listing
December 2020

Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma.

Pancreatology 2020 Sep 25;20(6):1175-1182. Epub 2020 Jul 25.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan.

Background/objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).

Methods: Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.

Results: The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.

Conclusions: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.
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http://dx.doi.org/10.1016/j.pan.2020.07.011DOI Listing
September 2020

Prognostic Impact of Geriatric Nutritional Risk Index in Patients With Synchronous Colorectal Liver Metastasis.

Anticancer Res 2020 Jul;40(7):4165-4171

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background/aim: The Geriatric Nutritional Risk Index (GNRI) is a prognostic indicator for several cancers; however, the association between the GNRI and colorectal liver metastasis (CRLM) remains unknown.

Patients And Methods: Eighty patients who underwent hepatectomy for synchronous CRLM were divided into two groups based on the GNRI.

Results: The preoperative CA19-9 levels were significantly higher in the low (GNRI ≤98; n=30) than the normal GNRI group (GNRI >98; n=50). Patients in the low GNRI group had poorer outcomes than those in the normal GNRI group. A low GNRI was an independent prognostic factor for recurrence-free survival and overall survival. Among 50 patients who experienced recurrence, only 16 of 22 patients (72.7%) in the low GNRI group could receive intensive treatment and 27 of 28 patients (96.4%) in the normal GNRI group.

Conclusion: The GNRI is a simplified prognostic factor for patients with CRLM.
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http://dx.doi.org/10.21873/anticanres.14416DOI Listing
July 2020

Laparoscopic Total Gastrectomy for Remnant Gastric Cancer: A Single-institution Experience and Systematic Literature Review.

In Vivo 2020 Jul-Aug;34(4):1987-1992

Department of Gastrointestinal Surgery, National Hospital Organization, Kyushu Cancer Center, Fukuoka, Japan.

Background/aim: The safety and efficacy of laparoscopic total gastrectomy (LTG) for remnant gastric cancer (RGC) remains unclear. The purpose of this study was to compare the clinical outcomes of LTG with open total gastrectomy (OTG) for RGC.

Patients And Methods: Twenty-two patients who underwent total gastrectomy for RGC were enrolled in this study.

Results: LTG was carried out in seven patients, and OTG was performed in the remaining 15 patients. The mean operation time in the LTG group was longer than that in the OTG group. The estimated blood loss in the LTG group was less than that in the OTG group. No cases in the LTG group required open conversion. Postoperatively, the first meal and defecation were earlier in the LTG group than in the OTG group. The overall survival rates of the two groups were comparable.

Conclusion: Laparoscopic total gastrectomy is a feasible surgical option for RGC.
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http://dx.doi.org/10.21873/invivo.11996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439895PMC
June 2021

Inferior Right Hepatic Vein-Preserving Hepatectomy for Large Liver Tumors: Anterior Approach Using the Two-Stage Modified Hanging Maneuver (with Video).

J Gastrointest Surg 2020 06 20;24(6):1444-1447. Epub 2020 Apr 20.

Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.

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http://dx.doi.org/10.1007/s11605-020-04602-wDOI Listing
June 2020

The Preoperative Prognostic Nutritional Index Predicts the Development of Deep Venous Thrombosis After Pancreatic Surgery.

Anticancer Res 2020 Apr;40(4):2297-2301

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background/aim: Pancreatic surgery is associated with a high risk of developing deep venous thrombosis (DVT) and malnutrition. We aimed to evaluate the factors predicting the development of DVT, focusing on nutrition assessment tools.

Patients And Methods: One hundred patients who underwent pancreatic surgery were postoperatively examined for DVT. We assessed the risk factors for the development of DVT after surgery.

Results: Postoperative DVT was detected in 11 patients (11%). Patients who developed DVT after surgery were significantly older (p=0.016) and had higher preoperative D-dimer levels (p=0.005) than those who did not. The preoperative prognostic nutritional index (PNI) was mostly associated with the development of DVT (p=0.079). Furthermore, PNI ≤44.3, BUN >20 mg/dl, D-dimer ≥1.9 μg/ml were independent predictors for the development of DVT after surgery.

Conclusion: A poor nutrition status and dehydration should be preoperatively improved for patients who are identified, as having a high risk of developing DVT after pancreatic surgery.
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http://dx.doi.org/10.21873/anticanres.14195DOI Listing
April 2020

Treatment strategies for neuroendocrine carcinoma of the upper digestive tract.

Int J Clin Oncol 2020 May 8;25(5):842-850. Epub 2020 Feb 8.

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.

Background: Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy.

Methods: Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12).

Results: Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively.

Conclusions: A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.
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http://dx.doi.org/10.1007/s10147-020-01631-yDOI Listing
May 2020

Laparoscopic spleen-preserving distal pancreatectomy for a solid-cystic intraabdominal desmoid tumor at a gastro-pancreatic lesion: a case report.

BMC Surg 2020 Feb 3;20(1):24. Epub 2020 Feb 3.

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background: We report a case of an intraabdominal desmoid tumor that occurred at a gastro-pancreatic lesion with spontaneous cystic features, and present the successful laparoscopic resection of the tumor.

Case Presentation: A 20-mm retroperitoneal cystic mass with a solid component was found adjacent to the stomach and pancreatic body in a 52-year-old woman with no history of familial adenomatous polyposis. Laparoscopic spleen-preserving distal pancreatectomy with wedge resection of the stomach was performed, and complete resection was achieved without intraoperative and postoperative complications. Histopathological examination by immunohistochemistry enabled diagnosis of a desmoid tumor that had originated from the stomach and invaded the pancreatic parenchyma with a spontaneous cystic change. We herein report an extremely rare case of an intraabdominal desmoid tumor with a spontaneous cystic change.

Conclusion: Regardless of its rarity, desmoid tumor should be included in the preoperative differential diagnosis of a cystic intraabdominal mass, and laparoscopic function-preserving surgery may be an optimal treatment option.
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http://dx.doi.org/10.1186/s12893-020-0691-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998096PMC
February 2020

Significance of bile culture surveillance for postoperative management of pancreatoduodenectomy.

World J Surg Oncol 2019 Dec 30;17(1):232. Epub 2019 Dec 30.

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.

Background: The management of infectious complications is important in pancreatoduodenectomy (PD). We sought to determine the significance of preoperative surveillance bile culture in perioperative management of PD.

Methods: This study enrolled 69 patients who underwent PD for malignant tumors at a single institute between 2014 and 2017. Surveillance bile culture was performed before or during surgery. Correlations between the incidence of infectious postoperative complications and clinicopathological parameters, including bile cultures, were evaluated.

Results: Preoperative positive bile culture was confirmed in 28 of 51 patients (55%). Bile culture was positive in 27 of 30 cases (90%) with preoperative biliary drainage, and 1 of 21 cases (5%) without drainage (p < 0.01). Preoperative isolated microorganisms in bile were consistent with those detected in surgical sites in 11 of 27 cases (41%). Cases with positive multi-drug-resistant bacteria in preoperative bile culture showed significantly higher incisional SSI after PD (p = 0.01). The risk factors for the incidence of organ/space SSI were soft pancreatic texture (p = 0.01) and smoking history (p = 0.02) by multivariate analysis. Preoperative positive bile culture was neither associated with organ/space SSI nor overall postoperative complications.

Conclusions: Preoperative surveillance bile culture is useful for the management of wound infection, prediction of causative pathogens for infectious complications, and the selection of perioperative antibiotic prophylaxis.
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http://dx.doi.org/10.1186/s12957-019-1773-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937703PMC
December 2019

GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor-suppressor gene TGFβR2 in colorectal cancer.

Cancer Sci 2020 Feb 27;111(2):343-355. Epub 2019 Dec 27.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

Chromosome 7q (Ch.7q) is clonally amplified in colorectal cancer (CRC). We aimed to identify oncogenes on Ch.7q that are overexpressed through DNA copy number amplification and determine the biological and clinical significance of these oncogenes in CRC. We identified general transcription factor 2I repeat domain-containing protein 1 (GTF2IRD1) as a potential oncogene using a CRC dataset from The Cancer Genome Atlas with a bioinformatics approach. We measured the expression of GTF2IRD1 in 98 patients with CRC using immunohistochemistry and RT-quantitative PCR (RT-qPCR). The biological effects of GTF2IRD1 expression were explored by gene set enrichment analysis (GSEA). Next, we undertook in vitro cell proliferation and cell cycle assays using siGTF2IRD1-transfected CRC cells. We further investigated the oncogenic mechanisms through which GTF2IRD1 promoted CRC progression. Finally, we assessed the clinical significance of GTF2IRD1 expression by RT-qPCR. GTF2IRD1 was overexpressed in tumor cells and liver metastatic lesions. The GSEA revealed a positive correlation between GTF2IRD1 expression and cell cycle progression-related genes. GTF2IRD1 knockdown inhibited cell proliferation and induced cell cycle arrest in Smad4-mutated CRC. GTF2IRD1 downregulated the expression of the gene encoding transforming growth factor β receptor 2 (TGFβR2), a tumor-suppressor gene in Smad4-mutated CRC. On multivariate analysis, high GTF2IRD1 expression was an independent poor prognostic factor. Clinicopathological analysis showed that GTF2IRD1 expression was positively correlated with liver metastasis. In conclusion, GTF2IRD1 promoted CRC progression by downregulating TGFβR2 and could be a prognostic biomarker on Ch.7q in CRC. GTF2IRD1 could also be a novel oncogene in CRC.
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http://dx.doi.org/10.1111/cas.14248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004548PMC
February 2020

The Impact of Immunonutritional and Physical Status on Surgical Outcome After Pancreaticoduodenectomy in Elderly Patients.

Anticancer Res 2019 Nov;39(11):6347-6353

Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Background/aim: The aim of this study was to determine the significance of immunonutritional and physical index in the assessment of risk associated with pancreaticoduodenectomy (PD) in the elderly.

Patients And Methods: This study enrolled 92 patients who underwent PD. They were divided into 2 groups: Group A included patients 79 years and younger (n=79) and Group B patients 80 years and older (n=13). Among 37 patients, physical function and body composition were also evaluated.

Results: Significantly higher neutrophil-lymphocyte ratio, lower prognostic nutritional index (PNI), and controlling nutritional score were observed in Group B. Muscle strength and walking ability were significantly impaired in Group B, although there was no significant difference in body composition. Age was not correlated with the incidence of postoperative complications, overall survival or recurrence-free survival by univariate and multivariate analysis.

Conclusion: PD is justified for the elderly, with acceptable morbidity and prognosis. However, immunonutritional status and physical function are significantly impaired; thus, appropriate case selection and active nutritional support are required for the elderly.
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http://dx.doi.org/10.21873/anticanres.13846DOI Listing
November 2019

The evolution of surgical treatment for gastrointestinal cancers.

Int J Clin Oncol 2019 Nov 14;24(11):1333-1349. Epub 2019 Sep 14.

Department of Molecular Cancer Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Introduction: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them.

Materials And Methods, And Results: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery.

Conclusion: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.
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http://dx.doi.org/10.1007/s10147-019-01499-7DOI Listing
November 2019

Plastin3 is associated with epithelial-mesenchymal transition and poor prognosis in gastric cancer.

Oncol Lett 2019 Feb 11;17(2):2393-2399. Epub 2018 Dec 11.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan.

The () gene, which encodes an actin bundling protein known to inhibit cofilin-mediated depolymerization of actin fiber, has been previously reported to serve an important role in the epithelial-mesenchymal transition (EMT) in cancer. The aim of the present study was to determine the clinical significance of and its role in regulating EMT, as well as in promoting cell invasion and migration in gastric cancer. The expression of plastin3 mRNA was measured in 163 resected gastric cancer specimens, in order to determine the clinicopathological significance. Furthermore, invasion and migration assays were performed on gastric cancer cells, which revealed that expression was suppressed. The high expression group had a higher incidence of advanced tumour stage, cancer differentiation, tumour invasion depth and distant metastases compared with the low expression group (P<0.05). In addition, the high expression group had a significantly poorer prognosis than the low expression group (P=0.012). Multivariate analysis indicated that high expression was an independent prognostic factor for survival. The present study also identified that suppression of in gastric cancer cells was associated with decreased cell invasion and migration. The findings from the present study indicate that high expression of in gastric cancer is independently associated with a poor prognosis, and that serves an important role in EMT.
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http://dx.doi.org/10.3892/ol.2018.9819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341793PMC
February 2019

Serial mutational tracking in surgically resected locally advanced colorectal cancer with neoadjuvant chemotherapy.

Br J Cancer 2018 08 3;119(4):419-423. Epub 2018 Aug 3.

Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan.

Background: We aim to investigate the utility of serial gene mutation tracking for locally advanced CRC in those who underwent curative resection following neoadjuvant chemotherapy.

Methods: We prospectively collected 10 locally advanced CRC cases for which curative resection was performed following preoperative neoadjuvant chemotherapy. Tissues from the primary tumour, distant metastatic tumours, and blood plasma were obtained during serial treatment. Comprehensive mutation analysis of 47 cancer-associated genes was performed using a pre-designed gene panel and next-generation sequencing.

Results: All cases showed a partial response to neoadjuvant chemotherapy, and pathological R0 resection was accomplished. In primary tumours, non-synonymous mutations were detected at between 1 and 14 sites before chemotherapy and at between 1 and 2 sites after. Founder mutations were precisely detected in blood plasma and metastatic tumours during longitudinal treatment.

Conclusions: Serial mutational analysis indicated that subclonal selection occurs during chemotherapy and that plasma can substitute for tumourous tissue in mutational analysis for drug selection and treatment decisions.
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http://dx.doi.org/10.1038/s41416-018-0208-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134007PMC
August 2018

Prognostic Significance of Preoperative Controlling Nutritional Status (CONUT) Score in Patients Undergoing Hepatic Resection for Hepatocellular Carcinoma: A Multi-institutional Study.

Ann Surg Oncol 2018 Oct 26;25(11):3316-3323. Epub 2018 Jul 26.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: The Controlling Nutritional Status (CONUT) score is an objective tool that is widely used to assess the nutritional status in patients, including those with cancer. The relationship between the CONUT score and prognosis in patients who have undergone hepatic resection has not been evaluated in a multi-institutional study.

Methods: Data were retrospectively collected for 2461 consecutive patients with hepatocellular carcinoma (HCC) who had undergone hepatic resection with curative intent at 13 institutions between January 2004 and December 2015. Patients were assigned to two groups: preoperative CONUT scores ≤ 3 (low CONUT score) and ≥ 4 (high CONUT score). Clinicopathological characteristics, surgical outcomes, and long-term survival were compared using propensity score matching analysis.

Results: Of the 2461 patients, 540 (21.9%) had high (≥ 4) and 1921 (78.1%) had low (≤ 3) preoperative CONUT scores. Overall, a high CONUT score was significantly associated with older age, female sex, low body mass index, low serum albumin, high serum total bilirubin, low lymphocyte count, low serum cholesterol, shorter prothrombin time, higher indocyanine green retention test at 15 min, Child-Pugh B (vs. A), liver cirrhosis, minor resection, shorter operation time, massive blood loss, blood transfusion, and postoperative complications. After propensity score matching, a higher CONUT score was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) using multivariate analysis.

Conclusions: This retrospective, multi-institutional analysis showed that, in patients who undergo curative hepatectomy for HCC, the preoperative CONUT score is predictive of worse OS and RFS, even after propensity score matching analysis.
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http://dx.doi.org/10.1245/s10434-018-6672-6DOI Listing
October 2018

A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer.

Nat Commun 2018 07 23;9(1):2884. Epub 2018 Jul 23.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Japan.

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.
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http://dx.doi.org/10.1038/s41467-018-05226-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056524PMC
July 2018

Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma.

Oncology 2018 15;95(3):179-187. Epub 2018 Jun 15.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

Objective: The involvement of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Here, we aimed to identify EMT-related genes associated with TGF-β in ESCC and to clarify the role of these genes in the progression of ESCC.

Methods: EMT-related genes associated with TGF-β expression were identified in patients with ESCC using microarray analysis and public datasets. The effects of ubiquitin-like with PHD and ring finger domains 2 (UHRF2) expression were analyzed in ESCC cell lines. Cell proliferation and invasion were measured using MTT and invasion assays, respectively. UHRF2 mRNA expression was also analyzed in 75 ESCC specimens to determine the clinical significance of UHRF2 in ESCC.

Results: Treatment of ESCC cell lines with TGF-β increased UHRF2 expression. UHRF2 overexpression increased CDH1 (E-cadherin) expression and decreased invasive capacity. The 75 ESCC specimens were divided into the UHRF2 high-expression group (n = 61) and the UHRF2 low-expression group (n = 14). Low UHRF2 expression was significantly correlated with vascular invasion (p = 0.034) and was an independent prognostic factor for poor prognosis (p = 0.005).

Conclusion: UHRF2 may be a negative regulator of EMT and a novel prognostic biomarker for ESCC.
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http://dx.doi.org/10.1159/000488860DOI Listing
September 2018

Clinicopathological characteristics of disseminated carcinomatosis of the bone marrow in breast cancer patients.

Mol Clin Oncol 2018 Jan 15;8(1):93-98. Epub 2017 Nov 15.

Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan.

Disseminated carcinomatosis of the bone marrow (DCBM) is characterized by diffuse infiltrative growth of tumor cells in the bone marrow and is associated with systemic hematological disorders. Bone marrow metastases from breast cancer are not rare, and they may lead to serious life-threatening conditions when there is an associated hematological disorder. Therefore, DCBM necessitates a definitive diagnosis and prompt systemic therapy. We herein present 4 such cases and a review of the previous relevant literature. Bone marrow biopsy is an effective method for diagnosing DCBM, and it may also be useful for selecting the optimal therapy. The malignant cells in the bone marrow biopsy specimens from all 4 patients were negative for progesterone receptor expression, and in 1 case, human epidermal growth factor receptor 2/neu expression was discordant between the primary tumor and the bone marrow metastases. Patients with DCBM often require granulocyte colony-stimulating factor and/or blood transfusions due to a DCBM-related hematological disorder. Although systemic chemotherapy for DCBM may temporarily exacerbate the need for hematological support, systemic chemotherapy may be effective for DCBM in breast cancer patients. In our experience, endocrine therapy has also been proven effective for DCBM. The aim of the present study was to review the clinical characteristics and the treatments used in 4 breast cancer patients with DCBM.
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http://dx.doi.org/10.3892/mco.2017.1502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772957PMC
January 2018
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