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Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma

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World Journal of Gastroenterology 2017年第31期23卷 5764-5772页

作者： Kohei Nishio Kenjiro Kimura Ryosuke Amano Bunzo Nakata Sadaaki Yamazoe Go Ohira Kotaro Miura Naoki Kametani Hiroaki Tanaka Kazuya Muguruma Kosei Hirakawa Masaichi Ohira Department of surgical oncology Osaka City University Graduate School of Medicine Department of Surgery Kashiwara Municipal Hospital

To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODSTumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of surgical oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker. RESULTSIn total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors. CONCLUSIONDCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

关键词： Doublecortin and CaM kinase-like-1 Pancreatic cancer Epithelial mesenchymal transition Cancer stem cell Prognostic factor

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MSH2 is required for cell proliferation,cell cycle control and cell invasiveness in colorectal cancer cells

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Chinese Science Bulletin 2012年第20期57卷 2580-2585页

作者： SHEN Kai YE YingJiang JIANG KeWei LIANG Bin YANG XiaoDong WANG Shan Department of Gastroenterological Surgery Surgical Oncology Laboratory Peking UniversityPeople's HospitalBeijing 100044China

We have investigated the role of MSH2,a mismatch repair gene in cell proliferation,cell cycle control and cell invasiveness in the SW480 human colorectal cancer cell ***-mediated inhibition of MSH2 expression was achieved using MSH2 shRNA lentiviral expression *** knockdown of endogenous MSH2 expression was determined by real-time PCR *** most efficient MSH2 knockdown vector was selected for subsequent studies using SW480 *** MSH2 mRNA levels decreased after lentiviral delivery of the MSH2-RNAi,indicating efficient silencing of MSH2 expression in SW480 *** proliferation,cell cycle progression and cell invasiveness were quantified by MTT assays,flow cytometry and transwell assays,***-mediated inhibition of MSH2 expression in SW480 cells resulted in decreased cell proliferation,cell cycle arrest at the G0/G1 phase and decreased cell *** together,these results provide evidence that MSH2 stimulates cell proliferation,promotes cell cycle progression and positively regulates cell invasiveness.

关键词：错配修复基因细胞周期调控细胞增殖侵袭癌细胞大肠细胞周期阻滞 RNAi

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Metastatic tumors to the pancreas: The role of surgery

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World Journal of Gastrointestinal oncology 2014年第10期6卷 381-392页

作者： Cosimo Sperti Lucia Moletta Giuseppe Patanè Department of Surgery Oncology and Gastroenterology 3rd Surgical Clinic University of Padua 35128 Padova Italy

Pancreatic metastases from other primary malignancies are a rare entity. By far, the most common primary cancer site resulting in an isolated pancreatic metastasis is the kidney, followed by colorectal cancer, melanoma, breast cancer, lung carcinoma and sarcoma. Only few data on the surgical outcome of pancreatic resections performed for metastases from other primary tumor have been published, and there are no guidelines to address the surgical treatment for these patients. In this study, we performed a review of the published literature, focusing on the early and long-term results of surgery for the most frequent primary tumors metastasizing to the pancreas. Results for the Literature's analysis show that in last years an increasing number of surgical resections have been performed in selected patients with limited pancreatic disease. Pancreatic resection for metastatic disease can be performed with acceptable mortality and morbidity rates. The usefulness of pancreatic resection is mainly linked to the biology of the primary tumor metastasizing to the pancreas. The benefit of metastasectomy in terms of patient survival has been observed for metastases from renal cell cancer, while for other primary tumors, such as lung and breast cancers, the role of surgery is mainly palliative.

关键词： Pancreas Pancreatic neoplasms/second-ary Pancreatectomy Renal cell cancer Breast cancer Melanoma Sarcoma Lung carcinoma

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Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

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World Journal of Gastroenterology 2013年第9期19卷 1424-1437页

作者： George Sgourakis Ines Gockel Hauke Lang Department of General and Abdominal Surgery Johannes Gutenberg University Hospital of Mainz 2nd surgical Department and surgical oncology Unit of "Korgialenio-Benakio" Red Cross Hospital of Athens

AIM: To investigate potential therapeutic recommendations for endoscopic and surgical resection of T1a/ T1b esophageal neoplasms. METHODS: A thorough search of electronic databases MEDLINE, Embase, Pubmed and Cochrane Library, from 1997 up to January 2011 was performed. An analysis was carried out, pooling the effects of outcomes of 4241 patients enrolled in 80 retrospective studies. For comparisons across studies, each reporting on only one endoscopic method, we used a random effects meta-regression of the log-odds of the outcome of treatment in each study. "Neural networks" as a data mining technique was employed in order to establish a prediction model of lymph node status in superficial submucosal esophageal carcinoma. Another data mining technique, the "feature selection and root cause analysis", was used to identify the most impor-tant predictors of local recurrence and metachronous cancer development in endoscopically resected patients, and lymph node positivity in squamous carcinoma (SCC) and adenocarcinoma (ADC) separately in surgically resected patients. RESULTS: Endoscopically resected patients: Low grade dysplasia was observed in 4% of patients, high grade dysplasia in 14.6%, carcinoma in situ in 19%, mucosal cancer in 54%, and submucosal cancer in 16% of patients. There were no significant differences between endoscopic mucosal resection and endoscopic submucosal dissection (ESD) for the following parameters: complications, patients submitted to surgery, positive margins, lymph node positivity, local recurrence and metachronous cancer. With regard to piecemeal resection, ESD performed better since the number of cases was significantly less [coefficient: -7.709438, 95%CI: (-11.03803, -4.380844), P < 0.001]; hence local recurrence rates were significantly lower [coefficient: -4.033528, 95%CI: (-6.151498, -1.915559),P < 0.01]. A higher rate of esophageal stenosis was observed following ESD [coefficient: 7.322266, 95%CI: (3.810146, 10.83439), P < 0.001]. A

关键词： Superficial esophageal cancer Endoscopic resection Mucosal infiltration Submucosal involvement Recurrent tumor Controversies in treatment Squamous cell carcinoma Adenocarcinoma Lymphatic invasion Vascular invasion Submucosal layer Superficial submucosal layer Middle third submucosal layer Deep third submucosal layer Esophageal cancer Endoscopic gastrointestinal surgical procedures Endoscopic gastrointestinal surgery Lymph node dissection Dysplasia

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surgical approach to synchronous colorectal liver metastases:staged, combined, or reverse strategy

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 25-34页

作者： Heather A. Lillemoe Jean-Nicolas Vauthey Department of surgical oncology The University of Texas MD Anderson Cancer CenterHoustonTXUSA

An increasing number of patients with colorectal cancer (CRC) are presenting with synchronous disease to the liver. The optimal surgical approach for this complex patient group is controversial, but ultimately depends on individual patient characteristics and institutional practices. surgical strategies include the traditional staged approach, a combined colorectal and liver resection, or a liver-first reverse approach. In this review, the authors will provide an overview of each strategy, including case examples demonstrating the benefits of the more recently described liver-first approach, while arguing for individualized planning and multidisciplinary discussion for every patient.

关键词： Synchronous colorectal liver metastases (SCRLM) liver-first reverse approach multidisciplinary discussion

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Comment on:local control and survival after induction chemotherapy and ablative radiation versus resection for pancreatic ductal adenocarcinoma with vascular involvement

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 672-674页

作者： Pauline Georges Alexandre Doussot Department of Digestive surgical oncology-Liver Transplantation Unit CHU BesanconBesanconFrance

We read with interest the study from Jolissaint et *** issued in the Annals of Surgery(1).In this single center retrospective study,the authors compared oncological outcomes in patients with pancreatic ductal adenocarcinoma(PDAC)and vascular involvement who underwent pancreatectomy(n=105)*** dose ablative radiation(A-RT,n=104).All patients received induction chemotherapy first,over a recent study period[2014-2018].While the rationale for submitting patients to pancreatectomy or A-RT was not clearly stated in the Methods section,comparison between the two groups showed that patients allocated to A-RT were frailer with higher Charlson Comorbidity indexes and Eastern Cooperative oncology Group(ECOG)scores and harbored significantly larger tumors,more often left-sided,with more arterial involvement as compared to patients in the pancreatectomy group.

关键词： involvement adenocarcinoma Surgery

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Efficacy of the fat-dissociation method for nodal harvesting in gastric cancer

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World Journal of Gastrointestinal Surgery 2020年第6期12卷 277-286页

作者： Shinichi Kinami Toshio Ohnishi Naohiko Nakamura Zhi Yong Jiang Takashi Miyata Hideto Fujita Hiroyuki Takamura Nobuhiko Ueda Takeo Kosaka Department of surgical oncology Kanazawa Medical UniversityKahoku-gunIshikawa920-0293Japan

BACKGROUND There is an increased need for accurate staging for gastric cancer ***, it is necessary to carefully examine all dissected lymph nodes for precise staging. Recently, the fat-dissociation method has been developed as a quick and accurate method for harvesting dissected lymph nodes of colorectal cancer *** To investigate the usefulness of the fat-dissociation method for harvesting dissected lymph nodes of gastric cancer *** Fifty-six resected specimens from gastric cancer patients who underwent standard curative gastrectomy and lymph node dissection at our hospital were used. Group 2 lymph nodes were separated from each specimen, and the remaining adipose tissue containing the group 1 lymph nodes was used. Some resected specimens were subjected to the fat-dissociation method. One vial of Imofully~? was dissolved in 50 m L of saline and injected into the tissue. The tissue was incubated for 1 h and the dissolved fat was removed. Subsequently, the nodes were identified, picked up with scissors, and mapped. The number of nodes in each lymphatic compartment and duration of lymph node harvest and mapping were *** The fat-dissociation method was used for 24 samples, while the conventional dissection method was used for 32 samples. The total number of harvested lymph nodes was 45.9 in the fat dissociation group and 44.3 in the control group, and there was no significant difference between the two groups. There were also no significant differences in the number of lymph nodes between the two groups based on a comparison of the lymphatic compartments. However, the total median duration of the fat-dissociation method was 38.2 min, reflecting a reduced duration of approximately 60 min compared to the control *** Based on our results, the fat-dissociation method is effective in shortening the duration of lymph node harvest in gastric cancer surgery.

关键词： Gastric cancer Lymph node dissection Staging Lymph node mapping Fatdissociationmethod Efficacy

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Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 188-193页

作者： Ramasamy Mahendran Mallika Tewari Vinod Kumar Dixit Hari Shankar Shukla Department of surgical oncology Institute of Medical Sciences Banaras Hindu University Department of Gastroenterology Institute of Medical Sciences Banaras Hindu University

Background: Enhanced recovery after surgery(ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy(PD). Methods: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube(NGT) was removed on postoperative day(POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula(POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications(defined as per the ISGPS definitions). Results: NGT was removed on POD1 in 45(90%) patients, abdominal drain removed by POD4 in 41(82%) and 43(86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three(6%) patients had delayed gastric emptying(DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay(LOS) with age( P < 0.05) and a marginal relation between LOS and postoperative albumin( P = 0.05). Conclusions: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.

关键词： Enhanced recovery protocol Pancreatic cancer Periampullary cancer Pancreaticoduodenectomy Early discharge

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To drain or not to drain after distal pancreatectomy: reflexions on the PANDORINA trial

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 675-677页

作者： Maxime Constant Alexandre Doussot Department of Digestive and surgical oncology Liver Transplantation UnitCHU BesanconBesançonFrance

We read with great interest the PANDORINA study(1).This international multicenter(mostly from the Netherlands)randomized controlled trial aimed at determining whether omitting drainage after distal pancreatectomy(DP)was equivalent in terms of complications to systematic drainage *** primary outcome was the occurrence of severe complications at 90 days defined as Dindo-Clavien grade≥*** main secondary outcome was the occurrence of grade B–C postoperative pancreatic fistula(POPF)at 90 *** both outcomes,the non-inferiority threshold was set at 8%.Randomization was performed intraoperatively,stratified by annual center volume(high volume defined as DP≥40/year)and the risk of POPF according to the distal fistula risk score(D-FRS)combining pancreas thickness(high risk,>19 mm)and main pancreatic duct diameter(high risk,>3 mm)measured both at the isthmus(2).

关键词： Drainage distal pancreatectomy(DP) randomized controlled trial

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Liver regeneration using decellularized splenic scaffold: a novel approach in tissue engineering

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Hepatobiliary & Pancreatic Diseases International 2015年第5期14卷 502-508页

作者： Jun-Xi Xiang Xing-Long Zheng Rui Gao Wan-Quan Wu Xu-Long Zhu Jian-Hui Li Yi Lv Department of Hepatobiliary Surgery First Affiliated Hospital of Xi'an Jiaotong University Department of surgical oncology Shaanxi Provincial People's Hospital

BACKGROUND： The potential application of decellularized liver scaffold for liver regeneration is limited by severe shortage of donor organs. Attempt of using heterograft scaffold is accompanied with high risks of zoonosis and immunological rejection. We proposed that the spleen, which procured more extensively than the liver, could be an ideal source of decellularized scaffold for liver regeneration. METHODS： After harvested from donor rat, the spleen was processed by 12-hour freezing/thawing ×2 cycles, then circulation perfusion of 0.02% trypsin and 3% Triton X-100 sequentially through the splenic artery for 32 hours in total to prepare decellularized scaffold. The structure and component characteristics of the scaffold were determined by hematoxylin and eosin and immumohistochemical staining, scanning electron microscope, DNA detection, porosity measurement, biocompatibility and cytocompatibility test. Recellularization of scaffold by 5×106 bone marrow mesenchymal stem cells（BMSCs） was carried out to preliminarily evaluate the feasibility of liver regeneration by BMSCs reseeding and differentiation in decellularized splenic ***： After decellularization, a translucent scaffold, which retained the gross shape of the spleen, was generated. Histological evaluation and residual DNA quantitation revealed the remaining of extracellular matrix without nucleus and cytoplasm residue. Immunohistochemical study proved the existence of collagens I, IV, fibronectin, laminin and elastin in decellularized splenic scaffold, which showed a similarity with decellularized liver. A scanning electron microscope presented the remaining three-dimensional porous structure of extracellular matrix and small blood vessels. The poros-ity of scaffold, aperture of 45.36±4.87 μm and pore rate of 80.14%±2.99% was suitable for cell engraftment. Subcutaneous implantation of decellularized scaffold presented good histocompatibility, and recellularization of the splenic scaffold demonstr

关键词： tissue engineering liver regeneration decellularized scaffold spleen bone marrow mesenchymal stem cells

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