Minimally invasive radical pancreatectomy for left-sided pancreatic cancer:Current status and future perspectives

Minimally invasive distal pancreatectomy with splenectomy has been regarded as a safe and effective treatment for benign and borderline malignant pancreatic lesions.However,its application for left-sided pancreatic cancer is still being debated.The clinical evidence for radical antegrade modular pancreatosplenectomy(RAMPS)-based minimally invasive approaches for leftsided pancreatic cancer was reviewed.Potential indications and surgical concepts for minimally invasive RAMPS were suggested.Despite the limited clinical evidence for minimally invasive distal pancreatectomy in left-sided pancreatic cancer,the currently available clinical evidence supports the use of laparoscopic distal pancreatectomy under oncologic principles in wellselected left sided pancreatic cancers.A pancreasconfined tumor with an intact fascia layer between the pancreas and left adrenal gland/kidney positioned more than 1 or 2 cm away from the celiac axis is thought to constitute a good condition for the use of margin-negative minimally invasive RAMPS.The use of minimally invasive(laparoscopic or robotic)anterior RAMPS is feasible and safe for margin-negative resection in wellselected left-sided pancreatic cancer.The oncologic feasibility of the procedure remains to be determined;however,the currently available interim results indicate that even oncologic outcomes will not be inferior to those of open radical distal pancreatosplenectomy.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy

Objective: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival.Methods: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation.Results: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age(year), symptom(no/yes), tumor size at initial diagnostic stage(cm), preoperative serum carbohydrate antigen(CA) 19-9 level after neoadjuvant treatment(<34/≥34 U/m L), and planned surgery [pancreaticoduodenectomy(PD)(pylorus-preserving PD)/distal pancreatectomy(DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration.The calibration plot showed good agreement between actual and predicted survival probabilities;the the Greenwood-Nam-D’Agostino(GND) goodness-of-fit test showed that the model was well calibrated(χ~2=8.24,P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups(P=0.044).Conclusions: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Negative oncologic impact of poor postoperative pain control in left-sided pancreatic cancer

AIMTo investigate the association between postoperative pain control and oncologic outcomes in resected pancreatic ductal adenocarcinoma (PDAC).METHODSFrom January 2009 to December 2014, 221 patients were diagnosed with PDAC and underwent resection with curative intent. Retrospective review of the patients was performed based on electronic medical records system. One patient without records of numerical rating scale (NRS) pain intensity scores was excluded and eight patients who underwent total pancreatectomy were also excluded. NRS scores during 7 postoperative days following resection of PDAC were reviewed along with clinicopathologic characteristics. Patients were stratified into a good pain control group and a poor pain control group according to the difference in average pain intensity between the early (POD 1, 2, 3) and late (POD 5, 7) postoperative periods. Cox-proportional hazards multivariate analysis was performed to determine association between postoperative pain control and oncologic outcomes.RESULTSA total of 212 patients were dichotomized into good pain control group (n = 162) and poor pain control group (n = 66). Median follow-up period was 17 mo. A negative impact of poor postoperative pain control on overall survival (OS) was observed in the group of patients receiving distal pancreatectomy (DP group; 42.0 mo vs 5.0 mo, P = 0.001). Poor postoperative pain control was also associated with poor disease-free survival (DFS) in the DP group (18.0 mo vs 8.0 mo, P = 0.001). Patients undergoing pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy (PD group) did not show associations between postoperative pain control and oncologic outcomes. Poor patients&#x02019; perceived pain control was revealed as an independent risk factor of both DFS (HR = 4.157; 95%CI: 1.938-8.915; P &#x0003c; 0.001) and OS (HR = 4.741; 95%CI: 2.214-10.153; P &#x0003c; 0.001) in resected left-sided pancreatic cancer.CONCLUSIONAdequate postoperative pain relief during the early postoperative period has important clinical implications for oncologic outcomes after resection of left-sided pancreatic cancer.

Preoperative defining system for pancreatic head cancer considering surgical resection

AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing &#x0201c;resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly&#x0201d;. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size &#x02265; 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 &#x02265; 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.

Minimally invasive vs open pancreatectomy for nonfunctioning pancreatic neuroendocrine tumors

BACKGROUND The mainstay of treating nonfunctioning-pancreatic neuroendocrine tumors(NFPNETs)is surgical resection.However,minimally invasive approaches to pancreatic resection for treating NF-PNETs are not widely accepted,and the longterm oncological outcomes of such approaches remain unknown.AIM To determine the short-and long-term outcomes of minimally invasive pancreatic resection conducted in patients with NF-PNETs.METHODS Prospective databases from Severance Hospital were searched for 110 patients who underwent curative resection for NF-PNETs between January 2003 and August 2018.RESULTS The proportion of minimally invasive surgery(MIS)procedures performed for NF-PNET increased to more than 75%after 2013.There was no significant difference in post-operative complications(P=0.654),including pancreatic fistula(P=0.890)and delayed gastric emptying(P=0.652),between MIS and open approaches.No statistically significant difference was found in disease-free survival between the open approach group and the MIS group(median follow-up period,28.1 mo;P=0.428).In addition,the surgical approach(MIS vs open)was not found to be an independent prognostic factor in treating NF-PNET patients[Exp(β)=1.062;P=0.929].CONCLUSION Regardless of the type of surgery,a minimally invasive approach can be safe and feasible for select NF-PNET patients.

International consensus statement on robotic pancreatic surgery

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of;evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

Two distinct stem cell-like subtypes of hepatocellular carcinoma with clinical significance and their therapeutic potentials

Dear Editor Hepatocellular carcinoma(HCC)is among the most com-mon cancers worldwide,causing about 600,000 deaths annully[1].In HCC,stem cell-like characteristics,which drive early recurrence and therapy resistance,are major contributors to poor prognosis[2].In this current study,we integrated and analyzed gene expression data from human fetal liver cells and primary HCC tumors(n=1231)and.uncovered two clinically and biologically distinct hepatic stem cell(HS)subtypes,potential biomarkers associated with these subtypes,and a potential new therapeutic inter-vention for these subtypes.