Developing an in vivo porcine model of duct-to-mucosa pancreaticojejunostomy (Yonsei-PJDTM)

Laparoscopic pancreaticoduodenectomy (LPD) is technically feasible, but its safety is still controversial. Pancreas texture and the small size of the main pancreatic duct indicate laparoscopic pancreaticoduodenectomy (LPD) as a challenging procedure. Thus, LPD could be a risk factor for postoperative pancreatic fistula (POPF), longer hospital stay, and delayed adjuvant chemotherapy that affects long-term oncologic outcome. So, it is important to promote education on LPD especially techniques for pancreaticojejunostomy. A porcine model for duct-to-mucosa pancreaticojejunostomy (PJ) (Yonsei-PJDTM) was developed, and details of the model will be described in this report.ope

Extremely high white blood cell counts on postoperative day 1 do not predict severe complications following distal pancreatectomy

BACKGROUNDS/AIMS: Distal pancreatectomy(DP) is associated with high morbidity. In clinical practice, postoperative white blood cell(WBC) counts are useful indicators of infection complications. The aim of this study was to determine the relevance of extremely high postoperative day (POD)1 WBC counts after DP and their relationship to perioperative outcomes. METHODS: From December 2005 to December 2016, data from patients who had open or minimally invasive DP surgery (robot or laparoscopy, MIS) for benign or borderline malignant tumors were retrospectively reviewed. Patients were divided into groups based on POD1 WBC count (>20K, High and <20K, Low) for comparisons. RESULTS: Twelve patients (4.6%) were categorized into the High group. There were significant differences in age (p=0.019), BMI (p=0.010), and spleen-preserving rate (p=0.002) between the High and Low groups. In binary logistic regression analysis, the risk factors for severe complication was age (p=0.032) and open DP (p=0.005), not POD1 WBC count. CONCLUSIONS: Extremely high WBC count after POD1 after DP was not associated with severe complications, but was associated with splenectomy. Surgical methods and age were associated with severe complications.ope

Diagnostic performance enhancement of pancreatic cancer using proteomic multimarker panel

Due to its high mortality rate and asymptomatic nature, early detection rates of pancreatic ductal adenocarcinoma (PDAC) remain poor. We measured 1000 biomarker candidates in 134 clinical plasma samples by multiple reaction monitoring-mass spectrometry (MRM-MS). Differentially abundant proteins were assembled into a multimarker panel from a training set (n=684) and validated in independent set (n=318) from five centers. The level of panel proteins was also confirmed by immunoassays. The panel including leucine-rich alpha-2 glycoprotein (LRG1), transthyretin (TTR), and CA19-9 had a sensitivity of 82.5% and a specificity of 92.1%. The triple-marker panel exceeded the diagnostic performance of CA19-9 by more than 10% (AUCCA19-9 = 0.826, AUCpanel= 0.931, P < 0.01) in all PDAC samples and by more than 30% (AUCCA19-9 = 0.520, AUCpanel = 0.830, P < 0.001) in patients with normal range of CA19-9 (<37U/mL). Further, it differentiated PDAC from benign pancreatic disease (AUCCA19-9 = 0.812, AUCpanel = 0.892, P < 0.01) and other cancers (AUCCA19-9 = 0.796, AUCpanel = 0.899, P < 0.001). Overall, the multimarker panel that we have developed and validated in large-scale samples by MRM-MS and immunoassay has clinical applicability in the early detection of PDAC.ope

Potential Nutritional and Metabolomic Advantages of High Fat Oral Supplementation in Pancreatectomized Pancreaticobiliary Cancer Patients

We examined the effect of high fat oral nutritional supplement (HFS) on the nutritional status, oral intake, and serum metabolites of postoperative pancreaticobiliary cancer patients. Pancreaticobiliary cancer patients were voluntarily recruited. The HFS group received postoperative oral high fat supplementation (80% of total calories from fat; n = 12) until discharge; the control group (non-HFS; n = 9) received none. Dietary intake, anthropometry, blood chemistry, nutritional risk index (NRI), and serum metabolites analyzed by liquid chromatography tandem mass spectrometry were evaluated. Overall, cumulative caloric supply via parental and oral/enteral routes were not different between groups. However, oral fat intake, caloric intake, and NRI scores of the HFS group were higher than those of the non-HFS group with increased oral meal consumption. Oral caloric, fat, and meal intakes correlated with NRI scores. Metabolomics analysis identified 195 serum metabolites pre-discharge. Oral fat intake was correlated with 42 metabolites relevant to the glycerophospholipid pathway. Oral high fat-specific upregulation of sphingomyelin (d18:1/24:1), a previously reported pancreatic cancer-downregulated metabolite, and lysophosphatidylcholine (16:0) were associated with NRI scores. Provision of HFS in postoperative pancreatic cancer patients may facilitate the recovery of postoperative health status by increasing oral meal intake, improving nutritional status, and modulating serum metabolites.ope

Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data

Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1-25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9-31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3-18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4-18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3-34.2) vs. 16.2 months (95% CI 7·9-24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.ope

Minimally Invasive (Laparoscopic or Robotic) Reduced Port (Single Port) Distal Pancreatectomy

In spite of lack of randomized control study, laparoscopic distal pancreatectomy (DP) is regarded as appropriate treatment in managing benign and low grade malignant tumor in distal part of the pancreas. With the advance of laparoscopic skills, innovative instruments, and perioperative management, clinical effort to reduce the access injury for laparoscopic DP has been attempted to enhance the cosmetic effect and the benefit of minimally invasive surgery. Due to inborn technical limitation of laparoscopic surgical system, it is not easy to perform laparoscopic reduced port-or single port-distal pancreatectomy (LRP/LSP-DP) in daily routine clinical practice, however, surgical technique for safe and effective LRP/LSP-DP has been developed. Till now, only a few experts reported the technical feasibility and safety of LRP/LSP-DP in selected patients. According to literature review, the number of the patients who underwent LRP/LSP-DP seems to gradually increase. In this moment, surgical experiences may be too limited to reach the conclusion, but, with the help of robotic surgical system, LRP/LSP-DP has potential room for further investigation. Therefore, minimally invasive surgeons need to pay attention to this innovative movement. In this review, currently available surgical techniques for LRP/LSP-DP has been summarized with some future perspectives on this technique.ope

Should Lymph Nodes Be Retrieved in Patients with Intrahepatic Cholangiocarcinoma? A Collaborative Korea-Japan Study

Background: This study was performed to investigate the oncologic role of lymph node (LN) management and to propose a surgical strategy for treating intrahepatic cholangiocarcinoma (IHCC). Methods: The medical records of patients with resected IHCC were retrospectively reviewed from multiple institutions in Korea and Japan. Short-term and long-term oncologic outcomes were analyzed according to lymph node metastasis (LNM). A nomogram to predict LNM in treating IHCC was established to propose a surgical strategy for managing IHCC. Results: A total of 1138 patients were enrolled. Of these, 413 patients underwent LN management and 725 did not. A total of 293 patients were found to have LNM. The No. 12 lymph node (36%) was the most frequent metastatic node, and the No. 8 lymph node (21%) was the second most common. LNM showed adverse long-term oncologic impact in patients with resected IHCC (14 months, 95% CI (11.4-16.6) vs. 74 months, 95% CI (57.2-90.8), p < 0.001), and the number of LNM (0, 1-3, 4≤) was also significantly related to negative oncologic impacts in patients with resected IHCC (74 months, 95% CI (57.2-90.8) vs. 19 months, 95% CI (14.4-23.6) vs. 11 months, 95% CI (8.1-13.8)), p < 0.001). Surgical retrieval of more than four (≥4) LNs could improve the survival outcome in resected IHCC with LNM (13 months, 95% CI (10.4-15.6)) vs. 30 months, 95% CI (13.1-46.9), p = 0.045). Based on preoperatively detectable parameters, a nomogram was established to predict LNM according to the tumor location. The AUC was 0.748 (95% CI: 0.706-0.788), and the Hosmer and Lemeshow goodness of fit test showed p = 0.4904. Conclusion: Case-specific surgical retrieval of more than four LNs is required in patients highly suspected to have LNM, based on a preoperative detectable parameter-based nomogram. Further prospective research is needed to validate the present surgical strategy in resected IHCC.ope

What We Learned from the Experience of an Introduction to Surgery Class for First Grade Premedical Students

Purpose : In order to enhance the goal of premedical education, we developed new clinical educational course of surgery for first-grade premedical students. Methods : In 2015, from September 4th to December 18th, the educational performance records of first-grade premedical students were evaluated, who attended the new, optional major class Introduction to surgery for future doctors. The non-compliance score was calculated as the sum of the total frequency of absences, number of late arrivals to class, and failure to submit the pre-lecture homework. This score was correlated with students’ educational performance records. The premedical students’ feed-back about this new class was summarized. RESULTS : Among 79 first-grade premedical students at Yonsei University College of Medicine, 43 premedical students (54.4%) chose to attend the new class. Premedical students’ individual non-compliance scores were inversely and significantly correlated to written test performance (R2=0.237, p=0.001). In survey analysis, the mean score for premedical students’ course satisfaction was 8.6. They strongly suggested this new educational course should be continued for first-grade premedical students with a mean rating of 9.1. Premedical students were very impressed and satisfied by laparoscopic surgical simulation and visiting the operating room, with ratings of 9.7 and 9.3, respectively. Conclusion : This class is the first movement to introduce the surgery to the premedical students in Yonsei University. In spite of their scanty medical knowledge, this clinical class can provide positive influence on educational motivation as premedical students. Further modification of this class is mandatory based on what we learned from this educational experience.ope

Postoperative serum metabolites of patients on a low carbohydrate ketogenic diet after pancreatectomy for pancreatobiliary cancer: a nontargeted metabolomics pilot study

A ketogenic diet is a potential adjuvant cancer therapy that limits glucose availability to tumours while fuelling normal tissues with ketone bodies. We examined the effect of a low carbohydrate ketogenic diet (LCKD) (80% kcal from fat, ketogenic ratio 1.75:1, w/w) compared to a general hospital diet (GD) on serum metabolic profiles in patients (n = 18, ≥ 19 years old) who underwent pancreatectomy for pancreatobiliary cancer. Serum samples collected preoperatively (week 0) and after the dietary intervention (week 2) were analysed with a nontargeted metabolomics approach using liquid chromatography-tandem mass spectrometry. Serum β-hydroxybutyrate and total ketone levels significantly increased after 2 weeks of LCKD compared to GD (p < 0.05). Principal component analysis score plots and orthogonal partial least squares discriminant analysis also showed significant differences between groups at week 2, with strong validation. In all, 240 metabolites differed between LCKD and GD. Pathways including glycerophospholipid and sphingolipid metabolisms were significantly enriched in the LCKD samples. LCKD decreased C22:1-ceramide levels, which are reported to be high in pancreatic cancer, while increasing lysophosphatidylcholine (18:2), uric acid, citrulline, and inosine levels, which are generally low in pancreatic cancer. Postoperative LCKD might beneficially modulate pancreatic cancer-related metabolites in patients with pancreatobiliary cancer.ope

Single-Port Laparoscopic and Robotic Cholecystectomy in Obesity (>25 kg/m2)

BACKGROUND AND OBJECTIVES: Single-port cholecystectomy has emerged as an alternative technique to reduce the number of ports and improve cosmesis. Few previous studies have assessed obesity-related surgical outcomes following single-port cholecystectomy. In this study, technical feasibility and surgical outcomes of single-port laparoscopic cholecystectomy (SPLC) and robotic single-site cholecystectomy (RSSC) in obese patients were investigated. METHODS: We conducted a two-center collaborative study and retrospectively reviewed initial experiences of RSSC and SPLC in patients whose body mass index was over 25 kg/m2. Medical records of patients were reviewed. Clinical characteristics and short-term oncologic outcomes were considered and compared between SPLC and RSSC groups. RESULTS: RSSC and SPLC were performed in 39 and 78 patients, respectively. In comparative analysis, the total operative time was longer in the RSSC group (109.92 minutes vs. 60.99 minutes; P .05). CONCLUSIONS: SPLC and RSSC could be safely performed in selected patients with high body mass index, showing no significant clinical differences.ope