Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Evaluation of quality of clinical management of neuroendocrine tumors.

Background: Neuroendocrine tumors (NETs) are a group of biologically and clinically heterogeneous neoplasms predominantly found in the gastrointestinal and bronchopulmonary tractus. Despite a rising incidence, implementation of evidence-based standardized care for this heterogenous group remains challenging. The European Neuroendocrine Tumor Society regularly reviews guidelines regarding diagnostic and treatment strategies for NETs. The aim of this study is to shed light on the care of patients with a NET in Belgian Limburg, to provide data as a basis for future studies and to check whether data and results are according to consensus guidelines and outcomes described in literature. Methods: Our study concerned a detailed observational data collection of two large Belgian hospitals (Jessa Hospital Hasselt and Hospital Oost-Limburg Genk) with special interest in patient profile, quality of pathology reports, use of diagnostic imaging, and overall survival. Data on 188 patients were assembled between January 2010 and December 2014 with follow-up until June 2016 (median follow-up: 33.6 months). Results: Fifty percent of patients were male. NETs were located mainly in the digestive tract (63.8%) and lung (20.2%). Appendiceal NETs were diagnosed at a significantly younger age than other tumors (41.3 vs. 64.0 years). Overall, a mean pathology report quality score of 3.0/5 was observed with the highest scores for small bowel NETs. Diagnostic and nuclear imaging was performed in 74.5% and 29.8% of cases, respectively. Seventy-four percent of the population survived until the end of the observation period with highest survival rates for appendiceal and small bowel NETs. Conclusion: Overall, epidemiological results were comparable with findings in the literature. Gastrointestinal NETs met most of the requirements of qualitative pathology reporting and diagnostic imaging as listed in the European Neuroendocrine Tumor Society consensus guidelines. However, consensus with regard to bronchopulmonary NETs is still scarce and remains an objective for future research. Moreover, discussing treatment strategies in specialized multidisciplinary tumor boards would facilitate regional care.

Comparison of the Clavien-Dindo and Comprehensive Complication Index systems for grading of surgical complications after colorectal resections.

INTRODUCTION: Postoperative complications are associated with prolonged hospital stay and a rise in costs of treatment. The Comprehensive Complication Index (CCI) was developed as a scoring system that does not only take the most severe complication into account but all complications after surgery. Our aim was to compare the Clavien-Dindo scoring system with the CCI in predicting length of hospital stay (LOHS) and in-hospital costs after colorectal resections. METHODS: Complications occurring after surgical procedures, performed between October 2012 and September 2013, were prospectively recorded. During this period 164 patients developed complication(s). Only patients that underwent a colorectal resection were included. Multivariable linear regression analysis was performed to find independent predictors of in-hospital costs and LOHS. RESULTS: 64 patients (age (range): 69 (10-91) years, M/F: 36/28) were retained. 46 (71.9%) patients had a Clavien-Dindo score ≥ IIIb. Median (IQR) CCI was 40 (30.2-53.9). Mean (±SD) in-hospitals costs for all patients were €12,920 ± €10,229. The adjusted difference (95% CI, p-value) in in-hospital costs for minor and major (Clavien-Dindo ≥ IIIb) complications was 10,021 (€4283 to €15,759, p = 0.001). A 10 point increase in CCI increased in-hospital costs by €2040. Multivariable analysis retained CCI > 40 as the only independent risk factor for increased in-hospital costs (Standard Beta Coeffic (p-value): 8063 (p = 0.022). CONCLUSION: CCI is a better predictor of in-hospital costs than Clavien-Dindo score to classify complications after colorectal resections, as it captures all complications. Further research is warranted to extrapolate our findings to other sub-specialities of surgery.

Perioperative radiotherapy is an independent risk factor for major LARS: a cross-sectional observational study.

PURPOSE: Sphincter-preserving surgery for rectal cancer is often associated with low anterior resection syndrome (LARS). The aim of our study was to determine the prevalence of LARS in our institution and identify possible risk factors for LARS. Furthermore, we evaluated which of the LARS symptoms was considered most disabling by patients and whether or not there is an adaptation of the LARS score over time. METHODS: This study includes a prospective database of 100 patients who underwent total or partial mesorectal excision between January 2009 and September 2014. Patients were contacted after a median postoperative time of 38 (5-45) months to determine the LARS score and to identify LARS symptoms that were considered most disabling. Uni- and multivariate regression analysis was performed to identify risk factors for LARS and major LARS. Finally, the LARS score was evaluated over time after restoration of bowel continuity. RESULTS: Out of the 100 patients, 16 had minor LARS (score 21-29) and 51 patients had major LARS (score 30-42). Radiotherapy was an independent risk factor for major LARS (p = 0.04). For the majority of patients with major LARS (22%), fragmentation was considered the most disabling complaint. There was no correlation between interval after restoration of bowel continuity and the severity of the LARS score. CONCLUSIONS: Perioperative radiotherapy is an independent risk factor for major LARS. Fragmentation is considered the most disabling complaint in the majority of patients with major LARS. There is no significant adaptation of the LARS score over time.

The interval approach: an adaptation of the liver-first approach to treat synchronous liver metastases from rectal cancer.

BACKGROUND: The waiting interval after chemoradiotherapy (CRT) is an interesting therapeutic window to treat patients with synchronous liver metastases (SLM) from rectal cancer. METHODS: A retrospective analysis was performed of 18 consecutive patients (M/F 10/8, age (range) 60 (51-75) years) from five institutions who underwent liver resection of SLM during the waiting interval after CRT for rectal adenocarcinoma. RESULTS: All patients underwent interval liver surgery for a median (range) of 4 (2-14) liver metastases. Metastases involved a median (range) of 4 (1-7) liver segments. Median (range) time between end of CRT and liver surgery was 22 (6-45) days. Laparoscopic liver surgery was performed in 12 (67%) patients. No severe complications (Clavien-Dindo ≥ 3b) occurred after liver surgery. Median (range) length of hospital stay after liver surgery was 5 (1-10) days. All patients subsequently underwent rectal resection at a median (range) of 10 (8-13) weeks after end of CRT. Median (IQR) time-to-progression after liver surgery was 4.2 (2.8-9.2) months. CONCLUSIONS: The waiting interval after neoadjuvant CRT is a valuable option to treat SLM from rectal cancer. More data are necessary to confirm its oncological efficacy.

Central Venous Pressure Drop After Hypovolemic Phlebotomy is a Strong Independent Predictor of Intraoperative Blood Loss During Liver Resection.

BACKGROUND: Intraoperative hypovolemic phlebotomy (HP) has been suggested to reduce central venous pressure (CVP) before hepatectomy. This study aimed to analyze the impact of CVP drop after HP on intraoperative blood loss and postoperative renal function. METHODS: A retrospective review of a prospective database including 100 consecutive patients (43 males and 57 females; mean age, 65 years; range 23-89 years) undergoing liver resection with HP was performed. The primary outcome variable was estimated blood loss (EBL), and the secondary outcome was postoperative serum creatinin (Scr). A multivariate linear regression analysis was performed to identify predictors of intraoperative blood loss. RESULTS: The median CVP before blood salvage was 8 mmHg (range 4-30 mmHg). The median volume of hypovolemic phlebotomy was 400 ml (range 200-1000 ml). After HP, CVP decreased to a median of 3 mmHg (range -2 to 16 mmHg), resulting in a median CVP drop of 5.5 mmHg (range 2-14 mmHg). The median EBL during liver resection was 165 ml (range 0-800 ml). The median preoperative serum creatinin (Scr) was 0.82 g/dl (range 0.5-1.74 g/dl), and the postoperative Scr on day 1 was 0.74 g/dl (range 0.44-1.68 g/dl). The CVP drop was associated with EBL (P < 0.001). There was no significant impact of CVP drop on postoperative Scr. CONCLUSION: A CVP drop after HP is a strong independent predictor of EBL during liver resection. The authors advocate the routine use of HP to reduce perioperative blood loss and transfusion rates in liver surgery. As a predictive tool, CVP drop might help surgeons decide whether a laparoscopic approach is safe.

The practice of laparoscopic liver surgery in Belgium: a national survey.

BACKGROUND: Laparoscopic liver surgery (LLS) gained popularity bringing several advantages including decreased morbidity and reduction of length of hospital stay compared to open. METHODS: To understand practice and evolution of LLS in Belgium, a 20-questions survey was sent to all members of the Royal Belgian Society for Surgery, the Belgian Section of Hepato-Pancreatic and Biliary Surgery and the Belgian Group for Endoscopic Surgery. RESULTS: Thirty-seven surgical units representing 61 surgeons performing LLS in Belgium responded: 50% from regional hospitals, 28% from university and 22% from peripheral hospitals. Replies from high volume centers (>50 liver-surgery/year) were 19%. More than 25% of liver procedures were performed laparoscopically in 35% of centers. LLS is adopted since more than 15-years in 14.5% of centers with an increasing rate reported in 59%. Low relevance of LLS in the hospital organization (26.5%) and lack of time in surgical schedules (12%) or of specific training (9%) are the main barriers for further diffusion. More than 80% of the responders agreed to participate to a national prospective registry. CONCLUSION: LLS is mainly performed in experienced HPB units with an increasing interest in peripheral centers. A prospective national registry will be useful by providing real data in terms of indications, morbidity and overall evolution.

A survey of European-African surgeons' management of common bile duct stones.

BACKGROUND: Common bile duct (CBD) stones can be managed by either endoscopic retrograde cholangiopancreatography (ERCP) or laparoscopic common bile duct exploration (LCBDE). The aim of this survey was to document the management of CBD stones by European-African HPB Association (E-AHPBA) members. METHODS: All 331 members of the E-AHPBA were invited by personal email to participate to an online survey. RESULTS: Ninety-three (28%) surgeons replied within 2 months. Responding surgeons were attending surgeons (84%), working as HPB surgeons (75%) in academic hospitals (73%). In patients with clinically suspected CBD stones, MRCP was the preferred diagnostic test for 61% of respondents. LCBDE was the preferred therapeutic strategy for 11 (12%) respondents only. Previous gastric surgery was an absolute contraindication to ERCP for 47% of respondents. Absence of CBD dilation was considered an absolute contraindication for LCBDE in 24% of respondents. Yearly caseload exceeded 10 patients for only 30% of 56 centers performing LCBDE. The transcystic approach was preferred by 39% of surgeons performing LCBDE. There was considerable variation amongst respondents with regard to type and duration of drainage, bile duct closure technique and follow-up after LCBDE. CONCLUSION: Indications for single-stage LCBDE are not standardized and do not appear well established across E-AHPBA members.

CT diagnosis of a post-embolization ischemic diverticulitis of Meckel.

A 23-year-old man presented with hypovolemic shock due to a lower gastrointestinal bleeding. Radiological and endoscopic investigation did not reveal the bleeding site. Emergency visceral angiography showed contrast extravasation at a right-sided branch of the superior mesenteric artery (SMA). Embolization of the bleeding point was performed, resulting in bleeding cessation. One week later, the patient presented with a new episode of moderate anal blood loss associated with diffuse abdominal pain. Computed tomography (CT) revealed an ischemic small bowel diverticulum that was treated by a laparoscopically-assisted segmental small bowel resection. Intraoperative and pathologic analysis confirmed a post-embolization ischemic diverticulitis of Meckel.

ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors compared with conventional-staged hepatectomies: results of a multicenter analysis.

BACKGROUND: Portal vein occlusion to increase the size of the future liver remnant (FLR) is well established, using portal vein ligation (PVL) or embolization (PVE) followed by resection 4-8 weeks later. Associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) combines PVL and complete parenchymal transection, followed by hepatectomy within 1-2 weeks. ALPPS has been recently introduced but remains controversial. We compare the ability of ALPPS versus PVE or PVL for complete tumor resection. METHODS: A retrospective review of all patients undergoing ALPPS or conventional staged hepatectomies using PVL or PVE at four high-volume HPB centres between 2003 and 2012 was performed. Patients with primary liver tumors and liver metastases were included. Primary endpoint was complete tumor resection. Secondary endpoints include 90-day mortality, complications, FLR increase, time to resection, and tumor recurrence. RESULTS: Forty-eight patients with ALPPS were compared with 83 patients with conventional-staged hepatectomies. Eighty-three percent (40/48 patients) of ALPPS patients achieved complete resection compared with 66 % (55/83 patients) in PVE/PVL (odds ratio 3.34, p = 0.027). Ninety-day mortality in ALPPS and PVE/PVL was 15 and 6 %, respectively (p = 0.2). Extrapolated growth rate was 11 times higher in ALPPS (34.8 cc/day; interquartile range (IQR) 26-49) compared with PVE/PVL (3 cc/day; IQR2-6; p = 0.001). Tumor recurrence at 1 year was 54 versus 52 % for ALPPS and PVE/PVL, respectively (p = 0.7). CONCLUSIONS: This study provides evidence that ALPPS offers a better chance of complete resection in patients with primarily unresectable liver tumors at the cost of a high mortality. The technique is promising but should currently not be used outside of studies and registries.

Hepatic Artery Embolization prior to En Bloc Resection of an Encased Common Hepatic Artery in Adenocarcinoma of the Head of the Pancreas.

A 64-year-old female patient with adenocarcinoma of the head of the pancreas with encasement of the common hepatic artery and portal vein stenosis was reexplored after six cycles of gemcitabine (1000 mg/m(2)). Prior to surgery, the patient underwent balloon dilation and stenting of the portal vein in addition to successful coil embolisation of the common hepatic artery, proper hepatic artery, and proximal gastroduodenal artery. After embolisation, a pylorus-preserving pancreaticoduodenectomy was performed with resection of the common hepatic artery and portal vein confluens. Pathological examination showed a moderately differentiated pT3N0 (Stage IIa, TNM 7th edition) tumor with negative section margins. We show with this case that in selected cases of periampullary cancer with encasement of the common hepatic artery, it is technically feasible to perform pancreaticoduodenectomy with hepatic artery resection and negative surgical margins. Nevertheless, the oncological benefit of extended arterial resections remains controversial.

Extended lymphadenectomy in patients with pancreatic cancer is debatable.

Lymph node staging is one of the most important factors in determining the prognosis after resection of pancreatic ductal adenocarcinoma. Despite ongoing efforts to further refine lymph node staging, the debate on the extent of lymphadenectomy during pancreaticoduodenectomy is still open. The purpose of this review was to summarize the evidence about performing standard lymphadenectomy during curative resection of pancreatic cancer. All four prospective randomized controlled trials published concluded that extended lymphadenectomy does not contribute to better oncologic outcome for patients with adenocarcinoma of the pancreatic head. Indeed, one major drawback of extended lymphadenectomy is the higher risk of persistent postoperative diarrhea. No prospective randomized studies could be found on the role of extended lymphadenectomy in patients with adenocarcinoma of the corpus and tail. Based on current evidence there is no indication that extended lymphadenectomy should be performed routinely during resection of pancreatic cancer.

Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.

BACKGROUND: Most cancer deaths are caused by metastases, resulting from circulating tumor cells (CTC) that detach from the primary cancer and survive in distant organs. The aim of the present study was to develop a CTC gene signature and to assess its prognostic relevance after surgery for pancreatic ductal adenocarcinoma (PDAC). METHODS: Negative depletion fluorescence activated cell sorting (FACS) was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumour (T), and non-tumoural pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. 'Ingenuity Pathway Analysis' software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). RESULTS: Using stringent statistical analysis, we retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway, TGF-ß1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were overexpressed in CTC. High co-expression of TGF-ß1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 6 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 - 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 - 1.861)). CONCLUSIONS: Pancreatic CTC isolated from blood samples using FACS-based negative depletion, express a cell motility gene signature. Expression of this newly defined cell motility gene signature in the primary tumour can predict survival of patients undergoing surgical resection for pancreatic cancer. TRIAL REGISTRATION: Clinical trials.gov NCT00495924.

Prophylactic cholecystectomy, a mandatory step in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass?

BACKGROUND: The aim of this study was to determine the incidence of symptomatic gallstone disease requiring cholecystectomy (CCE) after laparoscopic Roux-en-Y gastric bypass (LRYGBP) and to identify the peri-operative risk factors associated with postoperative symptomatic gallstone disease. METHODS: Between August 2003 and November 2009, 724 patients underwent LRYGBP at the Groeninge Hospital. Preoperative ultrasound was performed in 600 of 641 patients without history of CCE and 120 (20.0%) were diagnosed with cholecystolithiasis. RESULT: Six hundred twenty-five patients were included, 43(6.9%) developed delayed symptoms related to biliary disease. Of these 43 patients, 39 underwent post-LRYGBP CCE. Of these 39 patients, 9 (7.5%) had a positive ultrasound prior to LRYGBP. Multivariate analysis identified weight loss at 3 months post-LRYGB of more than 50% of excess weight [HR (95% CI), 2.04 (1.04-4.28); p = 0.037) as the sole significant independent predictor of delayed symptomatic cholecystolithiasis. CONCLUSIONS: Symptomatic gallstone disease occurred only in 6.9% of patients post-LRYGBP. Multivariate analysis identified weight loss at 3 months post-LRYGBP of more than 50% of excess weight as the sole significant independent predictor of delayed symptomatic cholecystolithiasis. Prophylactic CCE should not be recommended at the time of LRYGBP.

Perioperative cancer cell dissemination detected with a real-time RT-PCR assay for EpCAM is not associated with worse prognosis in pancreatic ductal adenocarcinoma.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) has been used as surrogate marker for the quantification of circulating tumour cells (CTC). Our aim was to prospectively study the value of a real-time RT-PCR assay for EpCAM detection in the peripheral blood and peritoneal cavity of patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: From 48 patients with PDAC (40 resectable, 8 unresectable) and 10 patients with chronic pancreatitis undergoing pancreatectomy 10 ml of venous blood was drawn preoperatively (PB) and postoperatively (POB, day 1 (D1B), day 7 (D7B) and after 6 weeks (6WB). Of all patients undergoing pancreatectomy, 40 ml peritoneal lavage fluid was taken preoperatively and postoperatively. A real-time RT-PCR assay (TaqMan, ABI Prism 7700) was developed for the detection of EpCAM mRNA. To discriminate between EpCAM-positive and negative samples a cut-off was applied. Median postoperative follow-up was 24.0 months (range: 0.7-41.3). RESULTS: PB was EpCAM-positive+ in 25% of patients versus 65% of patients in POB (p < 0.0001). EpCAM+ was noted at D1B, D7B and 6WB was found in 28.6%, 23.1% and 23.5% of patients respectively. Preoperative peritoneal lavage fluid was EpCAM+ in 10.3% versus 53.8% of patients postoperatively (p < 0.0001). At none of the time-points, an association was found between EpCAM positivity in blood and/or peritoneal cavity and cancer-specific or disease-free survival. Also, no significant associations were found between clinicopathological variables and perioperative EpCAM positivity. CONCLUSIONS: Despite a significant increase in EpCAM counts in postoperative blood and peritoneal lavage fluid this was not associated with worse prognosis after pancreatectomy for PDAC. TRIAL REGISTRATION: Clinicaltrials.gov NCT00495924.

Reversed arthroscopic subacromial decompression for symptomatic irreparable rotator cuff tears: mid-term follow-up results in 34 shoulders.

BACKGROUND: In the elderly, there is no guideline for the treatment of irreparable rotator cuff lesions. The results of open or arthroscopic repair are variable. We hypothesized that the use of a reversed arthroscopic subacromial decompression (RASD) would yield comparable results. MATERIAL AND METHODS: Between January 2004 and December 2006, thirty-eight patients underwent a RASD for irreparable cuff tears in 39 shoulders. The surgical procedure consisted of a tenotomy of the long head of the biceps tendon, a debridement of the torn rotator cuff and a tuberoplasty, without violation of the coracoacromial arch and the acromion. RESULTS: Thirty-three patients (age 69.9 +/- 7.3 years) were available for clinical and radiological evaluation of 34 shoulders (male/female ratio: 11/22), at a mean follow-up of 38 months (range: 21 months-52 months). Two of 33 patients had required revision surgery, and were excluded from further statistical analysis. In the remaining 31 patients (32 shoulders), the modified Constant-Murley score (CMS) improved from 34.9% +/- 11.6 to 84.0% +/- 11.6 (p < 0.0001). The preoperative mobility did not correlate with the final result. Preoperative pain was found to correlate negatively to the modified CMS at follow-up (p= 0.0038). Although the acromiohumeral height decreased with 2.58 mm +/- 1.68 and the severity of glenohumeral osteoarthritis increased with one grade (Samilson-Prieto classification), there was no correlation with the functional outcome. CONCLUSION: We conclude that for irreparable rotator cuff tears in the elderly, excellent mid-term results can be achieved with a RASD.

Prognostic relevance of extracapsular lymph node involvement in pancreatic ductal adenocarcinoma.

BACKGROUND: In several malignancies extracapsular lymph node involvement (ECLNI) identifies a subgroup of patients with worse prognosis but no data are available on its significance in pancreatic ductal adenocarcinoma (PDAC). The aim of our study was to assess the prognostic relevance of ECLNI in resectable PDAC. METHODS: A retrospective analysis was performed of 137 consecutive pancreatic resections for PDAC. Two investigators blinded for survival data systematically reviewed all pathological data. Survival curves were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of disease-free survival (DFS) and overall survival (OS). The median follow-up after surgery was 19 months. RESULTS: ECLNI was identified in 59 of 99 node-positive patients. The median DFS in patients with ECLNI vs. intracapsular LNI (ICLNI) was 6.8 vs. 12.0 months, respectively (P=.027). The median OS in patients with ECLNI vs. ICLNI was 16.1 and 21.8 months, respectively (P=.098). On multivariable analysis extracapsular lymph node ratio (ECLNR) was identified as an independent predictor of OS (P=.003). In patients with ECLNI, both OS and DFS were improved after adjuvant chemoradiation compared with those who did not receive adjuvant treatment (P=.01). CONCLUSIONS: Extracapsular lymph node ratio is an independent predictor of survival in patients with PDAC. Patients with ECLNI from pancreatic cancer seem to benefit from adjuvant chemoradiation but not from chemotherapy alone.

Role of cancer stem cells in pancreatic ductal adenocarcinoma.

As our understanding of pancreatic cancer evolves, evidence is growing to support a role for cancer stem cells in this devastating disease. Cancer stem cells constitute a distinct subpopulation in the tumor and are considered to drive both tumorigenesis and metastasis; these cells are thought to be highly resistant to standard treatment modalities. Here we review the current knowledge on pancreatic cancer stem cells and the implementation of cancer stem cell markers as prognostic or predictive biomarkers. We also discuss prospects for the use of cancer stem cells as targets for future therapeutic regimens in pancreatic cancer.