Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry.

BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4-11] vs. 12 [10-18], 12 [8-19] or 12 [9-17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien-Dindo grade ≥ IIIa) complications (OR 0.49 [95% CI 0.25-0.96], P = 0.037), whereas-compared to exploration only-biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48-8.64], P = 0.005; 3.50 [1.39-8.81], P = 0.008; 4.96 [2.15-11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered.

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc.

Isolated pulmonary metastases define a favorable subgroup in metastatic pancreatic cancer.

PURPOSE: Liver metastasis represents the first site of dissemination in >80% of metastatic pancreatic cancer (PC) patients. Pulmonary metastasis as first site of dissemination in PC is a rare event and might define a biologically distinct subgroup in metastatic PC. METHODS: Consecutive PC patients who were diagnosed or treated with isolated pulmonary metastases at our high-volume comprehensive cancer center were included in a prospectively maintained database between 2002 and 2015. Medical records and correlating computed tomography findings (CT) were retrospectively analyzed. RESULTS: A total of 40 PC patients with isolated pulmonary metastases were identified. Pulmonary metastases represented disease recurrence after initial resection of PC in 22 patients and disease progression of locally advanced pancreatic cancer in 5 patients. 14 out of 27 PC patients (56%) had received chemoradiotherapy for localized disease prior to pulmonary metastasis. Data on 1st-line treatment for pulmonary metastases was available for 38 patients: most patients (71%) received a gemcitabine-based chemotherapy regimen, 5 patients (13%) received best supportive care. After a median follow-up of 37.3 months, median survival after diagnosis of pulmonary metastasis was estimated with 25.5 months (95% CI 19.1-31.8); a significantly improved survival after diagnosis of pulmonary metastasis was observed for patients with less than 10 lung metastases (31.3 vs 18.7 months, p = 0.003) and for an unilateral localization of lung involvement (31.3 vs 21.8 months, p = 0.03). CONCLUSIONS: Our results suggest a favorable outcome of PC patients with isolated pulmonary metastases. Further research is warranted to elucidate the specific molecular characteristics of this rare subgroup.

Autologous but not Fibrin Sealant Patches for Stump Coverage Reduce Clinically Relevant Pancreatic Fistula in Distal Pancreatectomy: A Systematic Review and Meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) causes significant morbidity and mortality after distal pancreatectomy. Patch coverage of the pancreatic stump is often used with the intention to prevent POPF. Despite numerous investigations, the effects of patch coverage remain unclear. The present meta-analysis aims to clarify the effects of patch coverage in distal pancreatectomy on the incidence of POPF. METHODS: A systematic search of MEDLINE/PubMed and the Cochrane Database according to the PRISMA Statement was performed. Subsequently a meta-analysis on rates and overall incidence of POPF and length of hospital stay was carried out. By applying the inverse variance weighting method, the combined effect size and 95 % confidence interval were calculated. Heterogeneity was assessed using I 2 statistics. RESULTS: Five randomized controlled trials and six observational clinical studies were included for final analysis. A cumulative incidence of 43 % of POPF grades A-C was identified. Patch coverage in distal pancreatectomy is significantly associated with a decreased rate of POPF grade C (p = 0.006). Patches of autologous vascularized tissue significantly reduce the overall incidence of POPF (p = 0.04) and clinically relevant POPF grade B and C (p = 0.002). Fibrin sealant patches do not influence rates of POPF after distal pancreatectomy. None of the outcomes evaluated showed adverse results for the patch group. CONCLUSIONS: Patch coverage after distal pancreatectomy can reduce the rate of POPF. Patch coverage with autologous vascularized tissue but not fibrin sealant patches may be used to reduce clinically relevant POPF and postoperative morbidity in distal pancreatectomy.

Temporary Intraoperative Porto-Caval Shunts in Piggy-Back Liver Transplantation Reduce Intraoperative Blood Loss and Improve Postoperative Transaminases and Renal Function: A Meta-Analysis.

BACKGROUND: The value of temporary intraoperative porto-caval shunts (TPCS) in cava-sparing liver transplantation is discussed controversially. Aim of this meta-analysis was to analyze the impact of temporary intraoperative porto-caval shunts on liver injury, primary non-function, time of surgery, transfusion of blood products and length of hospital stay in cava-sparing liver transplantation. METHODS: A systematic search of MEDLINE/PubMed, EMBASE and PsycINFO retrieved a total of 909 articles, of which six articles were included. The combined effect size and 95 % confidence interval were calculated for each outcome by applying the inverse variance weighting method. Tests for heterogeneity (I 2) were also utilized. RESULTS: Usage of a TPCS was associated with significantly decreased AST values, significantly fewer transfusions of packed red blood cells and improved postoperative renal function. There were no statistically significant differences in primary graft non-function, length of hospital stay or duration of surgery. CONCLUSION: This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.

Total pancreatectomy for primary pancreatic neoplasms: renaissance of an unpopular operation.

OBJECTIVE: To assess the long-term survival and quality of life in total pancreatectomies and to identify risk factors for perioperative morbidity and mortality. BACKGROUND: Total pancreatectomy may be required in locally advanced or centrally located pancreatic neoplasms to achieve complete tumor clearance, but available data on short- and long-term results are limited. METHODS: A total of 434 consecutive total pancreatectomies for primary pancreatic or periampullary tumors were performed between October 2001 and September 2012 at the authors' institution and were prospectively documented and analyzed. Long-term outcome was assessed using Kaplan-Meier and quality of life analysis (EORTC-QLQ-C30 and PAN26). Uni- and multivariate analysis was performed to identify perioperative risk factors and predictors for long-term survival. RESULTS: Extended total pancreatectomies were performed in 54% of cases, with arterial and portal vein resections in 15% and 32%, respectively. Overall 30-day and in-hospital mortality rates were 3.7% and 7.8%, respectively. High blood loss, long operative time, and arterial resections were independently associated with increased perioperative mortality (P ≤ 0.018). In malignant disease, median and 5-year survival were good for standard total pancreatectomies (28.6 months and 24.3%, respectively) and were significantly impaired after vascular resections (P < 0.001). Poor tumor grading, high American Joint Commission on Cancer tumor stage, age more than 70 years, and an R1 resection were independent prognostic parameters. Long-term global quality of life was comparable with a matched healthy control group. CONCLUSIONS: Standard total pancreatectomy, if needed, is associated with good long-term outcome in pancreatic cancer. Marked surgical morbidity and impaired survival associated with vascular resections reflect the invasiveness of extended total pancreatectomies and the underlying advanced malignant disease.

Surgical resection strategies for locally advanced pancreatic cancer.

BACKGROUND: Despite all improvements in tumor diagnostics and treatment, pancreatic cancer is still the fourth leading cause of cancer-related death in the Western world. It is mostly diagnosed at a locally advanced or metastasized stage because of the lack of early symptoms. A radical margin-free surgical resection offers the only potential cure for locoregional disease. Over the last decades, several surgical strategies and techniques have evolved to optimize oncologic radical resections and thus to improve long-term outcome of patients. PURPOSE: The purpose of this review was to describe the various surgical strategies and techniques for locally advanced pancreatic cancer and to evaluate their influence on long-term outcome. CONCLUSIONS: Locally advanced pancreatic cancer should not generally be deemed unresectable. Various surgical techniques offer a good chance of margin-free tumor resection, even if surrounding organs or vessels are involved. Because of potentially higher peri- and postoperative morbidity rates, patients should be selected properly and are best treated in specialized high-volume centers.

Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements.

OBJECTIVE: Post-hepatectomy liver failure (PHLF) is the major cause of death following liver resection. The aim of this study was to evaluate the feasibility of an intraoperative simulation of post-resection liver function. METHODS: Intraoperative liver function was measured by indocyanine green (ICG) clearance using the LiMON technology. In 20 patients undergoing anatomic liver resection, ICG plasma disappearance rate (PDR (%/min) and ICG retention at 15 min (R15 ) (%) were measured immediately after the induction of anaesthesia (t0 ), after selective arterial and portovenous inflow trial clamping (TC) of the resected liver segments (t1 ), after the completion of resection (t2 ) and before the closure of the abdominal cavity (t3 ). RESULTS: The median baseline (t0 ) PDR was 16.5%/min. Trial clamping of the inflow (t1 ) resulted in a significant reduction in PDR to 10.5%/min. Results under TC were similar to those obtained after resection (t2 ) (median PDR: 10.5%/min). Linear regression modelling showed that post-resection liver volume could be accurately predicted by TC of liver inflow (P < 0.0001), but not by determining the resected liver volume. Simulated post-resection liver function under TC correlated well with PHLF and length of hospital stay. CONCLUSIONS: Intraoperative ICG clearance measurements allow real-time monitoring of intraoperative liver function during surgery. Trial clamping of arterial and portovenous inflow accurately predicts immediate post-resection liver function. The intraoperative measurement of liver function and simulation of post-resection liver function may help to avoid PHLF.

Radiologic versus endoscopic evaluation of the conduit after esophageal resection: a prospective, blinded, intraindividually controlled diagnostic study.

BACKGROUND: Anastomotic leakage is a major complication in esophageal surgery. Although contrast swallow is performed by many surgical centers before reintroduction of oral intake to exclude anastomotic leakage postoperatively, endoscopy is increasingly used in this situation and may be superior. This study compares radiographic contrast study and endoscopy for the identification of local complications after subtotal esophagectomy. METHODS: Between January 2006 and September 2007, a prospective, blinded, intraindividually controlled study was conducted in patients who underwent transthoracic esophagectomy due to esophageal cancer. A radiographic contrast study was performed prior to endoscopy on postoperative day 5-7. Technical feasibility, sensitivity, and specificity of the radiologic and endoscopic evaluations of the esophageal substitute were described. RESULTS: Radiographic contrast study was possible in only 64% of the patients (35 of 55). The contrast study could not be performed in 20 patients due to contraindications or mechanical ventilation. Endoscopy could be performed in all patients (p < 0.001). Pathologic findings were detected in 13 patients by endoscopy but in only 1 patient by contrast swallow. Leakage of the anastomosis or the conduit was correctly detected in 7 patients by endoscopy but in only 1 patient by contrast swallow (p = 0.01). Endoscopy detected focal conduit necrosis or ischemia in six additional patients. Contrast studies showed false-positive results in two patients. Both sensitivity and specificity of endoscopy were 100%, while sensitivity and specificity of the contrast study were only 20 and 94%. No complications resulted from postoperative endoscopy or radiologic imaging. CONCLUSIONS: Endoscopic evaluation of the esophageal substitute in the early postoperative course is possible in all patients without complications. Endoscopy is superior to the contrast study in detecting pathological findings after esophageal reconstruction. Radiologic contrast swallow in the early postoperative days is often not possible, has no further relevance, and should be replaced by endoscopic evaluation.

Acute cholecystitis: early versus delayed surgery.

Laparoscopic cholecystectomy is widely established as the standard operation in acute cholecystectomy. Valid data from several prospective studies, including a recent large randomized multicenter trial, are available, demonstrating that early cholecystectomy is associated with less morbidity, a shorter length of hospital stay, and lower total hospital costs compared with delayed cholecystectomy after a conservative treatment period with antibiotics. Early cholecystectomy within 24 hours of hospital admission is the therapy of choice in patients fit for surgery and should be implemented as the standard treatment algorithm for this condition.

Improvement of surgical results for pancreatic cancer.

Surgery is the only potential hope of cure for patients with pancreatic cancer. Advantageous tumour characteristics and complete tumour resection are the factors most relevant for a positive prognosis, so detection of premalignant or early invasive lesions, combined with safe and oncologically adequate surgery, is an important goal. The experience and volume of both the individual surgeon and hospital are of paramount importance to achieve low morbidity and adequate management of complications. Most pancreatic cancers are locally advanced or metastatic when diagnosed and need multimodal therapy. With increasing evidence on surgical and perioperative aspects of pancreatic cancer therapy, short-term and long-term outcomes of resectable and borderline resectable pancreatic cancer are improving.

Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival.

BACKGROUND: Local recurrence of pancreatic cancer occurs in 80% of patients within 2 years after potentially curative resections. Around 30% of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival. PURPOSE: To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer. METHODS: All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed. RESULTS: Of 97 patients with histologically proven recurrence, 57 (59%) had ILR. In 40 (41%) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72%) patients with ILR, while 16 (28%) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8% after resections and 10 and 0% after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival. CONCLUSIONS: Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.

CA19-9 in potentially resectable pancreatic cancer: perspective to adjust surgical and perioperative therapy.

PURPOSE: In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences. METHODS: Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels. RESULTS: The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135). CONCLUSIONS: In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.

Small (Sendai negative) branch-duct IPMNs: not harmless.

OBJECTIVE: The aim of this study was to evaluate existing management guidelines for branch-duct intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: According to current treatment guidelines (Sendai criteria), patients with asymptomatic branch-duct type IPMNs of the pancreas less than 3 cm in diameter without suspicious features in preoperative imaging should undergo conservative treatment with yearly follow-up examinations. Nevertheless, the risk of harboring malignancy or invasive cancer remains a significant matter of consequence. METHODS: All patients who were surgically resected for branch-duct IPMNs between January 2004 and July 2010 at the University Clinic of Heidelberg were analyzed. Clinical characteristics of the patients and preoperative imaging were examined with regard to the size of the lesions, presence of mural nodules, thickening of the wall, dilation of the main pancreatic duct, and tumor markers. Results were correlated with histopathological features and were discussed with regard to the literature. RESULTS: Among a total of 287 consecutively resected IPMNs, 123 branch-duct IPMNs were identified analyzing preoperative imaging. Some 69 branch-duct IPMNs were less than 3 cm in size, without mural nodules, thickening of the wall, or other features characteristic for malignancy ("Sendai negative"). Of all the Sendai negative branch-duct IPMNs, 24.6% (17/69) showed malignant features (invasive carcinoma or carcinoma in situ) upon histological examination of the surgical specimen. CONCLUSIONS: Although many branch-duct IPMNs are small and asymptomatic, they harbor a significant risk of malignancy. We believe that both main-duct and branch-duct IPMNs represent premalignant lesions. This should be taken into account for adequate therapeutic management. With regard to these results, the current Sendai criteria for branch-duct IPMNs need to be adjusted.

Clinical phase I/II trial to investigate neoadjuvant intensity-modulated short term radiation therapy (5 × 5 Gy) and intraoperative radiation therapy (15 Gy) in patients with primarily resectable pancreatic cancer - NEOPANC.

BACKGROUND: The current standard treatment, at least in Europe, for patients with primarily resectable tumors, consists of surgery followed by adjuvant chemotherapy. But even in this prognostic favourable group, long term survival is disappointing because of high local and distant failure rates. Postoperative chemoradiation has shown improved local control and overalls survival compared to surgery alone but the value of additional radiation has been questioned in case of adjuvant chemotherapy. However, there remains a strong rationale for the addition of radiation therapy considering the high rates of microscopically incomplete resections after surgery. As postoperative administration of radiation therapy has some general disadvantages, neoadjuvant and intraoperative approaches theoretically offer benefits in terms of dose escalation, reduction of toxicity and patients comfort especially if hypofractionated regimens with highly conformal techniques like intensity-modulated radiation therapy are considered. METHODS/DESIGN: The NEOPANC trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant short course intensity-modulated radiation therapy (5 × 5 Gy) in combination with surgery and intraoperative radiation therapy (15 Gy), followed by adjuvant chemotherapy according to the german treatment guidelines, in patients with primarily resectable pancreatic cancer. The aim of accrual is 46 patients. DISCUSSION: The primary objectives of the NEOPANC trial are to evaluate the general feasibility of this approach and the local recurrence rate after one year. Secondary endpoints are progression-free survival, overall survival, acute and late toxicity, postoperative morbidity and mortality and quality of life. TRIAL REGISTRATION: NCT01372735.

Growth inhibition of pancreatic cancer by experimental treatment with 4-phenylbutyrate is associated with increased expression of Connexin 43.

Histone deacetylase inhibitors are a new and promising drug family with a strong anticancer activity and potent modulation of connexin expression. The restoration of connexins in cancer cells has been suggested as a possible mechanism to control tumor progression. The aim of this study was to investigate the effects of 4-phenylbutyrate (4-PB) on the growth of human pancreatic cell lines in vitro and in vivo with a focus on connexin modulation. The proliferation of tumor cells was determined using an MTT assay, and the effect of 4-PB in vivo was studied in a chimeric mouse model. The expression and localization of connexin 43 (Cx43) were assessed by Western blot, immunofluorescence microscopy, and immunohistochemistry. Antitumoral activity was assessed by immunohistochemistry for Ki-67 and histone H4. Treatment with 4-PB resulted in the significant in vitro and in vivo growth inhibition of pancreatic tumor cells. The reduction of the xenograft tumor volume was associated with the inhibition of histone deacetylation and decrease in cell proliferation. Treatment with 4-PB caused a significant increase in the Cx43 expression in T3M4 cells (up to 2.8-fold). The newly synthesized Cx43 was localized in the cytoplasm but not on the cell membrane. Treatment with 4-PB inhibited the proliferation of human pancreatic tumor cells in vitro and in vivo and increased the expression of Cx43. Therefore, 4-PB might be useful in the therapy of pancreatic cancer.

Pancreatic cancer surgery in the new millennium: better prediction of outcome.

BACKGROUND: Surgery is the only therapy with potentially curative intention in pancreatic cancer. This analysis aimed to determine prognostic parameters in a patient cohort with resected pancreatic adenocarcinoma with a special focus on the revised R1-definition. METHODS: Between October 2001 and August 2009, data from 1071 consecutively resected patients with pancreatic adenocarcinoma were prospectively collected in an electronical database. Parameters tested for survival prediction in univariate analysis included patient, tumor, and resection characteristics as well as adjuvant therapy. The parameters with significant results were used for multivariate survival analysis. Identified parameters with positive or negative prognostic effect were used to define risk groups and to assess the effects on patient survival. RESULTS: Age, ASA-score, CEA and CA19-9 levels, preoperative insulin-dependent diabetes mellitus, T-, N-, M-, R-, G-tumor classification, advanced disease, and LNR were all significant in univariate analysis, whereas gender, NYHA score, BMI, insurance status, type of surgical procedure, and adjuvant therapy were not. In multivariate analysis, age ≥70 years, preoperative insulin-dependent diabetes, CA19-9 ≥400 U/mL, T4-, M1- or G3-status, and LNR > 0.2 were independent negative predictors, whereas Tis/T1/T2-status, G1-differentiation, and R0-status (revised definition) were independently associated with good prognosis. Using these risk factors, patients were stratified into 4 risk-groups with significantly different prognosis; 5-year survival varied between 0% and 54.5%. Risk stratification resulted in improved survival prognostication within the predominant AJCC IIA and AJCC IIB stages. CONCLUSIONS: A newly defined prognostic profiling including the revised R1-definition discriminates survival of patients with resectable pancreatic adenocarcinoma better than the AJCC staging system, and may be of particular relevance for patient-adjusted therapy in the heterogeneous group of AJCC stage II tumors.

Arterial resection during pancreatectomy for pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: The majority of pancreatic cancers are diagnosed at an advanced stage. As surgical resection remains the only hope for cure, more aggressive surgical approaches have been advocated to increase resection rates. Institutions have begun to release data on their experience with pancreatectomy and simultaneous arterial resection (AR), which has traditionally been considered a general contraindication to resection. The aim of the present meta-analysis was to evaluate the perioperative and long-term outcomes of patients with AR during pancreatectomy for pancreatic cancer. METHODS: The Medline, Embase, and Cochrane Library and J-East databases were systematically searched to identify studies reporting outcome of patients who underwent pancreatectomy with AR for pancreatic cancer. Studies that reported perioperative and/or long-term results after pancreatectomy with AR were eligible for inclusion. Meta-analyses included comparative studies providing data on patients with and without AR and were performed using a random effects model. RESULTS: The literature search identified 26 studies including 366 and 2243 patients who underwent pancreatectomy with and without AR. All studies were retrospective cohort studies and the methodological quality was moderate to low. Meta-analyses revealed AR to be associated with a significantly increased risk for perioperative mortality [Odds ratio (OR) = 5.04; 95% confidence interval (CI), 2.69-9.45; P < 0.0001; I² = 24%], poor survival at 1 year (OR = 0.49; 95% CI, 0.31-0.78; P = 0.002; I² = 35%) and 3 years (OR = 0.39; 95% CI, 0.17-0.86; P = 0.02; I² = 49%) compared with patients without AR. The increased perioperative mortality (OR = 8.87; 95% CI, 3.40-23.13; P < 0.0001; I² = 5%) and lower survival rate at 1 year (OR = 0.50; 95% CI, 0.31-0.82; P = 0.006; I² = 40%) was confirmed in the comparison to patients undergoing venous resection. Despite substantial perioperative mortality, pancreatectomy with AR was associated with more favorable survival compared with patients who did not undergo resection for locally advanced disease. CONCLUSIONS: AR in patients undergoing pancreatectomy for pancreatic cancer is associated with a poor short and long-term outcome. Pancreatectomy with AR may, however, be justified in highly selected patients owing to the potential survival benefit compared with patients without resection. These patients should be treated within the bounds of clinical trials to assess outcomes after AR in the era of modern pancreatic surgery and multimodal therapy.

Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections.

PURPOSE: Pancreatic surgery is a technically challenging intervention with high demands for preoperative diagnostics and perioperative management. A perioperative mortality rate below 5% is achieved in high-volume centers due to the high level of standardization in surgical procedures and perioperative care. Besides standard resections, certain indications may require individualized surgical concepts such as tumor enucleations. The aim of the study was to evaluate the indications, technique, and outcome of this limited local approach compared to major resections. MATERIALS AND METHODS: Data from patients undergoing pancreatic surgery were prospectively recorded. All patients with tumor enucleations were compared with classical resections (pancreaticoduodenectomy or left resection) in a matched-pair analysis (1:2). Tumor type, localization, operative parameters, complications, and outcome were evaluated. RESULTS: Fifty-three patients underwent pancreatic tumor enucleation between October 2001 and December 2009. Indications included cystic lesions, IPMNs, and neuroendocrine pancreatic tumors. Enucleations were associated with shorter operation time, less blood loss as well as shorter ICU and hospital stay compared to pancreaticoduodenectomy and left resections. The overall surgical morbidity of enucleations was 28.3% without major complications. Leading clinical problems were ISGPF type A fistulas (20.8%) requiring prolonged primary drainage. No surgical revisions were necessary, and no deaths occurred. CONCLUSIONS: Pancreatic tumor enucleations can be carried out with good results and no mortality. Decisions regarding enucleations are highly individual compared to standard resections, underlining the importance of treatment in experienced high-volume institutions. Enucleations should be carried out whenever possible and oncologically feasible to prevent the typical complications of major pancreatic resection.