Evaluation of response using FDG-PET/CT and diffusion weighted MRI after radiochemotherapy of pancreatic cancer: a non-randomized, monocentric phase II clinical trial-PaCa-DD-041 (Eudra-CT 2009-011968-11).

BACKGROUND: Pancreatic cancer is a devastating disease with a 5-year survival rate of 20-25%. As approximately only 20% of patients diagnosed with pancreatic cancer are initially staged as resectable, it is necessary to evaluate new therapeutic approaches. Hence, neoadjuvant (radio)chemotherapy is a promising therapeutic option, especially in patients with a borderline resectable tumor. The aim of this non-randomized, monocentric, prospective, phase II clinical study was to assess the prognostic value of functional imaging techniques, i.e., [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and diffusion weighted magnetic resonance imaging (DW-MRI), prior to and during neoadjuvant radiochemotherapy. METHODS: Patients with histologically proven resectable, borderline resectable or unresectable non-metastatic pancreatic adenocarcinoma received induction chemotherapy followed by neoadjuvant radiochemotherapy. Patients underwent FDG-PET/CT and DW-MRI including T1- and T2-weighted sequences prior to and after neoadjuvant chemotherapy as well as following induction radiochemotherapy. The primary endpoint was the evaluation of the response as quantified by the standardized uptake value (SUV) measured with FDG-PET. Response to treatment was evaluated by FDG-PET and DW-MRI during and after the neoadjuvant course. Morphologic staging was performed using contrast-enhanced CT and contrast-enhanced MRI to decide inclusion of patients and resectability after neoadjuvant therapy. In those patients undergoing subsequent surgery, imaging findings were correlated with those of the pathologic resection specimen. RESULTS: A total of 25 patients were enrolled in the study. The response rate measured by FDG-PET was 85% with a statistically significant decrease of the maximal SUV (SUVmax) during therapy (p < 0.001). Using the mean apparent diffusion coefficient (ADC), response was not detectable with DW-MRI. After neoadjuvant treatment 16 patients underwent surgery. In 12 (48%) patients tumor resection could be performed. The median overall survival of all patients was 25 months (range: 7-38 months). CONCLUSION: Based on these limited patient numbers, it was possible to show that this trial design is feasible and that the neoadjuvant therapy regime was well tolerated. FDG-PET/CT may be a reliable method to evaluate response to the combined therapy. In contrast, when evaluating the response using mean ADC, DW-MRI did not show conclusive results.

Prognostic impact of para-aortic lymph node metastases in non-pancreatic periampullary cancer.

BACKGROUND: Resection of the para-aortic lymph node (PALN) group Ln16b1 during pancreatoduodenectomy remains controversial because PALN metastases are associated with a worse prognosis in pancreatic cancer patients. The present study aimed to analyze the impact of PALN metastases on outcome after non-pancreatic periampullary cancer resection. METHODS: One hundred sixty-four patients with non-pancreatic periampullary cancer who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005 and 2016 were retrospectively investigated. The data were supplemented with a systematic literature review on this topic. RESULTS: In 67 cases, the PALNs were clearly assigned and could be histopathologically analyzed. In 10.4% of cases (7/67), tumor-infiltrated PALNs (PALN+) were found. Metastatic PALN+ stage was associated with increased tumor size (P = 0.03) and a positive nodal stage (P < 0.001). The median overall survival (OS) of patients with metastatic PALN and non-metastatic PALN (PALN-) was 24.8 and 29.5 months, respectively. There was no significant difference in the OS of PALN+ and pN1 PALN patients (P = 0.834). Patients who underwent palliative surgical treatment (n = 20) had a lower median OS of 13.6 (95% confidence interval 2.7-24.5) months. Including the systematic literature review, only 23 cases with PALN+ status and associated OS could be identified; the average survival was 19.8 months. CONCLUSION: PALN metastasis reflects advanced tumor growth and lymph node spread; however, it did not limit overall survival in single-center series. The available evidence of the prognostic impact of PALN metastasis is scarce and a recommendation against resection in these cases cannot be given.

The pathohistological subtype strongly predicts survival in patients with ampullary carcinoma.

Ampullary cancer represents approximately 6% of the malignant periampullary tumors. An early occurrence of symptoms leads to a 5-year survival rate after curative surgery of 30 to 67%. In addition to the tumor stage, the immunohistological subtypes appear to be important for postoperative prognosis. The aim of this study was to analyze the different subtypes regarding their prognostic relevance. A total of 170 patients with ampullary cancer were retrospectively analyzed between 1999 until 2016 after pancreatic resection. Patients were grouped according to their pathohistological subtype of ampullary cancer (pancreatobiliary, intestinal, mixed). Characteristics among the groups were analyzed using univariate and multivariate models. Survival probability was analyzed by the Kaplan-Meier method. An exact subtyping was possible in 119 patients. A pancreatobiliary subtype was diagnosed in 69 patients (58%), intestinal in 41 patients (34.5%), and a mixed subtype in 9 patients (7.6%). Survival analysis showed a significantly worse 5-year survival rate for the pancreatobiliary subtype compared with the intestinal subtype (27.5% versus 61%, p < 0.001). The mean overall survival of patients with pancreatobiliary, intestinal, and mixed subtype was 52.5, 115 and 94.7 months, respectively (p < 0.001). The pathohistological subtypes of ampullary cancer allows a prediction of the postoperative prognosis.

The impact of surgical experience and frequency of practice on perioperative outcomes in pancreatic surgery.

OBJECTIVE: We aimed to determine the impact of surgical experience and frequency of practice on perioperative morbidity and mortality in pancreatic surgery. METHODS: 1281 patients that underwent pancreatic resections from 1993 to 2013 were retrospectively analyzed using logistic regression models. All cases were stratified according to the surgeon's level of experience, which was based on the number of previously performed pancreatic resections and the extent of received supervision (novice: n <  20 / intensive; intermediate: n = 21-90 / decreasing; and experienced surgeon: n > 90 / none). Additional stratification was based on the frequency of practice (sporadic: 3 resections > 6 weeks, frequent: 3 resections ≤6 weeks). RESULTS: The novice and experienced categories were related to a decreased risk of postoperative pancreatic fistulas (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26-0.82 and 0.54, 95% CI 0.36-0.82) and in-hospital mortality (OR 0.45, 95% CI 0.17-1.16 and 0.42, 95% CI 0.21-0.83) compared to the intermediate category. Frequent practice was associated with a significantly lower risk of delayed gastric emptying (OR 0.56, 95% CI 0.38-0.83), postpancreatectomy hemorrhage (OR 0.64, 95% CI 0.42-0.98) and in-hospital mortality (OR 0.45, 95% CI 0.24-0.87). CONCLUSIONS: Our results emphasize the importance of supervision within a pancreatic surgery training program. In addition, our data underline the need of a sufficient patient caseload to ensure frequent practice.

Validation of prognostic risk scores for patients undergoing resection for pancreatic cancer.

BACKGROUND/OBJECTIVES: A better stratification of patients into risk groups might help to select patients who might benefit from more aggressive therapy. The aim of this study was to validate five prognostic scores in patients resected for pancreatic ductal adenocarcinoma (PDAC). METHODS: Included were 307 PDAC patients who underwent resection with curative intent. Five clinical risk scores were selected and applied to our study population. Survival analyses were carried out using univariate and multivariate proportional hazards regression. RESULTS: Prognostic stratification was strong for the Heidelberg score (p < 0.001) and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram (p = 0.001) and moderate for the Botsis score (p = 0.033). There was no significant prognostic value for the Early Mortality Risk Score (p = 0.126) and McGill Brisbane Symptom Score (p = 0.133). Positive resection margin (HR 1.53, 95% CI 1.08-2.16) and pain [pain (HR 1.40, CI 1.03-1.91), back pain (HR 1.67, 95% CI 1.08-2.57)] were independent prognostic factors on multivariate analysis. CONCLUSIONS: The Heidelberg score and MSKCC nomogram provided adequate risk stratification in our independent study cohort. Further studies in independent patient cohorts are required to achieve higher levels of validation.

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP). METHODS: Affymetrix microarrays were used to assess the islet transcriptome of islets isolated either by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and 19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2 diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs IGT and type 3c diabetes within the PPP group; and (2) identify transcription factors driving gene co-expression modules correlated with insulin secretion ex vivo and glucose tolerance in vivo. Selected genes of interest were validated for their expression and function in beta cells. RESULTS: Comparative transcriptomic analysis identified 19 genes differentially expressed (false discovery rate ≤0.05, fold change ≥1.5) in type 2 diabetic vs non-diabetic islets from OD and PPP. Nine out of these 19 dysregulated genes were not previously reported to be dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which inhibited Ca2+-influx and insulin secretion in beta cells, and ARG2 and PPP1R1A, which promoted insulin secretion. Systems biology approaches identified HNF1A, PDX1 and REST as drivers of gene co-expression modules correlated with impaired insulin secretion or glucose tolerance, and 14 out of 19 differentially expressed type 2 diabetic islet signature genes were enriched in these modules. None of these signature genes was significantly dysregulated in islets of PPP with impaired glucose tolerance or type 3c diabetes. CONCLUSIONS/INTERPRETATION: These studies enabled the stringent definition of a novel transcriptomic signature of type 2 diabetic islets, regardless of islet source and isolation procedure. Lack of this signature in islets from PPP with IGT or type 3c diabetes indicates differences possibly due to peculiarities of these hyperglycaemic conditions and/or a role for duration and severity of hyperglycaemia. Alternatively, these transcriptomic changes capture, but may not precede, beta cell failure.

Para-aortic lymph node metastases in pancreatic cancer should not be considered a watershed for curative resection.

No international consensus regarding the resection of the para-aortic lymph node (PALN) station Ln16b1 during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) has been reached. The present retrospectively investigated 264 patients with PDAC who underwent curative pancreatoduodenectomy or total pancreatectomy between 2005-2015. In 95 cases, the PALN were separately labelled and histopathologically analysed. Metastatic PALN (PALN+) were found in 14.7% (14/95). PALN+ stage was associated with increased regional lymph node metastasis. The median overall survival (OS) of patients with metastatic PALN and with non-metastatic PALN (PALN-) was 14.1 and 20.2 months, respectively. Five of the PALN+ patients (36%) survived >19 months. The OS of PALN+ and those staged pN1 PALN- was not significantly different (P = 0.743). Patients who underwent surgical exploration or palliative surgery (n = 194) had a lower median survival of 8.8 (95% confidence interval: 7.3-10.1) months. PALN status could not be reliably predicted by preoperative computed tomography. We concluded that the survival data of PALN+ cases is comparable with advanced pN+ stages; one-third of the patients may expect longer survival after radical resection. Therefore, routine refusal of curative resection in the case of PALN metastasis is not indicated.

Impact of Intraoperative Re-resection to Achieve R0 Status on Survival in Patients With Pancreatic Cancer: A Single-center Experience With 483 Patients.

OBJECTIVE: The aim of this study was to test the hypothesis that intraoperative frozen section (FS) and re-resection results to achieve R0 status are associated with different long-term outcomes in pancreatic cancer patients. BACKGROUND: Recent data have challenged the survival benefit of additional resection in patients with pancreatic cancer in case of positive FS to achieve clear pathological section (PS). METHODS: Patients who underwent surgery for exocrine pancreatic malignancy with curative intent were identified from a prospective database. Data were stratified by resection margin (group I: FS-R0 → PS-R0; group II: FS-R1 → PS-R0; group III: FS-R1 → PS-R1). Associations with survival were analyzed by univariate and multivariate analyses. RESULTS: A total of 483 patients met the inclusion criteria. Of these, 61 patients were excluded due to R2 or Rx status. Three hundred seventeen (75%) patients were allocated to margin group I, 32 (8%) to group II, and 73 (17%) to group III. Median overall survival in group I, II, and III was 29, 36, and 12 months (P < 0.001). There was no significant difference in survival between patients in Group I and II (P = 0.849), whereas patients in group III had significantly poorer outcome than group I (P < 0.001) and II (P = 0.039). The prognostic value of margin group status was confirmed on multivariate analysis (hazard ratio = 1.694, 95% confidence interval 1.175-2.442). CONCLUSIONS: FS analysis with intraoperative re-resection should be performed routinely in patients undergoing pancreatic cancer surgery with the aim to achieve a R0 resection.

Treatment of tailgut cysts by extended distal rectal segmental resection with rectoanal anastomosis.

PURPOSE: Complete surgical resection is the treatment of choice for tailgut cysts, because of their malignant potential and tendency to regrow if incompletely resected. We report our experience of treating patients with tailgut cysts, and discuss diagnostics, surgical approaches, and follow-up. METHODS: We performed extended distal rectal segmental resection of the tailgut cyst, with rectoanal anastomosis. We report the clinical, radiological, pathological, and surgical findings, describe the procedures performed, and summarize follow-up data. RESULTS: Two patients underwent en-bloc resection of a tailgut cyst, the adjacent part of the levator muscle, and the distal rectal segment, followed by an end-to-end rectoanal anastomosis. There was no evidence of anastomotic leakage postoperatively. At the time of writing, our patients were relapse-free with no, or non-limiting, symptoms of anal incontinence, respectively. CONCLUSIONS: This surgical approach appears to have a low complication rate and good recovery outcomes. Moreover, as the sphincter is preserved, so is the postoperative anorectal function. This approach could result in a low recurrence rate.

Impact of Portal Vein Involvement from Pancreatic Cancer on Metastatic Pattern After Surgical Resection.

BACKGROUND: The present study aims to evaluate the long-term outcome and metastatic pattern of patients who underwent resection of a pancreatic ductal adenocarcinoma (PDAC) with portal or superior mesenteric vein (PV/SMV) resection. METHODS: Patients who underwent a partial pancreatoduodenectomy or total pancreatectomy for PDAC between 2005 and 2015 were retrospectively analyzed. Three subgroups were generated, depending on PV/SMV resection (P+) and pathohistological PV/SMV tumor infiltration (I+): P+I+, P+I-, and P-I-. Statistical analysis was performed using the R software package. RESULTS: The study cohort included 179 patients, 113 of whom underwent simultaneous PV/SMV resection. Thirty-six patients (31.9 %) had pathohistological tumor infiltration of the PV/SMV (P+I+), and were matched with 66 cases without PV/SMV infiltration (P-I-). The study revealed differences in overall median survival (11.9 [P+I+] vs. 16.1 [P+I-] vs. 20.1 [P-I-] months; p = 0.01). Multivariate survival analysis identified true invasion of the PV/SMV as the only significant, negative prognostic factor (p = 0.01). Whereas the incidence of local recurrence was comparable (p = 0.96), the proportion of patients with distant metastasis showed significant differences (75 % [P+I+] vs. 45.8 % [P+I-] vs. 54.7 % [P-I-], p = 0.01). Furthermore, the median time to progression was significantly shorter if the PV/SMV was involved (7.4 months [P+I+] vs. 10.9 months [P+I-] vs. 11.6 months [P-I-]). Initial liver metastases occurred in 33 % of the patients. CONCLUSIONS: True invasion of the PV/SMV is an independent risk factor for overall survival, and is associated with a higher incidence of distant metastasis and shorter progressive-free survival. Radical vascular resection cannot compensate for aggressive tumor biology.

Evaluation of central pancreatectomy and pancreatic enucleation as pancreatic resections--A comparison.

INTRODUCTION: For minor pancreatic resection such as enucleation (PE) and central pancreatectomy (CP) comparative data are rare. These techniques provide parenchyma-sparing alternatives to major resections (e.g. pancreaticoduodenectomy) for neuroendocrine tumors, cystic tumors or metastases. This study retrospectively compares the morbidity and mortality of both techniques, with special regard to the formation of postoperative pancreatic fistulas (POPF). METHODS: Between December 1996 and November 2013 the postoperative events and clinical outcomes of 17 patients after pancreatic enucleation and 26 patients after central pancreatectomy were retrospectively analyzed from a prospectively collected database. RESULTS: Perioperative mortality was 0% in both groups. There was no significant difference in the overall peri-operative morbidity (CP 80.8% vs. PE 82.4%). The major cause of the high morbidity was the formation of a POPF with 26.9% of the patients after CP and 35.3% after PE. Univariate analysis showed a BMI over 30 kg/m(2) in the CP group to be an independent risk factor. Additional minor complications, e.g. urinary tract infection, pleural effusion, etc. furthermore contributed to the perioperative morbidity. CONCLUSION: PE and central CP are feasible techniques for selected patients, but the indications are limited. Morbidity after these resections is high with the major cause being the development of a POPF.

Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis.

BACKGROUND AND AIM: Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables. METHODS: In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial. The individuals were assigned based on their fasting glucose or oral glucose tolerance testing results into one of the following groups: (I) deteriorated, (II) stable or (III) improved glucose homeostasis three months after surgery. Co-variables associated with blood glucose dynamics were identified. RESULTS: Of the 84 participants, 25 (30%) displayed a normal oGTT, 17 (20%) showed impaired glucose tolerance, and 10 (12%) exhibited pathological glucose tolerance. Elevated fasting glucose was present in 32 (38%) individuals before partial pancreatic resection. Three months after partial pancreatic resection, 14 (17%) patients deteriorated, 16 (19%) improved, and 54 (64%) retained stable glucose homeostasis. Stability and improvement was associated with tumor resection and postoperative normalization of recently diagnosed glucose dysregulation, preoperatively elevated tumor markers and markers for common bile duct obstruction, acute pancreatitis and liver cell damage. Improvement was linked to preoperatively elevated insulin resistance, which normalized after resection and was accompanied by a decrease in fasting- and glucose-stimulated insulin secretion. CONCLUSIONS: Surgically reversible blood glucose dysregulation diagnosed concomitantly with a (peri-) pancreatic tumor appears secondary to compromised liver function due to tumor compression of the common bile duct and the subsequent increase in insulin resistance. It can be categorized as "cholestasis-induced diabetes" and thereby distinguished from other forms of hyperglycemic disorders.

Chronic pancreatitis of the pancreatic remnant is an independent risk factor for pancreatic fistula after distal pancreatectomy.

BACKGROUND: There is an ongoing debate about the best closure technique after distal pancreatectomy (DP). The aim of the closure is to prevent the formation of a clinically relevant post-operative pancreatic fistula (POPF). Stapler technique seems to be equal compared with hand-sewn closure of the remnant. For both techniques, a fistula rate of approximately 30% has been reported. METHODS: We retrospectively analyzed our DPs between 01/2000 and 12/2010. In all cases, the pancreatic duct was over sewn with a separately stitched ligation of the pancreatic duct (5*0 PDS) followed by a single-stitched hand-sewn closure of the residual pancreatic gland. The POPF was classified according to the criteria of the International Study Group for Pancreatic Fistula (ISGPF). Univariate and multivariate analyses of potential risk factors for the formation of POPF were performed. Indications for operations included cystic tumors (n = 53), neuroendocrine tumors (n = 27), adenocarcinoma (n = 22), chronic pancreatitis (n = 9), metastasis (n = 6), and others (n = 7). RESULTS: During the period, we performed 124 DPs (♀ = 74, ♂ = 50). The mean age was 57.5 years (18-82). The POPF rates according to the ISGPF criteria were: no fistula, 54.8% (n = 68); grade A, 24.2% (n = 30); grade B, 19.3% (n = 24); and grade C, 1.7% (n = 2). Therefore, in 21.0% (n = 26) of the cases, a clinically relevant pancreatic fistula occurred. The mean postoperative stay was significantly higher after grade B/C fistula (26.3 days) compared with no fistula/grade A fistula (13.7 days) (p < 0.05). The uni- and multivariate analyses showed chronic pancreatitis of the pancreatic remnant to be an independent risk factor for the development of POPF (p = 0.004 OR 7.09). CONCLUSION: By using a standardized hand-sewn closure technique of the pancreatic remnant after DP with separately stitched ligation of the pancreatic duct, a comparably low fistula rate can be achieved. Signs of chronic pancreatitis of the pancreatic remnant may represent a risk factor for the development of a pancreatic fistula after DP and therefore an anastomosis of the remnant to the intestine should be considered.

Future perspectives for surgical research in Germany.

BACKGROUND: During the last two decades, the complexity of surgical patient care has increased dramatically. Nonetheless, there is substantial need to improve the quality of surgical research in Germany. PURPOSE: Herein, we present the current concepts of the German Society of Surgery, the Section of Surgical Research, the Study Center of the German Surgical Society, and the German Surgical Trial Network (CHIR-Net) and their perspectives to promote young surgeons for a career in academic surgery and to improve the quality of surgical research in experimental studies as well as in clinical trials. The concepts include also education, teaching, and mentoring in order to strengthen the research profile of surgical departments and surgical research institutes. CONCLUSIONS: We feel that realization of these concepts should guarantee the survival of the surgeon-scientist across all surgical subspecialties, increase the attractiveness of academic positions in surgery, and promote translational research from bench to bedside with a benefit for patient care.

Malignancy in chronic pancreatitis: analysis of diagnostic procedures and proposal of a clinical algorithm.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis, and some benign conditions and syndromes, including chronic pancreatitis (CP), are risk factors for pancreatic carcinoma. However, the differential diagnosis of CP from PDAC is difficult for clinicians because PDAC frequently causes inflammation within the pancreas. Therefore, patients with CP exhibit not only an elevated risk of cancer, but they are also in danger of underdiagnosis. METHODS: The present study retrospectively analyzed 29 patients with pancreatic cancer who fulfilled our definition of "chronic pancreatitis" to identify characteristics to aid in the differential diagnosis between chronic pancreatitis with and without pancreatic cancer. All parameters were subjected to univariate analysis. RESULTS: We identified several factors that differed significantly between the CP patients and patients with CP and synchronous PDAC, and these characteristics were used to develop a diagnostic algorithm. The performance of the algorithm was externally validated in a different panel of patients from the Department of Surgery, Medical Faculty Mannheim. CONCLUSION: The present study succeeded in identifying characteristics that significantly differed in patients with and without PDAC in CP. These characteristics were integrated in a diagnostic algorithm that might help to improve diagnostic of PDAC in CP.

Evaluation of survival in patients after pancreatic head resection for ductal adenocarcinoma.

BACKGROUND: Surgery remains the only curative option for the treatment of pancreatic adenocarcinoma (PDAC). The goal of this study was to investigate the clinical outcome and prognostic factors in patients after resection for ductal adenocarcinoma of the pancreatic head. METHODS: The data from 195 patients who underwent pancreatic head resection for PDAC between 1993 and 2011 in our center were retrospectively analyzed. The prognostic factors for survival after operation were evaluated using multivariate analysis. RESULTS: The head resection surgeries included 69.7% pylorus-preserving pancreatoduodenectomies (PPPD) and 30.3% standard Kausch-Whipple pancreatoduodenectomies (Whipple). The overall mortality after pancreatoduodenectomy (PD) was 4.1%, and the overall morbidity was 42%. The actuarial 3- and 5-year survival rates were 31.5% (95% CI, 25.04%-39.6%) and 11.86% (95% CI, 7.38%-19.0%), respectively. Univariate analyses demonstrated that elevated CEA (p = 0.002) and elevated CA 19-9 (p = 0.026) levels, tumor grade (p = 0.001) and hard texture of the pancreatic gland (p = 0.017) were significant predictors of a poor survival. However, only CEA >3 ng/ml (p < 0.005) and tumor grade 3 (p = 0.027) were validated as significant predictors of survival in multivariate analysis. CONCLUSIONS: Our results suggest that tumor marker levels and tumor grade are significant predictors of poor survival for patients with pancreatic head cancer. Furthermore, hard texture of the pancreatic gland appears to be associated with poor survival.

Long-term quality of life of abdominal aortic aneurysm patients under surveillance or after operative treatment.

BACKGROUND: The objective of this study was to determine the long-term quality of life (QOL) in patients with an abdominal aortic aneurysm (AAA) undergoing surveillance or after operative treatment. METHODS: 249 patients with AAAs completed the WHO Quality of Life-BREF (WHOQOL-BREF) test and Short Form (36) Health Survey (SF-36) survey: 78 patients with small AAAs under surveillance, 26 after ruptured AAAs (rAAAs), 47 after endovascular aneurysm repair (EVAR), and 98 after elective open repair. The results were compared with WHOQOL-BREF and SF-36 standard values from a matched German population using the Student's 2-tailed t-test. RESULTS: Long-term results of the WHOQOL-BREF test showed that patients undergoing AAA surveillance had a significantly lower physical QOL (P = 0.04). Patients after EVAR or open repair rated their environmental QOL significantly higher than the age- and sex-matched general population (open repair: P = 0.006; EVAR: P < 0.001). Patients with rAAAs had the same QOL as the matched German population. Long-term results of the QOL SF-36 showed that patients undergoing AAA surveillance rated their QOL significantly lower in the subgroup of role-physical (P = 0.02) and role-emotional (P = 0.003). Patients with rAAAs rated lower scores for role-physical (P = 0.02) and had more bodily pain (P = 0.02). Patients who underwent elective open repair had the same high QOL as the matched German population, whereas patients who underwent EVAR reported significant improvement in vitality (P = 0.002) and mental health (P = 0.03) compared with the matched German population. CONCLUSIONS: Based on measurements from 2 independent QOL tests, the well-established operative treatment of AAAs provided patients with a QOL comparable to that of a matched German population. The electively treated AAA groups rated environmental QOL factors significantly higher than the control group. The impaired physical and emotional QOL of the AAA group under surveillance suggests that more intense patient education could be beneficial.

Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

OBJECTIVE: To investigate different subtypes of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and their prognostic value. BACKGROUND: IPMNs of the pancreas are estimated to have a better prognosis than pancreatic ductal adenocarcinomas (PDACs). In addition to the different growth types (ie, main duct vs. branch duct types), the histological subtypes of IPMNs (ie, intestinal, pancreatobiliary, gastric, and oncocytic type) are prognostically relevant. These subtypes can be characterized by different mucin (MUC) expression patterns. In this study, we analyzed the IPMNs from 2 pancreatic cancer referral centers by correlating the MUC expression, histological subtype, and clinical outcome. METHODS: We re-evaluated all resections due to a pancreatic tumor over a period of 15 years. Cases with IPMNs were identified, and the subtypes were distinguished using histopathological analysis, including the immunohistochemical analysis of MUC (ie, MUC1, MUC2, and MUC5AC) expression. Furthermore, we determined clinical characteristics and patient outcome. RESULTS: A total of 103 IPMNs were identified. On the basis of the MUC profile, histopathological subtypes were classified into the following categories: intestinal type [n = 45 (44%)], pancreatobiliary type [n = 41 (40%)], gastric type [n = 13 (12%)], and oncocytic type [n = 4 (4%)]. The following types of resections were performed: pancreatic head resections [n = 77 (75%)], tail resections [n = 16 (15%)], total pancreatectomies [n = 5 (5%)], and segment resections [n = 5 (5%)]. The 5-year survival of patients with intestinal IPMNs was significantly better than pancreatobiliary IPMNs (86.6% vs. 35.6%; P < 0.001). The pancreatobiliary subtype was strongly associated with malignancy [odds ratio (OR): 6.76], recurrence (P < 0.001), and long-term survival comparable with that of PDAC patients. CONCLUSIONS: Evaluation of IPMN subtypes supports postoperative patient prognosis prediction. Therefore, subtype differentiation could lead to improvements in clinical management. Potentially identifying subgroups with the need for adjuvant therapy may be possible.

Google goes cancer: improving outcome prediction for cancer patients by network-based ranking of marker genes.

Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice.

Colorectal liver metastases: an update on palliative treatment options.

Only approximately 30% of patients with colorectal cancer liver metastasis qualify for curative therapy, which is in most cases liver lesion resection. Due primarily to the extent of the tumors and patient comorbidities, palliative therapy remains the only option in non-resection cases. Palliation enables local, symptomatic control and prolonged survival in some cases. As established methods are continuously improved, new palliative therapy methods are tested in clinical trials and subsequently introduced into clinical practice. The present review provides an overview of current colorectal liver metastasis treatment when resection is not an option. This review gives the basis for an interdisciplinary decision making process for the treatment of liver metastasis.