Perioperative outcome and long-term survival for intrahepatic cholangiocarcinoma after portal vein embolization and subsequent resection: A propensity-matched study.

INTRODUCTION: In view of the high therapeutic value of surgical resection for intrahepatic cholangiocarcinomas (ICC), our study addresses the question of clinical management and outcome in case of borderline resectability requiring hypertrophy induction of the future liver remnant prior to resection. METHODS: Clinical data was collected of all primary ICC cases receiving major liver resection with or without prior portal vein embolization (PVE) from a single high-volume center. PVE was performed via a percutaneous transhepatic access. Propensity score matching was performed. Perioperative morbidity was assessed as well as long-term survival with a minimum follow-up of 36 months. RESULTS: No significant difference in perioperative morbidity was seen between the PVE and the control group. For the PVE group, median OS was 28 months vs. 37 months for the control group (p = 0.418), median DFS 18 and 14 months (p = 0.703). Disease progression during hypertrophy was observed in 38% of cases. Here, OS and DFS was reduced to 18 months (p = 0.479) and 6 months (p = 0.013), respectively. In case of positive N-status or multifocal tumor (MF+) OS was also reduced (18 vs. 26 months, p = 0.033; MF+: 9 vs. 36months p = 0.013). CONCLUSION: Our results suggest that the surgical therapy in case of borderline resectability offers acceptable results with non-inferior OS rates compared to cases without preoperative hypertrophy induction and comparable oncological features. In the presence of additional risk factors (multifocal tumor, lymph node metastasis, PD during hypertrophy) the OS is notably reduced.

Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113).

BACKGROUND: The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs). PATIENTS AND METHODS: A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin)] followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate. RESULTS: From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months [95% confidence interval (CI) 13.0-19.4] and R0 resection (n = 31; 23%) was associated with a significant survival benefit [40.8 months (95% CI 21.7-59.8)], while R1 resected patients (n = 14; 11%) had no survival benefit [14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001]. After ICT most patients showed a CA 19-9 response (median change from baseline: -82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS [27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013], whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection. CONCLUSIONS: CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery. CLINICAL TRIAL NUMBER: ClinicalTrials.govNCT02125136; https://clinicaltrials.gov/ct2/show/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results.

A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial.

BACKGROUND: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness. PATIENTS AND METHODS: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. FINDINGS: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFß signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001). INTERPRETATION: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effectiveness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients.

Impact of a specialised palliative care intervention in patients with advanced soft tissue sarcoma - a single-centre retrospective analysis.

BACKGROUND: Soft tissue sarcomas (STS) account for less than 1% of all malignancies. Approximately 50% of the patients develop metastases with limited survival in the course of their disease. For those patients, palliative treatment aiming at symptom relief and improvement of quality of life is most important. However, data on symptom burden and palliative intervention are limited in STS patients. AIM: Our study evaluates the effectiveness of a palliative care intervention on symptom relief and quality of life in STS patients. DESIGN/SETTING: We retrospectively analysed 53 inpatient visits of 34 patients with advanced STS, admitted to our palliative care unit between 2012 and 2018. Symptom burden was measured with a standardised base assessment questionnaire at admission and discharge. RESULTS: Median disease duration before admission was 24 months, 85% of patients had metastases. The predominant indication for admission was pain, weakness and fatigue. Palliative care intervention led to a significant reduction of pain: median NRS for acute pain was reduced from 3 to 1 (p < 0.001), pain within the last 24 h from 5 to 2 (p < 0.001) and of the median MIDOS symptom score: 18 to 13 (p < 0.001). Also, the median stress level, according to the distress thermometer, was reduced significantly: 7.5 to 5 (p = 0.027). CONCLUSIONS: Our data underline that specialised palliative care intervention leads to significant symptom relief in patients with advanced STS. Further efforts should aim for an early integration of palliative care in these patients focusing primarily on the identification of subjects at high risk for severe symptomatic disease.

CONKO-006: A randomised double-blinded phase IIb-study of additive therapy with gemcitabine + sorafenib/placebo in patients with R1 resection of pancreatic cancer - Final results.

BACKGROUND: CONKO-006 was designed for patients with pancreatic adenocarcinoma with postsurgical R1 residual status to evaluate the efficacy and safety of the combination of gemcitabine and sorafenib (GemSorafenib) compared with those of gemcitabine + placebo (GemP) for 12 cycles. PATIENTS AND METHODS: This randomised, double-blind, placebo-controlled, multicenter study was planned to detect an improvement in recurrence-free survival (RFS) from 42% to 60% after 18 months. Secondary objectives were overall survival (OS), safety and duration of treatment. RESULTS: 122 patients were included between 02/2008 and 09/2013; 57 were randomised to GemSorafenib and 65 to GemP. Patient characteristics were wellbalanced (GemSorafenib/GemP) in terms of median age (63/63 years), tumour size (T3/T4: 97/97%), and nodal positivity (86/85%). Grade 3/4 toxicities comprised diarrhoea (GemSorafenib: 12%; GemP: 2%), elevated gamma-glutamyl transferase (GGT) (19%; 9%), fatigue (5%; 2%) and hypertension (5%; 2%), as well as neutropenia (18%; 25%) and thrombocytopenia (9%; 2%). By August 2017, 118 (97%) RFS event had occurred. There were no difference in RFS (median GemSorafenib: 8.5 versus GemP: 9.4 months; p = 0.730) nor OS (median GemSorafenib: 17.6 versus GemP: 17.5 months; p = 0.481). Landmark analyses suggest that patients who received more than six cycles of postoperative chemotherapy had significantly longer OS (p = 0.021). CONCLUSION: CONKO-006 is the first randomised clinical trial to include exclusively patients with PDAC with postsurgical R1 status thus far. Sorafenib added to gemcitabine did neither improve RFS nor OS. However, postoperative treatment exceeding six months seemed to prolong survival and should be further investigated in these high-risk patients. CLINICAL TRIAL INFORMATION: German Tumor Study Registry (Deutsches Krebsstudienregister), DRKS00000242.

Randomized, double-blind, placebo-controlled phase II study of istiratumab (MM-141) plus nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine in front-line metastatic pancreatic cancer (CARRIE).

BACKGROUND: Preclinical data suggest that dual blockade of the insulin-like growth factor-1 receptor (IGF-1R) and HER3 pathways has superior activity to IGF-1R blockade alone in pancreatic ductal adenocarcinoma (PDAC). We tested whether istiratumab, an IGF-1R- and ErbB3-bispecific antibody, can enhance the efficacy of standard of care (SOC) chemotherapy in patients with metastatic PDAC selected for high IGF-1 serum levels. PATIENTS AND METHODS: CARRIE was an international, randomized, double-blind, placebo-controlled phase II study for patients with previously untreated metastatic PDAC. In part 1, 10 patients were evaluated for pharmacokinetics and safety. In part 2, patients with high free serum IGF-1 levels were randomized 1 : 1 to receive either istiratumab [2.8 g intravenously (i.v.) every 2 weeks] or placebo combined with gemcitabine/nab-paclitaxel at approved dose schedule. The co-primary endpoints were progression-free survival (PFS) in patients with high IGF-1 levels and PFS in patients with both high serum IGF-1 levels and heregulin (HRG)+ tumors. Key secondary endpoints were overall survival (OS), objective response rate (ORR) by RECIST v.1.1, and adverse events (AEs) rate. RESULTS: A total of 317 patients were screened, with 88 patients randomized in part 2 (experimental arm n = 43; control n = 45). In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42). Median OS and ORR for the overall population were similar between two arms. No significant difference in serious or grade ≥3 AEs was observed, although low-grade AEs leading to early discontinuation were higher in the experimental (39.5%) versus control arm (24.4%). CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. High serum IGF-1 levels did not appear to be an adverse prognostic factor when compared with non-biomarker-selected historic controls. CLINICAL TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov: NCT02399137; EUDRA CT: 2014-004572-34.

The Falciform Ligament for Mesenteric and Portal Vein Reconstruction in Local Advanced Pancreatic Tumor: A Surgical Guide and Single-Center Experience.

BACKGROUND: Since local tumor infiltration to the mesenteric-portal axis might represent a challenging assignment for curative intended resectability during pancreatic surgery, appropriate techniques for venous reconstruction are essential. In this study, we acknowledge the falciform ligament as a feasible and convenient substitute for mesenteric and portal vein reconstruction with high reliability and patency for local advanced pancreatic tumor. METHODS: A retrospective single-center analysis. Between June 2017 and January 2018, a total of eleven consecutive patients underwent pancreatic resections with venous reconstruction using falciform ligament. Among them, venous resection was performed in nine cases by wedge and in two cases by full segment. Patency rates and perioperative details were reviewed. RESULTS: Mean clamping time of the mesenteric-portal blood flow was 34 min, while perioperative mortality rate was 0%. By means of Duplex ultrasonography, nine patients were shown to be patent on the day of discharge, while two cases revealed an entire occlusion of the mesenteric-portal axis. Orthograde flow demonstrated a mean value of 34 cm/s. All patent grafts on discharge revealed persistent patency within various follow-up assessments. CONCLUSION: The falciform ligament appears to be a feasible and reliable autologous tissue for venous blood flow reconstruction with high postoperative patency. Especially the possibility of customizing graft dimensions to the individual needs based on local findings allows an optimal size matching of the conduit. The risk of stenosis and/or segmental occlusion may thus be further reduced.

Human equilibrative nucleoside transporter 1 expression analysed by the clone SP 120 rabbit antibody is not predictive in patients with pancreatic cancer treated with adjuvant gemcitabine - Results from the CONKO-001 trial.

BACKGROUND: High expression of human equilibrative nucleoside transporter 1 (hENT1) is considered to predict survival in patients treated with adjuvant gemcitabine for pancreatic cancer. A standard evaluation system for immunohistochemical analysis (antibody, scoring system) has not yet been established. METHODS: CONKO-001, a prospective randomised phase III study investigated the role of adjuvant gemcitabine (gem) as compared to observation (obs). Tumour samples of 156 patients were analysed by immunohistochemistry with the rabbit monoclonal antibody SP120 (Ventana Medical Systems) for expression of hENT1. Kaplan-Meier analyses for median disease-free survival (DFS) and overall survival (OS) were performed in dependence of hENT1 expression measured analogously to Farrell et al. 2009 and Poplin et al. 2013. RESULTS: For the 88 gem and 68 obs patients, median DFS/OS was 12.9/22.7 months and 6.2/19.1 months. High hENT1 expression was not associated with improved median DFS (Farrell: no hENT1 22.2 months, low hENT1 13.7 months, high hENT1 12.1 months, p=0.248; Poplin: low hENT1 13.2 months versus high hENT1 11.5 months, p=0.5) or median OS (Farrell: no hENT1 21.7 months, low hENT1 24.7 months, high hENT1 19.5, p=0.571; Poplin: low hENT1 24.4 months versus high hENT1 19.7 months, p=0.92;) in the gem group or in the obs group (median DFS Farrell: no hENT1 5.1 months, low hENT1 6.2 months, high hENT1 7.5 months, p=0.375; Poplin: low hENT1 6.2 months versus high hENT1 5.9 months, p=0.83; median OS Farrell: no hENT1 20.2months, low hENT1 17.7 months, high HENT1 19.1 months, p=0.738; Poplin: low hENT1 17.7 months versus high hENT1 20.4 months, p=0.65) measured by the Farrell or Poplin Score. CONCLUSIONS: We cannot confirm a predictive role of hENT1 measured by the clone SP120 rabbit antibody in our study population. Reproducible standard procedures are urgently needed prior to the implementation or exclusion of hENT1 as a predictive biomarker in the treatment of pancreatic cancer. TRIAL REGISTRATION: ISRCTN34802808.

Intensity-modulated and image-guided radiotherapy in patients with locally advanced inoperable pancreatic cancer after preradiation chemotherapy.

BACKGROUND: Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. METHODS: Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. RESULTS: 15 (68%) women and 7 men (median age 64 years; range 40-77) were identified. Median duration of PRCT was 11.1 months (range 4.3-33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9-54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P = 0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P = 0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P = 0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT < 9 months group (P = 0.049). CONCLUSIONS: IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy.

α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study.

BACKGROUND: Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients. METHODS: CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome. RESULTS: High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival. CONCLUSIONS: Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.

SPARC expression in resected pancreatic cancer patients treated with gemcitabine: results from the CONKO-001 study.

BACKGROUND: Previous investigations in pancreatic cancer suggested a prognostic role for secreted protein acidic and rich in cysteine (SPARC) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared with untreated patients. PATIENTS AND METHODS: CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine when compared with observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue microarrays to evaluate its impact on patient outcome. RESULTS: Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011). Again the effect was restricted to patients treated with gemcitabine (DFS: P = 0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was independently predictive of patient outcome. CONCLUSIONS: Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.

[Multimodal treatment of pancreatic cancer]. / Multimodale Therapie des Pankreaskarzinoms.

Adenocarcinoma of the exocrine pancreas is one of the most aggressive types of solid tumor and stands at fourth position in the tumor death frequency scale due to a high mortality rate. Effective screening methods are not available and only radical surgery offers a curative option. With adjuvant chemotherapy the median survival time can be prolonged up to 23 months and approximately 25 % of patients are still alive after 5 years. Of these patients approximately 75-80 % are already in a palliative therapy situation at the time of diagnosis. In the last 5 years treatment options have been increased by the introduction of new chemotherapeutic drugs. For patients with metastasized disease median survival times of 6-12 months can currently be achieved depending on the general performance status at diagnosis but less than 5 % of these patients are still alive after 5 years. Neoadjuvant treatment strategies, radiation and immunotherapy do not play a role in evidence-based clinical practice. Despite progress in the understanding of cancer biology and new treatment options, non-resectable adenocarcinoma of the pancreas remains a disease with a very poor prognosis.

[Primary pharmacological prevention of thromboembolic events in ambulatory patients with advanced pancreatic cancer treated with chemotherapy?]. / Primäre medikamentöse Thromboembolieprophylaxe bei ambulanten Patienten mit fortgeschrittenem Pankreaskarzinom unter Chemotherapie?

BACKGROUND AND OBJECTIVE: The indication for medical venous thrombosis prophylaxis in ambulatory cancer patients is still under discussion. To provide more data on this topic we conducted an analysis in ambulatory patients with advanced pancreatic adenocarcinoma, reflecting a patient cohort at high risk of symptomatic venous thromboembolism (sVTE). PATIENTS AND METHODS: Data from 312 consecutively recruited patients of the CONKO-004 trial were analysed according to predefined parameters and additionally with respect to established scores. To focus on patients with highest risk of sVTE unvaried and multivariate analyses were conducted. RESULTS: The global analyses had educed a number needed to treat (NNT) by medical thrombosis prophylaxis of 12 patients to prevent one sVTE. The modified score model did not provide further clinical benefit. However, the regression model can identify single parameters with a trend to higher risk of sVTE or higher risk of severe bleeding. Most of the parameters do not have enough power to be significant, but they can support clinical decisions. CONCLUSION: These data suggest that medical thrombosis prophylaxis should be performed in patients with advanced pancreatic cancer at least for the initial 3 months of first line chemotherapy.

Blood group determinates incidence for pancreatic cancer in Germany.

BACKGROUND: Genetic risk factors for sporadic pancreatic cancer are largely unknown but actually under high exposure. Findings of correlations between the AB0 blood group system (Chromosome 9q34,1-q34,2) and the risk of pancreatic cancer (PC) in patients from Asia, America and south Europe have already been published. So far it is unclear, whether this correlation between blood group an PC incidence can be found in German patients as well. METHODS: One hundred and sixty-six patients who underwent a resection of PC were evaluated in a period between 2000 and 2010. Blood group reference distribution for the German population is given as: 0: 41%; A: 43%; B: 11%; AB: 5%; Rhesus positive: 85%; Rhesus negative: 15%. Analyses were done using the non-parametric Chi(2)-test (p-value two sided; SPSS 19.0). RESULTS: Median age was 62 (34-82) years. Gender: female 73/44%; male: 93/56%. Observed blood group proportions: 0: 43 (25.9%)/A: 94 (56.6%)/B: 16 (9.6%)/AB: 13 (7.8%)/Rhesus positive: 131 (78.9%)/negative: 35 (21.1%). We detected a significant difference to the German reference distribution of the AB0 system (Chi(2) 19.34, df 3, p < 0.001). Rhesus factor has no impact on AB0-distribution (Chi(2) 4.13, df 3, p = 0.25), but differs significantly from reference distribution-probably due to initial AB0-variation (Chi(2) 4.82, df 1, p = 0.028). The odds ratio for blood group A is 2.01 and for blood group 0 is 0.5. CONCLUSIONS: The incidence of PC in the German cohort is highly associated with the AB0-system as well. More patients with blood group A suffer from PC (p < 0.001) whereas blood group 0 was less frequent in patients with PC (p < 0.001). Thus, our findings support the results from other non-German surveys. The causal trigger points of this carcinogenesis correlation are still not known.

The impact of simultaneous liver resection for occult liver metastases of pancreatic adenocarcinoma.

Backround. Pancreas resection is the only curative treatment for pancreatic adenocarcinoma. In the event of unexpected incidental liver metastases during operative exploration patients were traditionally referred to palliative treatment arms. With continuous progress in the surgical expertise simultaneous pancreas and liver resections seem technically feasible nowadays. The aim of this study therefore was to analyze the impact of synchronous liver-directed therapy on operative outcome and overall survival in patients with hepatic metastasized pancreatic adenocarcinoma (HMPA). Methods. 22 patients who underwent simultaneous pancreas resection and liver-directed therapy for HMPA between January 1, 2004 and January 1, 2009 were compared to 22 patients who underwent classic pancreas resection for nonmetastasized pancreatic adenocarcinoma (NMPA) in a matched pair study design. Postoperative morbidity, preoperative, and operative data and overall survival were analyzed. Results. Overall survival was significantly decreased in the HMPA group. Postoperative morbidity and mortality and median operation time did not significantly differ between the groups. Conclusion. The results of our study showed that simultaneous pancreas resection and liver-directed therapy may safely be performed and may therefore be applied in individual patients with HMPA. However, a potential benefit of this radical surgical approach with regard to overall survival and/or quality of life remains to be proven.

First-line chemotherapy in advanced pancreatic cancer.

This chapter focuses on first-line therapy in inoperable pancreatic cancer.

Second-line chemotherapy in advanced pancreatic cancer.

This chapter focuses on second-line therapy in inoperable pancreatic cancer.