Biliary palliation for unresectable pancreatic adenocarcinoma: surgical bypass or self-expanding metal stent?

BackgroundStandard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration.MethodsSingle institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration. Short-term, long-term, and lifetime risk of biliary occlusion and survival were compared after adjustment for stage and comprehensive complication index (CCI).ResultsBaseline demographics and tumor characteristics were equivalent between cohorts. Short-term complications were more frequent after OSBB, whereas late complications were greater after SEMS. The cumulative incidence of recurrent biliary obstruction was greater after SEMS, but lifetime complication burden and median survival were equivalent.ConclusionOSBB was associated with longer hospital stays and more short-term complications, and SEMS was associated with a higher risk of recurrent biliary obstruction among surgical patients with unresectable PDAC. Patient preference should be defined pre-operatively in the case the unresectable disease is encountered during attempted resection.     

Celiac plexus neurolysis in the management of unresectable pancreatic cancer: When and how?

Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20% resectability at diagnosis, and overall 5-year survival of 5%. Pain is common in pancreatic cancer patients with 70%-80% suffering substantial pain. Celiac plexus neurolysis (CPN) is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption. CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia. This review sets out to explore the current status of CPN in non-resectable pancreatic cancer. We will examine: (1) the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN; (2) specific technique modifications including bilateral (vs central) injections and celiac ganglia neurolysis; and (3) the issue of CPN timing, early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.     

Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27–3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death.     

Thymidylate synthase expression in resectable and unresectable pancreatic cancer: role as predictive or prognostic marker?

Background and aims Thymidylate synthase (TS) is an important enzyme for DNA synthesis and the target for 5-fluorouracil (5-FU). Its expression may determine the outcome of patients with gastrointestinal cancers. We examined the prognostic and predictive value of TS-protein expression in patients with ductal adenocarcinoma of the pancreas.Methods TS expression from 131 patients with ductal adenocarcinoma of the pancreas was analyzed by immunohistochemistry in paraffin-embedded primary tumour specimens or biopsies.Results The median disease-specific survival among all patients (n=131) was 13 months. The invasion depth, the presence of metastases, grading and Union Internationale Contre le Cancer [International Union Against Cancer] (UICC) stage were associated with survival. Among resected patients (n=98), a difference in median survival was seen in the group receiving postoperative adjuvant treatment (21.1 months) compared with the group treated by surgery alone (12.4 months) (p=0.025). Low- and high-TS immunoreactivity was present in 74 (56%) and 56 (43%) of the cancers, respectively. One sample was not evaluable. No difference in median survival was observed among low- and high-TS-expressing tumours. Among patients undergoing resection and receiving postoperative intra-arterial chemotherapy (n=23), a marked trend to a longer median survival was seen for the group with low-TS-expressing tumours compared with the corresponding high-TS group (25.0 vs 16.0 months) (p=0.3834). There was no difference in survival among all palliative treated patients with low- and high-TS-expressing tumours.Conclusion Especially patients undergoing tumour resection with low-TS values seemed to have taken advantage from an intensified postoperative chemotherapeutic protocol. However due to the heterogeneous group of patients in the present report, larger trials of more homogenous patient populations will be necessary to confirm this hypothesis.     

Chemotherapy as initial treatment of locally advanced unresectable pancreatic cancer: a valid option?

INTRODUCTION: Radio-chemotherapy is the standard treatment for locally advanced unresectable pancreatic cancer (LAPC). Chemotherapy has been shown to be effective in the treatment of metastatic disease and we therefore evaluated its use as a first-line treatment for LAPC. PATIENTS AND METHODS: We carried out a retrospective analysis of all consecutive patients treated for LAPC (N=33) between July 1997 and April 2005, analysing the results of first-line chemotherapy (CT group) and radio-chemotherapy (RCT group) in this setting. RESULTS: The first-line treatment was RCT in six patients (18.3%) and CT in 26 patients (78.8%). Secondary treatment was administered to nine patients of CT group with well-controlled disease: "closure" radio-chemotherapy for seven patients (26.9%) and secondary resection for three (12%). After a median follow-up of 27 months, 23 patients died (69.7%). Overall survival was 13.8 months [95% CI: 10.1-19.4] for the whole population, 9.5 months [95% CI: 4.6-] for the RCT and 18.0 months [95% CI: 12.4-25.5] for the CT. Overall survival for the CT patients undergoing secondary surgery or "consolidation" radio-chemotherapy was 28.8 months [95% CI: 13.8-]. CONCLUSION: First-line chemotherapy is a valid option for LAPC treatment, making it possible to identify the patients who may benefit from secondary resection or radio-chemotherapy.     

Does pre‐operative chemoradiation for initially unresectable or borderline resectable pancreatic adenocarcinoma increase post‐operative morbidity? A case‐matched analysis

Background

Neoadjuvant chemoradiation therapy for locally unresectable and borderline resectable pancreatic cancer may allow some patients to a undergo a resection, but whether or not this increases post-operative morbidity remains unclear.

Methods

The post-operative morbidity of 29 patients with initially locally unresectable/borderline pancreatic cancer who underwent a resection were compared with 29 patients with initially resectable tumours matched for age, gender, the presence of comorbidities (yes/no), American Society of Anesthesiology (ASA) score, tumour location (head/body-tail), procedure (pancreaticoduodenectomy/distal pancreatectomy) and vascular resection (yes /no). Wilcoxon''s signed ranks test was used for continuous variables and McNemar''s chi-square test for categorical variables.

Results

Compared with patients with initially resectable tumours, patients who underwent a resection after pre-operative chemoradiation therapy had similar rates of overall post-operative complications (55% versus 41%, P = 0.42), major complications (21% versus 21%, P = 1), pancreatic leaks and fistulae (7% versus 10%, P = 1) and mortality (0% versus 1.7%, P = 1).

Conclusion

Although some previous studies have suggested differences in post-operative morbidity after chemoradiation, our case-matched analysis did not find statistical differences in surgical morbidity and mortality associated with pre-operative chemoradiation therapy.     

Cachexia and pancreatic cancer: Are there treatment options?

Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods.     

Neoadjuvant treatment for resectable pancreatic cancer: Time for phase Ⅲ testing?

This paper discusses the rationale for phaseⅢtesting of neoadjuvant therapy in patients affected by resectable pancreatic adenocarcinoma.The therapeutic management of patients affected by resectable pancreatic cancer is particularly troublesome due to the aggressiveness of the disease and to the limited efficacy and sometimes unfavourable risk-benefit ratio of the available therapeutic tools.Conflicting data on the role of adjuvant chemoradiation have been reported,while adjuvant single-agent chemotherapy significantly improved overall survival(OS)when compared to surgery alone. However,the OS figures for adjuvant chemotherapy remain disappointing.In effect,pancreatic cancer exhibits a prominent tendency to recur after a brief median time interval from surgery and extra-pancreatic dissemination represents the predominant pattern of disease failure.Neoadjuvant treatment has a strong rationale in this disease but limited information on the efficacy of this approach is available from single arm trials with low levels of evidence.Thus,in spite of two decades of investigation there is currently no evidence to support the routine use of pre-surgical therapy in clinical practice. To foster knowledge on the optimal management of this disease,and to produce evidence-based treatment guidelines,there is no alternative to well designed randomized trials.Systemic chemotherapy is a candidate for testing because it is supported by a more robust rationale than chemoradiation.Combination chemotherapy regimens with elevated activity in advanced disease warrant investigation.Caution would suggest the running of an exploratory phaseⅡrandomized trial before embarking on a large phase Ⅲ study.     

Minimally invasive surgical techniques for pancreatic cancer: ready for prime time?

Background

Minimally invasive surgical techniques for pancreatic cancer are being applied with increasing frequency. With support of the literature, the location of the tumor within the pancreas is the factor which determines if these techniques can be safely used routinely by pancreatic surgeons.

Methods

Literature supporting minimally invasive techniques for all types of resections for pancreatic cancer was reviewed.

Results

Multiple meta-analysis regarding laparoscopic distal pancreatectomy all support the routine use of laparoscopy for these lesions. There are several case series describing the safety and efficacious use of laparoscopy in pancreaticoduodenectomy, and results have been promising in these highly specialized centers.

Conclusions

The location of the tumor within the pancreas remains the most critical factor in the use of laparoscopy as the standard of care. Lesions in the body and tail, which are readily resected with a distal or subtotal pancreatectomy should be performed laparoscopically unless there is a clear reason why not to do so. Lesions in the head of the pancreas have been shown to be removed safely and effectively with laparoscopy. However, the technical skills necessary and the ability to teach these to trainees are the limiting factors to widespread use. Further series are necessary to assess if the laparoscopic approach to pancreaticoduodenectomy will play a similar role as the one it plays in the surgical treatment for distal lesions.     

Adjuvant strategies for resectable pancreatic cancer: have we made progress?

Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206).     

Intra-arterial therapies for unresectable and chemorefractory colorectal cancer liver metastases: a systematic review and meta-analysis

Background

A large proportion of patients with colorectal cancer liver metastases (CRCLM) not amenable to curative liver resection will progress on systemic therapy. Intra-arterial therapies (IAT) including conventional transarterial chemoembolization (cTACE), drug eluting beads (DEB-TACE) and yttrium-90 radioembolization (Y-90) are indicated to prolong survival and palliate symptoms. The purpose of this systematic review and meta-analysis is to compare the survival benefit and radiologic response of three intra-arterial therapies in patients with chemorefractory and unresectable CRCLM.

Editorial: Neurolysis for pancreatic cancer pain: same song, different verse?

Since Kappis first performed percutaneous neurolysis in 1914, investigators have employed innumerable technical variations in an effort to enhance the efficacy. Similar efforts have been underway by endosonographers since Wiersema performed the first endoscopic ultrasound (EUS)-guided celiac plexus neurolysis in 1996. Although such efforts are important, the availability of multiple procedural options is indicative of the controversy and lack of meaningful progress. If one particular method was clearly superior, the other techniques would have become obsolete. Sakamoto et al. present a new method of EUS-guided neurolysis in an attempt to improve the outcomes. Although their data are promising, we eagerly await rigorously designed studies that may validate their findings.