Palliative care of pancreatic cancer. Highlights from the "2011 ASCO Annual Meeting". Chicago, IL, USA; June 3-7, 2011

Pancreatic cancer is one of the most fatal malignancies. Palliative care represents an important aspect of management in patients with pancreatic malignancy. Identifying and treating disease related symptoms are very important. As a physician taking care of these patients it is essential to know these symptoms and treatment modalities. Common problems include biliary obstruction, anticoagulation, and pain management. This review discusses the data presented at the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting symptom management and supportive care strategies including Abstracts #e14665, #e14622, and #LBA9014. Success is needed in managing these symptoms to palliate patients with advanced pancreatic cancer. It is important for oncologists to recognize the importance of supportive measures that can minimize the symptoms of advanced disease and side effects of cancer treatment.     

Survival analysis according to treatment modality in pancreatic cancer patient]

BACKGROUND/AIMS: Pancreatic cancer is the 5(th) leading cause of cancer death in Korea and its incidence is increasing. At present, surgical resection offers the best chance of cure. However, most of pancreatic cancers are already unresectable at initial diagnosis. Thus, the majority of patients depend on chemotherapy, radiotherapy, or supportive care. We investigated the effect of treatment modalities on the survival in pancreatic cancer. METHODS: Between September 1994 and May 2003, one hundred and fifty four patients with pancreatic cancer were treated by surgery, radiotherapy, chemotherapy or conservative management. The clinical datas were analyzed retrospectively for survival according to stage and treatment modality. RESULTS: Overall median survival time was 5.7 months and 1 year survival rate was 18.3%. In patients with stage I to III disease, the median survival time was 13.9 months in surgery group, 10.2 months in radiation group, and 6.1 months in supportive care group (p%lt;0.01). Survival rate according to treatment modality was significantly different among groups. In patients with stage IV disease, the median survival time was 6.1 months in radiation therapy group, 7.1 months in chemotherapy group, and 2.7 months in supportive care group. Overall survival was significantly higher in treatment groups than in supportive care group (p<0.01), but there was no difference in survival between chemotherapy group and radiotherapy group. CONCLUSIONS: In patients with stage I to III pancreatic cancer, surgery can improve median survival. In patients with stage IV, either chemotherapy or radiotherapy can prolong survival compared to supportive care. These results suggest that more active treatment of pancreatic cancer even in advanced stage will be needed to prolong the survival.     

Quality of life in patients with pancreatic cancer

Pancreatic cancer is a rapidly fatal disease with palliation often serving as the main goal of treatment. The end of life is often marked by severe symptoms and poor quality of life (QoL). Several studies presented at the 2012 ASCO Gastrointestinal Cancers Symposium addressed the importance of symptom identification and management for patients with pancreatic cancer: 1) a study evaluating the correlation between patient-reported symptoms, disease burden and treatment duration in patients with advanced pancreatic cancer undergoing gemcitabine-based chemotherapy (Abstract #370); 2) a Japanese study found that patients without worsening of pain or sleep symptoms at one month of chemotherapy had higher frequency of disease control (Abstract #195); and 3) a study showed that fear of cancer recurrence is a substantial problem following resection and should be targeted (Abstract #289). The authors summarize the findings and discuss the importance of QoL in these patients. The results of these studies may facilitate in identifying symptom changes as predictive markers, and improving care and QoL for patients with this devastating disease.     

Endoscopic retrograde cholangiopancreatography guided interventions in the management of pancreatic cancer

Pancreatic cancer is the leading cause of cancer-related morbidity and mortality with an overall five-year survival of less than 9% in the United States. At presentation, the majority of patients have painless jaundice, pruritis, and malaise, a triad that develops secondary to obstruction, which often occurs late in the course of the disease process. The technical advancements in radiological imaging and endoscopic interventions have played a crucial role in the diagnosis, staging, and management of patients with pancreatic cancer. Endoscopic retrograde cholangiopancreatography(ERCP)-guided diagnosis(with brush cytology, serial pancreatic juice aspiration cytologic examination technique, or biliary biopsy) and therapeutic interventions such as pancreatobiliary decompression, intraductal and relief of gastric outlet obstruction play a pivotal role in the management of advanced pancreatic cancer and are increasingly used due to improved morbidity and complication rates compared to surgical management. In this review, we highlight various ERCP-guided diagnostic and therapeutic interventions for the management of pancreatic cancer.     

Surgical and interventional treatment of chronic pancreatitis.

The management of patients with chronic pancreatitis (CP) remains a challenging problem. Main indications for surgery are intractable pain, suspicion of malignancy, and involvement of adjacent organs. The main goal of surgical treatment is improvement of patient quality of life. The surgical treatment approach usually involves proximal pancreatic resection, but lateral pancreaticojejunal drainage may be used for large-duct disease. The newer duodenum-preserving head resections of Beger and Frey provide good pain control and preservation of pancreatic function. Thoracoscopic splanchnicectomy and the endoscopic approach await confirmatory trials to confirm their efficiency in the management of CP. Common bile duct obstruction is addressed by distal Roux-en-Y choledochojejunostomy but when combined with dudodenal obstruction must be treated by pancreatic head resection. Pancreatic ascites due to disrupted pancreatic duct should be treated by internal drainage. The approach to CP is multidisciplinary, tailoring the various therapeutic options to meet each individual patient's needs.     

Pancreatic cancer: A review of clinical diagnosis,epidemiology, treatment and outcomes

This review aims to outline the most up-to-date knowledge of pancreatic adenocarcinoma risk, diagnostics, treatment and outcomes, while identifying gaps that aim to stimulate further research in this understudied malignancy. Pancreatic adenocarcinoma is a lethal condition with a rising incidence, predicted to become the second leading cause of cancer death in some regions. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Better understanding of the risk factors and symptoms associated with this disease is essential to inform both health professionals and the general population of potential preventive and/or early detection measures. The identification of high-risk patients who could benefit from screening to detect pre-malignant conditions such as pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is urgently required, however an acceptable screening test has yet to be identified. The management of pancreatic adenocarcinoma is evolving, with the introduction of new surgical techniques and medical therapies such as laparoscopic techniques and neo-adjuvant chemoradiotherapy, however this has only led to modest improvements in outcomes. The identification of novel biomarkers is desirable to move towards a precision medicine era, where pancreatic cancer therapy can be tailored to the individual patient, while unnecessary treatments that have negative consequences on quality of life could be prevented for others. Research efforts must also focus on the development of new agents and delivery systems. Overall, considerable progress is required to reduce the burden associated with pancreatic cancer. Recent, renewed efforts to fund large consortia and research into pancreatic adenocarcinoma are welcomed, but further streams will be necessary to facilitate the momentum needed to bring breakthroughs seen for other cancer sites.     

Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer

Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy. The only curative option is surgical resection, but only 15%-20% of patients are resectable at presentation because more than 50% of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer (LAPC). The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy. Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC. There are increasing number of studies evaluating these novel ablative techniques, including radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation. Most studies which included pancreatic tumor ablation, demonstrated improved overall survival in LAPC patients. However, the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations. Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%. The most common metastatic site is the liver as 90% of pancreatic cancer patients develop liver metastasis. Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer. However, when the tumor is not responding to chemotherapy or severe drug toxicity develops, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients. During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients. These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures. This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.     

Preoperative diagnosis of extrapancreatic neural invasion in pancreatic cancer.

BACKGROUND & AIMS: Pancreatic cancer recurs in most patients after resection with curative intent. Recurrence is particularly common in patients with extrapancreatic neural invasion (EPNI), the presence of which correlates with poor prognosis. Macroscopic EPNI may be detected with conventional noninvasive imaging and endoscopic ultrasound (EUS) imaging, but microscopic EPNI has required postoperative pathologic examination of surgical specimens. We report the preoperative diagnosis of cancer infiltration into celiac ganglia. We hypothesized that microscopic pancreatic cancer metastasis to neural ganglia can be detected by EUS-guided biopsy examination. METHODS: We performed a retrospective review of patients with pancreatic cancer undergoing EUS in whom celiac ganglia were sampled to exclude malignant infiltration. RESULTS: Six patients with pancreatic cancer underwent EUS-guided fine-needle aspiration or trucut biopsy examination of presumed celiac ganglia. Metastatic cancer was found in ganglia of 2 patients. Specimen review identified adenocarcinoma and neural tissue in the absence of lymphocytes. At laparoscopy, 1 of the 2 patients with positive celiac biopsy specimens also had several unexpected peritoneal metastatic deposits. The other patient was considered to have locally advanced unresectable disease. Both patients are receiving supportive care. CONCLUSIONS: EPNI may be shown preoperatively in patients with pancreatic cancer using EUS-guided sampling of celiac ganglia. A preoperative diagnosis of EPNI has the potential to improve staging accuracy and patient outcomes.     

Selection criteria in resectable pancreatic cancer: A biological and morphological approach

Pancreatic ductal adenocarcinoma (PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.     

A case of a bloated face: SVC syndrome relieved by an endovascular approach

Superior vena cava (SVC) syndrome, or obstruction of blood returning from the head and upper extremities, is a syndrome that is rapidly increasing in the cardiovascular patient population due to the increasing use of transvenous devices such as permanent pacemakers, implantable cardioverter defibrillators (ICDs), and indwelling venous access devices for hemodialysis. This syndrome in the past has been seen predominately in the cancer population with malignancy being the most common reason for SVC syndrome. The management of this syndrome has largely been with a medical/supportive care approach or with surgical bypass. Given the advancement in the field of endovascular interventions and the increasing expertise in performing these procedures, an endovascular approach to relieving the SVC obstruction is rapidly becoming the treatment of choice for these patients. We describe a case of a patient who had a chronic indwelling port-a-cath who developed SVC syndrome, which was treated with an endovascular approach with stenting of the SVC/brachiocephalic vein junction.     

Current options for palliative treatment in patients with pancreatic cancer

Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression.     

Surgery for pancreatic cancer: recent controversies and current practice

Pancreatic duct carcinoma remains a common disease with a poor prognosis. More than 30,000 Americans will die of the disease in 2004, making it the fourth leading cause of cancer death. Despite significant advances in the treatment of many other human tumors, the 5-year survival rate for persons diagnosed with pancreatic cancer has not changed in decades and remains <5%. This is due both to the inherently aggressive biology of the disease and to its late diagnosis in most cases. Surgical resection of localized disease remains the only hope for cure of pancreatic cancer. Over the past 2 decades, significant advances in diagnostic imaging, staging, surgical technique, and perioperative care have led to marked improvement in the surgical management of pancreatic cancer patients. Operative mortality rates for pancreaticoduodenectomy are now <5% at major centers, and the average length of hospital stay has been reduced to <2 weeks. Improvements in patient outcome after pancreatic cancer surgery have made possible, for the first time, the design and conduct of large adjuvant therapy studies in pancreatic cancer. Such clinical trials are critical for improving outcomes for pancreatic cancer patients.     

What's new in pancreatic cancer treatment?

Pancreatic cancer represents a major challenge to oncologists because of its high chemoresistant nature and dismal outcomes. Conventional therapy for advanced disease relied for a long time on palliative 5‐fluorouracil (5‐FU)‐based chemotherapy, but with unsatisfactory results. The introduction of the novel antimetabolite gemcitabine provides new optimism for patients with advanced pancreatic cancer, as multiple clinical trials have demonstrated the superiority of gemcitabine over 5‐FU and other agents for these patients. The benefits of gemcitabine over conventional therapies include improved response rate and enhanced survival, as well as improvement in disease‐related symptoms and quality of life in these patients. With these data, gemcitabine is widely accepted worldwide as the therapy of choice by many oncologists for advanced pancreatic cancer. The current review presents an overview of the clinical studies of gemcitabine over the past decade for the treatment of patients with advanced pancreatic cancer. Other investigational regimens or uses (e.g., fixed dose‐rate infusion, intraarterial infusion, adjuvant use, chemo‐radiation, etc) are also reviewed.     

Advances in cryoablation for pancreatic cancer

Pancreatic carcinoma is a common cancer of the digestive system with a poor prognosis. It is characterized by insidious onset, rapid progression, a high degree of malignancy and early metastasis. Atpresent, radical surgery is considered the only curative option for treatment, however, the majority of patients with pancreatic cancer are diagnosed too late to undergo surgery. The sensitivity of pancreatic cancer to chemotherapy or radiotherapy is also poor. As a result, there is no standard treatment for patients with advanced pancreatic cancer. Cryoablation is generally considered to be an effective palliative treatment for pancreatic cancer. It has the advantages of minimal invasion and improved targeting, and is potentially safe with less pain to the patients. It is especially suitable in patients with unresectable pancreatic cancer. However, our initial findings suggest that cryotherapy combined with 125-iodine seed implantation, immunotherapy or various other treatments for advanced pancreatic cancer can improve survival in patients with unresectable or metastatic pancreatic cancer. Although these findings require further in-depth study, the initial results are encouraging. This paper reviews the safety and efficacy of cryoablation, including combined approaches, in the treatment of pancreatic cancer.     

舒缓护理在晚期结直肠癌合并肠梗阻患者中的应用探索

目的探讨舒缓护理在晚期结直肠癌合并肠梗阻患者中的应用。 方法收集2015年3月到2017年3月两年间对晚期结直肠癌合并肠梗阻的患者采取常规护理基础上给予舒缓护理的326例,于舒缓护理前后进行及时问卷调查或访谈,了解患者生理和生活质量等各项指标的变化情况。 结果晚期结直肠癌合并肠梗阻的患者在接受常规基础上的舒缓护理后,肠梗阻症状及其导致的其他不适症状如睡眠质量差、焦虑、烦躁等症状得到很好改善,更愿意与医护人员主动进行交流,对疾病治疗和生活更有信心,患者与家属情绪更和缓,关系更和谐。 结论舒缓护理的应用有助于缓解结直肠癌合并肠梗阻患者的症状,提高患者生活质量,在临床中具有应用价值。     

Supportive care for symptom relief in pancreatic cancer

Unfortunately, only a minority of patients with pancreatic cancers are suitable for resection and potential cure. Despite recent advances in systemic treatment of patients with advanced pancreatic cancer, the prognosis still remains poor. The median survival of patients in whom pancreatic cancers are surgically unresectable is 6 months. Thus, optimal palliation of symptoms to maximize remaining quality of life is of primary importance to most patients. Common problems include pain, unexplained weight loss, nausea, vomiting, streatorrhea, dyspepsia, depression, and jaundice. Management is directed at the palliation of symptoms. Treatment of patients with locally unresectable, recurrent, or metastatic disease is individualized, considering the patient age, patient wishes, family influence, and insurance constraints. Success in managing progressive symptoms is needed to palliate patients with advanced pancreatic cancer.     

Adjuvant and neoadjuvant treatment in pancreatic cancer

Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes "standard" adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.     

Molecular targets for the treatment of pancreatic cancer:Clinical and experimental studies

Pancreatic cancer is the fourth most common cause of cancer deaths worldwide. Although recent therapeutic developments for patients with pancreatic cancer have provided survival benefits, the outcomes for patients with pancreatic cancer remain unsatisfactory. Molecularly targeted cancer therapy has advanced in the past decade with the use of a number of pathways as candidates of therapeutic targets. This review summarizes the molecular features of this refractory disease while focusing on the recent clinical and experimental findings on pancreatic cancer. It also discusses the data supporting current standard clinical outcomes, and offers conclusions that may improve the management of pancreatic cancer in the future.     

Pancreatic adenocarcinoma: Beyond first line,where are we?

Pancreatic cancer is considered one of the most aggressive cancers, with an increasing incidence in recent years. To date, chemotherapy is still the standard of care for advanced metastatic disease, unfortunately providing only a slight advantage in terms of survival. The molecular and cellular characteristics of pancreatic cancer cells, as well as the cells that characterize the pancreatic tumour microenvironment, are the basis of the mechanisms of resistance to treatment. After progression during first-line treatment, few patients are eligible for second-line treatment due to the loss of performance status. To date, a clear survival advantage has not yet been demonstrated for second-line chemotherapy. Precision medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat disease. In this review, we analyze current recommendations in the second-line setting and potential future prospects.     

Therapeutic options for the management of pancreatic cancer

Since its initial characterization, pancreatic ductal adenocarcinoma has remained one of the most devastating and difficult cancers to treat. Pancreatic cancer is the fourth leading cause of death in the United States, resulting in an estimated 38460 deaths annually. With few screening tools available to detect this disease at an early stage, 94% of patients will die within five years of diagnosis. Despite decades of research that have led to a better understanding of the molecular and cellular signaling pathways in pancreatic cancer cells, few effective therapies have been developed to target these pathways. Other treatment options have included more sophisticated pancreatic cancer surgeries and combination therapies. While outcomes have improved modestly for these patients, more effective treatments are desperately needed. One of the greatest challenges in the future of treating this malignancy will be to develop therapies that target the tumor microenvironment and surrounding pancreatic cancer stem cells in addition to pancreatic cancer cells. Recent advances in targeting pancreatic stellate cells and the stroma have encouraged researchers to shift their focus to the role of desmoplasia in pancreatic cancer pathobiology in the hopes of developing newer-generation therapies. By combining novel agents with current cytotoxic chemotherapies and radiation therapy and personalizing them to each patient based on specific biomarkers, the goal of prolonging a patient’s life could be achieved. Here we review the most effective therapies that have been used for the treatment of pancreatic cancer and discuss the future potential of therapeutic options.