Pancreatic cancer–Palliative therapy: stenting

Pancreatic cancer remains a common and very lethal malignancy with a median survival of approximately 6 months. Surgical resection offers the only potentially curative approach but many patients (80% or more) are ineligible for this kind of therapy, because of age, comorbidities, or locally advanced or metastatic disease that does not benefit from resection. Thus, for many patients with pancreatic cancer treatment remains palliative and endoscopic therapy to relieve bile duct or gastric outlet obstruction becomes of special importance. Although both surgical and non surgical palliative procedures can relieve biliary and duodenal obstruction particularly endoscopic treatment with plastic prostheses or self expanding metal stents was shown to be not only highly effective but also to be burdened with only few complications. The present article summarizes the palliative endoscopic treatment in patients with non resectable pancreatic cancer.

Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer

In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.

Palliative external-beam radiotherapy for bone metastases from hepatocellular carcinoma

The incidence of bone metastases(BMs)from hepatocellular carcinoma(HCC)is relatively low compared to those of other cancers,but it has increased recently,especially in Asian countries.Typically,BMs from HCC appear radiologically as osteolytic,destructive,and expansive components with large,bulky soft-tissue masses.These soft-tissue masses are unique to bone metastases from HCC and often replace the normal bone matrix and exhibit expansive growth.They often compress the peripheral nerves,spinal cord,or cranial nerves,causing not only bone pain but also neuropathic pain and neurological symptoms.In patients with spinal BMs,the consequent metastatic spinal cord compression(MSCC)causes paralysis.Skull base metastases(SBMs)with cranial nerve involvement can cause neurological symptoms.Therefore,patients with bony lesions often suffer from pain or neurological symptoms that have a severe,adverse effect on the quality of life.External-beam radiotherapy(EBRT)can effectively relieve bone pain and neurological symptoms caused by BMs.However,EBRT is not yet widely used for the palliative management of BMs from HCC because of the limited number of relevant studies.Furthermore,the optimal dosing schedule remains unclear,despite clinical evidence to support single-fraction ra-diation schedules for primary cancers.In this review,we outline data describing palliative EBRT for BMs from HCC in the context of(1)bone pain;(2)MSCC;and(3)SBMs.

Real-world evidence on first-and second-line palliative chemotherapy in advanced pancreatic cancer

In spite of recent diagnostic and therapeutic advances,the prognosis of pancreatic ductal adenocarcinoma(PDAC)remains very poor.As most patients are not amenable to curative intent treatments,optimized palliative management is highly needed.One key question is to what extent promising results produced by randomized controlled trials(RCTs)correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial.To answer such questions,real-world evidence is necessary.The present paper reviews and discusses the current literature on first-and second-line palliative chemotherapy in PDAC.Notably,a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens,i.e.gemcitabine plus nabpaclitaxel(GnP)and folfirinox(FFX),is similar in RCTs and real-life populations.Outcomes of second-line therapy following failure of first-line regimens are still dismal,and considerable uncertainty of the optimal management remains.Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence,such as FFX followed by GnP or vice versa,are urgently needed.Finally,the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.

Tunneled peritoneal catheters for the palliative therapy of malignant ascites

Objective:Malignant ascites presents difficult management issues in the palliative care population and results in distressing symptoms and recurrent hospital admissions.The palliative care services in Our Lady of Lourdes Hospital have been using radiologically guided tunneled peritoneal catheters for the palliative therapy of troublesome malignant ascites.We conducted a review of this management strategy.Methods:There were 10 catheters inserted in 9 patients between May 2007 and June 2011 in patients with malignant ascites.Results:There were no procedural related mortalities or major complications.Mean catheter life was 98.9 days.Post catheter re-hospitalization rate was 1.55 times per patient.Mean patient survival post insertion was 140 days.Eighty eight percent of patients achieved death at home.Conclusion:We conclude that this is a safe and useful strategy in the management of malignant ascites in a palliative care population.

Management of stage Ⅳ rectal cancer: Palliative options

Approximately 30% of patients with rectal cancer present with metastatic disease. Many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease.

Cryotherapy in the management of premalignant and malignant conditions of the esophagus

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.

Palliative surgery for hilar cholangiocarcinoma

OBJECTIVE: To evaluate the results of palliative surgical treatment of hilar cholangiocarcinoma in terms of quality of life, survival period and cholangitis rate. MFTHODS: The clinical data on 232 patients with hilar cholangiocarcinoma in the last 22 years were analyzed retrospectively. Palliative operations included extrahepatic or intrahepatie choledochojejunostomy (123 patients), bridge internal drainage (15), endoscopic biliary drainage (49), percutaneous transhepatic biliary drainage or celiotomy biliary drainage (29), and exploratory celiotomy external drainage (16). RESULTS: In this series, the operative mortality rate was 9.1%, and no significant difference was observed between groups. The rate of cholangitis after operation was significantly lower in Roux-en-Y choledochojejunostomy group (16.2%) and bridge internal drainage group (15.4%) than in internal drainage group (35.5%, P<0.01), including percutaneous transhepatic biliary drainage (PTBD), endoscopic retrograde biliary drainage (ERBD), and celiotomy (or PTBD) external biliary drainage group (39.1%, P<0.01). No significant difference in survival was observed between the Roux-en-Y choledcthojejunostomy group (9.3±1.8 months) and PTBD (or ERBD) internal drainage group (8.7±2.2 months), but the survivals of the above groups were significantly longer than those of the bridge internal drainage group (6.5±1.7 months, P<0.05) and celiotomy (or PTBD) external biliary drainage group (4.4±2.1 months, P<0.01). CONCLUSIONS: In unresectable cholangiocarcinomas, either operative bilioenteric bypass or percutaneous transhepatic biliary drainage can achieve significant palliation. Roux-en-Y choledochojejunostomy is the best choice for palliative operation. The use of U-tube is recommended for internal radiation therapy.

Complete response to radiation therapy of orbital metastasis from hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC)is increasing in the United States,and 50%-75%o patients with HCC will develop metastatic disease Orbital metastases from HCC are extremely rare.We report the case of a 52-year-old male with known metastatic HCC,who presented with severe proptosis and diplopia.An orbital mass was identified on magnetic resonance imaging(MRI)and confirmed to have hypermetabolic activity on positron emission tomography/computed tomography.He received a palliative course of external beam radiation therapy to the right orbit.Intensity modulated radiation therapy (IMRT)was used to allow sparing of critical norma tissues in close proximity to the tumor.One month after completion of IMRT to 58 Gray in 30 fractions delivered over 6 wk,the patient had a complete clinical,radiologic(MRI)and symptomatic response The patient continues to have local control in the orbi 1.7 years after therapy completion.All critical norma structures were kept below the tolerance dose using IMRT,and no toxicities were observed.

Endoscopic cryotherapy:Indications,techniques,and outcomes involving the gastrointestinal tract

Endoscopic cryotherapy is a technique utilized for the ablation of target tissue within the gastrointestinal tract.A cryotherapy system utilizes the endoscopic application of cryogen such as liquid nitrogen,carbon dioxide or liquid nitrous oxide.This leads to disruption of cell membranes,apoptosis,and thrombosis of local blood vessels within the target tissue.Several trials utilizing cryotherapy for Barrett’s esophagus(BE)with variable dysplasia,gastric antral vascular ectasia(GAVE),esophageal carcinoma,radiation proctitis,and metastatic esophageal carcinomas have shown safety and efficacy.More recently,liquid nitrogen cryotherapy(cryodilation)was shown to be safe and effective for the treatment of a benign esophageal stricture which was refractory to dilations,steroid injections,and stenting.Moreover,liquid nitrogen cryotherapy is associated with less post procedure pain as compared to radiofrequency ablation in BE with comparable ablation rates.In patients with GAVE,cryotherapy was found to be less tedious as compared to argon plasma coagulation.Adverse events from cryotherapy most commonly include chest pain,esophageal strictures,and bleeding.Gastric perforations did occur as well,but less often.In summary,endoscopic cryotherapy is a promising and growing field,which was first demonstrated in BE,but the use now spans for several other disease processes.Larger randomized controlled trials are needed before its role can be established for these different diseases.

Developments in metastatic pancreatic cancer:Is gemcitabine still the standard?

In the past 15 years, we have seen few therapeutic advances for patients with pancreatic cancer, which is the fourth leading cause of cancer-related death in the United States. Currently, only about 6% of patients with advanced disease respond to standard gemcitabine therapy, and median survival is only about 6 mo. Moreover, phase Ⅲ trials have shown that adding various cytotoxic and targeted chemotherapeutic agents to gemcitabine has failed to improve overall survival, except in cases in which gemcitabine combined with erlotinib show minimal survival benefi t. Several metaanalyses have shown that the combination of gemcitabine with either a platinum analog or capecitabine may lead to clinically relevant survival prolongation, especially for patients with good performance status. Meanwhile, many studies have focused on the pharmacokinetic modulation of gemcitabine by fi xed-dose administration, and metabolic or transport enzymes related to the response and toxicity of gemcitabine. Strikingly, a phase Ⅲ trial in 2010 showed that, in comparison to gemcitabine alone, the FOLFIRINOX regimen in patients with advanced disease and good performance status, produced better median overall survival, median progression-free survival, and objective response rates. This regimen also resulted in greater, albeit manageable toxicity.

Colorectal stenting for palliation and as a bridge to surgery:A 5-year follow-up study

AIM: To evaluate the long-term effectiveness of colonic stents in colorectal tumors causing large bowel obstruction.METHODS: We retrospectively analyzed data from 49 patients with colorectal cancer who had undergone colorectal stent placement between January 2008 and January 2013. Patients' symptoms,characteristics and clinicopathological data were obtained by reviewing medical records. The obstruction was diagnosed clinically and radiologically. Histopathological diagnosis was achieved endoscopically. Technical success rate(TSR)was defined as the ratio of patients with correctly placed SEMS upon stent deployment across the entire stricture length to total number of patients. Clinical success rate(CSR) was defined as the ratio of patients with technical success and successful maintenance of stent function before elective surgery(regardless of number of SEMS deployed) to total number of patients. The surgical success rate(SSR) of colorectal stent as a bridge to surgery was defined as the ratio of patients with successful surgical procedures. Unsuccessful surgical outcomes were defined as being due to insufficient colonic decompression. The technical,clinical,surgical success rates and complications after stenting were assessed.RESULTS: The median age of patients was 64(36 to 89). 44.9% of patients were male and 55.1% were female. Eighteen patients had the obstruction located in the rectum,15 patients in the rectosigmoid region,10 patients in the sigmoid region,and 6 patients had a tumor causing obstruction in the proximal colon. Each patient was categorized pathologically as stage 2(32.7%,16 patients) or stage 3(42.9%,21 patients) and 12 patients(24.4%) had metastatic disease. None of the patients received chemotherapy before stenting. Stenting was undertaken in 37 patients as a bridge to surgery,and in 12 patients stents were used for palliation. Median time to surgery after stenting was 30 ± 91.9 d. All surgery was completed in one single operation and thus no colostomy with stoma was needed. The median overall survival rate of patients with stage 2-3 colorectal cancer was 53.1 mo and stage 4 was 37.1 mo(P = 0.04). Metastatic colorectal patients who were treated palliatively with stents had backbone chemotherapy with oxaliplatin and/or irinotecan-based regimens plus antiangiogenic therapies,especially bevacizumab. Resolution of the obstruction and clinical improvement was achieved in all patients. The technical,clinical and surgical success rates were 95.9%,100% and 94.6%,respectively.CONCLUSION: The efficacy and safety of colonic stents was demonstrated both as a bridge to surgery and for palliative decompression. In addition,results emphasize the importance of the skills of the endoscopist in colonic stenting.

The effect of advance care planning in patients with dementia: a protocol of systematic review and meta-analysis

Aim:To comprehensively synthesize and compare the effect of advance care planning for dementia patients.Design:Systematic review and meta-analysis.Methods:Ten electronic databases will be searched:the Cochrane Library,PubMed,Medline,Embase,PsycINFO,CINAHL PLUS,Scopus,Web of Science,British Nursing Index,clinical Trials,and grey literature sources.Individually or cluster randomized controlled trials that evaluated advance care planning in people with dementia will be incorporated.The research screening flow diagrams will be detailed in the PRISMA flow chart.Data extraction will be carried out in Microsoft Excel 2019 independently by two researchers,any disagreements will be discussed with the third researcher and resolved.We will use the Cochrane Risk of Bias tool to assess the methodological quality.Review Manager 5.3 Software will be used for data synthesis.If sufficient data from studies are available,we will conduct a subgroup analysis of the main outcomes.Conclusion:The systematic review will combine existing trials which may contribute to more convincing conclusions,providing new ideas for medical workers to implement palliative therapy in dementia patients,and further promoting the application of advance care planning for dementia patients.

Esophageal Cancer Metastasis to the Eye: A Case Report and Literature Review

Ocular metastasis is an uncommon occurrence that usually has a poor prognosis. The most frequent causes of intraocular metastases as reported in the literature are breast and lung cancers. Intraocular metastasis originating from esophageal cancer is very rare. We discuss a case of 58 years old man known case of adenocarcinoma of the esophagogastric junction presenting with ocular metastasis in King Abdulaziz Medical City, Jeddah, Saudi Arabia. Clinical symptoms led to the investigations and diagnosis of the ocular metastasis which without these symptoms it would have been missed. We concluded that a careful and good review of the whole body is essential in the optimal diagnosis of metastatic lesions especially when it comes to a rare metastasis like ocular metastasis from esophageal cancer.

Endoscopic pancreatic duct stenting for pain palliation in selected pancreatic cancer patients:a systematic review and meta-analysis

Background Abdominal pain is a debilitating symptom affecting-80%of pancreatic cancer(PC)patients.Pancreatic duct(PD)decompression has been reported to alleviate this pain,although this practice has not been widely adopted.We aimed to evaluate the role,efficacy,and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain.Methods A systematic review until 7 October 2020 was performed.Two independent reviewers selected studies,extracted data,and assessed the methodological quality.Results We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain,in whom PD decompression was attempted,and was successful in 167 patients(mean age 62.5 years,58.7%males).The use of plastic stents was reported in 159 patients(95.2%).All included studies reported partial or complete improvement in pain levels after PD stenting,with an improvement rate of 93%(95%confidence interval,79%-100%).The mean duration of pain improvement was 94616 days.Endoscopic retrograde cholangiopancreatography(ERCP)-related adverse events(AEs)were postsphincterotomy bleeding(1.8%),post-ERCP pancreatitis(0.6%),and hemosuccus pancreaticus(0.6%).AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression.In the 167 patients with technical success,the stent-migration and stent-occlusion rates were 3.6%and 3.0%,respectively.No AE-related mortality was reported.The methodological quality assessment showed the majority of the studies having low or unclear quality.Conclusion In this exploratory analysis,endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain.However,a randomized–controlled trial is needed to delineate the role of this invasive practice.