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Current Problems in Surgery Sep 2018Colorectal cancer commonly metastasizes. The liver is the most frequent site of metastases and dominates the length of survival for this disease. As surgical and... (Review)
Review
Colorectal cancer commonly metastasizes. The liver is the most frequent site of metastases and dominates the length of survival for this disease. As surgical and systemic therapies have become accepted and now are proven to be potentially curative, other sites of metastases have become more clinically relevant in terms of clinical symptoms and influence on survival. Treatment of extrahepatic metastases by surgical and ablative procedures is increasingly accepted and is proving to be effective at palliating symptoms, as well as life prolonging. In this review, we will first summarize key issues with metastatic colorectal cancer to the liver and available treatments. We will then discuss surgical and ablative treatments of other sites of disease including lung, lymph nodes, peritoneum, bone, and brain. Best available evidence for treatment strategies will be presented as well as potential new directions.
Topics: Bone Neoplasms; Brain Neoplasms; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Palliative Care; Peritoneal Neoplasms; Prognosis; Survival Rate
PubMed: 30526930
DOI: 10.1067/j.cpsurg.2018.08.004 -
World Journal of Gastrointestinal... Jun 2021Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and... (Review)
Review
Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.
PubMed: 34194610
DOI: 10.4240/wjgs.v13.i6.516 -
Gut and Liver Sep 2023Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in... (Review)
Review
Neoadjuvant and Adjuvant Treatments for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: The Current Status of Pancreatic Ductal Adenocarcinoma Treatment in Japan.
Resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Although the outcome of technically resectable PDAC has improved with advances in surgery and adjuvant therapy, the 5-year survival rate remains low at 20% to 40%. More effective therapy is needed. Almost 15 years ago, the National Comprehensive Cancer Network guidelines proposed a resectability classification of PDAC based on preoperative imaging. Since then, treatment strategies for PDAC have been devised based on resectability. The standard of care for resectable PDAC is adjuvant chemotherapy after R0 resection, as shown by the results of pivotal clinical trials. With regard to neoadjuvant treatment, several recent clinical trials comparing neoadjuvant treatment with upfront resection have been conducted on resectable PDAC and borderline resectable PDAC, and the benefits and efficacy of neoadjuvant treatment for pancreatic cancer has become clearer. The significance of neoadjuvant treatment for resectable PDAC remains controversial, but in borderline resectable PDAC the efficacy of neoadjuvant treatment has been further recognised, although the standard of care has not yet been established. Several promising clinical trials for PDAC are ongoing. This review presents previous and ongoing trials of perioperative treatment for resectable and borderline resectable PDAC, focusing on the difference between Asian and Western countries.
Topics: Humans; Neoadjuvant Therapy; Japan; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Antineoplastic Combined Chemotherapy Protocols; Pancreatectomy
PubMed: 36843421
DOI: 10.5009/gnl220311 -
Frontiers in Oncology 2022Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease....
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic neoplasm. Surgery is the factual curative option, but most patients present with advanced disease. In order to increase resectability, results of neoadjuvant chemotherapy (NAC) on metastatic disease were extrapolated to the neoadjuvant setting by many centers. The aim of our study was to retrospectively evaluate the outcome of patients who underwent upfront surgery (US)-PDAC and borderline (BR)-PDAC, and those resected after NAC to determine prognostic factors that might affect the outcome in these resected patients.
METHODS
One hundred fifty-one patients between January 2012 and March 2021 in our department were reviewed. Epidemiological characteristics and pre-operative induction treatment were assessed. Pathological reports were analyzed to evaluate the quality of oncological resection (R0/R1). Post-operative mortality and morbidity and survival data were reviewed.
RESULTS
One hundred thirteen patients were addressed for US, and 38 were considered BR and referred for surgery after induction chemotherapy. The pancreatic resection R0 was 71.5% and R1 28.5%. pT3 rate was significantly higher in the US than BR (58,4% vs 34,2%, p= 0.005). The mean OS and DFS rates were 29.4 months 15.9 months respectively. There was no difference between OS and DFS of US vs BR patients. N0 patients had significantly longer OS and DFS (p=<0.001). R0 patients had significantly longer OS (p=0.03) and longer DFS (P=0.08). In the multivariate analysis, the presence of postoperative pancreatic fistula, R1 resection, N+ and not access to adjuvant chemotherapy were bad prognostic factors of OS.
CONCLUSIONS
Our study suggests the benefits of NAC for BR patients in downstaging tumors and rendering them amenable to resection, with same oncological result compared to US.
PubMed: 36387257
DOI: 10.3389/fonc.2022.980659 -
American Society of Clinical Oncology... 2016Pancreatic cancer is an aggressive cancer that continues to have single-digit 5-year mortality rates despite advancements in the field. Surgery remains the only curative... (Review)
Review
Pancreatic cancer is an aggressive cancer that continues to have single-digit 5-year mortality rates despite advancements in the field. Surgery remains the only curative treatment; however, most patients present with late-stage disease deemed unresectable, either due to extensive local vascular involvement or the presence of distant metastasis. Resection guidelines that include a borderline resectable group, as well as advancements in neoadjuvant chemotherapy and radiation that improve resectability of locally advanced disease, may improve outcomes for patients with more invasive disease. Multi-agent chemotherapy regimens fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel with gemcitabine improved response rates and survival in metastatic pancreatic cancer and are now being used in earlier stages for patients with localized potentially resectable and unresectable disease, with goals of downstaging tumors to allow margin-negative resection and reducing systemic recurrence. Chemoradiotherapy, although still controversial for both resectable and unresectable pancreatic cancer, is being used in the context of contemporary chemotherapy backbone regimens, and novel radiation techniques such as stereotactic body frame radiation therapy (SBRT) are studied on the premise of maintaining or improving efficacy and reducing treatment duration. Patient selection for optimal treatment designation is currently provided by multidisciplinary tumor boards, but biomarker discovery, in blood, tumors, or through novel imaging, is an area of intense research. Results to date suggest that some patients with unresectable disease at the outset have survival rates as good as those with initially resectable disease if able to undergo surgical resection. Long-term follow-up and improved clinical trials options are needed to determine optimal treatment modalities for patients with localized pancreatic cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Fluorouracil; Humans; Leucovorin; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Radiosurgery
PubMed: 27249726
DOI: 10.1200/EDBK_160827 -
World Journal of Gastroenterology Jun 2017Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious...
Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious postoperative complications or rapid disease progression may preclude completion of multimodal treatment. The sequence of treatment interventions has therefore become an important concern, and numerous ongoing randomized controlled trials compare clinical outcome after upfront surgery and neoadjuvant treatment with subsequent resection. In previous years, borderline resectable and locally advanced pancreatic cancer was most often considered unresectable. More effective chemotherapy together with the latest improvements in surgical expertise has resulted in extended operations, pushing the borders of resectability. Multivisceral resections with or without resection of major mesenteric vessels are now performed in numerous patients, resulting in better outcome, recorded as overall survival and/or patient reported outcome. But postoperative morbidity increases concurrently, and clinical benefit must be carefully evaluated against risk of potential harm, associated with new comprehensive multimodal treatment sequences. Even though cost/utility analyses are deficient, extended surgery has resulted in significantly longer and better life for many patients with no other treatment alternative. Improved selection of patients to surgery and/or chemotherapy will in the near future be possible, based on better tumor biology insight. Clinically available biomarkers enabling personalized treatment are forthcoming, but these options are still limited. The importance of surgical resection for each patient's prognosis is presently increasing, justifying sustained expansion of the surgical treatment modality.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Humans; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Reported Outcome Measures; Patient Selection; Postoperative Complications; Prognosis; Quality of Life; Risk Assessment; Treatment Outcome
PubMed: 28638216
DOI: 10.3748/wjg.v23.i21.3765 -
World Journal of Gastrointestinal... Aug 2021Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for... (Review)
Review
Surgical resection for colorectal liver metastases (CRLM) may offer the best opportunity to improve prognosis. However, only about 20% of CRLM cases are indicated for resection at the time of diagnosis (initially resectable), and the remaining cases are treated as unresectable (initially unresectable). Thanks to recent remarkable developments in chemotherapy, interventional radiology, and surgical techniques, the resectability of CRLM is expanding. However, some metastases are technically resectable but oncologically questionable for upfront surgery. In pancreatic cancer, such cases are categorized as "borderline resectable", and their definition and treatment strategies are explicit. However, in CRLM, although various poor prognosis factors have been identified in previous reports, no clear definition or treatment strategy for borderline resectable has yet been established. Since the efficacy of hepatectomy for CRLM was reported in the 1970s, multidisciplinary treatment for unresectable cases has improved resectability and prognosis, and clarifying the definition and treatment strategy of borderline resectable CRLM should yield further improvement in prognosis. This review outlines the present status and the future perspective for borderline resectable CRLM, based on previous studies.
PubMed: 34512899
DOI: 10.4240/wjgs.v13.i8.756 -
Translational Gastroenterology and... 2019Extended surgery with arterial resection in pancreatic cancer remains a controversial topic. Although not recommended as a standard procedure, arterial resection may be... (Review)
Review
Extended surgery with arterial resection in pancreatic cancer remains a controversial topic. Although not recommended as a standard procedure, arterial resection may be feasible in selected patients and with the availability of new multimodal treatment approaches it may gain increasing impact in pancreatic cancer therapy as a complete tumor removal is still the only opportunity to achieve long-term survival for this disease. With regard to the surgical approach, one must differentiate between resection and reconstruction of the celiac axis and the hepatic artery as its most important branch, and resection/reconstruction of the superior mesenteric artery. Both procedures are technically possible and require a distinct level of surgical experience as well as interdisciplinary management for preoperative diagnosis and treatment of postoperative complications to achieve good outcomes. Besides arterial resection followed by reconstruction, there are specific situations when arteries may be resected without reconstruction, e.g., during distal pancreatectomy with celiac axis resection. In addition, in some cases arterial resections can be avoided despite a suspected tumor attachment by sharp dissection on the adventitial layer of the respective artery, especially after neoadjuvant therapy which is increasingly performed for borderline resectable and locally advanced tumor findings. This review summarizes definitions, diagnostics, technical aspects and outcomes of arterial resection in pancreatic cancer surgery in the context of the current literature and evidence.
PubMed: 30976711
DOI: 10.21037/tgh.2019.01.07 -
HPB : the Official Journal of the... Jan 2015To determine the benefits and risks of hepatic resection versus non-resectional liver-directed treatments in patients with potentially resectable neuroendocrine liver... (Review)
Review
AIM
To determine the benefits and risks of hepatic resection versus non-resectional liver-directed treatments in patients with potentially resectable neuroendocrine liver metastases.
METHODS
A systematic review identified 1594 reports which alluded to a possible liver resection for neuroendocrine tumour metastases, of which 38 reports (all retrospective), comprising 3425 patients, were relevant.
RESULTS
Thirty studies reported resection alone, and 16 studies reported overall survival (OS). Only two studies addressed quality-of-life (QoL) issues. Five-year overall survival was reported at 41-100%, whereas 5-year progression-free survival (PFS) was 5-54%. We identified no robust evidence that a liver resection was superior to any other liver-directed therapies in improving OS or PFS. There was no evidence to support the use of a R2 resection (debulking), with or without tumour ablation, to improve either OS or QoL. There was little evidence to guide sequencing of surgery for patients presenting in Stage IV with resectable disease, and none to support a resection of asymptomatic primary tumours in the presence of non-resectable liver metastases.
CONCLUSION
Low-level recommendations are offered to assist in the management of patients with neuroendocrine liver metastases, along with recommendations for future studies.
Topics: Carcinoma, Neuroendocrine; Hepatectomy; Humans; Liver Neoplasms; Neoplasm Staging; Patient Selection; Quality of Life; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 24636662
DOI: 10.1111/hpb.12225 -
BMJ Clinical Evidence May 2010Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% even in people presenting with early-stage... (Review)
Review
INTRODUCTION
Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% even in people presenting with early-stage cancer. Risk factors include smoking, high alcohol intake, and dietary factors, while diabetes mellitus and previous pancreatitis may also increase the risk.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of surgical treatments in people with pancreatic cancer considered suitable for complete tumour resection? What are the effects of interventions to prevent pancreatic leak after pancreaticoduodenectomy in people with pancreatic cancer considered suitable for complete tumour resection? What are the effects of adjuvant treatments in people with completely resected pancreatic cancer? What are the effects of interventions in people with non-resectable (locally advanced or advanced) pancreatic cancer? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 46 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: chemoradiotherapy; chemoradiotherapy for non-resectable pancreatic cancer; chemoradiotherapy for resected pancreatic cancer; fibrin glue; fluorouracil-based chemotherapy (adjuvant) for resected pancreatic cancer (with or without surgery); fluorouracil-based chemotherapy for non-resectable pancreatic cancer; fluorouracil-based chemotherapy (systemic); fluorouracil-based combination chemotherapy; fluorouracil-based monotherapy for non-resectable pancreatic cancer; gemcitabine-based chemotherapy (adjuvant) for resected pancreatic cancer; gemcitabine-based chemotherapy (systemic); gemcitabine-based combination chemotherapy; gemcitabine-based monotherapy for non-resectable pancreatic cancer; lymphadenectomy (extended [radical], or standard) in people having pancreaticoduodenectomy; pancreatic duct occlusion; pancreaticoduodenectomy (pylorus-preserving); pancreaticoduodenectomy (Whipple's procedure); pancreaticogastrostomy reconstruction; pancreaticojejunostomy; and somatostatin and somatostatin analogues.
Topics: Fluorouracil; Humans; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pylorus
PubMed: 21729338
DOI: No ID Found