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.     

Pancreatic cancer: A review of epidemiology,trend, and risk factors

Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2050, with the average annual growth of 1.1%, meaning that pancreatic cancer will pose a significant public health burden. Due to the special anatomical location of the pancreas, the development of pancreatic cancer is usually diagnosed at a late stage with obvious clinical symptoms. Therefore, a comprehensive understanding of the risk factors for pancreatic cancer is of great clinical significance for effective prevention of pancreatic cancer. In this paper, the epidemiological characteristics, developmental trends, and risk factors of pancreatic cancer are reviewed and analyzed in detail.     

Prevalence of pancreatic exocrine insufficiency after pancreatic surgery measured by 13C mixed triglyceride breath test: A prospective cohort study

BackgroundPatients undergoing pancreatic surgery are at risk of pancreatic exocrine insufficiency (PEI) and needing pancreatic enzyme replacement therapy (PERT).MethodsThis study included 254 patients undergoing pancreatic surgery for oncologic indications. A¹³C mixed triglyceride breath test was performed immediately preoperative and postoperative. This test analyzes the pancreatic remnant lipase activity measuring ¹³CO₂ in breath samples after a test meal with 1.3-distearyl-(¹³C-Carboxyl)octanol-glycerol. Cumulative percent dose recovery after 6 h of less than 23% confirms PEI. In addition, PEI was compared between pathology subgroups.ResultsIn 197 patients undergoing pancreaticoduodenectomy, cPDR-6h decreased significantly from a median of 32.84% before to 15.80% after surgery (p < 0.0001). This decrease in exocrine function was significant in all pathology subgroups except in pancreatic neuroendocrine tumors. Exocrine function decreased most in pancreatic ductal adenocarcinoma (PDAC). In addition, the percentage of patients needing PERT because of PEI increased from 25.9% to 68.0% postoperative (p < 0.001). Overall, patients with an MPD diameter of more than 3 mm had a higher risk of developing postoperative PEI: 62.7% compared to 37.3% (p = 0.009), OR = 3.11.In contrast, the majority of the 57 patients undergoing a distal pancreatectomy did not experience any significant change in exocrine function.ConclusionsThe vast majority of patients undergoing pancreaticoduodenectomy for oncologic indications experience a significant drop in exocrine function, are at high risk of developing pancreatic exocrine insufficiency and consequently need to be treated with pancreatic enzyme replacement therapy. Therefore, systematic screening for pancreatic exocrine insufficiency is needed after pancreaticoduodenectomy.     

Solid-pseudopapillary tumor of the pancreas： Clinical experience and literature review

AIM: To evaluate the clinical presentations of solid-pseudopapillary tumor of the pancreas (SPT) and examine the diagnosis, treatment, low grade malignant potential of this rare disease. METHODS: We retrospectively reviewed a series of seven patients with SPT managed in our hospital between July 1990 and October 2003. Six females and one male with mean age of 31 years (range 13 to 50 years) were diagnosed with SPT at our institution. RESULTS: Clinical presentation included a palpable abdominal mass in two patients and vague abdominal discomfort in another two. Two patients were asymptomatic; their tumors were found incidentally on abdominal sonographic examination for other reasons. The final patient was admitted with hemoperitoneum secondary to tumor rupture. The mean diameter of the tumors in the seven patients was 10.5 cm (range 5 to 20 cm). The lesions were located in the body and tail in five cases and in the head of the pancreas in two. Surgical procedures included distal pancreatectomy (3), distal pancreatectomy with splenectomy (2), pancreaticoduodenectomy (1) and a pylorus-preserving Whipple procedure (1). There were gross adhesions or histological evidence of infiltration to the adjacent pancreas and/or splenic capsule in four cases. None of the patients received adjuvant therapy. The mean follow up was 7 years (range 0.5 to 14 years). One patient developed multiple liver metastases after 14 years of follow up. CONCLUSION: SPT is a rare tumor that behaves less aggressively than other pancreatic tumor. However, in cases with local invasion, long-term follow up is advisable.     

A review of physical activity in pancreatic ductal adenocarcinoma: Epidemiology,intervention, animal models,and clinical trials

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, and the increasing incidence of PDAC may be related to the prevalence of obesity. Physical activity (PA), a method known to mitigate obesity by increasing total energy expenditure, also modifies multiple cellular pathways associated with cancer hallmarks. Epidemiologic evidence has shown that PA can lower the risk of developing a variety of cancers, reduce some of the detrimental side effects of treatments, and improve patient's quality of life during cancer treatment. However, little is known about the pathways underlying the correlations observed between PA interventions and PDAC. Moreover, there is no standard dose of PA intervention that is ideal for PDAC prevention or as an adjuvant of cancer treatments. In this review, we summarize relevant literature showing how PDAC patients can benefit from PA, the potential of PA as an adjuvant treatment for PDAC, the studies using preclinical models of PDAC to study PA, and the clinical trials to date assessing the effects of PA in PDAC.     

Pancreatic cancer: Advances in treatment

Pancreatic cancer is a leading cause of cancer mortality and the incidence of this disease is expected to continue increasing. While patients with pancreatic cancer have traditionally faced a dismal prognosis, over the past several years various advances in diagnosis and treatment have begun to positively impact this disease. Identification of effective combinations of existing chemotherapeutic agents, such as the FOLFIRINOX and the gemcitabine + nab-paclitaxel regimen, has improved survival for selected patients although concerns regarding their toxicity profiles remain. A better understanding of pancreatic carcinogenesis has identified several pre-malignant precursor lesions, such as pancreatic intraepithelial neoplasias, intraductal papillary mucinous neoplasms, and cystic neoplasms. Imaging technology has also evolved dramatically so as to allow early detection of these lesions and thereby facilitate earlier management. Surgery remains a cornerstone of treatment for patients with resectable pancreatic tumors, and advances in surgical technique have allowed patients to undergo resection with decreasing perioperative morbidity and mortality. Surgery has also become feasible in selected patients with borderline resectable tumors as a result of neoadjuvant therapy. Furthermore, pancreatectomy involving vascular reconstruction and pancreatectomy with minimally invasive techniques have demonstrated safety without significantly compromising oncologic outcomes. Lastly, a deeper understanding of molecular aberrations contributing to the development of pancreatic cancer shows promise for future development of more targeted and safe therapeutic agents.     

Pancreatic exocrine insufficiency after pancreaticoduodenectomy:Current evidence and management

Pancreaticoduodenectomy(PD) is the commonest procedure performed for pancreatic cancer. Pancreatic exocrine insufficiency(PEI) may be caused or exacerbated by surgery and remains underdiagnosed and undertreated. The aim of this review was to ascertain the incidence of PEI, its consequences and management in the setting of PD for indications other than chronic pancreatitis.A literature search of databases(MEDLINE, EMBASE, Cochrane and Scopus) was carried out with the MeSH terms "pancreatic exocrine insufficiency" and"Pancreaticoduodenectomy". Studies that analysed PEI and its complications in the setting of PD for malignant and benign disease were included. Studies reporting PEI in the setting of PD for chronic pancreatitis, conference abstracts and reviews were excluded. The incidence of PEI approached 100% following PD in some series. The pre-operative incidence varied depending on the characteristics of the patient cohort and it was higher(46%-93%) in series where pancreatic cancer was the predominant indication for surgery. Variability was also recorded with regards to the method used for the diagnosis and evaluation of pancreatic function and malabsorption. Pancreatic enzyme replacement therapy is the mainstay of the management. PEI is common and remains undertreated after PD. Future studies are required for the identification of a welltolerated, reliable and reproducible diagnostic test in this setting.     

Recent advances in artificial intelligence for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains the most lethal type of cancer. The 5-year survival rate for patients with early-stage diagnosis can be as high as 20%, suggesting that early diagnosis plays a pivotal role in the prognostic improvement of PDAC cases. In the medical field, the broad availability of biomedical data has led to the advent of the “big data” era. To overcome this deadly disease, how to fully exploit big data is a new challenge in the era of precision medicine. Artificial intelligence (AI) is the ability of a machine to learn and display intelligence to solve problems. AI can help to transform big data into clinically actionable insights more efficiently, reduce inevitable errors to improve diagnostic accuracy, and make real-time predictions. AI-based omics analyses will become the next alterative approach to overcome this poor-prognostic disease by discovering biomarkers for early detection, providing molecular/genomic subtyping, offering treatment guidance, and predicting recurrence and survival. Advances in AI may therefore improve PDAC survival outcomes in the near future. The present review mainly focuses on recent advances of AI in PDAC for clinicians. We believe that breakthroughs will soon emerge to fight this deadly disease using AI-navigated precision medicine.     

Tips and tricks of laparoscopic distal pancreatectomy for ductal adenocarcinoma

Laparoscopic distal pancreatectomy for pancreatic cancer can be a challenging procedure that requires adherence to surgical principles respecting tissue planes and critical vascular structures to obtain the optimal surgical margins and peripancreatic node harvest, while minimizing damage to surrounding structures. This report provides a basic approach with some tips and tricks based on my experience with this procedure.     

Somatostatin analogues and the risk of post-operative pancreatic fistulas after pancreatic resection - A systematic review & meta-analysis

BackgroundPost-operative pancreatic fistula (POPF) is a common complication of pancreatic resection. Somatostatin analogues (SA) have been used as prophylaxis to reduce its incidence. The aim of this study is to appraise the current literature on the effects of SA prophylaxis on the prevention of POPF following pancreatic resection.MethodsThe review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from studies that reported the effects of SA prophylaxis on POPF following pancreatic resection were extracted, to determine the effect of SA on POPF morbidity and mortality.ResultsA total of 15 studies, involving 2221 patients, were included. Meta-analysis revealed significant reductions in overall POPF (Odds ratio: 0.65 (95% CI 0.53–0.81, p < 0.01)), clinically significant POPF (Odds ratio: 0.53 (95% CI 0.34–0.83, p < 0.01)) and overall morbidity (OR: 0.69 (95% CI: 0.50–0.95, p = 0.02)) following SA prophylaxis. There is no evidence that SA prophylaxis reduces mortality (OR: 1.10 (95%CI: 0.68–1.79, p = 0.68)).ConclusionSA prophylaxis following pancreatic resection reduces the incidence of POPF. However, mortality is unaffected.     

Prehabilitation prior to surgery for pancreatic cancer: A systematic review

IntroductionPrehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection.MethodsA systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting.ResultsSix studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes.ConclusionEarly evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.     

Pancreatic body and tail cancer and favorable metastatic lymph node behavior on the left edge of the aorta

BackgroundLymph node (LN) metastasis in pancreatic body-tail cancer is a poor prognostic factor and the optimal LN dissection area for distal pancreatectomy (DP) remains unclear. Lymphatic flow from the tumors is thought to depend on the tumor sites. We examined LN metastasis frequency based on tumor site and recurrent patterns post-DP.MethodsWith a retrospective, single institutional study, we examined 100 patients who underwent DP as an upfront surgery for pancreatic cancer over 17 years. Tumor sites were classified as tumor confined to pancreatic body (and neck) (Pb(n)); and pancreatic tail (Pt). We compared metastatic LN and recurrence patterns based on tumor site. The median overall survival (OS) and disease-free survival (DFS) were analyzed.ResultsLN metastasis occurred in 59/100 (59.0%), with 23 and 25 tumors located in the Pb(n), and Pt, respectively. Those with the tumor in Pt had metastases to #10, #11d/p, and #18 LN mainly. However, the patients with the Pb(n) tumor had metastases to #8a/p, #11p, and #14p/d LN. There was no metastasis to #10 and #11d LN. The OS and DFS were 34 and 15 months, respectively. No significant difference was found in the OS, DFS, and recurrence patterns based on tumor sites.ConclusionDifferences in metastatic LN sites were observed in pancreatic body-tail cancer when tumors were confined to the left or right of the left aortic edge. Although it is necessary to validate this finding with a large-scale study, organ-preserving DP might be a treatment option for selected patients depending on the tumor sites.     

Molecular advances in pancreatic cancer: A genomic,proteomic and metabolomic approach

Pancreatic ductal adenocarcinoma (PDAC) represents a challenging pathology with very poor outcomes and is increasing in incidence within the general population. The majority of patients are diagnosed incidentally with insidious symptoms and hence present late in the disease process. This significantly affects patient outcomes: the only cure is surgical resection but only up to 20% of patients present with resectable disease at the time of clinical presentation. The use of “omic” technology is expanding rapidly in the field of personalised medicine - using genomic, proteomic and metabolomic approaches allows researchers and clinicians to delve deep into the core molecular processes of this difficult disease. This review gives an overview of the current findings in PDAC using these “omic” approaches and summarises useful markers in aiding clinicians treating PDAC. Future strategies incorporating these findings and potential application of these methods are presented in this review article.     

Achalasia: A review of clinical diagnosis,epidemiology, treatment and outcomes

Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function.Historically,annual achalasia incidence rates were believed to be low,approximately 0.5-1.2 per 100000.More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations.The aetiology of achalasia is still unclear but is likely to be multi-factorial.Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus,which elicits an autoimmune response.Risk of achalasia may be elevated in a sub-group of genetically susceptible people.Improvement in the diagnosis of achalasia,through the introduction of high resolution manometry with pressure topography plotting,has resulted in the development of a novel classification system for achalasia.This classification system can evaluate patient prognosis and predict responsiveness to treatment.There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller’s myotomy procedure in the treatment of achalasia.A recent com-parative study found equal efficacy,suggesting that patient preference and local expertise should guide the choice.Although achalasia is a relatively rare condition,it carries a risk of complications,including aspiration pneumonia and oesophageal cancer.The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia,however the absolute excess risk is small.Therefore,it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective.     

Pancreatic carcinoma with brain metastases: case report and literature review

The case of a patient developing multiple brain metastases from carcinoma of the exocrine pancreas has been described. A 56-year-old man with stage IV pancreatic cancer attained a clinical and radiographic response while receiving the G-FLIP chemotherapy regimen (biweekly gemcitabine, irinotecan, 5-fluorouracil, leucovorin and cisplatin). After 4 months of therapy, he developed gait imbalance and weakness in the right hand. An MRI of the brain showed multiple 1-2 mm enhancing nodules in the cerebral hemispheres and pons. A subsequent biopsy confirmed that these were pancreatic carcinoma metastases. The patient experienced a rapid deterioration in his neurological status and died 3 days after brain biopsy. Previously reported cases of brain metastases from pancreatic cancer are reviewed.     

Should a standard lymphadenectomy include the No. 9 lymph nodes for body and tail pancreatic ductal adenocarcinoma?

Objectives

This study aimed to use a retrospective data base to investigate whether a standard lymphadenectomy during distal pancreatectomy should include the No. 9 lymph nodes (LNs) for resectable pancreatic ductal adenocarcinoma (PDAC) located in the body and tail of the pancreas.

Middle segmental pancreatectomy: A safe and organ-preserving option for benign and low-grade malignant lesions

AIM: To study the feasibility and safety of middle segmental pancreatectomy (MSP) compared with pancreaticoduodenectomy (PD) and extended distal pancreatectomy (EDP). METHODS: We studied retrospectively 36 cases that underwent MSP, 44 patients who underwent PD, and 26 who underwent EDP with benign or low-grade malignant lesions in the mid-portion of the pancreas, between April 2003 and December 2009 in Ruijin Hospital. The perioperative outcomes and long-term outcomes of MSP were compared with those of EDP and PD. Periop-erative outcomes included operative time, intraoperative hemorrhage, transfusion, pancreatic fistula, intraabdominal abscess/infection, postoperative bleeding, reoperation, mortality, and postoperative hospital time. Long-term outcomes, including tumor recurrence, newonset diabetes mellitus (DM), and pancreatic exocrine insufficiency, were evaluated. RESULTS: Intraoperative hemorrhage was 316.1 ± 309.6, 852.2 ± 877.8 and 526.9 ± 414.5 mL for the MSP, PD and EDP groups, respectively (P < 0.05). The mean postoperative daily fasting blood glucose level was significantly lower in the MSP group than in the EDP group (6.3 ± 1.5 mmol/L vs 7.3 ± 1.5 mmol/L, P < 0.05). The rate of pancreatic fistula was higher in the MSP group than in the PD group (42% vs 20.5%, P = 0.039), all of the fistulas after MSP corresponded to grade A (9/15) or B (6/15) and were sealed following conservative treatment. There was no significant difference in the mean postoperative hospital stay between the MSP group and the other two groups. After a mean follow-up of 44 mo, no tumor recurrences were found, only one patient (2.8%) in the MSP group vs five (21.7%) in the EDP group developed new-onset insulin-dependent DM postoperatively (P = 0.029). Moreover, significantly fewer patients in the MSP group than in the PD (0% vs 33.3%, P < 0.001) and EDP (0% vs 21.7%, P = 0.007) required enzyme substitution. CONCLUSION: MSP is a safe and organ-preserving option for benign or low-grade malignant lesions in the neck and pr     

Comparison of laparoscopic versus open pancreaticoduodenectomy in patients with resectable pancreatic ductal adenocarcinoma: A propensity score-matching analysis of long-term survival

BackgroundMany studies have shown the short-term feasibility and effectiveness of laparoscopic pancreaticoduodenectomy (LPD) are comparable to open pancreaticoduodenectomy (OPD). However, the long-term oncological safety of LPD in patients with pancreatic ductal adenocarcinoma (PDAC) remains to be elucidated.MethodsPatients who underwent LPD or OPD between July 2014 and July 2018 at our institution were identified, and those with resectable, pathologically diagnosed PDAC were analyzed. The primary outcome was overall survival (OS). Propensity score-matching (PSM) analysis was performed to balance the baseline characteristics between groups. Cox proportional hazards model was constructed to determine independent predictors of OS.ResultsThe original cohort consisted of 64 LPD and 80 OPD cases, in which, the laparoscopic group had a significantly longer median OS (25 vs. 17 months; P = 0.034). A higher proportion of laparoscopic patients received adjuvant therapy (51.6 vs. 32.5%; P = 0.021). PSM analysis identified 47 patient pairs. No significant differences in OS (21 vs. 17 months; P = 0.220) or adjuvant therapy utilization (53.2 vs. 38.3%; P = 0.248) were observed between the matched groups. Multivariate Cox analyses showed that receiving adjuvant therapy (HR = 0.44; 95% CI, 0.28–0.68), histopathological differentiation (poor vs. moderate-to-well differentiation; HR = 1.93; 95% CI, 1.26–2.95), and sex (female vs. male, HR = 0.47, 95% CI, 0.30–0.75) were independent predictors of OS.ConclusionsLPD can be comparable to OPD in terms of long-term safety for patients with resectable pancreatic ductal adenocarcinoma when performed in a high-volume center.