This review of the influence of host systemic inflammatory response(SIR) on the outcome of pancreatic ductal adenocarcinoma (PDAC)was the kernel of the 2014 George E Palade Memorial Prize Lecture at the Combined IAP-EPC Meeting held June 25-8 in Southampton,UK. The ability of the modified Glasgow Prognostic Score(mGPS) to stratify cancer outcomes has been demonstrated in >50 studies including >25000 patients from many countries. Other markers of SIR such as Prognostic Index and neutrophil/lymphocyte ratio(NLR) may also be used emphasising the non homogeneity of the PDAC patients. The mGPS score 0 is associated with better outcome,while scores of 1 & 2 are linked to poor performance status, greater weight loss, comorbidity and earlier death. Two papers show in resectable PDAC that longer life (27-37 months) occurs with mGPS 0, and < 18 months for mGPS 1 and 2, such that alternative therapy employing RFA may well be better than resection in those patients. In the greater number of PDAC patients unsuitable for resection the JAK-STAT inhibitor, ruxolitinib, has been found only to favourably modify PDAC in those with mGPS 1 or 2. Likewise the possible benefits of older anti inflammatory agents may be confined to these patients. An urgent reappraisal of the prognostic and therapeutic implications is now required in PDAC. Local inflammatory responses(LIR) are beneficial in PDAC and other cancers. Four grade stratification systems using Klintrup histology, T cell subtype analysis and Galon immune scores are accurate prognosticators.

Background. Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial.Methods. An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology.Results. The incidence of benign disease after PD for a presumed malignancy is 5–13%. Diagnosis by endoscopic cholangiopancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by endoscopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AIP) in the benign resected specimens is 30–43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis.Conclusion. In the presence of a solid mass suspicious for malignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline resectable disease to be treated with neoadjuvant therapy before exploration for …

The epidemiology of chronic pancreatitis (CP) is incompletely understood. A number of difficulties exist in estimating the prevalence and incidence of CP. Long-term follow-up is often problematic, especially in chronic alcoholics, and obtaining a formal and standardised diagnosis can take years. The available studies are reasonably consistent in their estimation of the incidence of CP but few studies have attempted to estimate prevalence. Although life expectancy in CP is diminished compared with control populations, median survival lies in the range of 15-20 years. Such a survival would suggest a prevalence of CP rather higher than that determined from the survey studies. A recent epidemiological study in France found an annual incidence of 7.8 per 100,000. Assuming a survival of 15-20 years, the annual prevalence should be between 120 to 143 per 100,000. Overall, our understanding of the epidemiology of CP is poor compared with other illnesses. We consider that both prevalence and the rate of pancreatic insufficiency and of CP are currently underestimated. There is a distinct need for more studies to remedy this lack of knowledge.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is diagnosed on the basis of pancreatic pain and hyperamylasemia. However, because the diagnosis of abdominal pain is not objective, there may be some cases of painless pancreatitis among patients with post-ERCP hyperamylasemia (PEH). We reviewed the computed tomography (CT) findings of PEH cases to determine the incidence of painless pancreatitis.Between July, 2005 and December, 2011, CT was performed in 91 patients with hyperamylasemia 18 h after ERCP. We reviewed the CT findings and graded the severity of pancreatitis according to the Balthazar grading system. Grades C, D, and E were defined as pancreatitis.Thirty-four patients (37%) had pancreatitis according to the CT findings. There was a significant difference in the serum amylase levels between the positive- and negative-CT finding groups (1306 ± 833 vs. 786 ± 315 IU/L, respectively; p = 0.0012). Receiver operating characteristic curve analysis showed that the amylase cut-off value for discriminating between the 2 groups was 795 IU/L (6.36 times the upper normal limit).Thirty-seven percent of PEH patients had painless pancreatitis. CT is useful to determine pancreatitis in patients taking analgesics, steroids, or anti-immunological drugs and those with diabetes mellitus and 18-h serum amylase levels of >6 times the normal upper limit.

64 Comparison of the staging of regional lymph nodes using the sixth and seventh editions of the tumor-node-metastasis (TNM) classification system for the evaluation of overall survival in gastric cancer patients: Findings of a case-control analysis involving a single institution in China

Background. This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.Methods. An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.Results. The International Study Group of Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1 mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include:(1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant …

Background. Pancreatoduodenectomy (PD) provides the best chance for cure in the treatment of patients with localized pancreatic head cancer. In patients with a suspected, clinically resectable pancreatic head malignancy, the need for histologic confirmation before proceeding with PD has not historically been required, but remains controversial.Methods. An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature and worked together to establish a consensus on when to perform a PD in the absence of positive histology.Results. The incidence of benign disease after PD for a presumed malignancy is 5-13%. Diagnosis by endoscopic cholangiapancreatography brushings and percutaneous fine-needle aspiration are highly specific, but poorly sensitive. Aspiration biopsy guided by enclascopic ultrasonography (EUS) has greater sensitivity, but it is highly operator dependent and increases expense. The incidence of autoimmune pancreatitis (AlP) in the benign resected specimens is 30-43%. EUS-guided Trucut biopsy, serum levels of immunoglobulin G4, and HISORt (Histology, Imaging, Serology, Other organ involvement, and Response to therapy) are used for diagnosis. If AIP is suspected but not confirmed, the response to a short course of steroids is helpful for diagnosis.Conclusion. In the presence of a solid mass suspicious formalignancy, consensus was reached that biopsy proof is not required before proceeding with resection. Confirmation of malignancy, however, is mandatory for patients with borderline. resectable disease to be treated with neoadjuvant therapy before exploration for resection. When a diagnosis of AIP is highly suspected, a biopsy is recommended, and a short course of steroid treatment should be considered if the biopsy does not reveal features suspicious for malignancy.

Mammalian sirtuins (SIRT1–7) are members of the nicotine adenine dinucleotide (NAD+)-dependent family of enzymes critical for histone deacetylation and posttranslational modification of proteins. Sirtuin family members regulate a wide spectrum of biological processes and are best known for maintaining longevity. Sirtuins are well characterized in metabolic tissues such as the pancreas, liver and adipose tissue (AT). They are regulated by a diverse range of stimuli, including nutrients and metabolic changes within the organism. Indeed, nutrient-associated conditions, such as obesity and anorexia nervosa (AN), were found to be associated with bone fragility development in osteoporosis. Interestingly, it has also been demonstrated that sirtuins, more specifically SIRT1, can regulate bone activity. Various studies have demonstrated the importance of sirtuins in bone in the regulation of bone homeostasis and maintenance of the balance between bone resorption and bone formation. However, to understand the molecular mechanisms involved in the negative regulation of bone homeostasis during overnutrition (obesity) or undernutrition, it is crucial to examine a wider picture and to determine the pancreatic, liver and adipose tissue pathway crosstalk responsible for bone loss. Particularly, under AN conditions, sirtuin family members are highly expressed in metabolic tissue, but this phenomenon is reversed in bone, and severe bone loss has been observed in human subjects. AN-associated bone loss may be connected to SIRT1 deficiency; however, additional factors may interfere with bone homeostasis. Thus, in this review, we focus on sirtuin activity in the pancreas, liver and AT in cases of over- and undernutrition, especially the regulation of their secretome by sirtuins. Furthermore, we examine how the secretome of the pancreas, liver and AT affects bone homeostasis, focusing on undernutrition. This review aims to lead to a better understanding of the crosstalk between sirtuins, metabolic organs and bone. In long term prospective it should contribute to promote improvement of therapeutic strategies for the prevention of metabolic diseases and the development of osteoporosis.

Introduction Thiopurine drugs are metabolised by a complex network of enzymes, each with individual genetic variability. Measurement of active metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN), can have a role in optimising therapy for inflammatory bowel disease (IBD) patients.1 Aims/Background To evaluate how testing thiopurine metabolite(TPM) levels affects the management of patients with IBD receiving azathioprine or 6-mercaptopurine. Method A retrospective laboratory database search for TPM levels. The results were analysed in conjunction with outpatient letters and concurrent laboratory data. The primary outcome: how had measuring TPM levels affected patient management? Secondary objective: to combine demographic and test result data to provide information on the patterns of thiopurine drug use in this population. Results One hundred samples from 78 patients. 45% of samples led directly to changes in patient management. 15% led to dose escalation whilst 9% required dose reduction. The results of 8% led to the use of biological therapy. Treatment was stopped due to potential toxicity in 3%. In 8% of samples, patients were found to be poorly compliant with thiopurine treatment. 3 patients were completely non-compliant. In a sub-group of patients with low Thiopurine S-methyltransferase (TPMT), 78% had high levels of TGN despite the use of low drug doses. Conclusion Measuring TPMs is useful in the management of patients with IBD on thiopurines. They can reveal non-compliance and lead to dose alterations, treatment escalations and the prevention of drug toxicity. We would support the wider use of TPM testing in these patient groups.

Introduction At present, there are guidelines from the US and Europe regarding the formation of transition clinics for adolescents with IBD. This includes a UK Inflammatory Bowel Disease (IBD) Standards guidance on optimal service provision for paediatric and adolescent care. However most of these guidelines come from intuitive reasoning and opinion, as there is a lack of data on what constitutes an ideal service for young patients with IBD. The aim of this study was to develop a comprehensive knowledge and understanding of the key service requirements of young people with IBD as well as their parents. Methods Paediatric and adolescent patients age 6–18 years, were identified from databases in two teaching hospitals and from the membership of the N Ireland branch of Crohn9s and Colitis UK, which is a patient support group. Anonymous questionnaires were sent to these patients and their parents separately. The questionnaires asked about their perceived quality of care, clinic care, general comments, input from specialists, support and information, plus any suggestions. Results 105 questionnaires were sent and 51 responded (49%); of these 21 were from patients and 30 from their parents. Over 84% were happy with the quality of care they are receiving. Reasons patients and parents were reluctant to attend clinics included: blood tests, nurse specialist or doctor not available, lack of car parking. 90% preferred to see the attending (Consultant) rather than a fellow. Nurse specialist, dietetics, specialist IBD surgeon, psychologist, skin/eye specialist input was thought to be beneficial by 95%, 81%, 71%, 59%, and 45% respectively. The following support service and information were considered important: immediate contact with healthcare personnel for disease flare, support groups for young adults, insurance and financial advice, knowledge about IBD developments and research, email service, surgical input regarding stomas. Conclusion The majority of young patients with IBD and their parents are satisfied with the care they are receiving. Support from specialist services such as nurse specialist, dietitians, specialist IBD surgeons, psychologist, plus rapid access to services when the disease flares were thought to be important by the patients and their parents. Knowledge of what these patients and their parents want will help to design an optimal IBD service. Competing interests R Little: None Declared, C Imrie Conflict with: Mead Johnson, Falk Pharma, Nutricia, Warner Chilcott, SHS, Norgine, Wyeth, A Derby: None declared, P Gillespie: None declared, G Caddy: None declared, T Tham Speaker bureau with: Warner Chilcott, Shire, Conflict with: Abbott, MSD.

The tumor-associated inflammatory cell infiltrate is recognized to have prognostic value in various common solid tumors. However, the prognostic value of the tumor inflammatory cell infiltrate has not been established in pancreatic ductal adenocarcinoma (PDAC) nor has its relationship with the systemic inflammatory response.

Outcome prediction after resection with curative intent for pancreatic ductal adenocarcinoma remains a challenge. There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients undergoing resection for a variety of common solid tumors. Our aim was to prospectively evaluate the prognostic value of tumor- and patient-related factors including the systemic inflammatory response in patients undergoing potentially curative surgery for pancreatic ductal adenocarcinoma of the head of pancreas.

Jamieson, Nigel B. MRCS; Imrie, Clem W. FRCS; McKay, Colin J. MD; Carter, C. Ross MD; Foulis, Alan K. MD Author Information

Pseudoaneurysm of the hepatic artery is an uncommon complication of laparoscopic cholecystectomy which is potentially life-threatening if not diagnosed and treated promptly.