Hepatolithiasis:Epidemiology,presentation,classification and management of a complex disease

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.

Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services.Type 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and outcome.Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period.The incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve outcomes.While various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined,a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis.Therefore,pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams.With the ongoing accumulation of evidence,it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.

Liver transplantation in the management of cholangiocarcinoma:Evolution and contemporary advances

Cholangiocarcinoma(CCA)is an aggressive malignancy arising from the biliary epithelium.It may occur at any location along the biliary tree with the perihilar area being the most common.Prognosis is poor with 5-year overall survival at less than 10%,typically due to unresectable disease at presentation.Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours,but is frequently not possible due to locally advanced disease.On the other hand,orthotopic liver transplantation(LT)allows for a radical and potentially curative resection for these patients,but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes.In patients with perihilar CCA,within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT,excellent results have been achieved in the last decades,resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience.However,in intrahepatic CCA,the role of LT remains controversial and owing to dismal previous results it is not an accepted indication.Nevertheless,more recent studies have demonstrated favourable results with LT in early intrahepatic CCA,indicating that,under defined criteria,its role may increase in the future.This review highlights the history and contemporary advances of LT in CCA,with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.

Role of routine lymph node dissection alongside resection ofintrahepatic cholangiocarcinoma: Systematic review and metaanalysis

BACKGROUND The global incidence of intrahepatic cholangiocarcinoma(ICCA)is soaring.Due to often delayed presentation,only a narrow spectrum of the disease is usually surgically resectable.To more accurately stage the disease,reduce recurrence,and improve overall survival,surgical teams are increasingly performing intraoperative lymph node dissection(LND)as well.This procedure has its associated morbidity,while there is no consensus or formal guidelines on its role in this setting.Hence,there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA.AIM To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA.METHODS We performed a systematic literature search using Pubmed,Medline,Embase,and the Cochrane Library,for all studies involving LND,ICCA,and surgical resection using several keywords,Medical Subject Headings(MeSH)tags,and appropriate synonyms.All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included,while single-arm case series,studies with insufficient data,and duplicates were excluded.We included all English-language studies from the different academic databases up till early December 2022.The primary outcome measures were set for overall survival(OS)and disease-free survival(DFS).RESULTS This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA,of whom 6424(56.3%)underwent hepatectomy with LND while the remainder underwent hepatectomy only.In patients who underwent LND,on average,27.7%of the resected lymph nodes were positive for metastatic disease.Overall,the results showed that performing LND did not significantly improve OS or DFS.However,the effect of LND on OS showed a degree of variability by geographical region,in Eastern and Western countries.As LND is increasingly being performed,further time-based analysis was undertaken to identify time-dependent changes in the role of LND.An increasing adoption of LND was not associated with improved OS.Furthermore,no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either.CONCLUSION LND might aid in staging,prognosticating,and deciding further management of resected ICCA,but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.

Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis

Primary sclerosing cholangitis(PSC)is a premalignant condition and a welldocumented risk factor for cholangiocarcinoma(CCA)which is the most common malignancy in this setting and the leading cause of deaths in the recent years,with an increasing incidence.PSC-associated CCA has a geographical distribution that follows the incidence of PSC,with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries.It may arise at any location along the biliary tree but is most common in the perihilar area.Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection,which is otherwise the treatment of choice with curative intent in patients with resectable tumours,providing a radical resection with clear margins can be achieved.This largely relates to the commonly advanced stage of liver disease at presentation,which allows consideration for liver resection only for a very limited number of suitable patients with PSC.On the other hand,remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation(OLT)for the treatment of perihilar CCA,within specific criteria.Excellent results have been achieved particularly for PSC patients with this cancer,who seem to benefit the most from this treatment,having converted this into an accepted indication for transplantation and the standard of care in several experienced centres.Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results.However,as recent studies have shown favourable outcomes in early intrahepatic CCA,it may be that under defined criteria,OLT may play a more prominent role in the future.Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent,when feasible.This review provides insight about particular features of CCA in the setting of PSC,with a main focus on its incidence,considerations relating to its anatomical location and implications to treatment and outcomes,through the viewpoint of historical evolution of management,and future perspectives.

Surgical ampullectomy:A comprehensive review

Tumours of the ampulla of Vater are relatively uncommon lesions of the digestive system.They are typically diagnosed at an earlier stage than other types of tumours in this region,due to their tendency to invoke symptoms by obstructing the bile duct or pancreatic duct.Consequently,many are potentially curable by excision.Surgical ampullectomy(SA)(or transduodenal ampullectomy)for an ampullary tumour was first described in 1899,but was soon surpassed by pancreatoduodenectomy(PD),which offered a more extensive resection resulting in a lower risk of recurrence.Ongoing innovation in endoscopic techniques over recent decades has led to the popularization of endoscopic papillectomy(EP),particularly for adenomas and even early cancers.The vast majority of resectable ampullary tumours are now treated using either PD or EP.However,SA continues to play a role in specific circumstances.Many authors have suggested specific indications for SA based on their own data,practices,or interpretations of the literature.However,certain issues have attracted controversy,such as its use for early ampullary cancers.Consequently,there has been a lack of clarity regarding indications for SA,and no evidence-based consensus guidelines have been produced.All studies reporting SA have employed observational designs,and have been heterogeneous in their methodologies.Accordingly,characteristics of patients and their tumours have differed substantially across treatment groups.Therefore,meaningful comparisons of clinical outcomes between SA,PD and EP have been elusive.Nevertheless,it appears that suitably selected cases of ampullary tumours subjected to SA may benefit from favourable peri-operative and long-term outcomes with very low mortality and significantly long survival,hence its role in this setting warrants further clarification,while it can also be useful in the management of specific benign entities.Whilst the commissioning of a randomised controlled trial seems unlikely,well-designed observational studies incorporating adjustments for confounding variables may become the best available comparative evidence for SA,potentially informing the eventual development of consensus guidelines.In this comprehensive review,we explore the role of SA in the modern management of ampullary lesions.

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.