Editorial

In this issue of HPB are published manuscripts of presentations at the 8th World Congress of the IHPBA held in Mumbai from 27^th ‘February to 2^nd March, 2008.

I am very grateful to Drs Farges, Humar, Ardhanari and Werner who have contributed reviews of the liver, liver transplant, biliary and pancreas presentations. These follow as guest editorials.

GUEST EDITORIALSLiver Summary – IHPBA 2008

Colorectal liver metastases have been the major focus of interest throughout the meeting. After surgery alone, 10 years actual and DF survival are 16 and 14% (FP12.02). However, approximately one-third of the 10 years DF survivors had undergone repeat surgery and the same proportion of five years DF survivors developed recurrence. The latter undermines the need for continued follow-up which has been suggested by another group to be a three monthly surveillance during the first two years (FP12.03). Besides classical risk factors of recurrence, the lack of normalisation of CEA level within six weeks of surgery has been identified (FP12.04). Response to preoperative chemotherapy is however emerging as more powerful than the classical Memorial Sloan-Kettering Cancer Center (MSKCC) score (FP31.03) and although still a rare event, complete response is increasingly reported (FP27.07, FP35.01, FP35.03, FP35.04). There remains however much controversies on the potential side effects of neoadjuvant chemotherapy. In itself, neither the classical (FP27.02) nor the new antiangiogenic agents (FP31.01) affect the perioperative outcome. However, severe sinusoidal obstructive syndrome may increase the risk of postoperative insufficiency (PL1.01, FP27.04). Attempts to further assess these chemotherapy associated injuries have included electron microscopy (FP31.05), measurement of portal pressure (FP27.05), Aspartate amino transferase (AST)/platelets ratio (FP27.04) and MRI (PP11.04). Although portal vein embolisation (PVE) – or portal vein ligation which is as effective (AP5.04) – may be used to increase respectability, there is some evidence that it may increase cancer cell proliferation (AP3.02).

HepatoCellular Carcinoma (HCC) continues to be a major focus of interest in both the East and the West including northern European countries were the prevalence of this cancer was traditionally low. The efficacy of RF is confirmed in the long term with five years survival of 43% that reaches 59% for tumours up to 3 cm (AP5.02). On the other hand, there is an increasing trend to consider resection (besides transplantation) in some patients fulfilling the Milan criteria. There have been attempts to improve, through non-invasive means, staging of the fibrosis grade through the AST/platelets ratio (FP13.05), liver function through branched chain amino acids/Thyrosine ratio (FP13.06) and microscopic portal vein invasion through the measurement of the perfusion defect area during CT arterial portography (FP13.04). It is still unclear whether anatomical resection is superior (PP1.09) or equal to (FP2.08) non-anatomical resection. HCC located in segment 1, a troublesome location, have a prognosis comparable to those in segment 4 (PP1.07) and can be successfully treated by RF (FP22.05).

Clamping of the hepatic pedicle did not receive much attention but the trend is to use it more and more selectively as a meta-analysis failed to demonstrate any benefit in perioperative outcome (PP57.09). The Hong Kong group, who first reported through a randomized controlled trial (RCT) the benefit of the Pringle manoeuvre 10 years ago, currently use it in less than 3% of their patients (FP25.06). Microdialysis catheters placed in the liver have been used to monitor the biochemical consequence of ischemia/reperfusion (PP4.08) and may help in the future to tailor the duration of clamping. Several groups have presented their experience with laparoscopic liver resections. The trend is to extend this approach to malignancies that now account for up to 80% of the indications in some centres (FP37.01 and PP2.01). Eighteen right hepatectomies have also been reported, without conversion (FP37.07). Laparoscopic right portal vein ligation is also feasible (FP37.04) which may prove useful at a time when laparoscopic colorectal resections also develop.

Rehabilitation is obviously becoming a focus of interest. Fast track liver major surgery is starting to develop (AP3.06) and the only RCT on liver surgery presented during the meeting was devoted to pain control through wound instillation of Ropivacaine (FP25.08). This is probably not fortuitous, as the sample size of a hypothetical RCT aiming to show a reduction in mortality or morbidity is so high (>5000) that it is hardly feasible (PP33.03).

Transplantation summary – IHPBA 2008

Liver transplantation has become an integral part of the practice of HPB surgery, and the most current topics in the field were very well covered at the 2008 IHPBA meeting. These topics included living donor liver transplant (LDLT), methods to expand the deceased donor (DD) pool, recurrence of disease (HCC, Hep C, Hep B), and morbidity associated with long-term immunosuppression.

Worldwide, LDLT is a rapidly growing procedure, with likely > 10,000 such procedures performed to date. Donor morbidity and mortality associated with the procedure remain a significant concern. By some reports, there have been 28 donor deaths and an additional four donors receiving liver transplants themselves ¹. The problem, however, has been that poor reporting has made both the number of such transplants, and the number of donor deaths difficult to quantify accurately. Based on the results summarized from a recent worldwide forum, the estimated risk of donor mortality is 0.5%, and morbidity 35%. Individual center reports suggest that 95% of donors returned to predonation level of quality of life within six months, but long-term follow-up is necessary. Recipient results with LDLT have improved, and are now equivalent to DD results ². According to North American data, technical complications, especially biliary complications, remain high but significant surgical advances have been made ³. The Asan Medical Center in South Korea presented an over 1500 LDLTs, 286 of them performed in 2007. Multiple graft types were utilized including right lobe (with and without middle hepatic vein [MHV]), left lobe, dual left lobe, and combined right and left lobes. Keys to achieving technical success were adequate graft volume, secure biliary anastomosis, sufficient inflow, and good outflow ⁴. Survival rates of >80% at five years were reported from the center. Several controversies were addressed in different sessions including right vs. left lobe, routine inclusion of MHV, and technique for biliary reconstruction.

Methods to increase the DD pool were discussed; including donation after cardiac death (DCD) and split-liver transplantation (SLT). With DCD donors, biliary complications and poor survival rates remain a concern. But with careful donor selection (donor age <45, WIT < 30 min and CIT < 10 h) combined with careful recipient selection (MELD 15–30), centers such as Leeds, UK have reported good results. Similarly, SLTs represent another method to expand the donor pool successfully, as illustrated by results from the European split database with 2107 SLTs performed between 1997 and2004. The results have improved, but ongoing issues including in situ vs. ex situ splitting, appropriate centers and recipient selection, allocation, and adult/adult utilization remain.

Hepatocellular carcinoma (HCC) represents an increasingly common indication for transplant, and data was presented on the ideal candidate. While the Milan criteria provides good results, is it too restrictive? Data on expanded indications, such as the UCSF criteria, show that equivalent results can be obtained with low rates of recurrence. Recurrence of Hep B after transplant seems to be well controlled with current antiviral regimens, but Hep C recurrence remains a major problem with poor options available at present.

With the success of liver transplantation, numerous new centers have been established in areas such as Africa, India, and China. An interesting session discussed some of the issues relevant to these programs, including establishment of infrastructure, cost issues, development of appropriate teams and expertise, and establishment of DD protocols. It was clear that the upcoming few years would see a dramatic increase in activity at these centers.

Pancreas transplantation, both whole organ and islet cell, was covered briefly. Long-term results remain significantly superior with whole organ vs. islet cell transplantation. Surgical complications remain higher after whole organ transplant, but have improved with surgical refinements and better donor selection.

Biliary summary – IHPBA 2008

The Biliary session began on 28th February with a symposium on hilar cholangiocarcinoma. First up, was a talk by Prof. Jarnagin of MSKCC on preoperative staging of hilar cholangiocarcinoma. He stressed that MRCP, Duplex scanning to visualise blood vessels and FDG-PET were most useful preoperative imaging modalities. Staging laparotomy may help identify a subset of patients with advanced disease. 3D imaging is promising. Despite all these, local resectability may be underestimated.

Prof. Hideki Nishio talked about the Nagoya strategy in surgical treatment of hilar cholangiocarcinoma. He showed that over time major resection showed shorter operating time, less blood loss, lesser operative mortality and improved long-term survival. This was attributed to portal vein embolisation, bile replacement, use of synbiotics and autologus transfusion.

Subsequently, Prof. Peter Neuhaus discussed extended lymphadenectomy and portal vein excision in hilar cholangiocarcinoma. He stressed upon preoperative portal vein embolisation, biliary drainage, extended resection and routine portal vein resection. This led to 10% mortality but gave 60% five-year survival. However, the MSKCC group objected to routine portal vein excision.

Lastly, Prof. Nakeeb Attila discussed the role of adjuvant therapy in hilar cholangiocarcinoma. The addition of inter and postoperative radiotherapy has shown to improve survival in some studies. Todoroki showed this to improve survival from 13.5 to 39.2%. However, others did not show benefit of radiotherapy. Chemotherapy is still under evaluation.

A symposium on choledochal cysts was conducted. First, Prof. Adarsh Chaudhary spoke on complications of choledochal cyst. He classified them as septic and non-septic. Portal hypertension was a major factor in morbidity and mortality of choledochal cyst surgery.

Prof. Garden discussed management of Caroli's disease. In the rare localised type resection may be appropriate. Obstructing stones may need removal and hepaticojejunostomy to be done. Transplantation is an option in case of liver failure.

A wider debate on open versus laparoscopic hepaticojejunostomy seemed to indicate that as yet open hepaticojejunostomy is the standard. Laparoscopic hepaticojejunostomy needs advanced skills and may be appropriate for large ducts.

A debate on preoperative biliary drainage in type III Hilar Cholangiocarcinoma had Prof. Nimura supporting it. He stressed that, it had therapeutic value with lesser morbidity and better survival. It was also of diagnostic value in changing the classification in some patients. However, Bill Janargin showed that MSKCC data showed improved results without routine preoperative biliary drainage. Clearly, cholangitis entails drainage but in other patients it is controversial.

Prof. Tadahiro Takada presented the international consensus guidelines on cholangitis and cholecystitis. The methodology of arriving at the guidelines was discussed. The guidelines can be downloaded from the Internet. They broadly cover acute cholecystitis and cholangitis. It stresses early laparoscopic cholecystectomy for acute cholecystitis and endoscopic drainage for cholangitis.

A debate on the neoplasms of gallbladder discussed open or laparoscopic approach. Laparoscopic cholecystectomy was preferred unless frozen section showed invasive carcinoma when conversion to open procedure was mandatory.

On March 1st, a symposium on carcinoma Gallbladder was held. First, Prof. Anil Agarwal stressed that for T1a – Cholecystectomy alone is sufficient. For T1b, radical cholecystectomy needs to be done. In a postoperative patient with histopathology of carcinoma gallbladder, early resection is to be done. Involvement of Rokitansky – Aschoff sinus has a poor outcome in Prof. Aretxabala's view. If this is seen then radical surgery is needed. Prof. Kondo showed that presence of para-aortic lymphadenopathy is metastatic disease. Any positive lymph nodes show poor prognosis and the best chance of survival is R0 resection. Adjuvant treatment of carcinoma gall bladder is shown to be ineffective at present and needs to be further evaluated.

A debate on whether bile duct resection should be routine for carcinoma gallbladder had Prof. Miyazaki state that this helps in better tumour clearance and lymphadenectomy. However, Prof. Sadiq Sikora did not support the concept that routine bile duct excision leads to better survival or lymphadenectomy.

Prof. Nimura, in his keynote address in ‘Lessons learnt in management of Biliary malignancies’ stressed on MDCT before stenting. Routine Percutaneous Transhepatic Biliary Drainage (PTBD) and Portal vein Embolisation (PVE) improved results. Extended resection with vascular reconstruction and neo-adjuvant chemoradiation improved results.

Prof. Gouma discussed the management of complex bile duct injury. He stressed on a multidisciplinary approach and that stenting was useful in 20% of patients. Acute repair, higher injury and intervention had poor results. Drainage does not affect results. Short term (<6 months) stenting does not affect outcome of operation.

Dr. Strasberg in his talk on ‘Exercising safety in Biliary Surgery’ stressed on the ‘error traps’ in cholecystectomy. He showed that in conversion of laparoscopic to open cholecystectomy ‘fundus down’ led to some major vascular or biliary injury.

The Ganga study, an epidemiological study was presented. It assessed the prevalence of carcinoma gallbladder and stone disease. It seemed to implicate heavy metals in gallbladder cancer.

Prof. VK Kapoor talked on evidence-based medicine in biliary tract. He felt that endo biliary metal stents should be used in malignancy if life expectancy is <6 months. Surgery is better for patients who expected to live longer. Metal stents are to be avoided in benign strictures. In India, early carcinoma gallbladder should be treated aggressively with palliation for advanced tumours.

On 2nd March, a symposium on Intrahepatic Cholangiocarcinoma (ICC) was conducted. Three main types of ICC are identified – Mass, periductal and intraductal, with mass being the predominant type. Mass alone has a better prognosis. Positive lymph nodes, intrahepatic metastasis, grading, presence of jaundice and raised CA19-9 have poor prognosis.

ICC has hepatolithiasis as a risk factor. Western and Eastern experiences are similar. Extended R0 resection for single and lymph node negative tumours have better survival. Overall, 24% five-year survival was reported.

Lastly, a session of CBD stones was conducted. The conclusion was that available expertise makes the choice. Both endoscopic and laparoscopic approaches are effective. Small ducts should be tackled endoscopically. LCBDE offers advantage of one stage procedure and intact ampulla.

Pancreas summary – IHPBA 2008

The 8th World Congress of the IHPBA in Mumbai was a fantastic event for the HPB community. Over 500 abstracts focused on multiple aspects of pancreatic diseases including acute and chronic pancreatitis, pancreatic tumors, as well as pancreatic trauma transplantation were presented as keynote lectures, video sessions, symposia, oral and poster presentations. Thus, in this summary I can only focus on some of the highlights presented.

Over the past years it became evident, that the surgeon and high-volume hospitals are main factors for the outcome for pancreatic surgery (Strasberg and Bassi, SY15). Sethi et al. from London, UK (PP 31.06) and Mittal et al. from Soutfield, USA (FP 17.02) could demonstrate that specialization of physicians and centralization of the treatment of hepato-pancreato-biliary diseases exert positive effects on resection rate, morbidity and mortality, as well as on costs at their institutions. In addition, data from Newcastle upon Tyne, UK (PP.05.02) proofed for the first time in an observational study of 18 hospitals that caseload also affects mortality in the treatment of acute pancreatitis.

Acute pancreatitis – Early prediction of severity of the disease is one of the main issues in the management of acute pancreatitis. An artificial neural network which applies data from a large population to an individual and identifies patterns within data that are associated with a particular outcome was proven to be superior to conventional scoring systems (R. Parks, SY 7.01). Increased D-dimer levels seem to predict the development of organ failure already on admission (AP2.04). However, the routine applicability of these new predictors needs to be validated. Today, prevention of infection during the course of pancreatitis is the main treatment goal. So far, no treatment agent has successfully decreased either infection rate or mortality. In fact, a recent randomized multicenter trial showed that probiotics increase mortality and should not be used in acute pancreatitis. Thus, supportive intensive care is the only treatment that can be advocated in severe pancreatitis (J. Werner, SY 7.01).

Chronic pancreatitis – Tropical pancreatitis is a special form of chronic pancreatitis which is not observed in the Western world. In India, the disease pattern has changed over the last 30 years due to change of lifestyle, nutrition, and alcohol consumption. Most patients today present with a mixture of alcoholic and tropical form of pancreatitis (UL 8.01). Mihir et al. (PP 28.10) demonstrated that the combination of pancreatic head resections and surgical drainage result in an excellent pain relief in over 95% of all patients. These results support the latest randomized controlled trial which showed that surgical drainage is superior to endoscopic drainage in patients with pancreatic duct stenosis. Two other presentations (Vashist et al. FP 15.03, Van der Gaag et al. FP 15.06) demonstrated that reoperations in patients with chronic pancreatitis are needed in 5–15%, most frequently for recurrent pain. The Hamburg group could show that most of the time a duodenum-preserving pancreatic head resection can successfully be performed even as a redo-resection. These reports underline the important role of surgical treatment in chronic pancreatitis today.

Pancreatic tumors – Radical surgical approaches for pancreatic cancer have been reported for advanced pancreatic tumors. To achieve free resection margins the early dissection of the superior mesenteric artery has been advocated by two groups as the “artery first approach” (Büchler, Heidelberg, Germany) or the “hanging maneuver” (Jaeck, Strasbourg, France). While venous resection is a well-accepted standard in case of infiltration in pancreatic cancer, arterial resection is rarely reported. Two abstracts from Japan (Miyazaki et al. FV 1.01; Hirano et al. FV 6.05) reported on distal pancreatectomy with en bloc resection of the celiac trunk with a median survival of 21 months in 23 patients. The resection of the hepatic artery is also technically feasible, but median survival was only 10 months (Hoshino et al. FV 1.04, Jaeck et al. PP 17.10). Today, many rare pancreatic tumors are identified more frequently secondary to the frequent usage and technical advances of imaging techniques. Alone seven abstracts reported about solid pseudopapillary neoplasms (Frantz tumors) so that we can expect a lot of interesting results on the pathologies of these rare tumors in the near future.

Surgical techniques – Minimal invasive surgical techniques have been advocated for almost any pancreatic disease and procedure. Twenty-three presentations reported that laparoscopic approaches are safe and feasible in experienced hands. However, no randomized controlled study has been published so far. An exception is the multicenter PANTER trial of the Dutch Acute Pancreatitis Study Group which compares conventional open necrosectomy with a minimal invasive step-up approach in necrotizing pancreatitis which will close recruitement soon.

The pancreatic anastomosis is the most demanding one in pancreatic surgery. Peng et al. demonstrated a leakage rate of 0.5% with a simple binding technique in over 300 cases (SY4.03). However, reports from other institutions on the safety of this technique from Hong Kong (FP 32.05) and India (PP 63.10) with fistula rates of 53% (11/21) and 7.5% (1/15) demonstrate that caseload is a key factor in pancreatic surgery and that standardized definitions of complications need to be used for comparisons of results between institutions. Internationally accepted and standardized definitions of pancreatic complications including fistula have been published recently. The ISGPF definition of pancreatic fistula was used in nine studies presented at this meeting demonstrating the importance of such standardizations.