In the field of hilar cholangiocarcinoma (HCCA) treatment, the value of caudate lobe resection (CLR) has not been fully elucidated. Most scholars advocate that the caudate lobe should be routinely resected. To further investigate this issue, this study aims to evaluate the impact of CLR on surgical outcomes of HCCA patients who are judged to have no obvious tumor invasion in the caudate lobe. A retrospective analysis was performed on Bismuth type II, III, or IV HCCA patients who underwent radical resection between October 2005 and April 2023 at three Chinese medical centers. Patients were divided into the CLR group and the no caudate lobe resection (No-CLR) group according to whether CLR was performed or not. Baseline and tumor characteristics as well as perioperative outcomes were compared between the two groups using propensity score matching (PSM). A total of 397 HCCA patients underwent radical resection and there were 146 patients in each group after PSM. After PSM, the mortality was similar between the two groups. However, patients in the CLR group had a higher incidence of postoperative ascites (43.8% vs 30.1%, P=0.021), liver failure (15.8% vs 6.2%, P=0.014) and intra-abdominal infection (19.2% vs 8.2%, P=0.010). The R0 rate in the CLR group was significantly higher than that in the No-CLR group (88.4% vs 76.0%, P=0.009). Nevertheless, patients undergoing CLR did not show any improvement in overall survival (OS) or recurrence-free survival (RFS). Multivariate analysis showed that CLR was not associated with improved long-term surgical outcomes. The high level of CA19-9 and lower tumor differentiation were associated with worse OS, and adjuvant therapy can significantly improve OS. Lower tumor differentiation and N2 were associated with worse RFS. In summary, there is not yet sufficient evidence to support the routine resection of the caudate lobe during surgery for HCCA. For patients without obvious tumor invasion in the caudate lobe, resection of the lobe should be carefully weighed for its benefits and risks.

Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.

Many liver surgeons have updated their understanding of the liver in recent years because of detailed studies on the liver anatomy and the rapid advances in laparoscopic liver surgery. Despite newer approaches, concepts and methods, research on the caudate lobe continues to be based on case reports and several persistent challenges concerning caudate lobe surgery that are worth discussing. Based on the literature and the author's experience, this study considers and addresses the challenges associated with caudate lobectomy encountered by most liver surgeons. We searched PubMed for relevant articles in English for 'caudate lobe', 'cholangiocellular carcinoma', 'laparoscopic caudate resection', 'right-side boundary of the caudate lobe' and 'assessment of hepatic functional reserve' published up to May 2022. This study reviewed the anatomical history of the caudate lobe, focusing on the challenges associated with caudate lobe-related surgical resection. Due to the unique anatomical position of the caudate lobe, surgical strategy for caudate lobe resection is particularly important, and the technical requirements for hepatobiliary surgeons are also extremely strict. Therefore, understanding the anatomical history of the caudate lobe and discussing the challenges associated with caudate lobectomy is essential.

Hepatic resection of Klatskin tumors usually requires postoperative intensive care unit (ICU) admission because of its high morbidity and mortality. Identifying surgical patients who will benefit most from ICU admission is important because of scarce resources but remains difficult. Sarcopenia is characterised by the loss of skeletal muscle mass and is associated with poor surgical outcomes.

We retrospectively analysed th.e relationship between preoperative sarcopenia and postoperative ICU admission and length of ICU stay (LOS-I) in patients who underwent hepatic resection for Klatskin tumors. Using preoperative computed tomography scans, the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra was measured and normalised to the patient's height. Using these values, the optimal cut-off for diagnosing sarcopenia was determined using receiver operating characteristic curve analysis for each sex.

Of 330 patients, 150 (45.5%) were diagnosed with sarcopenia. Patients with preoperative sarcopenia presented significantly more frequently to the ICU (77.3% vs. 47.9%, p < 0.001) and had longer total LOS-I (2.45 vs 0.89 days, p < 0.001). Moreover, patients with sarcopenia showed a significantly higher postoperative length of hospital stay, severe complication rate, and in-hospital mortality.

Sarcopenia correlated with poor postoperative outcomes, especially with the increased requirement of postoperative ICU admission and prolonged LOS-I after hepatic resection in patients with Klatskin tumors.

The aim of the present study was to investigate the relationship between the mutational gene profile and recurrence in biliary tract cancers (BTC). A total of 103 specimens of patients with BTC, who underwent curative surgery in a single tertiary HPB surgery referral center from 1990 to 2012, were assessed for mutational status in 52 cancer-related genes. Considering the different types of BTC, the 5-year recurrence-free survival (RFS) rate was 16.7% (median RFS 7 months) in gallbladder cancer, 42.9% (median RFS 26.4 months) in intrahepatic cholangiocarcinoma, and 19.7% (median RFS 16.5 months) in perihilar cholangiocarcinoma, p = 0.166. At the multivariate analysis including clinical, pathological, and molecular features, the factors independently related to RFS were radicality of surgery (OR 2.050, CI 1.104-3.807, p = 0.023), LN status (OR 1.835, CI 1.006-3.348, p = 0.048), mutational status of ARID1A (OR 2.566, CI 1.174-5.608, p = 0.018), and TP53 (OR 2.805, CI 4.432-5.496, p = 0.003). ARID1A mutation was associated with a local and systemic recurrence in the 43% and 29% of cases, respectively; and TP53 mutation was associated with a local and systemic recurrence in the 29% and 41% of cases. Moreover, TP53 was most commonly mutated in tumor of patients with early recurrence, p = 0.044. ARID1A and TP53 mutations seem to be related to poor outcome after surgery and may be considered molecular predictors of the biological aggressiveness in BTC.

Surgical resection remains the only potentially curative therapy for hilar cholangiocarcinoma (CCC) patients. This meta-analysis aimed to review the current evidence on perioperative and long-term outcomes of routine caudate lobe resection (CLR) for surgical treatment of hilar CCC.

A systematic literature search using MEDLINE, EMBASE and Cochrane databases was performed for studies providing comparative data on perioperative and long-term outcomes of patients undergoing resection for hilar CCC with and without CLR. The MINORS score was used for quality assessment. For time-to-event outcomes hazard ratios (HRs) and associated 95% CI were extracted from identified studies, whereas risk ratios (RRs) were calculated for overall morbidity, mortality, and resection margin status. Meta-analyses were carried out using random-effects models.

Eight studies involving 1350 patients met the inclusion criteria. The quality of the included studies was low to moderate. CLR resulted in significantly improved overall survival (HR 0.49; 95%CI 0.32-0.75, P < 0.01). Postoperative morbidity (RR 0.93; 95% CI 0.77-1.13; P = 0.48) and mortality (RR 1.01; 95% CI 0.42-2.41; P = 0.99) rates were comparable between both groups. Patients without concomitant CLR were at higher risk for residual tumor at the resection margin (RR 1.40; 95% CI 1.09-1.80; P = 0.01).

CLR is associated with improved long-term survival and negative tumor margins after resection of hilar CCC with no adverse impact on perioperative outcomes. CLR might provide the potential to become a standard-of-care procedure in the surgical management of hilar CCC.

No worldwide consensus on the assessment tool for liver functional reserve is currently available. The aim of this study was to evaluate the correlation between liver elasticity of both hepatic lobes and liver functional reserve tests. This prospective observational study comprised 40 patients scheduled for hepatectomy. Liver elasticity was assessed by Virtual Touch Quantification (VTQ). The mean VTQ value for the right and left lobes was defined as the mVTQ. Liver functional reserve was measured with technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin scintigraphy as LHL15 and HH15 and the indocyanine green (ICG) excretion test as ICG-R15 and ICG-K. All examinations were measured after biliary decompression confirmed serum a total bilirubin level ≤2 mg/dL. Mean VTQ values were moderately correlated with LHL15 (r = -0.42, p < 0.01), HH15 (r = 0.48, p < 0.01), ICG-R15 (r = 0.53, p < 0.01) and ICG-K (r = -0.61, p < 0.01) values. In conclusion, the liver elasticity determined by VTQ would be a useful predictor of liver functional reserve in patients scheduled for hepatectomy.

The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma.

A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes.

A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival.

Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.

To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations.

Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis.

Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups.

Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.

Hilar cholangiocarcinoma provides a surgical challenge. Successful outcome depends upon preoperative imaging, appropriate use of biliary drainage and portal vein embolisation as well as appropriate liver resection with caudate lobe excision and nodal clearance.

To clarify the value of resection of gallbladder cancer involving the extrahepatic bile duct.

: Several recent studies have proven that jaundice and extrahepatic biliary involvement are independent predictors of a poor outcome. Only a few authors recommend resection of such advanced disease.

One hundred patients with pT3/4, pN0/1, M0 disease were the subjects of this study. Mortality and long-term outcome were analyzed using a prospectively collected database.

The only factor associated with mortality in univariate and multivariate analyses was intraoperative blood loss. The 5-year survival rate and median survival time were 23% and 1.5 years for patients with pathologic extrahepatic biliary invasion (pEBI), and 54% and 15.4 years for patients without pEBI. Twelve patients with pEBI survived beyond 5 years. Multivariate analysis revealed that R1/2 resection and combined resection of adjacent organs other than the liver and extrahepatic bile duct (CRAO) were independent predictors of poor outcome. Five-year survival rate and median survival time after R0 resection without CRAO were 36% and 3.8 years even in patients with pEBI. In contrast, after R0 resection with CRAO 5-year survival and median survival time were 16% and 0.8 years, respectively.

Patients with advanced gallbladder cancer with pEBI are candidates for resection when distant metastases are absent and R0 resection is achievable. When CRAO is unnecessary, surgical resection should be aggressively planned.

Postoperative liver failure (PLF) is a relatively frequent and life-threatening complication after extended liver resection. This study describes the economic burden of PLF from the hospitals' perspective and explores the role of liver function capacity.

Economic data of total costs and cost distribution were analyzed for 48 patients who had participated in a prospective study with the LiMAx test, a novel test for liver function capacity. For this population, detailed individual data were available. The economic data were analyzed and adjusted for relevant covariates. In addition, economic data of 916 patients who had undergone liver resection during 2005-2007 were retrieved from the hospitals' medical controlling office for comparison.

A significant difference between the costs of patients with regular recovery (25,980 Euro [95% confidence interval (95%CI) = 9,559 to 42,401]) versus patients developing PLF (82,199 Euro [95%CI = 42,812 to 121,586]; p = 0.013) was observed. The mean additional costs of PLF were 56,219 Euro. An equivalent cost difference of mortality was obtained from the analysis of 916 patients. Patients developing PLF had a decreased LiMAx of 61 microg/kg/h compared to the regular group 122 microg/kg/h (p < 0.001) after surgery. Initial postoperative LiMAx and total costs revealed a linear correlation coefficient of r = -0.340 (p = 0.018).

PLF is a very relevant medical and economic problem. Liver function capacity does not only predict PLF but also correlates with total costs in general.

Locoregional recurrence following resection of hilar biliary cancers could be caused by the microscopic dissemination of cancer cells during dissection of the portal vein from the involved bile duct at the hilar region. This retrospective study assessed the feasibility and safety of a new procedure consisting of right-sided hepatectomy, caudate lobectomy, and bile duct resection combined with routine resection of the portal bifurcation to enable no-touch resection of hilar malignancies.

Of 64 patients who underwent right-sided hepatectomy for hilar biliary cancer, the portal bifurcation was routinely resected by the above new procedure in 25 patients, based on preoperative imaging diagnoses. Perioperative outcomes were compared with those in patients who underwent conventional portal reconstruction (n = 18) and with those in patients who had preservation of the portal bifurcation (n = 21).

Perioperative data from patients with routine portal reconstruction were similar to those in the patients with conventional portal reconstruction and the patients without portal reconstruction. There were no postoperative complications directly related to portal reconstruction.

No-touch resection of hilar malignancies with right hepatectomy and the routine use of portal reconstruction was feasible and safe. The oncologic impact of this technique merits further evaluation.

Left-sided cholangiocarcinoma includes hilar cholangiocarcinoma (HC), predominantly involving the left hepatic duct, and intrahepatic cholangiocarcinoma (ICC) in the left liver. Left hepatectomy, or left hepatic trisectionectomy, is indicated as radical surgery of left-sided HC or ICC with or without hilar bile duct invasion. Left lateral sectionectomy, or left medial sectionectomy, is performed for the small mass-forming type ICC. Left hepatic trisectionectomy is indicated for left-sided HC with further cancer progress along the right anterior sectional duct or left-sided ICC involving the right anterior section over the middle hepatic vein and/or the right anterior pedicle. Combined caudate lobe and extrahepatic bile duct resection are mandatory in cases of HC or ICC involving the hepatic confluence. Preoperative biliary drainage should be performed not only for jaundiced patients but also for non-icteric patients with right-sided biliary dilatation of the future remnant liver. Preoperative left trisegment portal vein embolization after biliary drainage of the right posterior section should be carried out prior to left hepatic trisectionectomy. Left hepatectomy has been used as a radical and safer surgical procedure, but in European countries has still been associated with higher morbidity and about 10% operative mortality. Japanese surgeons have had no hospital deaths after carrying out left hepatic trisectionectomy done after preoperative biliary drainage followed by left trisegment portal vein embolization to increase safety and to prolong postoperative survival for patients with locally advanced left-sided cholangiocarcinoma.

Recent progress in vascular surgical techniques has made it possible to combine liver and portal vein and/or hepatic artery (HA) or retrohepatic inferior vena cava (IVC) resection and reconstruction in cases of locally advanced cholangiocarcinoma. Reports of the success of this difficult surgery have been published. Aggressive Japanese surgeons have applied hepatopancreatoduodenectomy (HPD) not just in cases of advanced gallbladder cancer, but also in locally advanced cholangiocarcinoma with or without superficial spread. The above extended surgeries were associated with high postoperative morbidity and mortality, but recent progress in perioperative management and surgical techniques has improved the outcome of these types of surgery. Combined portal vein and liver resection provides R0 resection and contributes to longer survival in resected patients with locally advanced cholangiocarcinoma than in unresected patients. Portal vein invasion is a strong prognostic factor of cholangiocarcinoma and the actual number of 5-year survivors is limited. The number of clinical cases of liver resection combined with IVC or HA resection and reconstruction is still limited, and therefore the long-term survival benefit from these procedures has not been clarified. HPD carried high morbidity and mortality rates in the 1990s, but the outcome has been improving and an increasing number of 5-year survivors has been reported. Although the clinical value of the above extended surgeries has not been evaluated prospectively, with the increasing number of retrospective studies it has been concluded that combined liver and portal vein and/or HA or IVC resection or HPD could be indicated for selected patients with locally advanced cholangiocarcinoma.

High hepatic duct resection sometimes is unavoidable in achieving curative resection of hilar cholangiocarcinoma, as tumor cells can extend further than expected along the bile ducts from the macroscopically evident cancer. In patients undergoing left hemihepatectomy with caudate lobectomy whose bile duct must be severed at the subsegmental bile duct levels, the orifices of the posterior bile ducts would lie behind the right portal vein. Conventional hepaticojejunostomy would be risky in such cases because an anastomosis performed in the usual manner would be subjected to strain. Instead, between 2002 and 2004, three patients underwent retroportal hepaticojejunostomy using a jejunal limb mobilized and positioned behind the hepatoduodenal ligament. Primary tumors were classified as type IV in the Bismuth-Corlette classification. Tension-free hepaticojejunal anastomosis was performed successfully in all three patients; insufficiency of the hepaticojejunostomy did not develop. Neither early nor late complications directly related to this method occurred. Retroportal hepaticojejunostomy, thus, permits more peripheral resection of the hepatic duct while providing a sufficient operative field for safe, tension-free anastomosis. This technique is very useful for patients undergoing left hemihepatectomy requiring high hilar resection of the bile duct.

We investigated the role of Nek2, a member of the serine/threonine kinase family, Nek, in the tumorigenic growth of cholangiocarcinoma cells. Expression of Nek2 is elevated in cholangiocarcinoma in a tumor-specific manner as compared with that of normal fibroblast cells. Expression of exogenous Nek2 did not perturb the growth of cholangiocarcinoma cells, whereas suppression of the Nek2 expression with siRNA resulted in the inhibition of cell proliferation and induced cell death. In xenograft-nude mouse model, s.c. injection of Nek2 siRNA around the tumor nodules resulted in reduction of tumor size as compared with those of control siRNA injection. In peritoneal dissemination model, Nek2 siRNA-treated mice showed statistically longer survival periods in comparison with those of the control siRNA-treated mice. Taken together, our data indicate a pivotal role of Nek2 in tumorigenic growth of cholangiocarcinoma.

Hilar cholangiocarcinoma is a rare disease departing from the biliary convergence. It is primarily revealed by the onset of retention jaundice. Only 20%-30% of patients can undergo resection at diagnosis. The only chance for survival for these patients is R0 resection, which requires hepatectomy associated with resection of the common bile duct and pedicle lymph node removal, whatever the classification of the cholangiocarcinoma. No adjuvant treatment has been shown to be effective to date. Palliative treatment is most often based on implanting a biliary stent. Dynamic phototherapy may be beneficial in these situations. Improvements in survival for selected N0 hilar cholangiocarcinoma may be obtained with neoadjuvant treatment with radiochemotherapy followed by liver transplantation.

The purpose of this study was to increase the tolerance of the liver to radiation injury with the proven effect of ischemic precondition (IP) in decreasing oxygen-derived free radicals, and to compare the effect of intraoperative radiotherapy (IORT) during ischemia and during reperfusion on rat liver.

Two hundred fifty to 280 g male Wistar rats underwent 45 min of normothermic, segmental liver ischemia with or without IP/5 min ischemia and 10 min reperfusion, in two cycles. During ischemia or reperfusion, IORT doses of 0, 25, or 50 Gy were applied to the ischemic liver lobe. Hepatic microcirculation was monitored by laser Doppler flowmeter. Short- and long-term histological, alkaline phosphatase, bilirubin and tumor necrosis factor-alpha levels, liver tissue, and serum antioxidant alterations were measured.

Histological, laboratory, as well as flowmetry alterations caused by 25 Gy were reversible after 6 mo. Three mo following IORT, histological examination revealed parenchymal fibrosis, bridging, liver cell atrophy, and bile duct proliferation in the group that was irradiated with 50 Gy during reperfusion, without IP. In this group, the changes were present 6 mo following IORT, and also the levels of tumor necrosis factor-alpha and oxygen-derived free radicals after reperfusion were increased. All these changes were significantly milder in groups with IP, especially those that were irradiated during ischemia.

IORT to the liver, up to 25 Gy, can be applied without short- or long-term treatment morbidity. Doses of up to 50 Gy are tolerated with IP, which has never been described before. Irradiation during ischemia is less toxic for the liver tissue.

The aim of the present study was to assess whether an aggressive surgical approach in the management of patients with hilar cholangiocarcinoma was associated with improved operative and survival outcomes.

Eighty-two patients with hilar cholangiocarcinoma treated between 1989 and 1998 (period 1), and 60 patients treated between 1999 and 2004 (period 2), were evaluated. Modifications to management in period 2 primarily included percutaneous biliary drainage instead of endoscopic drainage for relief of obstructive jaundice, preoperative right portal vein embolization before right-sided hepatectomy, routine total caudate lobectomy and radical lymphadenectomy during surgical resection of the tumour.

The surgical resection rate was significantly higher in period 2 than in period 1 (45 versus 16 per cent; P < 0.001). All patients in period 2 underwent major hepatectomy with concomitant caudate lobectomy. The operative morbidity and hospital mortality rates decreased significantly in period 2 compared with period 1, with significantly better survival outcomes. In multivariate analysis, resection of the tumour in period 2 and operative blood loss of 1.5 litres or less were the significant independent factors associated with improved survival.

An aggressive surgical approach was associated with improved operative and survival outcomes for patients with hilar cholangiocarcinoma.

Biliary tract cancers are uncommon malignancies arising from biliary epithelium intrahepatically (peripheral cholangiocarcinoma), in the extrahepatic bile duct, the gall bladder and the ampulla of Vater. Treatment has been challenging because of late presentation, complex surgery, complex biliary obstruction with jaundice and a paucity of high quality data on which to establish standard care. With improvements in imaging, biliary stenting, surgical management and the establishment of a national investigational programme we hope to define the modern management of biliary tract cancers and enable a platform for further research.

Use of synbiotics has been reported to benefit human health, but clinical value in surgical patients remains unclear.

To investigate the effect of perioperative oral administration of synbiotics upon intestinal barrier function, immune responses, systemic inflammatory responses, microflora, and surgical outcome in patients undergoing high-risk hepatobiliary resection.

Patients with biliary cancer involving the hepatic hilus (n = 101) were randomized before hepatectomy, into a group receiving postoperative enteral feeding with synbiotics (group A); or another receiving preoperative plus postoperative synbiotics (group B). Lactulose-mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, natural killer (NK) cell activity, interleukin-6 (IL-6), fecal microflora, and fecal organic acid concentrations were determined before and after hepatectomy. Postoperative infectious complications were recorded.

Of 101 patients, 81 completed the trial. Preoperative and postoperative changes in L/M ratio and DAO activity were similar between groups. Preoperatively in group B, NK activity, and lymphocyte counts increased, while IL-6 decreased significantly (P < 0.05). Postoperative serum IL-6, white blood cell counts, and C-reactive protein in group B were significantly lower than in group A (P < 0.05). During the preoperative period, numbers of Bifidobacterium colonies cultured from and total organic acid concentrations measured in feces increased significantly in group B (P < 0.05). Postoperative concentrations of total organic acids and acetic acid in feces were significantly higher in group B than in group A (P < 0.05). Incidence of postoperative infectious complications was 30.0% (12 of 40) in group A and 12.1% (5 of 41) in group B (P < 0.05).

Preoperative oral administration of synbiotics can enhance immune responses, attenuate systemic postoperative inflammatory responses, and improve intestinal microbial environment. These beneficial effects likely reduce postoperative infectious complications after hepatobiliary resection for biliary tract cancer.

Liver surgeons favor using the entity called the 'dorsal liver' (i.e. the caudate lobe and other paracavally located liver parenchyme of segments 7 and 8). According to minute dissection of 48 livers, we describe the territories of the left/right portal veins, hepatic ducts and hepatic arteries in the dorsal liver. In the caudate lobe, the right hepatic artery, rather than the left hepatic artery (23/48 vs 19/48 for right vs left, respectively), tended to supply the 'left' portal vein territory. Similarly, paradoxical drainage patterns, such as the right hepatic duct draining the left portal vein territory, were found in seven of 48 livers. In the territory of the hilar bifurcation, right hepatic artery dominance was also evident and various bile drainage patterns were found. These included double drainage by the bilateral hepatic ducts (3/48) and drainage into the confluence of bilateral ducts (6/48). In contrast, the arterial supply and biliary drainage of the paracavally located parenchyme of segments 7 and 8 usually depended on the proper segmental arteries and ducts and their variations were within the range of those found in other parts of the right lobe. Therefore, the dorsal liver concept may not be anatomical but, rather, simply aimed at usefulness in surgery. Nevertheless, clear subdivision of the caudate lobe according to biliary drainage and/or arterial supply seemed difficult because of the paradoxical relatioships among the portal vein, hepatic artery and bile duct. Consequently, the present results support extended surgery based on the dorsal liver concept for carcinomas involving the caudate lobe.

The clinical value of synbiotics in surgical patients remains unclear. The aim of this study was to investigate the effect of synbiotics on intestinal integrity and microflora, as well as on surgical outcome, in patients undergoing high-risk hepatectomy.

Fifty-four patients with biliary cancer were randomly allocated to two groups before hepatectomy. One group received postoperative enteral feeding that included synbiotics; the other received enteral feeding only. Lactulose/mannitol (L/M) ratio, serum diamine oxidase (DAO) activity, and fecal microflora and organic acid concentrations were determined. Postoperative infectious complications were recorded.

Of the 54 patients, 44 completed the trial (21 receiving synbiotics and 23 others as controls). Postoperative changes in L/M ratios and serum DAO activities were identical between the two groups. Numbers of beneficial bacteria increased in the synbiotics group after surgery but decreased in controls. Numbers of harmful microorganisms decreased in the synbiotics group but increased in controls. Total organic acid concentrations increased in the synbiotics group but decreased in controls. Incidence of infectious complications was 19% (4/21) in the synbiotics group and 52% (12/23) in controls (P<0.05). All study patients tolerated surgery (mortality 0%).

Synbiotics, combined with early enteral nutrition, can reduce postoperative infections. This beneficial effect presumably involves correction of an intestinal microbial imbalance induced by surgical stress.

Using drip-infusion cholangiography-computed tomography (DIC-CT), we successfully identified the bile ducts draining the caudate lobe in 138 of 179 consecutive patients with extrahepatic cholelithiasis (179 ducts from Spiegel's lobe and 154 from the paracaval portion; 1-5 ducts per patient). The dorsal subsegmental duct of S8 (B8c) was often identified and could be discriminated from the paracaval caudate ducts, thus acting as a landmark for the right margin of the caudate lobe. Notably, in more than one-third of the 138 patients, at least one of the Spiegel's lobe ducts drained into the right hepatic duct or its branches (30.2% of the 179 ducts overall; all ducts joined branches of the right lobe in 25 patients). Similarly, 34.4% of the 154 paracaval caudate lobe ducts drained into the left hepatic duct or its branches. These "anatomical left/right dissociations" between the drainage territory and route were much more frequent than previously reported. Our results confirm the effectiveness of DIC-CT as a classical, noninvasive method for presurgical evaluation of the biliary system, but they also suggest that anatomical partial resection of the dorsal liver in patients with hilar cholangioma is often impossible because of contralateral biliary drainage.

From September 1986 until December 2001, 42 patients (20 males and 22 females) underwent a combined extrahepatic bile duct resection (EHBDR) and liver resection (LR) for hilar cholangiocarcinoma (HC). The aim of this study was to analyze patient survival, morbidity, and mortality as well as to seek predictive factors. The 1-, 3-, and 5-year actuarial patient survival was 72%, 37%, and 22%, respectively. Median survival was 19 months. Hospital mortality, all due to septic complications, was 12%. Morbidity was observed in 32 patients (76%). Infections were the most dominant complication. Patients (n=11) with American Joint Committee on Cancer (AJCC) stage I or stage II tumors exhibited a superior survival compared with patients (n=31) with stage III or IV tumors (p=0.023). Patients with tumor-free lymph nodes (n=26) indicated a greater survival compared with patients with tumor-positive lymph nodes (n=16) (p=0.004). Patients undergoing vascular reconstructions indicated a trend toward higher mortality and lower survival (p=0.068). Over 20% of the patients with hilar cholangiocarcinoma can survive more than 5 years after a combined EHBDR and LR at the cost of 12% perioperative mortality and a 76% morbidity. Results might improve with the prevention of infectious complications and improved selection of patients to avoid vascular reconstruction and to predict a negative nodal state.

To investigate the effect of bile replacement following percutaneous transhepatic biliary drainage, ie, external drainage, on intestinal permeability, integrity, and microflora in a clinical setting.

Several authors have reported that internal biliary drainage is superior to external drainage. However, it is unclear whether bile replacement following external drainage is beneficial.

Twenty-five patients with biliary cancer underwent percutaneous transhepatic biliary drainage (PTBD) as a part of presurgical management. All externally drained bile was replaced either per os or by administration through a nasoduodenal tube. The interval between PTBD and the beginning of bile replacement was 21.3 +/- 19.7 days, and the length of bile replacement was 20.7 +/- 9.6 days. The lactulose-mannitol test, measurement of serum diamine oxidase (DAO) activity, and analyses of fecal microflora and organic acids were performed before and after bile replacement.

The volume of externally drained bile varied widely from patient to patient, ranging from 220 +/- 106 mL/d to 1616 +/- 394 mL/d (mean, 714 +/- 346 mL/d). Biliary concentrations of bile acids, cholesterol, and phospholipids increased significantly after bile replacement. The lactulose-mannitol (L/M) ratio decreased from 0.063 +/- 0.060 before bile replacement to 0.038 +/- 0.032 after bile replacement (P < 0.05). Serum DAO activity increased from 3.9 +/- 1.4 U/L before bile replacement to 5.1 +/- 1.6 U/L after bile replacement (P < 0.005), and the magnitude of change in serum DAO activity correlated with the length of bile replacement (r = 0.483, P < 0.05). Neither the L/M ratios nor serum DAO activities before bile replacement correlated with the interval between PTBD and the beginning of bile replacement. Fecal microflora and organic acids were unchanged.

Impaired intestinal barrier function does not recover by PTBD without bile replacement. Bile replacement during external biliary drainage can restore the intestinal barrier function in patients with biliary obstruction, primarily due to repair of physical damage to the intestinal mucosa. Our results support the hypothesis that bile replacement during external drainage is beneficial.

To better determine the role of portal vein resection and its effect on survival, as well as to appreciate the impact of portal vein invasion on prognosis in hilar cholangiocarcinoma.

Hepatectomy with portal vein resection is sometimes performed for locally advanced hilar cholangiocarcinoma. However, the significance of microscopic invasion of the portal vein has not been determined.

Medical records of 160 patients with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion of the portal vein was assessed histologically on the surgical specimen, and results were correlated with clinicopathologic features and survival.

Surgical mortality, including all hospital deaths, was similar in patients who did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary tumor was more advanced in patients who underwent portal vein resection. Histologically, no invasion was found in 16 (30.8%) of resected portal veins. However, dense fibrosis adjacent to the portal vein was common, and the mean distance between the leading edge of cancer cells and the adventitia of the portal vein was 437 +/- 431 mum. The prognosis was worse in patients with than without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The presence or absence of microscopic invasion of the resected portal vein did not influence survival (16.6 months in patients with microscopic invasion vs. 19.4 months in those without; P = 0.1506). Multivariate analysis identified histologic differentiation, lymph node metastasis, and macroscopic portal vein invasion as independent prognostic factors.

Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Donor-specific immune tolerance has been reported in isolated cases of kidney transplantation associated with bone marrow transplantation. The following is a description of a living donor liver transplantation for a hilar cholangiocarcinoma in a previous recipient of an allogeneic bone marrow transplant.

A right hemi-liver transplantation was performed using a liver allograft obtained from the same previous bone marrow donor. A neoadjuvant chemo-irradiation protocol was implemented before the procedure. Because of the presence of full chimerism, no immunosuppression has been necessary for the last 22 months.

Liver graft function has remained excellent, and a magnetic resonance imaging scan at one and a half years has shown no tumor recurrence. A control liver biopsy at 1 year showed no rejection.

Neoadjuvant chemo-irradiation therapy and removal of all immunosuppression after liver transplantation formed the basic structure of this approach. Additional benefits provided by living donor liver transplantation included limitation of tumor progression by diminishing the pretransplantation waiting time, radical excision of the tumor through a complete hepatectomy, and optimal timing of the transplant procedure within a neoadjuvant chemo-irradiation protocol.

The functional recovery of the remnant liver after an extended hepatectomy is critical for the outcome of the patient. The aim of this prospective study was to examine whether biliary bile acids could be an indicator for postoperative liver function.

Externally drained bile samples were obtained from 51 patients with biliary or periampullary carcinomas before and after surgery. Patients were categorized into 3 groups: group A, 29 hepatectomized patients without liver failure; group B, 7 hepatectomized patients with liver failure (maximum serum bilirubin level, >10 mg/dL); and group C, 15 patients who underwent biliopancreatic resection without hepatectomy, with a good postoperative course. Bile samples were withdrawn 1 day before surgery and on postoperative days 1, 2, 3, 4, 6, and 7. Total bile acids were measured with a 3 alpha-hydroxysteroid dehydrogenase method.

Before surgery, the concentration of bile acids was higher in groups A and C than in group B, and correlated significantly with the indocyamine green disappearance rate (KICG) values (R(2) = 0.557; P <.0001). After surgery, bile acid concentrations decreased in all 3 groups until postoperative day 2, which was followed by a gradual increase. The concentration recovered to the preoperative level in groups A and C but remained low in group B. Biliary bile acid concentrations on day 2 correlated significantly with remnant liver KICG values (R(2) = 0.257; P =.0019). Among several parameters studied, including KICG, remnant liver KICG, biliary bile acids, and biliary bilirubin, biliary bile acid concentration had the most predictive power for occurrence of postoperative liver failure.

Biliary bile acid concentration could be a simple, real-time, reliable indicator of preoperative and postoperative liver function.

Recently, the caudate lobe has seemed to be the final target for aggressive cancer surgery of the liver. This lobe has five surfaces: the dorsal, left and hilar-free surfaces and the right and ventral-border planes. Surgeons have divided the caudate lobe into three parts: Spiegel's lobe, which is called the 'caudate lobe and papillary process' by anatomists, the caudate process, viewed as almost the same entity by anatomists, and the paracaval portion corresponding to the dorsally located parenchyma in front of the inferior vena cava. All three parts are supplied by primary branches originating from the left and right portal veins, including the hilar bifurcation area. The hilar bifurcation branch often (50%) supplies the paracaval portion and it sometimes (29%) extends its territory to Spiegel's lobe. It was postulated by Couinaud that the paracaval portion or the S9 is not defined by its supplying portal vein branch but by its 'dorsal location' in the liver. Couinaud's caudate lobe or dorsal-liver concept cause, and still now causes, great logical confusion for surgeons. We attempt here to describe the margins of the lobe, border branches of the portal vein, the left/right territorial border of the portal vein or Cantile's line and other topics closely relating to the surgery within these contexts. Finally, the caudate lobe as a liver segment will be discussed.

The topographic anatomy of the ventral margin of the paracaval portion of the caudate lobe of the human liver has not been clearly described to date. To this end we hypothesize the existence of a precaudate plane, a flat or slightly curved plane defined by the ventral margins of the ligamentum venosum and the hilar plate. Using 76 cadaveric livers, we investigated whether the paracaval portion of the caudate lobe extended ventral to this plane and whether the paracaval caudate branch of the portal vein (PC) ran through this plane to its ventral side. In 28 of the specimens (36.8%), the PC extended over the plane to a variable depth: less than 10 mm in 10 specimens, 10-20 mm in 10, and more than 20 mm in eight specimens. This ventral extension of the PC consistently included its penetration into the dome-like area under the terminals of the three major hepatic veins; therefore, the ventrally extended PC often interdigitated with these veins and their tributaries (in practice, the ventral margin of the paracaval portion of the caudate lobe could generally be considered to run alongside the middle hepatic vein). Moreover, the ventral extension of the PC often reached the upper, diaphragmatic surface or the dorsal surface of the liver immediately to the right of the inferior vena cava. Several branches (termed border branches) in the ventral extension were difficult to identify as belonging to the PC. We discuss both the marginal configuration of the paracaval portion of the caudate lobe and how to identify and operate on the ventrally extended PC and related border branches during liver surgery.

The configuration of the right portion of the caudate lobe (CL), and especially the exact location of its right margin, remains obscure. This study aimed to identify this right margin according to reliable landmarks suitable for use during clinical examinations and surgery: (1) the bifurcation of the right portal vein, (2) the end of the right hepatic vein, and (3) the notch on the gallbladder fossa. The plane defined by these three landmarks is called the right paracaval plane. Dissection of 55 livers demonstrated that the entire CL was usually contained within the left half of the specimen after cutting along the right paracaval plane (Type A: 65.4%, 36/55). However, its right portion sometimes extended beyond this plane into the right half of the liver (34.6%, 19/55), forming one or two islands when viewed from the paracaval plane (Types B and C). We found two separate marginal configurations among the 19 rightward extensions of the paracaval portion: a tree-like, deep protrusion (11/19) and a relatively smooth border (8/19). The present results suggest the existence of reliable landmarks that will allow a right-side limit for surgical resection of the CL to be established: (1) the right paracaval plane (60% reliability), (2) 10 mm to the right of the plane, including the terminal of the right hepatic vein (80% reliability), and (3) the widest margin, including the 30 mm to the right of the right paracaval plane, the right side running along the inferior vena cava, and the diaphragmatic surface around the end portions of the three main hepatic veins (100% reliability).

Interest in the lymphatic system and its relationship to metastases has developed owing to renewed interest in sentinel node biopsy. This article summarizes the anatomy, physiology, and biology of the lymphatic system and lymph node metastases, and reviews studies of lymph node metastases and surgical resection of cancers in different anatomic sites. On the basis of these studies, the authors conclude that lymph node metastasis functions as an indicator of prognosis, not the controlling or determining factor of prognosis. Thus, varying degrees of treatment of regional lymph nodes and metastases do not seem to be controlling factors in the outcome of cancer.

Hilar cholangiocarcinoma is one of the most difficult tumors to stage and treat. This study aims to evaluate (1) the best diagnostic imaging, (2) the usefulness of preoperative biliary drainage, (3) the resectability rate, and (4) the results of palliative treatments and surgical resection. Seventy-six patients with hilar cholangiocarcinoma with a mean age of 64 +/- 11 years were treated at our institution from 1989 to 1999. Patients were studied preoperatively using ultrasound, computed tomography (CT), and percutaneous cholangiography or magnetic resonance cholangiography. Forty-eight patients (63%) underwent palliative treatment. Twenty-eight patients underwent surgical curative therapy; 20 resections and 8 orthotopic liver transplantations (OLTs). Percutaneous transhepatic cholangiography was performed in 18 of 28 patients (64%), and magnetic resonance cholangiography in 5 patients; both methods were equally effective in establishing tumoral invasion of the biliary ducts. Five patients did not undergo either diagnostic modality. Excluding the patients who underwent OLT, no significant differences were found in surgical mortality (1 v 2 patients) or postoperative morbidity (100% v 66%) for patients with and without preoperative biliary drainage. The postoperative mortality rate was 11% (3 of 28 patients). The overall resectability rate was 37%. Mean survival in the surgical and palliative groups was 35 and 6 months, respectively (P <.0001). Patients who underwent OLT had a better 5-year survival rate than those treated by tumor resection (36% v 21%; P =.02). Combined chemotherapy and radiotherapy apparently did not provide a significant survival benefit. Helical CT and magnetic resonance cholangiography are useful techniques to delineate tumor extent and rule out vascular invasion and lymph node or liver metastases. No clear conclusions regarding preoperative drainage can be drawn from this study. A high resectability rate (37%) is feasible with major hepatectomy.

1. Resection rates for cholangiocarcinoma (unrelated to primary sclerosing cholangitis) have increased to 54% to 79%, and the subsequent 5-year survival rates are 24% to 31%. 2. Multimodality approaches involving various combinations of chemotherapy, irradiation, and surgery increasingly are being used to treat cholangiocarcinoma. 3. The role of liver transplantation in the management of cholangiocarcinoma is limited by the perception that it is inappropriate to use scarce organs when 5-year survival rates are 25%. 4. Liver transplantation is an important intervention in patients with tumors that remain unresectable after chemotherapy. The role of liver transplantation in patients with extrahepatic disease that responds to chemotherapy is controversial. Careful timing of surgery is required to avoid secondary drug resistance. 5. Liver transplantation has been successfully applied to a range of rare hepatic malignancies, but small numbers preclude strong recommendations on the appropriateness of this practice.

The function of the remnant liver is critical to survival of patients following an extended hepatectomy. The aim of this study was to determine whether proliferating hepatocytes in the remnant liver preserve the expression of liver-specific genes.

Using regenerating rat livers after 30, 70, and 90% partial hepatectomy (PHx), Northern blot analyses were performed with probes for seven liver-specific genes, six growth-related genes, two housekeeping genes and two acute phase reactant protein genes.

During the regeneration after 90% PHx, the transcription of liver-specific genes showed three chronological patterns: transcription of serum albumin and cytochrome P450 2B decreased rapidly and reached a nadir at 6 to 24 h after PHx; those of apolipoprotein A-1, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreased gradually until 24 to 48 h; those of UDP-glucuronosyltransferase and hepatocyte nuclear factor 4 did not show any changes until 48 h after PHx. In contrast, expression levels of all the growth-related genes and of housekeeping genes increased rapidly after PHx. After 30 and 70% PHx, expression of these genes changed in a similar manner to the 90% PHx case but to a lower extent.

Based upon the fractions of Ki-67 positive hepatocytes in remnant livers, we could estimate the degree of expression of each liver-specific gene in the proliferating hepatocytes. The serum albumin gene was completely suppressed, while that encoding UDP-glucuronosyltransferase was not affected. These results correlated well with the patterns of albumin and bilirubin in rat serum after PHx. Other liver-specific genes were moderately suppressed in proliferating hepatocytes. Thus, expression of liver-specific gene is differentially suppressed when hepatocytes enter a proliferation cycle. Those that are unaffected may be indispensable for maintaining the homeostasis of the living organism.

Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection.

A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone.

The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis.

This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.

The objective of this study was to determine the benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma (Klatskin tumor).

We conducted a retrospective review of 63 patients who underwent surgical resection of Stage IVA Klatskin tumor. Of the 63 patients, 47 had microscopic tumor residue (RT1). Twenty-eight of the 47 patients with RT1 were treated by adjuvant radiotherapy and the remaining 19 patients were treated exclusively by surgical resection. Seventeen of the 28 patients with RT1 were treated by both intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT); of the remaining 11 patients with RT1, 6 underwent resection and IORT, and 5 underwent resection and PORT.

The major complication and 30-day operative death rates were significantly lower in the radiation group (9.5% and 0.0%, respectively) than in the resection alone group (28.5% and 9.5%, respectively). Of the eight 5-year survivors with RT1, 6 had adjuvant radiotherapy and the remaining 2 had resection alone. Adjuvant radiotherapy for patients with RT1 yielded significantly (p = 0.0141) higher 5-year survival rates (33.9%) than in the resection alone group (13.5 %). The best 5-year survival rate (39.2 %) was found in patients who underwent a combination of IORT and PORT after resection. The local-regional control rate was significantly higher in the adjuvant radiation group than in the resection alone group (79.2% vs. 31.2%).

Our data clearly suggest the improved prognosis of patients with locally advanced Klatskin tumor by integrated adjuvant radiotherapy with IORT and PORT to complete gross tumor resection with acceptable treatment mortality and morbidity.

The diagnostic value of percutaneous transhepatic portography (PTP) for assessing cancer invasion of the portal bifurcation in patients with hilar cholangiocarcinoma has not been studied previously.

From April 1977 to March 1998 combined hepatobiliary and portal vein resection was performed in 45 patients. In 25 patients, PTP was carried out before operation and the resected portal bifurcation was examined histologically. Correlation between portographic and microscopic findings at the portal bifurcation was studied retrospectively.

Portographic and microscopic findings were classified into three groups (type A, B or C, and grade 0, I or II respectively) according to the findings at the portal bifurcation. There was a significant correlation between the portographic type and degree of cancer invasion (P = 0.0001). In seven of the eight patients with type A portograms, there was no microscopic cancer invasion of the portal bifurcation. In 15 of the 17 patients with type B or C portograms, cancer invasion was found microscopically. All patients with microscopic grade II invasion had type C portograms.

PTP can be used to evaluate cancer invasion of the portal bifurcation with sufficient reliability for preoperative staging of hilar cholangiocarcinoma.