New Insights in the Setting of Transplant Oncology.

Background and Objectives: Liver transplantation (LT) is the best strategy for curing several primary and secondary hepatic malignancies. In recent years, growing interest has been observed in the enlargement of the transplant oncology indications. This paper aims to review the most recent developments in the setting of LT oncology, with particular attention to LT for unresectable colorectal liver metastases (CRLM) and cholangiocellular carcinoma (CCA). Materials and Methods: A review of the recently published literature was conducted. Results: Growing evidence exists on the efficacy of LT in curing CRLM and peri-hilar and intrahepatic CCA in well-selected patients when integrating this strategy with (neo)-adjuvant chemotherapy, radiotherapy, or locoregional treatments. Conclusion: For unresectable CCA and CRLM management, several prospective protocols are forthcoming to elucidate LT's impact relative to alternative therapies. Advances in diagnosis, treatment protocols, and donor-to-recipient matching are needed to better define the oncological indications for transplantation. Prospective, multicenter trials studying these advances and their impact on outcomes are still required.

Does Adjuvant Therapy Benefit Low-Risk Resectable Cholangiocarcinoma? An Evaluation of the NCCN Guidelines.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant therapy for patients with resectable cholangiocarcinoma (CCA). The trends in utilization and receipt of adjuvant therapy and its association with overall survival have not been well studied among patients with low-risk CCA. METHODS: Patients who received systemic chemotherapy for low-risk CCA after surgical resection (2010-2017) were identified in the National Cancer Database. Low-risk CCA was defined according to NCCN guidelines as patients with R0 margins and negative regional lymph nodes. Multivariable analysis was performed to assess predictors of NCCN guideline concordance and its association with overall survival. RESULTS: Among 4519 patients who underwent resection for low-risk CCA, 55.5% (n = 2510) had intrahepatic, 15.0% (n = 680) had perihilar, and 29.4% (n = 1329) had distal cholangiocarcinoma. Adherence to NCCN guidelines increased from 27.7% in 2010 to 41.6% in 2017 (ptrend < 0.001) for low-risk CCA. On multivariable analysis, receipt of NCCN guideline-concordant care was associated with a nearly 15% decrease in mortality hazards (HR 0.86, 95%CI 0.78-0.95, [Formula: see text]). Increased distance travelled (Ref < 12.5 miles, 50-249 miles: OR 0.55, 95%CI 0.49-0.69; ≥ 250 miles: OR 0.41, 95%CI 0.25-0.6), and care in the South (OR 0.78, 95%CI 0.64-0.95) or Midwest (OR 0.66, 95%CI 0.53-0.81) of the United States versus the Northeast was associated with not receiving guideline-concordant care. CONCLUSION: Adherence to evidence-based NCCN guidelines was associated with improved survival among low-risk CCA patients. Geographical disparities in the receipt of NCCN guideline-concordant care exist and may influence long-term outcomes among CCA patients.

Clinical application of indocyanine green fluorescence imaging in laparoscopic lymph node dissection for intrahepatic cholangiocarcinoma: A pilot study (with video).

BACKGROUND: Intrahepatic cholangiocarcinoma is a highly lethal malignancy characterized by lymph node metastasis. This study aimed to evaluate the efficacy of indocyanine green fluorescence for visualization of lymphatic drainage and to assess its clinical application during laparoscopic lymph node dissection for intrahepatic cholangiocarcinoma. METHODS: All patients with intrahepatic cholangiocarcinoma who underwent laparoscopic left hepatectomy and lymph node dissection between October 2018 and January 2021 were reviewed. The patients were assigned to the indocyanine green group or non-intrahepatic cholangiocarcinoma group based on the staining technique used. RESULTS: Of 38 patients with left hemiliver intrahepatic cholangiocarcinoma, 20 underwent intrahepatic cholangiocarcinoma tracer-guided laparoscopic radical left hepatectomy; 12 procedures were successful (indocyanine green group). During the same period, 18 patients were treated with traditional laparoscopic resection (control group). Their intraoperative factors were comparable and there were no differences in the incidence or severity of their postoperative complications 30 days after surgery (P > .05). In the indocyanine green group, more lymph nodes were harvested (mean [range]: 7.0 [6.0-8.0] vs 3.5 [3.0-5.0], P < .001) and the proportion of confirmed pathologic lymph nodes was higher (75.0%, 66.7%-87.5% vs 40%, 33.3%-50.0%, P < .001). ICG staining was observed in all (12/12, 100%) patients in the intrahepatic cholangiocarcinoma group at stations 8 and 12, and 9 (9/12, 75%) and 10 (11/12, 91.7%) patients at Stations 13 and 7, respectively. CONCLUSION: The indocyanine green fluorescence imaging system is feasible, safe, and effective for tracing lymph nodes. It can be used to identify regional lymphatic drainage patterns and help define the scope of lymph node dissection in patients with intrahepatic cholangiocarcinoma.

The efficacy and safety of 5-fluorouracil based adjuvant therapy in resected biliary tract cancer: A systematic review and meta-analysis.

OBJECTIVES: The adjuvant therapy (AT) for biliary tract cancer (BTC) patients after surgery has always been controversial. More therapeutic regimens and high-quality evidence were needed to evaluate AT's survival benefit further. Thus, this study was performed to investigate the efficacy and safety of the 5-fluorouracil (5-FU) regimen in resected BTC patients. METHODS: PubMed, Cochrane Library, Web of Science, and the Embase were systematically searched from inception to Feb.3, 2021, for eligible studies. The pooled analyses were performed using Review Manager, Stata, and SPSS software. RESULTS: A total of 9 trials involving 1339 participants were included in the meta-analysis. Resected BTC patients could significantly benefit from a 5-FU regimen (HR:0.51, 95%CI, 0.38-0.69, P<0.0001), regardless of gallbladder carcinoma (GBC) or cholangiocarcinoma (CCA). Moreover, both adjuvant chemotherapy (HR:0.61, 95%CI, 0.47-0.79, P=0.0003) and chemoradiotherapy (HR:0.35, 95%CI, 0.14-0.83, P=0.02) could significantly improve clinical survival of resected BTC patients than the surgery alone group. In the subgroup analyses, patients with node-positive (P=0.02) or vascular invasion disease (P=0.002) could better benefit from postoperative AT. CONCLUSION: This study provides the latest evidence to support the 5-FU regimen in resected BTC patients regardless of GBC or CCA. Furthermore, high-risk patients are more likely to benefit from it, such as node-positive or vascular invasion disease.

The role of lymph node dissection in intrahepatic cholangiocarcinoma: a multicenter retrospective study.

BACKGROUND: Lymph node dissection (LND) is of great significance in intrahepatic cholangiocarcinoma (ICC). Although the National Comprehensive Cancer Network (NCCN) guidelines recommend routine LND in ICC, the effects of LND remains controversial. This study aimed to explore the role of LND and some related issues and of in ICC. METHODS: Patients were identified in two Chinese academic centers. Inverse probability of treatment weighting (IPTW) was used to reduce bias. Kaplan-Meier curves and Cox proportional hazards models were used to compare overall survival (OS) and disease-free survival (DFS). RESULTS: Of 232 patients, 177 (76.3%) underwent LND, and 71 (40.1%) had metastatic lymph nodes. A minimum of 6 lymph nodes were dissected in 66 patients (37.3%). LND did not improve the prognosis of ICC. LNM > 3 may have worse OS and DFS than LNM 1-3, especially in the LND > = 6 group. For patients who did not underwent LND, the adjuvant treatment group had better OS and DFS. CONCLUSIONS: The proportions of patients who underwent LND and removed > = 6 lymph nodes were not high enough. LND has no definite predictive effect on prognosis. Patients with 4 or more LNMs may have a worse prognosis than patients with 1-3 LNMs. Adjuvant therapy may benefit patients of nLND.

Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report.

Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient's survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.

The role of lymph node dissection and a new N-staging system for intrahepatic cholangiocarcinoma: a study from the SEER database.

BACKGROUND: Although the National Comprehensive Cancer Network guidelines recommend routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC), the role of LND remains controversial, and the node (N) stage is oversimplified. METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results research data 18 (SEER 18). Propensity score matching (PSM) was used to reduce bias, and Kaplan-Meier curves and Cox proportional hazards models were used to compare overall survival (OS). The best cutoff values were found using X-tile software. RESULTS: Of 2037 patients included in SEER 18, 1147 underwent LND (56.3%); 389 (34.3%) had pathologically confirmed lymph node metastasis (LNM), and 316 (27.6%) had at least 6 LNDs. The median OS was worse for LND patients (34 months vs. 40 months, respectively), and this result remained after PSM. Male sex, age ≥60 years, tumor size > 5 cm, and LNM were independent prognostic risk factors for ICC. LNM ≥3 was associated with worse OS. CONCLUSIONS: Only a few LNDs met the requirements per the guidelines. LND does not improve OS in ICC, and the best approach to LND and a better N staging method should be explored further.

Disparities in NCCN Guideline Compliant Care for Resectable Cholangiocarcinoma at Minority-Serving Versus Non-Minority-Serving Hospitals.

BACKGROUND: Racial/ethnic disparities in cancer outcomes may relate to variations in receipt of National Comprehensive Cancer Network (NCCN) guideline compliant care. PATIENTS AND METHODS: Patients undergoing resection of cholangiocarcinoma (CCA) between 2004 and 2015 were identified using the National Cancer Database (NCDB). Institutions treating Black and Hispanic patients within the top decile were categorized as minority-serving hospitals (MSH). Factors associated with receipt of NCCN-compliant care, and the impact of NCCN compliance on overall survival (OS), were evaluated. RESULTS: Among 16,108 patients who underwent resection of CCA, the majority of patients were treated at non-MSH (n = 14,779, 91.8%), while a smaller subset underwent resection of CCA at MSH (n = 1329, 8.2%). Patients treated at MSH facilities tended to be younger (MSH: 65 years versus non-MSH: 67 years), Black or Hispanic (MSH: 59.9% versus non-MSH: 13.4%), and uninsured (MSH: 11.6% versus non-MSH: 2.2%). While overall compliance with NCCN care was 73.0% (n = 11,762), guideline-compliant care was less common at MSH (MSH: 68.8% versus non-MSH: 73.4%; p < 0.001). On multivariable analyses, the odds of receiving non-NCCN compliant care remained lower at MSH (OR 0.76, 95% CI 0.65-0.88). While white patients had similar odds of NCCN-compliant care with minority patients when treated at MSH (OR 0.98, 95% CI 0.75-1.28), minority patients had lower odds of receiving guideline-compliant care when treated at non-MSH (OR 0.85, 95% CI 0.75-0.96). Failure to comply with NCCN guidelines was associated with worse long-term outcomes (HR 1.60, 95% CI 1.52-1.69). CONCLUSIONS: Patients treated at MSH had decreased odds to receive NCCN-compliant care following resection of CCA. Failure to comply with guideline-based cancer care was associated with worse long-term outcomes.

Trends in centralization of surgical care and compliance with National Cancer Center Network guidelines for resected cholangiocarcinoma.

BACKGROUND: A retrospective study was performed to characterize trends in centralization of care and compliance with National Comprehensive Cancer Network (NCCN) guidelines for resected cholangiocarcinoma (CCA), and their impact on overall survival (OS). METHODS: Using the National Cancer Database (NCDB) 2004-2015 we identified patients undergoing resection for CCA. Receiver Operating Characteristic (ROC) analyses identified time periods and hospital volume groups for comparison. Propensity score matching provided case-mix adjusted patient cohorts. Cox hazard analysis identified risk factors for OS. RESULTS: Among the 40,338 patients undergoing resection for CCA, the proportion of patients undergoing surgery at high volume hospitals increased over time (25%-44%, p < 0.001), while the proportion of patients undergoing surgery at low volume hospitals decreased (30%-15%, p < 0.001). Using ROC analyses, a hospital volume of 14 operations/year was the most sensitive and specific value associated with mortality. Surgery at high volume hospitals [HR] = 0.92, 95% CI: 0.88-0.97, p < 0.001) and receipt of care compliant with NCCN guidelines (HR = 0.87, 95% CI: 0.83-0.91, p < 0.001) were independently associated with improved OS. CONCLUSIONS: Both centralization of surgery for CCA to high volume hospitals and increased compliance with NCCN guidelines were associated with significant improvements in overall survival.

Chylothorax after hepatectomy: a case report.

BACKGROUND: Chylothorax is the accumulation of chyle within the pleural space. Chylothorax can occur as a complication after multiple different types of surgery, most frequently after thoracic surgery, albeit with an incidence rate of less than 1%. Chylothorax after abdominal surgery is extremely rare, and there are only a few case reports. CASE PRESENTATION: A 74-year-old Japanese woman presented with jaundice. She was diagnosed as having hilar cholangiocarcinoma and underwent right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and lymph node dissection after preoperative percutaneous transhepatic portal vein embolization. Postoperative liver function was normal. She developed chylous ascites on postoperative day 5, for which conservative treatment was initially effective. Dyspnea developed suddenly on postoperative day 42, and she had a massive right pleural effusion and a small amount of ascites. Management with pleural drainage, total parenteral nutrition, and octreotide injections decreased the chylothorax. However, the chylous effusion reaccumulated on postoperative day 57. As conservative treatments ultimately failed, lymphangiography was performed on postoperative day 62. Lymphangiography with Lipiodol (ethiodized oil) revealed extravasation into the pleural space, but the location of the leak was not identified. There was neither obstruction nor dilation of the thoracic duct. A lymphatic leak in her abdominal cavity was not demonstrated. A chest tube was placed after lymphangiography, and the chylothorax was diminished by postoperative day 71. She was discharged on postoperative day 72. Two and a half years after surgery, she is doing well with no evidence of recurrence of either chylothorax or cancer. CONCLUSIONS: Chylothorax can occur after hepatectomy and pleural effusion should raise suspicion for chylothorax. Lymphangiography may be effective for both diagnosis and treatment in the case of chylothorax after hepatectomy.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei in a liver-transplanted patient: a case report.

BACKGROUND: Diagnostic work-ups in transplanted immunosuppressed patients are a challenge as non-specific findings may be interpreted as transplant-related complications. If the disease in question is rare and slowly developing like pseudomyxoma peritonei (PMP), it is even more difficult. Cytoreductive surgery (CRS) and subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP even with extensive peritoneal spread. CRS-HIPEC for PMP after liver transplantation (LTX) has not been described before. CASE PRESENTATION: A 48-year-old female patient with end-stage primary sclerosing cholangitis (PSC) underwent orthotopic LTX and subsequent pancreaticoduodenectomy after the finding of cholangiocarcinoma in situ in the native common bile duct. Ten years after the transplantation, she developed symptoms and signs suspected to represent graft-related complications. An extensive work-up revealed PMP. Upon reassessment, a cystic mass near the coecum could be seen on computed tomography scan 1 year after transplantation. The multidisiplinary team was hesitant to accept the patient for CRS-HIPEC because of extensive PMP and possible risk to the graft. However, she was eventually accepted and underwent the procedure. The Peritoneal Cancer Index (PCI) was 28 of 39, and surgical debulking was performed followed by HIPEC. The transplant control 2 months after surgery showed no harm to the graft. CONCLUSIONS: Previous LTX should not exclude the possibility for CRS-HIPEC in PMP, even with extensive burden of disease.

Effect of Adjuvant Gemcitabine Combined with Low-dose 5-Fluorouracil and Cisplatin Chemotherapy for Advanced Biliary Carcinoma.

BACKGROUND/AIM: The aim of this retrospective study was to clarify the effectiveness of chemotherapy with gemcitabine combined with low-dose 5-fluorouracil and cisplatin (GFP) for advanced biliary carcinoma after hepatectomy. PATIENTS AND METHODS: Sixty-two patients had biliary carcinoma with lymph node metastasis, intrahepatic metastasis or positive surgical margins, including intrahepatic cholangiocarcinoma (IHC, n=25), hilar cholangiocarcinoma (HC, n=14), and gallbladder cancer (GBC, n=23). Twenty-eight patients (IHC; n=9, HC; n=8, GBC; n=11) received adjuvant GFP chemotherapy. RESULTS: We found no significant difference in clinicopathological factors in patients treated with or without adjuvant GFP chemotherapy. Overall, survival in the adjuvant GFP group was significantly better than that in the non-adjuvant GFP group (3-year survival: 61.9% vs. 8.8%, p<0.001), as was relapse-free survival. CONCLUSION: Adjuvant GFP chemotherapy after hepatectomy may be a promising option for improving surgical outcomes in patients with advanced biliary carcinoma.

A case report of posterior reversible encephalopathy syndrome in a patient receiving gemcitabine and cisplatin.

RATIONALE: Posterior reversible encephalopathy syndrome (PRES) is a subacute syndrome causing characteristic neurologic and radiologic findings. PRES is predominantly caused by malignant hypertension though it has been associated with immunosuppressive treatments such as chemotherapy. PATIENT CONCERNS: We describe a case of a 58 year old female who developed fluctuant level of consciousness, agitation. DIAGNOSIS: MRI findings were in keeping with posterior reversible encephalopathy syndrome following cycle 6 of palliative gemcitabine and cisplatin therapy for metastatic cholangiocarcinoma. INTERVENTIONS: The patient was managed with magnesium supplementation for hypomagnesemia and amlodipine. OUTCOMES: The patient's level of consciousness returned to normal though she had residual neurologic deficits impairing her ability to drive and impacting her balance. CONCLUSIONS: Cisplatin is a documented causative agent of PRES though gemcitabine is rarely associated with the syndrome. Combination cisplatin and gemcitabine therapy causing radiologically proven PRES has been documented in only 3 previous case reports. Gemcitabine's poor blood-brain barrier penetration makes it an unlikely culprit of central nervous system (CNS) toxicities. Our case and previous reports suggest higher doses may contribute to CNS toxicities such as PRES. Additionally, an emerging trend of hypomagnesemia associated with PRES has been documented inside and outside the context of malignancy and suggests a possible target for treatment and prevention warranting further investigation.

Oncologic and Perioperative Outcomes Following Selective Application of Laparoscopic Pancreaticoduodenectomy for Periampullary Malignancies.

BACKGROUND: Data are sparse regarding patient selection criteria or evaluating oncologic outcomes following laparoscopic pancreaticoduodenectomy (LPD). Having prospectively limited LPD to patients with resectable disease defined by National Comprehensive Cancer Network (NCCN) criteria, we evaluated perioperative and long-term oncologic outcomes of LPD compared to a similar cohort of open pancreaticoduodenectomy (OPD). METHODS: Consecutive patients (November 2010-February 2014) undergoing pancreaticoduodenectomy (PD) for periampullary adenocarcinoma were reviewed. Patients were excluded from further analysis for benign pathology, conversion to OPD for portal vein resection, and contraindications for LPD not related to their malignancy. Outcomes of patients undergoing LPD were analyzed in an intention-to-treat manner against a cohort of patients undergoing OPD. RESULTS: These selection criteria resulted in offering LPD to 77 % of all cancer patients. Compared to the OPD cohort, LPD was associated with significant reductions in wound infections (16 vs. 34 %; P = 0.038), pancreatic fistula (17 vs. 36 %; P = 0.032), and median hospital stay (9 vs. 12 days; P = 0.025). Overall survival (OS) was not statistically different between patients undergoing LPD vs. OPD for periampullary adenocarcinoma (median OS 27.9 vs. 23.5 months; P = 0.955) or pancreatic adenocarcinoma (N = 28 vs. 22 patients; median OS 20.7 vs. 21.1 months; P = 0.703). CONCLUSIONS: The selective application of LPD for periampullary malignancies results in a high degree of eligibility as well as significant reductions in length of stay, wound infections, and pancreatic fistula. Overall survival after LPD is similar to OPD.

Mitochondrial bioenergetics and posthepatectomy liver dysfunction.

BACKGROUND: Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome. MATERIALS AND METHODS: Prospective study of thirty patients undergoing hepatectomy. Measurement of mitochondrial membrane potential, respiration and adenosine triphosphate content in intra-operative liver biopsies performed in nonresected parenchyma. Correlation of findings with duration of hepatic pedicle clamping, postoperative markers of hepatocellular necrosis and function (aminotransferases, arterial lactate, international normalized ratio, bilirubin), and morbidity. RESULTS: Longer hepatic pedicle clamping was associated with worse mitochondrial depolarization (r = -0·519; P = 0·011) and longer lag phase (r = 0·568; P = 0·006). Higher postoperative peak aminotransferases, international normalized ratio and bilirubin correlated with worse mitochondrial function (P < 0·05). After major hepatectomy, mitochondrial respiration correlated with postoperative arterial lactate clearance (r = 0·756; P = 0·049). Mitochondrial bioenergetic parameters were significantly decreased in patients with liver-specific morbidity and postoperative liver failure (P < 0·05). On multivariate analysis, decrease in mitochondrial potential was an independent risk factor for liver-specific morbidity (OR = 13·7; P = 0·043). Worse lag phase was highly predictive of posthepatectomy liver failure (area under the curve: 0·933; P = 0·008). CONCLUSIONS: There is a relationship between mitochondrial function, duration of hepatic pedicle clamping and clinical outcome after hepatectomy. Mitochondrial bioenergetics can potentially translate into clinical practice, assisting in earlier diagnosis of postoperative liver dysfunction, and as a target for future pharmacological therapies.

Adjuvant Transarterial Chemoembolization Following Liver Resection for Intrahepatic Cholangiocarcinoma Based on Survival Risk Stratification.

BACKGROUND: The effectiveness of adjuvant transarterial chemoembolization (TACE) for intrahepatic cholangiocarcinoma (ICC) after hepatectomy remains unclear. This study was performed to identify ICC patients who would benefit from adjuvant TACE. PATIENTS AND METHODS: The study included 553 patients who underwent hepatectomy for ICC between January 2008 and February 2011 at the Eastern Hepatobiliary Surgery Hospital and who were treated with or without TACE (122 with TACE and 431 without TACE). Survival risk stratification was performed using the established prognostic nomogram (ICC nomogram). The predictive performance was evaluated by concordance index and calibration. The tumor recurrence and overall survival (OS) rates were analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). RESULTS: The predictive performance of the ICC nomogram was demonstrated by the well-fitted calibration curves and an optimal c-index of 0.71 for OS prediction. In the whole cohort, the 5-year recurrence and OS rates between the TACE and non-TACE groups were significantly different (5-year recurrence: 72.9% vs. 78.1%; OS: 38.4% vs. 29.7%). After 1:1 PSM, the TACE and non-TACE groups (122 patients each) had similar 5-year recurrence and OS rates (5-year recurrence: 72.9% vs. 74.2%; OS: 38.4% vs. 36.0%). By survival risk stratification based on ICC nomogram, only the patients in the lowest tertile (nomogram scores ≥77) benefited from adjuvant TACE (TACE vs. non-TACE groups: 90.4% vs. 95.9% for 5-year recurrence; 21.3% vs. 6.2% for 5-year OS). CONCLUSION: Adjuvant TACE following liver resection might be suitable for ICC patients with high ICC nomogram scores (≥77). IMPLICATIONS FOR PRACTICE: The accurate predictive performance of the established prognostic nomogram for intrahepatic cholangiocarcinoma (ICC) following liver resection was reconfirmed in an independent cohort with 553 patients. Based on the survival risk stratification using the nomogram, adjuvant transarterial chemoembolization following liver resection might be suitable only for ICC patients with high scores from the nomogram.

Operative management of cholangiocarcinoma.

Cholangiocarcinomas (CCAs) are rare malignancies that originate from the epithelial cells of the bile ducts. It is the second most-common primary liver cancer after hepatocellular carcinoma. Recent epidemiologic studies have shown that the overall incidence and mortality rates of CCAs are increasing. Diagnosis is often challenging due to the difficulty in getting tissue/cytology for confirmation, and it comprises a combination of cross-imaging, tumor markers, histology, and cholangiography. Surgery involving major resections of liver, bile duct, pancreas, and at times adjacent vessels is the only chance for cure. Evaluation should be focused on the assessment of tumor resectability, hepatic reserve, and patient physiological fitness for major surgery. In patients not fit for major surgery, biliary drainage for jaundice is an appropriate intervention and if there is histologic confirmation of a CCA, palliative therapies focused on local and systemic disease control should be considered. The endeavor to expand the indications for liver transplantation reflects the efforts to provide an effective form of therapy for a previously untreatable disease. A multidisciplinary specialized approach should be the platform for providing the best comprehensive care for these patients.

Adjuvant chemotherapy in resectable cholangiocarcinoma patients.

BACKGROUND AND AIM: Cholangiocarcinoma patients usually have poor treatment outcome and a high mortality rate. The role of adjuvant chemotherapy (AC) is controversial. Our study aimed to evaluate benefits of AC in resectable cholangiocarcinoma patients. METHODS: A retrospective study included 263 patients who underwent curative resection in Srinakarind University Hospital. These patients had pathological reports showing a clear margin (R0) or microscopic margin (R1) of lesion-free tissue. RESULTS: There were 138 patients who received AC. This group had a significantly lower mean age than patients not receiving adjuvant chemotherapy (NAC) group (57.7 ± 8.5 vs 60.4 ± 9.0 years, P = 0.01). The level of serum albumin above 3 g/dL was more common in AC group than the NAC one (87.7% vs 79.2%, P = 0.04). Patients who received AC had significantly longer overall median survival time (21.6 vs 13.4 months, P = 0.01). Patients with a combination of gemcitabine and capecitabine regimen had the longest survival time (median overall survival time of gemcitabine and capecitabine 31.5, 5-fluorouracil and mitomycin 17.3, 5-fluorouracil alone 22.2, capecitabine alone 21.6, and gemcitabine alone 7.9 months, P = 0.02). Benefits of AC were likely to be found in patients who had high-risk features, that is, high level of carbohydrate antigen 19-9, advanced stage, T4 stage, lymph node involvement, and R1 margin. CONCLUSIONS: AC significantly prolongs survival time in resectable cholangiocarcinoma patients, particularly in the high risk group.

Contemporary management of perihilar cholangiocarcinoma in a nontransplant hepatopancreatobiliary center.

BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0 status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques.

SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma.

OBJECTIVES: Gallbladder and cholangiocarcinomas represent a heterogeneous group of malignant diseases that commonly present at an advanced stage and have limited therapeutic options. Based on the role of the Ras-Raf-Mek-Erk pathway and the VEGF axis in biliary carcinomas, we conducted a phase II study of sorafenib in patients with advanced biliary cancers. METHODS: Eligible patients had no prior therapy for metastatic or unresectable disease. Sorafenib was administered at 400 mg po twice daily continuously. RESULTS: The study was terminated after the first stage of accrual due to failure to meet the primary objective. A confirmed response rate of 0% (0%-11%) was observed. Thirty-nine percent of patients demonstrated stable disease (including 2 with unconfirmed PR). PFS was 3 months (95% CI: 2-4 months) and OS 9 months (95% CI: 4-12 months). The most common grade 3 and 4 toxicities included hand-foot skin reaction (13%), bilirubin elevation (13%), venous thromboembolism (10%), AST/ALT elevation (10%) and elevated alkaline phosphatase (10%). CONCLUSION: While treatment with sorafenib did not result in objective responses, patients with biliary cancers receiving this drug had some therapeutic benefit. Additional studies with sorafenib in combination with chemotherapy or other targeted agents may be warranted.