Intrabiliary metastases in colorectal cancer: a systematic review.

BACKGROUND: Liver metastases emerge during the course of colorectal cancer (CRC) in 25-50% of patients. A small proportion of patients present intrabiliary growth. The absence of large series means that little is known about intrabiliary metastasis (IBM), its radiological diagnosis, the most suitable surgical techniques, and its prognostic implications. METHODS: A systematic search without limits was performed. The studies selected included patients with a diagnosis of CRC and associated IBM, either synchronous or metachronous. RESULTS: Of 40 studies selected, 30 were case reports and 10 case series. The median time between diagnosis and IBM was 46.7 months (range 0-180). Most CRC metastases are CK7-/CK20+. Surgical treatment performed ranged from endoscopic resection to major hepatic resections combined with pancreatectomies. It seems that patients with IBM have a better survival than patients without this metastasis. CONCLUSION: In a patient with a history of CRC presenting dilatation of the bile duct, IBM should be considered. More studies are needed to determine the most appropriate type of liver resection. It is also necessary to standardize the definition and terminology of this pathology, since the existing definitions may cause confusion and make it difficult to carry out case studies and case series.

Histologically Verified Biliary Invasion was Associated with Impaired Liver Recurrence-Free Survival in Resected Colorectal Cancer Liver Metastases.

BACKGROUND AND AIMS: The impact of biliary invasion on recurrence and survival, after resection of colorectal cancer liver metastases, is not well known as publications are limited to small patient series. The aim was to investigate if biliary invasion in liver resected patients associated with liver relapses and recurrence-free survival. Secondary endpoints included association with other prognostic factors, disease-free survival and overall survival. MATERIALS AND METHODS: All patients with histologically verified biliary invasion (n = 31, 9%) were identified among 344 patients with liver resection between January 2009 and March 2015. Controls (n = 78) were selected from the same time period and matched for, among others, size and number of colorectal cancer liver metastasis. RESULTS: Median liver recurrence-free survival was significantly shorter in patients with biliary invasion than in controls (15.3 months versus not reached; p = 0.031) and more relapses were noted in the liver (61.3% versus 33.3%; p = 0.010), respectively. In univariate analyses for liver recurrence-free survival, biliary invasion was the only significant prognostic factor; p = 0.034. There were no statistical differences in disease-free and overall survival between the groups. CONCLUSION: Biliary invasion was associated with higher liver recurrence rates and shorter liver recurrence-free survival in patients with resected colorectal cancer liver metastasis.

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

OBJECTIVES: Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. MATERIALS AND METHODS: A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. RESULTS: The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). CONCLUSIONS: Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.

Peribiliary liver metastases MR findings.

We described magnetic resonance (MR) features of peribiliary metastasis and of periductal infiltrative cholangiocarcinoma. We assessed 35 patients, with peribiliary lesions, using MR 4-point confidence scale. T1-weighted (T1-W), T2-weighted (T2-W) and diffusion-weighted images (DWI) signal intensity, enhancement pattern during arterial, portal, equilibrium and hepatobiliary phase were assessed. We identified 24 patients with periductal-infiltrating cholangiocellular carcinoma. The lesions in 34 patients appeared as a single tissue, while in a single patient, the lesions appeared as multiple individual lesions. According to the confidence scale, the median value was 4 for T2-W, 4 for DWI, 3.6 for T1-W in phase, 3.6 for T1-W out phase, 3 for MRI arterial phase, 3.2 for MRI portal phase, 3.2 for MRI equilibrium phase and 3.6 for MRI hepatobiliary phase. According to Bismuth classification, all lesions were type IV. In total, 19 (54.3%) lesions were periductal, 15 (42.9%) lesions were intraperiductal, and 1 (2.8%) lesion was periductal intrahepatic. All lesions showed hypointense signal in T1-W and in ADC maps and hyperintense signal in T2-W and DWI. All lesions showed a progressive contrast enhancement. There was no significant difference in signal intensity and contrast enhancement among all metastases and among all metastases with respect to CCCs, for all imaging acquisitions (p value >0.05). MRI is the method of choice for biliary tract tumors thanks to the possibility to obtain morphological and functional evaluations. T2-W and DW sequences have highest diagnostic performance. MRI does not allow a correct differential diagnosis among different histological types of metastasis and between metastases and CCC.

Diagnostic accuracy of magnetic resonance, computed tomography and contrast enhanced ultrasound in radiological multimodality assessment of peribiliary liver metastases.

PURPOSE: We compared diagnostic performance of Magnetic Resonance (MR), Computed Tomography (CT) and Ultrasound (US) with (CEUS) and without contrast medium to identify peribiliary metastasis. METHODS: We identified 35 subjects with histological proven peribiliary metastases who underwent CEUS, CT and MR study. Four radiologists evaluated the presence of peribiliary lesions, using a 4-point confidence scale. Echogenicity, density and T1-Weigthed (T1-W), T2-W and Diffusion Weighted Imaging (DWI) signal intensity as well as the enhancement pattern during contrast studies on CEUS, CT and MR so as hepatobiliary-phase on MRI was assessed. RESULTS: All lesions were detected by MR. CT detected 8 lesions, while US/CEUS detected one lesion. According to the site of the lesion, respect to the bile duct and hepatic parenchyma: 19 (54.3%) were periductal, 15 (42.8%) were intra-periductal and 1 (2.8%) was periductal-intrahepatic. According to the confidence scale MRI had the best diagnostic performance to assess the lesion. CT obtained lower diagnostic performance. There was no significant difference in MR signal intensity and contrast enhancement among all metastases (p>0.05). There was no significant difference in CT density and contrast enhancement among all metastases (p>0.05). CONCLUSIONS: MRI is the method of choice for biliary tract tumors but it does not allow a correct differential diagnosis among different histological types of metastasis. The presence of biliary tree dilatation without hepatic lesions on CT and US/CEUS study may be an indirect sign of peribiliary metastases and for this reason the patient should be evaluated by MRI.

[Posthepatectomy Liver Failure in Extended Liver Resections: An Overview Based on a Retrospective Single-Centre Analysis]. / Postoperatives Leberversagen nach erweiterten Leberresektionen - eine Übersicht, gestützt durch eine retrospektive Single-Center-Analyse.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. METHODS: We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. RESULTS: Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). CONCLUSION: Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.

Crecimiento endobiliar de las metástasis de carcinoma colorrectal / Intrabiliary growth of colorectal liver metastases

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The role of intraoperative ultrasound in establishing the surgical strategy regarding hepato-bilio-pancreatic pathology.

Intraoperative ultrasound examination plays a more and more important role in open or laparoscopic abdominal surgery,satisfying the surgeon's need to correctly characterize lesions,bringing various benefits regarding topography and local regional extension, relations between neighbouring structures and, finally, disease staging. Intraoperative ultrasound is used especially in hepato-bilio-pancreatic tract interventions, given its diagnostic and therapeutic values. Between 2009-2012 in the IOB First Surgery Clinic 57 intraoperative echo graphies were performed, in patients with hepato-bilio-pancreatic pathologies, leading to intraoperative guided punctures with diagnostic or therapeutic purpose (in case of hepatic abscesses),detection of new hepatic metastases, their ablation under ultrasound guidance, exploration of the local-regional topography with the aim of an optimal hepatic resection. Intraoperative ultrasound allowed radioablation under echographic guidance in 43 patients, the majority presenting multiple hepatic metastases in different areas, this method also enabling control over complete lesional destruction. Also, in 11 cases (22.915), a number of hepatic 20 metastases which had not been visible on preoperative imaging scans were detected, and afterwards treated through RFA; also, in 14 cases intraoperative echography revealed the presence and nature of the hepatic tumours, leading to a correct histopathological diagnostic and an adequate therapy. The method was useful in pancreatic pathologies as well, in complicated forms of acute or chronic pancreatitis, tracking the Wirsung duct within the scleral and calcified mass of pancreatic tissue, through an ultrasound guided puncture, as well as in locating pancreatic cystic masses,determining the optimal puncture or pericystic-digestive drainage areas. Intraoperative ultrasound is an inexpensive, easy method, which allows real time exploration throughout the entire surgical process of hepato-bilio-pancreatic lesions, aiding the surgeon in modifying decisions regarding the intervention and preventing complications.

Intrabiliary growth of colorectal liver metastasis: spectrum of imaging findings and implications for surgical management.

OBJECTIVE: The propensity for colorectal liver metastasis to invade the biliary tree is increasingly recognized, placing particular emphasis on the risk of postoperative recurrence. This article illustrates the spectrum of imaging findings when colorectal metastasis invades the biliary tree. CONCLUSION: Knowledge of the imaging features of intrabiliary invasion by colorectal liver metastasis improves the quality of preoperative staging and is crucial in an era in which nonanatomic wedge resection and radiofrequency ablation are routinely performed.

Optimizing the administration of fixed-dose rate gemcitabine plus capecitabine using an alternating-week schedule: a dose finding and early efficacy study in advanced pancreatic and biliary carcinomas.

OBJECTIVES: This multisite study sought to optimize the dosing, schedule, and administration of fixed-dose rate (FDR) gemcitabine plus capecitabine for advanced pancreatic and biliary tract cancers using an alternating-week dose schedule of both agents. METHODS: Patients with previously untreated advanced pancreatic and biliary tract cancers with Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. For the dose-finding portion, a standard 3+3 dose-escalation schema was used, with the gemcitabine dose kept at 1000 mg/m(2) administered by FDR (10 mg/m(2)/min) on day 1 of each 14-day cycle, and capecitabine given on days 1 to 7 at doses ranging from 800 to 1500 mg/m(2) twice daily. Primary study objective was determination of maximum tolerated dose (MTD). The cohort at MTD was expanded for further efficacy assessment. RESULTS: A total of 45 patients (median age 61 y; 93% pancreatic/7% biliary; 84% with metastatic disease) were enrolled. Median number of cycles received was 11.5. The MTD using this dose schedule was FDR gemcitabine 1000 mg/m(2) plus capecitabine 1000 mg/m(2) bid, due to a high incidence of late hand-foot syndrome observed at the next higher dose level. Most common nonhematologic adverse events related to treatment included nausea/vomiting (overall rate, 64%; all grade 1/2) and hand-foot syndrome (overall rate, 60%; grade 3, 22%). The incidence of grade 3/4 hematologic adverse events was 24%. Six of 41 evaluable patients (14.6%) had a partial response; 18 of 31 patients (58%) with elevated baseline CA 19-9 level had ≥50% biomarker decline during treatment. Estimated median time to tumor progression and overall survival were 5.5 and 9.8 months, respectively (5.5 and 10.1 mo in the metastatic pancreatic cancer cohort). CONCLUSIONS: This dosing schedule of FDR gemcitabine plus capecitabine is active in patients with advanced pancreatobiliary cancers. Given its favorable toxicity profile and convenience, this regimen represents an appropriate front-line option for this patient population and may serve as the foundation on which new investigational agents are added in future trial design.

Patterns of referral and resection among patients with liver-only metastatic colorectal cancer (MCRC).

BACKGROUND: Rates of metastatectomy vary among patients with liver-only metastatic colorectal cancer (MCRC). This study describe predictors of referral to a hepatobiliary surgeon (HBS) and hepatic resection in a population-based setting. MATERIALS AND METHODS: Patients referred to the British Columbia Cancer Agency (BCCA) with synchronous or relapsed MCRC isolated to the liver in 2002-2004 were identified. Classification of tumor burden as "high" or "low" was based on prognostic features defined by LiverMetSurvery registry. Metastases larger than 5 cm, bilobar, or more than 3 metastases were classified as high tumor burden. Multivariate logistic regression models were used to identify predictors of HBS referral and subsequent metastatectomy. Overall survival was calculated by the Kaplan-Meier method. RESULTS: Of 618 patients with isolated hepatic metastasis, 148 (24%) were referred to a HBS and 99 (16%) underwent resection. Advanced age was the most common reason for not referring 64 patients (10%) with ECOG performance status 0/1 and low tumor burden. In multivariate analysis, variables associated with referral were younger age (P < .001), ECOG performance status 0/1 (P < .002), chemotherapy for metastatic disease (P = .007), 1-3 metastasis (P < .001), and unilobar disease (P < .001). Median patient survival was 0.99 years (95% confidence interval [95% CI], 0.89-1.10 years) among nonreferred, 1.83 years (95% CI, 1.37-2.31 years) if referred but not resected, and 3.85 years (95% CI, 2.90-4.80 years) if resected. CONCLUSION: A significant proportion of patients are not referred to a HBS because of advanced chronological age. Resection of hepatic metastases was associated with improved overall survival irrespective of initial tumor burden.

Biliary epithelial metastasis of squamous carcinoma of the anus.

INTRODUCTION: The liver and biliary tree are common sites of initial metastasis for many primary tumors. However, we recently encountered a patient who presented with biliary-tree tumor encasement as a first metastasis from squamous carcinoma of the anus. METHODS: To our knowledge, this has not been previously described in the literature. CONCLUSIONS: As obstructive jaundice is a relatively common presenting sign in the emergency room and in general surgical clinics, we thus recommend early consideration of metastatic disease as a differential diagnosis in patients post-chemoradiotherapy for anal carcinoma who present with obstructive jaundice.

Clinical outcome of malignant biliary obstruction caused by metastatic gastric cancer.

BACKGROUND: The clinical outcome of malignant biliary obstruction caused by metastatic gastric cancer remains unclear. This study was designed to evaluate the clinical outcome and predictive factors of survival in patients who underwent percutaneous transhepatic biliary drainage (PTBD) for malignant biliary obstruction caused by metastatic gastric cancer. METHODS: Between April 1997 and March 2006, 38 consecutive patients with malignant biliary obstruction caused by metastatic gastric cancer were retrospectively analyzed. All patients underwent PTBD. RESULTS: After PTBD, serum bilirubin levels significantly decreased in 29 (76%) of 38 patients. Pruritus, fever, jaundice, anorexia, abdominal pain, and general fatigue improved significantly in 100%, 100%, 78%, 64%, 53%, and 48% of patients, respectively. Early complications related to the intervention occurred in ten patients. Seven patients developed symptoms of recurrent jaundice or cholangitis. Overall median survival was 79 days, and 6-month and 1-year survival rates after PTBD were 39.5% and 13.2%, respectively. Serum bilirubin level after PTBD (P < 0.0001), chemotherapy after PTBD (P < 0.0001), and performance status at presentation (P = 0.0363) were found to be independent predictors of survival. CONCLUSION: PTBD with metallic stent placement is a safe and effective palliation for patients with malignant biliary obstruction caused by metastatic gastric cancer. Our results suggest that patients in good clinical condition are candidates for aggressive treatment with a combination of PTBD with metallic stent placement and chemotherapy.

Preoperative right portal vein embolisation: indications and results.

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy of right portal vein embolisation (PVE) in inducing contralateral liver hypertrophy before extended hepatectomy. MATERIALS AND METHODS: Twenty-six consecutive patients, 14 with liver metastases (ten from colorectal cancer; four from carcinoid tumours) and 12 with biliary cancers (ten Klatskin tumours; one gallbladder tumour; one intrahepatic cholangiocarcinoma) with insufficient predicted future remnant liver (FRL) underwent right PVE to induce hypertrophy of the contralateral hemiliver prior to surgical resection. Total liver volume, tumour volume and FRL volume were calculated on a 3D workstation. The ratio of the FRL to the total functional liver volume was <30% in all patients. RESULTS: The FRL volume increased by 5%-25% (15% on average) after right PVE in patients with liver metastases and by 9%-19% (14% on average) in patients with biliary cancers. In all patients, the ratio of FRL to functional liver volume was >or=30% after right PVE. No postoperative deaths due to severe liver failure occurred in the 20 patients who underwent extended hepatectomy. CONCLUSIONS: Right PVE extends the indications for hepatectomy in patients with liver metastases and those with biliary cancers who have an insufficient potential hepatic functional reserve.

Aggressive surgical approach for stage IV gallbladder carcinoma based on Japanese Society of Biliary Surgery classification.

BACKGROUND/PURPOSE: The role of aggressive surgery for stage IV gallbladder carcinoma remains controversial. Survival and prognostic factors were analyzed in patients with stage IV disease, based on the Japanese Society of Biliary Surgery (JSBS) classification, to identify the group of patients who could benefit from radical surgery. METHODS: A retrospective analysis was done of 79 patients with JSBS stage IV gallbladder carcinoma who had undergone surgical resection with curative intent at our institution. The standard procedures were anatomical S4a + S5 subsegmentectomy (n = 29) with extrahepatic bile duct resection and extended lymphadectomy, but when right Glisson's sheath and/or the hepatic hilum were involved, right extended hepatectomy (n = 34) or right trisegmentectomy (n = 3) was selected. To achieve a tumor-free margin combined pancreaticoduodenectomy was performed in 12 patients, and major vascular resection in 17 patients. RESULTS: In the patients with stage IV gallbladder carcinoma, the curative resection rate was 65.8% and the hospital mortality rate was 11.4%. The postoperative 5-year survival rate following curative resection was 13.7%. Univariate analysis indicated that curability, hepatoduodenal ligament invasion, nodal involvement, and vascular resection were significant prognostic factors. Neither hepatic invasion nor liver metastasis was a significant factor. CONCLUSIONS: Aggressive surgical resection should be considered even in stage IV patients when hepatoduodenal ligament invasion and nodal involvement are absent or limited. Acceptable survival may be expected among such patients only when curative resection is achieved.

[The hepatic artery injection chemotherapy and prostaglandin E1 administration for hepatocellular carcinoma invading the biliary tract with jaundice].

A 69-year-old man had radiofrequency ablation therapy (following RFA) for type C cirrhosis with hepatoma (following HCC) of S7 in November 2001. Afterward the patient was followed as an outpatient, but he had been admitted to our hospital due to jaundice confirmed in March 2004. His abdominal wall appeared to be soft and flat, and we could not detect a tumor mass by palpating either. Even though he exhibited no actual symptom of anemia, jaundice was found in the bulbar conjunctiva at the time of admission. Laboratory findings showed a mild inflammation and anemia on his admission, and biochemical data showed a rise of hepatobiliary enzyme with jaundice. A rise of tumor marker (AFP, PIVKA-II) was recognized, too. We performed percutaneous transhepatic bile duct drainage (following PTBD) to decrease jaundice because abdominal echography and CT showed an extension of tumor thrombosis in bile duct and right hepatic duct by HCC of S8. However, a check of T-Bil. was 7.29 mg/dl and showed some slight decrease. Therefore, we administered prostaglandin E1 (following PGE1) at first with an intra-arterial injection catheter aiming to protect the hepatocyte. One week later, we performed hepatic artery injection chemotherapy (CDDP+5-FU) for four weeks. We confirmed a manifested improvement in T-Bil to be 1.92 mg/dl at the end of hepatic artery injections as well as a manifested decrease in hepatobiliary enzyme. We confirmed a decrease of HCC of S8 by abdominal CT, and the response rate was PR. Afterward the patient was conservatively treated even though pancytopenia was present, and was discharged from the hospital in June 2004. The hepatic artery injection chemotherapy used together with PGE1 was effective for the HCC patient with jaundice.