Francesca Bertuzzo

Hepatocellular carcinoma: Surgical perspectives beyond the barcelona clinic liver cancer recommendations

The barcelona clinic liver cancer (BCLC) staging system has been approved as guidance for hepatocellular carcinoma (HCC) treatment guidelines by the main Western clinical liver associations. According to the BCLC classification, only patients with a small single HCC nodule without signs of portal hypertension or hyperbilirubinemia should undergo liver resection. In contrast, patients with intermediate-advanced HCC should be scheduled for palliative therapies, even if the lesion is resectable. Recent studies report good short-term and long-term outcomes in patients with intermediate-advanced HCC treated by liver resection. Therefore, this classification has been criticised because it excludes many patients who could benefit from curative resection. The aim of this review was to evaluate the role of surgery beyond the BCLC recommendations. Safe liver resection can be performed in patients with portal hypertension and well-compensated liver function with a 5-year survival rate of 50%. Surgery also offers good long-term result in selected patients with multiple or large HCCs with a reported 5-year survival rate of over 50% and 40%, respectively. Although macrovascular invasion is associated with a poor prognosis, liver resection provides better long-term results than palliative therapies or best supportive care. Recently, researchers have identified several genes whose altered expression influences the prognosis of patients with HCC. These genes may be useful for classifying the biological behaviour of different tumours. A revision of the BCLC classification should be introduced to provide the best treatment strategy and to ensure the best prognosis in patients with HCC.

Measured versus estimated total liver volume to preoperatively assess the adequacy of the future liver remnant: Which method should we use?

Objectives:To determine which method of liver volumetry is more accurate in predicting a safe resection. Background:Before major or extended hepatectomy, assessment of the future liver remnant (FLR) is crucial to reduce the risk of postoperative hepatic insufficiency. The FLR volume is usually expressed as the ratio of FLR to nontumorous total liver volume (TLV), which can be measured directly by computed tomography (mTLV) or estimated (eTLV) on the basis of correlation existing with the body surface area. To date, these 2 methods have never been compared. Methods:All consecutive, noncirrhotic patients who underwent resection of 3 or more liver segments between April 2000 and April 2012 and for whom (i) preoperative computed tomographic scans and (ii) body surface area were available entered the study. The mTLV (calculated as TLV − tumor volume) was compared with the eTLV (calculated as −794.41 + 1267.28 × body surface area) using volumetric data (cm3) and clinical outcome measures (specifically, hepatic insufficiency and 90-day mortality). Definition of hepatic insufficiency was peak postoperative serum total bilirubin level of more than 7 mg/dL or, in jaundiced patients, an increasing bilirubin level on day 5 or thereafter. Results:Two-hundred forty-three patients who had undergone major (n = 135) or extended (n = 108) hepatectomies met the inclusion criteria. Twenty-eight patients (11.5%) developed hepatic insufficiency, whereas 7 patients (2.9%) died postoperatively. Compared with the eTLV, the mTLV underestimated the liver volume in 60.1% of the patients (P < 0.01). Forty-seven and 73 patients had an inadequate FLR based on mTLV and eTLV, respectively. Portal vein occlusion (PVO) was used in 44 patients. In patients (n = 162) in whom both methods did not evidence the need for PVO, postoperative hepatic insufficiency and mortality were 4.9% and 0.6%, respectively. Conversely, in patients (n = 27) in whom the eTLV but not the mTLV evidenced the need for PVO, and thus PVO was not performed, hepatic insufficiency (22.2%; P = 0.001) and mortality (3.7%; P = ns) were higher. Conclusions:The use of eTLV identifies a subset of patients (∼11%) in whom liver volumetry with the mTLV underestimates the risk of hepatic insufficiency.

A novel serum marker for biliary tract cancer: diagnostic and prognostic values of quantitative evaluation of serum mucin 5AC (MUC5AC)

BACKGROUND AND AIMS Mucin 5AC (MUC5AC) is a glycoprotein found in different epithelial cancers, including biliary tract cancer (BTC). The aims of this study were to investigate the role of MUC5AC as serum marker for BTC and its prognostic value after operation with curative intent. PATIENTS AND METHOD From January 2007 to July 2012, a quantitative assessment of serum MUC5AC was performed with enzyme-linked immunoassay in a total of 88 subjects. Clinical and biochemical data (including CEA and Ca 19-9) of 49 patients with BTC were compared with a control population that included 23 patients with benign biliary disease (BBD) and 16 healthy control subjects (HCS). RESULTS Serum MUC5AC was greater in BTC patients (mean 17.93 ± 10.39 ng/mL) compared with BBD (mean 5.95 ± 5.39 ng/mL; P < .01) and HCS (mean 2.74 ± 1.35 ng/mL) (P < .01). Multivariate analysis showed that MUC5AC was related with the presence of BTC compared with Ca 19-9 and CEA: P < .01, P = .080, and P = .463, respectively. In the BTC group, serum MUC5AC ≥ 14 ng/mL was associated with lymph-node metastasis (P = .050) and American Joint Committee on Cancer and International Union for Cancer Control stage IVb disease (P = .047). Moreover, in patients who underwent operation with curative intent, serum MUC5AC ≥ 14 ng/mL was related to a worse prognosis compared with patients with lesser levels, with 3-year survival rates of 21.5% and 59.3%, respectively (P = .039). CONCLUSION MUC5AC could be proposed as new serum marker for BTC. Moreover, the quantitative assessment of serum MUC5AC could be related to tumor stage and long-term survival in patients with BTC undergoing operation with curative intent.

Assessment of bile and serum mucin5AC in cholangiocarcinoma: Diagnostic performance and biologic significance

BACKGROUND Recent studies have showed the efficacy of mucin5AC (MUC5AC) as a diagnostic and prognostic serum biomarker in biliary tract tumors. The aim of the present investigation was to improve the current knowledge on the biologic relevance of MUC5AC in malignant and benign biliary disorders by comparing its diagnostic performance in both bile and serum samples of patients with cholangiocarcinoma (CCA) or benign biliary disorders. METHODS A quantitative determination of MUC5AC by enzyme-linked immunosorbent assay was performed in bile and serum specimens from 26 patients with extrahepatic CCA and 20 subjects with benign biliary disorders (10 with biliary stones and 10 with cholangitis). Verification analysis was made by immunoblot. RESULTS MUC5AC of serum and biliary origin contributed to different extent to total levels of MUC5AC in the different groups of patients. In particular, the transition toward a greater degree of injury of bile duct epithelium was accompanied by a greater amount of MUC5AC in serum than in bile. The diagnostic performance of MUC5AC expressed as serum/bile ratio showed excellent diagnostic performance for differentiating CCA from cholangitis (area under the curve [AUC], 0.94; 95% CI, 0.86-1.00; P < .0001), CCA from biliary stones (AUC, 0.99; 95% CI, 0.98-1.00; P < .0001), as well as cholangitis from biliary stones (AUC, 0.93; 95% CI, 0.82-1.00; P = .001). CONCLUSION These findings provide new insight into the biologic importance of MUC5AC in biliary disorders and suggest that combined assessment of MUC5AC in bile and serum with expression of data in terms of serum to bile ratio may improve the diagnostic performance of MUC5AC quantification in serum alone.

Assessment of nodal status for perihilar cholangiocarcinoma location, number, or ratio of involved nodes

Surgical treatment of perihilar cholangiocarcinoma (PCC) is the treatment of choice that can achieve long term results. Unfortunately the presence of lymph node metastases is frequent and it is one of the major negative prognostic factors in patients submitted to surgery. In literature there are few data about the prognostic significance of location, number and ratio of involved nodes. Moreover guidelines about the extent of lymph node dissection are not available. In this commentary the data of literature about prognostic significance of lymph node involvement are described and analysed.

Impact of age on short-term outcomes of liver surgery: Lessons learned in 10-years’ experience in a tertiary referral hepato-pancreato-biliary center

Abstract We investigate the surgical outcomes of patients undergoing hepatectomy according to different age intervals, identify the clinical factors related to surgical outcomes, and propose clinical risk scores for severe morbidity and mortality based on the clinical factors. Eight hundred three patients undergoing liver resection were divided into 3 groups: young patients (YP), <65 years (n = 387), elderly patients (EP), from 65 to 74 years (n = 279); very-elderly patients (VEP), ≥75 years (n = 137). Severe morbidity was 10.6%, 12.2%, and 17.5% (P = .103), and mortality was 0.3%, 1.4%, and 4.4% (P = .002) in group YP, EP, and VEP, respectively. Ischemic heart disease, cirrhosis, major hepatectomy, biliary tract-associated procedure, and red blood cells (RBC) transfusion ≥3 U were related with severe morbidity. Ischemic heart disease, cirrhosis, major hepatectomy, and RBC transfusion were independent risk factors for postoperative mortality. Age did not result an independent factor related to mortality and severe morbidity. Two different scores were developed and have proved to be statistically related with severe morbidity and mortality. Moreover, in patients with score ≥2, severe morbidity increased from 24.2% in YP, to 29.3% in EP, and to 40.0% in VEP, P = .047. Likewise, mortality increased from 2.3% in YP, to 7.0% in EP, and to 22.7% in VEP, in patients with score ≥2, P = .017. Age alone should not be considered a contraindication for hepatectomy. We identified factors and proposed 2 scores that can be useful to stratify the risk of morbidity and mortality after hepatectomy. Moreover, severe morbidity and mortality increases according to the different age intervals in patients with scores ≥2.

Total Dorsal Pancreatectomy, an Alternative to Total Pancreatectomy: Report of a New Case and Literature Review

Background: Total dorsal pancreatectomy (TDP) is a conservative pancreatic resection that should be considered in cases of benign or low malignant tumors confined to the dorsal pancreas to preserve the viability of both digestive and biliary tracts, and to avoid the endocrine and metabolic consequences of total pancreatectomy. We report a new case of TDP and provide a literature review of this procedure. Methods: The case reported was a 35-year-old female patient with a solid pseudopapillary tumor. We resected the dorsal segment of the pancreas while preserving the common bile duct, gastroduodenal artery, and pancreaticoduodenal arcades, and the spleen and splenic vessels. The MEDLINE® and Embase® databases were searched for English language studies, case series, or case reports published through August 31, 2017. Results: The postoperative course was uneventful and patient was discharged on postoperative day 11. The patient was alive and in good condition at the 10-year follow-up. To date in English literature, there are only 3 reported cases of TDP, and all cases were patients with intraductal papillary mucinous neoplasia and pancreas divisum. There was no postoperative mortality, and 2 grade B pancreatic fistulas healed 1 month postoperatively. Conclusions: TDP is a feasible and safe operation for benign or low grade malignant pancreatic tumors involving the dorsal pancreas, as an alternative to total pancreatectomy.

Dorsal Pancreatectomy: An Alternative to the Total Pancreatectomy. Report of Two Cases and Review of the Literature

Context For the last three decades several advances in technique in pancreatic surgery have been performed in order to preserve pancreatic parenchyma. Dorsal pancreatectomy is a parenchyma-sparing segmental pancreatic resection, carried out to avoid exocrine or endocrine failure or biliary and gastrointestinal reconstruction. Case reports In this paper two cases of dorsal pancreatectomy were reported. In both cases, the excision of the entire dorsal pancreas was performed with preservation of the biliary duct and the spleen, the gastroduodenal artery was preserved to avoid ischemia of the bile duct and duodenum. The first patient was a 71-year-old female affected by IPMN of the tail of pancreas with a small liver metastasis intra-operatively detected and removed. The post-operative course was uneventful. The patient was discharged 13 days after surgery and then submitted to systemic and intra-arterial regional chemotherapy (FLEC regimen). This patient died 30 months after surgery for liver and peritoneal recurrences, without signs of endocrine insufficiency but with necessity to intake a low-dose pancreatic enzymes. The second patient was a 35-year-old female affected by solid pseudopapillary tumor involving the head and the neck of the pancreas with atrophy of the distal part of pancreatic parenchyma. The post-operative course was uneventful and the patient was released on the 11 th post-operative day. Seventy-five months after surgery the patient is still alive, in absence of diabetes or exocrine impairment.