Jun-Ke Wang

Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: A single-institution experience in China

AIM To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution. METHODS Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated by univariate and multivariate analyses. RESULTS Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio (HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease (HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation (HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion (HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins (HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease (HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation (HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion (HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins (HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio (OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter (OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures (OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage (OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion (OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumor-free margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent factors for OS and DFS. Surgical procedures can indirectly affect survival outcome by influencing the tumor resection margin.

Coexisting cancers: a mixture of neuroendocrine carcinoma and adenocarcinoma in the gallbladder: A case report.

Background:Neuroendocrine carcinoma is rare with a proportion of less than 2% in gallbladder malignancies, cases of gallbladder neuroendocrine cell carcinoma coexisting with adenocarcinoma are exceptionally rare, and the prognosis is dismal. Methods:Herein, we presented an unusual case of poorly differentiated gallbladder neuroendocrine cell carcinoma coexisting with poorly differentiated adenocarcinoma who survived 20 months after the multimodal treatment (MT) of extended surgery and postoperative chemotherapy. Results:Our result indicated that for advanced gallbladder neuroendocrine cell carcinoma coexisting with adenocarcinoma, MT including extended surgical approach combined with postoperative chemotherapy may contribute to a relatively good survival outcome. Conclusion:MT may contribute to a relatively good survival outcome for advanced gallbladder neuroendocrine cell carcinoma coexisting with gallbladder adenocarcinoma.

Relationship of tumor size with pathological and prognostic factors for hilar cholangiocarcinoma

Objective To determine the correlation of different tumor-size cutoffs with prognostic factors and survival outcomes to provide a reference for the modification of the T-stage classification in the DeOliveira staging system for hilar cholangiocarcinoma (HCCA). Materials and Methods We retrospectively analyzed 216 patients who underwent curative surgery for HCCA (mean tumor diameter, 2.8 cm) between 2000 and 2013. Univariate and multivariate logistic regression were used to assess the correlation of tumor-size cutoffs with various factors. Results Tumor differentiation (odds ratio [OR]: 1.649, 95% confidence interval [CI]: 1.065–2.555, P = 0.025), node status (OR: 1.971, 95% CI: 1.060–3.664, P = 0.032), resection margin (OR: 2.465, 95% CI: 1.024–5.937, P = 0.044), and hepatectomy (OR: 2.373, 95% CI: 1.226–4.593, P = 0.01) were independently correlated with the 2-cm cutoff, while tumor differentiation (OR: 1.755, 95% CI: 1.062–2.091, P = 0.028), node status (OR: 2.166, 95% CI: 1.054–4.452, P = 0.035), and tumor margin (OR: 2.539, 95% CI: 1.089–5.919, P = 0.031) were independently associated with the 3-cm cutoff. Conclusions The 2-cm and 3-cm cutoffs were strongly correlated with resection margin, node status, tumor differentiation and survival. The 2-cm cutoff may be added to the DeOliveira staging system.

Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?

Background To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. Results In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216–9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391–28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107–14.459; P = 0.034). Materials and Methods Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. Conclusions In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.

Inflammatory Myofibroblastic Tumor of the Liver: Challenges in the Preoperative Diagnosis and Treatment

A 48-year-old Chinese woman was presented to our department with a hepatic mass on routine physical examination. She was almost asymptomatic. She denied previous radiotherapy or industrial chemical exposure. Physical examination was unremarkable. Liver function was within reference range. Serological testing for tumor markers, hepatitis B, and C were also negative. Magnetic resonance imaging (MRI) of the upper abdomen showed a 3.2 × 3.5 cm, appearing hypo-intense relative to the liver on T1-weighted images (Fig. 1a) and hyper-intense on T2-weighted images (Fig. 1b). Due to the similar appearance, hepatocellular adenoma, intrahepatic cholangiocarcinoma, or hepatic alveolar echinococcosis was considered for preoperative diagnosis. The patient eventually underwent a liver resection of segment VII. Microscopically, the hepatic lesion exhibited a mixture of chronic inflammatory cells and spindle cells (Fig. 2a). Immunohistochemical analysis showed tumor cells positive for smooth muscle actin (Fig. 2b), anaplastic lymphoma kinase-1 (Fig. 2c), and negative for CD34, CD99, EMA, PCK, supporting the diagnosis of inflammatory myofibroblastic tumor of the liver (IMTL). Postoperative recovery of the patient was well. IMTL is a rare neoplasm and the accurate incidence is not known. The etiology and pathogenesis of IMTL are not completely clear. The clinical presentation includes nonspecific and variable clinical presentation, ranging from asymptomatic to fever, chills, nausea, weight loss, back pain, or right-upper-quadrant abdominal pain. There is no known unique diagnostic clinical, laboratory, or radiological features. Thus, the diagnosis of IMTL is still difficult till now. Percutaneous needle liver biopsy may be able to improve the chance of preoperative diagnosis. Management remains controversial, including surgery, radiotherapy, steroids, chemotherapy, nonsteroidal anti-inflammatory drugs, and antibiotics. IMTL could abate spontaneously and is typically treated conservatively, with a good prognosis. If the diagnosis can be established pre-operatively, antibiotics and nonsteroidal anti-inflammatory drugs are sufficient in certain cases. Recently, anaplastic lymphoma kinase (ALK) inhibitors may provide therapeutic benefit in patients with ALKexpressing IMT. Most authors suggest surgical resection should be the preferred treatment. A study revealed a significant recurrence rate (24.5%), with a low risk of distant metastases. The value of resection has been demonstrated in patients in whom a definitive histological diagnosis could not be made preoperatively or intraoperatively by frozen section. If the diagnosis can be established pre-operatively, radical and extensive surgery may be avoided or at best less radical, thus reducing the surgical complications. Multicenter studies based on the analysis of more effective and practical diagnostic tools are required to establish better programs and subsequently guide the preoperative diagnosis of IMTL. Further studies focusing on the etiology of IMTL to improve diagnosis are also required. * Fu-Yu Li lfy_74@hotmail.com

Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma

Background The survival benefits of additional resection of the positive proximal ductal margin (PM) in hilar cholangiocarcinoma (HCCA) remains controversial. This retrospective study investigated the effectiveness of additional resection of the invasive cancer PM under different levels of preoperative carbohydrate antigen 19-9 (CA19-9). Methods Patients who underwent hepatectomy for HCCA from 2000 to 2017 were analyzed. Surgical variables, resection margin status, length of the PM (LPM), prognostic factors, and survival were evaluated. Results A total of 228 patients were enrolled: 175 PM(-) without additional resection patients (group A), 21 PM(-) after additional resection (group B), 16 PM(+) without additional resection (group C), and 16 PM(+) after additional resection (group D). The median survival of group B (20.99 months) was similar to that of group A (23.00 months; P=0.16), and both were significantly better than those of group C (11.60 months) and D (9.50 months), especially when preoperative CA19-9>150 U/mL (P<0.05). The survival of patients with an LPM >10 mm was significantly better compared with those with an LPM ≤10 mm, especially when preoperative CA19-9 was >150 U/mL (P<0.05). Only in the LPM >10 mm group, the survival of group B was comparable with that of group A (P>0.05). Conclusions HCCA patients could get a survival benefit from a negative PM resulting from additional resection. Survival could be comparable with that of negative PM without additional resection among HCCA patients. An LPM >10 mm is possibly more associated with better survival compared with whether additional resection of the positive PM is performed under different levels of preoperative CA19-9.

Comparative analysis of different hepatico-jejunostomy techniques for treating adult type I choledochal cyst

Abstract Objective To compare Roux-en-Y hepatico-jejunostomy with complete resection of the cyst or incomplete resection with 1-cm remnant proximal cyst wall in treating adult type I choledochal cyst (CC). Methods The medical records of 267 adult patients with type I CC from January 1998 to December 2015 were reviewed retrospectively. Among them, 171 underwent Roux-en-Y hepatico-jejunostomy with complete resection (PBD 0-cm group) and 96 underwent Roux-en-Y hepatico-jejunostomy with 1-cm proximal cyst wall left (PBD 1-cm group). The short- and long-term post-operative complications were compared between the two groups. Results No significant difference was observed in operative time or anastomotic diameter between the two groups. The incidence of perioperative complications was significantly higher in the PBD 1-cm group than that in the PBD 0-cm group (28.1% vs 14.0%, p=0.005), especially post-operative cholangitis (7.3% vs 1.2%, p=0.021). The incidence of long-term post-operative complications was not significantly different, including anastomotic stricture, reflux cholangitis, intra-hepatic bile duct stones and bile leak (all p >0.05). Post-operative intra-pancreatic biliary malignancy occurred in one patient in the PBD 0-cm group at 25 months and one patient in the PBD 1-cm group at 5 month, respectively. Anatomical site malignancy was observed in one patient in the PBD 1-cm group at 10 months. Conclusion Ease of performing anastomosis does not justify retaining a segment of choledochal cyst in type I CC due to its higher risk of post-operative complication and malignancy. A complete excision of the CC with anastomosis to the healthy proximal bile duct is necessary in treatment of type I CC.

Effective Treatment of Chronic Proliferative Cholangitis by Local Gentamicin Infusion in Rabbits

Background Hepatolithiasis is highly prevalent in East Asia characterized by the presence of gallstones in the biliary ducts of the liver. Surgical resection is the potentially curative treatment but bears a high risk of stone recurrence and biliary restenosis. This is closely related to the universal presence of chronic proliferative cholangitis (CPC) in the majority of patients. Recent evidence has indicated the association of bacterial infection with the development of CPC in hepatolithiasis. Thus, this study aims to investigate the feasibility and efficacy of local infusion of gentamicin (an antibiotic) for the treatment of CPC in a rabbit model. Methods The rabbit CPC model was established based on previously published protocols. Bile duct samples were collected from gentamicin-treated or control animals for pathological and molecular characterization. Results Histologically, the hyperplasia of biliary epithelium and submucosal glands were inhibited and the thickness of the bile duct wall was significantly decreased after gentamicin therapy. Consistently, the percentage of proliferating cells marked by ki67 was significantly reduced by the treatment. More importantly, this treatment inhibited interleukin 2 production, an essential inflammatory cytokine, and the enzyme activity of endogenous β-Glucuronidase, a key factor in the formation of bile pigment. Conclusions Local gentamicin infusion effectively inhibits the inflammation, cell proliferation, and lithogenesis in a rabbit model of CPC. This approach represents a potential treatment for CPC and thus prevents recurrent hepatolithiasis.

Clinical value of preoperative CA19-9 levels in evaluating resectability of gallbladder carcinoma: CA19-9 in evaluating resectability of GBC

This study evaluated the predictive ability of preoperative carbohydrate antigen 19‐9 (CA19‐9) level in assessing tumour resectability in patients with gallbladder carcinoma (GBC).

Minimally invasive surgery for hilar cholangiocarcinoma: state of art and future perspectives: Minimally invasive surgery for HCCA

Hilar cholangiocarcinoma (HCCA) occurs in the core section of the biliary system and has a strong tendency to broadly invade the surrounding vascular system, perineural tissue and major liver parenchyma. Thus, minimally invasive resection can only be achieved in limited cases. This article reviews the current laparoscopic and robotic surgery techniques for HCCA and analyses the difficulties and limitations of the current minimally invasive surgical techniques for HCCA.