Surgical Outcomes of the Mass-Forming plus Periductal Infiltrating Types of Intrahepatic Cholangiocarcinoma: A Comparative Study with the Typical Mass-Forming Type of Intrahepatic Cholangiocarcinoma

Background The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcomes of patients with the mass-forming (MF) plus periductal infiltrating (PI) type of intrahepatic cholangiocellular carcinoma (ICC). Methods Between January 1, 1998, and December 31, 2004, a total of 94 patients with ICC underwent macroscopic curative resection, and the macroscopic type of the tumors was assessed prospectively. Among the 74 patients with the MF type (n = 46) and the MF plus PI type (n = 28) of ICC, multivariate analysis was conducted to identify the potential prognostic factors. The clinicopathologic data of the two groups were compared. Results The results revealed two independent prognostic factors: presence/absence of intrahepatic metastasis and the macroscopic type of the tumor. ICCs categorized macroscopically as the MF plus PI type were significantly associated with jaundice (p < 0.001), bile duct invasion (p < 0.001), portal vein invasion (p = 0.025), lymph node involvement (p = 0.017), and positive surgical margin (p = 0.038). Conclusion Identification of the macroscopic type of the tumor is useful for predicting survival after hepatectomy in patients with ICC. The MF plus PI type of ICC appears to have a more unfavorable prognosis, even after radical surgery, than the MF type of ICC.     

Clinicopathological Prognostic Factors After Hepatectomy for Patients with Mass-Forming Type Intrahepatic Cholangiocarcinoma: Relevance of the Lymphatic Invasion Index

Background  

The present study was conducted to clarify the pathological factors in patients who underwent surgery for mass-forming type intrahepatic cholangiocarcinoma (IHC).     

170例Ⅲ型肝门胆管癌的治疗及预后分析

目的探讨Ⅲ型肝门胆管癌的治疗及其预后的影响因素。方法回顾性分析2002年1月至2011年12月期间笔者所在医院收治的170例Ⅲ型肝门胆管癌患者的临床资料。结果170例患者中,行手术切除60例,行姑息性支架或u管支撑引流49例,行经皮经肝胆管外引流14例,未治疗47例。60例手术切除患者中,R0切除50例,R1切除10例。手术切除患者预后影响因素的Cox比例风险模型结果显示,手术切缘（HR=4．621,95％ CI：1．907-11．199,P=0．001）、肝叶切除（HR=3．003,95％ CI：1．373-6．569,P=0．006）及淋巴结转移（HR=2．792,95％ CI：1．393-5．598,P=0．004）与预后均相关。所有患者预后影响因素的Cox比例风险模型结果显示,治疗方法【R0切除（HR=0．177,95％ CI：0．081-0．035,P〈0．001）,未治疗（舰=5．568,95％ CI：2．733-11．342,P〈0．001）]及血管侵犯（HR=I．667,95％ CI：1．152-2．412,P=-0．007）与预后均相关。结论治疗方式与血管是否受侵犯与Ⅲ型肝门胆管癌的预后相关;可行手术切除患者中联合肝叶切除、R0切除及无淋巴结转移者的预后相对较好。     

Reappraisal of Prognostic Impact of Tumor SUVmax by 18F-FDG-PET/CT in Intrahepatic Cholangiocarcinoma

World Journal of Surgery - We previously reported that tumor standardized uptake value (SUVmax) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) was a potential...     

Prognostic Significance of Tumor Deposits in Stage III Colon Cancer

Background

The American Joint Committee on Cancer includes extranodal tumor deposits in the tumor–node–metastasis classification of colon cancer. However, it is unclear how tumor deposits compare with lymph node metastases in prognostic significance. This study evaluated the survival impact of tumor deposits relative to lymph node metastases in stage III colon cancer.

Methods

The US National Cancer Database (2010–2012) was reviewed for resectable stage III adenocarcinoma of the colon, and stratified by presence of tumor deposits and lymph node metastases. Univariate and multivariate survival analyses were performed.

Results

Of 6424, 10.1% had both tumor deposits and lymph node metastases [5-year survival (5YS) 40.2%], 2.5% had tumor deposits alone (5YS 68.1%), and 87.4% had lymph node metastases alone (5YS 55.4%). Patients with lymph node metastases alone tended to have a greater number of lymph nodes retrieved (20.9 versus 18.8, p?=?0.0126) and were more likely to receive adjuvant therapy (66.9 vs 58.0%, p?=?0.003) than those with only tumor deposits. Patients with both had significantly worse survival at all T stages (p?<?0.05, all). There was no significant difference in survival between tumor deposits alone and lymph node metastases alone at any T stage (p?>?0.8, all). After controlling for patient, disease, and treatment characteristics, patients with tumor deposits alone [hazard ratio (HR) 0.56, p?=?0.001] or only lymph node metastases (HR 0.64, p?<?0.001) were associated with improved survival relative to patients with both.

Conclusions

Concomitant presence of tumor deposits and lymph node invasion carries poor prognostic significance. Tumor deposits alone appear to have prognostic implications similar to lymph node invasion alone.

     

Prognostic Significance of Tumor Size in T3 Gastric Cancer

Background  Clinical significance of tumor size remains elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of tumor size in T3 gastric cancer. Methods  A total of 273 patients with T3 gastric cancer who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. In terms of average value of tumor size, patients were divided into two groups according to tumor size: small-size group (SSG, tumor ≤6 cm) and large-size group (LSG, tumor >6 cm). The prognostic value of tumor size and the correlation between tumor size and other clinicopathologic factors were investigated. Results  LSG accounted for 34.8% in all patients. Tumor size was correlated with histological type, lymphatic invasion, venous invasion, and resection type. The prognosis of LSG patients was worse than that of SSG patients. Multivariate analysis showed that type of resection, status of lymph nodes, metastatic lymph node ratio, and tumor size were defined as independent prognostic factors for patients with T3 gastric cancer. A comparison between LSG patients and SSG patients showed differences in the survival of those with stage IIIB and IV disease. Conclusions  Tumor size is a simple and reliable prognostic factor for patients with T3 gastric cancer; it might be a candidate for the gastric cancer staging system.     

Intratumoral IL-17+ Cells and Neutrophils show Strong Prognostic Significance in Intrahepatic Cholangiocarcinoma

Background

Inflammatory reactions at a tumor site have both detrimental and beneficial effects on tumor progression. This study was designed to assess the clinical significance of tumor-infiltrating inflammatory cells in patients with intrahepatic cholangiocarcinoma (ICC).

Methods

A total of 123 consecutive ICC patients who underwent curative resection were enrolled. Tissue microarray and immunohistochemistry were used to analyze the distribution and clinical relevance of IL-17⁺, FOXP3⁺, CD8⁺, CD66b⁺ cells, and microvessel density (CD34) in different microanatomical areas.

Results

IL-17⁺ cells, FOXP3⁺ lymphocytes, CD66b⁺ neutrophils, and microvessels were enriched predominantly in intratumor (IT) area, whereas CD8⁺ lymphocytes were most abundant in tumor invasive front. On univariate analyses, increasing IL-17 _IT ⁺ and neutrophils_IT were significantly associated with worse patient survival. Multivariate analyses revealed that IL-17 _IT ⁺ (hazard ratio [HR]?=?1.59; 95% confidence interval [CI], 1.05?C2.41; P?=?0.028), neutrophils_IT (HR?=?1.76; 95% CI, 1.16?C2.65; P?=?0.007), and their combination (HR 2.8; 95% CI 1.72?C4.57; P? _IT ⁺ significantly correlated with the presence of lymph node metastasis, intrahepatic metastasis, and advanced stages, whereas neutrophils_IT correlated with the presence of vascular invasion. In addition, significant positive correlations were detected among densities of IL-17⁺ cells, neutrophils, and microvessel density.

Conclusions

Our data suggested that intratumor IL-17⁺ cells, neutrophils are novel, powerful predictors of prognosis in patients with ICC.     

Surgical Treatment of Mass-Forming Intrahepatic Cholangiocarcinoma: An 11-Year Western Single-Center Experience in 107 Patients

Hepatic resection is the only cure for intrahepatic cholangiocellular carcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcome of patients with ICC. We retrospectively studied the records of 67 patients who underwent laparotomy for ICC from January 1995 through December 2005. Univariate and multivariate analyses were conducted for several variables to evaluate their influence on the outcome. Forty-five patients underwent hepatic resection. In 19 patients, the tumors were found to be unresectable at the time of laparotomy. Median 2- and 5-year survival rates in the 45 resected patients were 62% and 35%, respectively. For 36 patients who underwent curative resection, the 2- and 5-year survival were 67% and 41%, respectively; with a median survival of 43 months. The overall 5-year recurrence-free survival was 30%. The 90-day postoperative mortality rate was 4% and morbidity 28%. Multivariate analyses confirmed resection margin, lymph node involvement, blood loss, and blood transfusion to be independent significant variables for overall survival. Predictors of longer recurrence-free survival were lymph node involvement, vascular infiltration, blood loss, and transfusion. Surgical treatment of ICC by curative hepatic resection in patients without nodal invasion provides good long-term results. In contrast, incomplete tumor removal does not provide a survival benefit. An improved quality of preoperative staging was able to increase the resectability rate to acceptable 70%.     

Significance of Tumor Length as Prognostic Factor for Esophageal Cancer

Our study indicated the relationship between tumor length and clinicopathologic characteristics as well as long-term survival in esophageal cancer. A total of 116 patients who underwent curative surgery for thoracic esophageal cancer with standard lymphadenectomy in 2 fields between 2000 and 2010 were included in the study. The medical records of these patients were retrospectively reviewed. The patients with tumor length ≥3 cm had a highly significant difference in the involvement of adventitia and lymph node stations. The patients with tumor length ≤3 cm had significantly lower rates of involvement of the adventitia and lymph node stations. Tumor length could have a significant impact on both the overall survival and disease-free survival of patients with resected esophageal carcinomas and may provide additional prognostic value to the current tumor, node, and metastasis staging system before patients receive any cancer-specific treatment.     

Expression and Clinical Significance of Hepatoma-Derived Growth Factor as a Prognostic Factor in Human Hilar Cholangiocarcinoma

Background

Overexpressions of hepatoma-derived growth factor (HDGF) and vascular endothelial growth factor (VEGF) play important roles in the development and progression of cancers. This study investigates the expression of HDGF combined with VEGF, their correlation with clinicopathologic features, and their prognosis in human hilar cholangiocarcinoma.

Materials and Methods

The expressions of HDGF and VEGF were analyzed by immunohistochemistry using the streptavidin peroxidase complex method for 58 patients with hilar cholangiocarcinoma receiving surgery. Their correlation with clinicopathologic features was then investigated. The relationships between them and the survival time of patients were retrospectively analyzed.

Results

HDGF and VEGF were positively expressed in 27 (46.6%) and 42 (72.4%) patients, respectively. HDGF and VEGF had a positive correlation (r = 0.370, P = 0.004) in the Spearman rank correlation analysis. HDGF expression was associated with gender and histological type. Patients with positive HDGF expression had a significantly poorer overall survival rate than those with negative HDGF expression (35.7 vs. 73.3%, P = 0.003). Multivariate analysis showed that HDGF expression is an independent prognostic factor.

Conclusions

HDGF expression significantly correlates with VEGF expression and is a valuable prognostic factor for human hilar cholangiocarcinoma.     

Prognostic Significance and Molecular Associations of Tumor Growth Pattern in Colorectal Cancer

Background

Infiltrative growth pattern at the tumor margin has been associated with shorter patient survival. However, little is known about the prognostic significance of tumor growth pattern, independent of tumoral molecular alterations and other histologic features.

Methods

Utilizing a database of 1139 colon and rectal cancer patients in two prospective cohort studies, histologic features including tumor growth pattern, tumor differentiation, lymphocytic reaction, mucinous component, and signet ring cell component were recorded by a single pathologist. Cox proportional hazard model was used to compute mortality hazard ratio, adjusting for clinical, pathologic, and tumor molecular features, including microsatellite instability, the CpG island methylator phenotype, long interspersed nucleotide element 1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutations.

Results

Among 1139 colorectal cancers, we observed expansile growth pattern in 372 tumors (33%), intermediate growth pattern in 610 tumors (54%), and infiltrative growth pattern in 157 tumors (14%). Compared to patients with expansile growth pattern, those with infiltrative growth pattern experienced shorter cancer-specific survival (log rank P?P?P _interaction with stage?=?0.0001).

Conclusions

Infiltrative growth pattern was associated with worse prognosis among stage I?CIII colorectal cancer patients, independent of other clinical, pathologic, and molecular characteristics.     

Patterns and Prognostic Significance of Lymph Node Dissection for Surgical Treatment of Perihilar and Intrahepatic Cholangiocarcinoma

Introduction

The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement.

Material and Methods

A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012.

Results

Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients (p?=?0.05) and 42 and 22 months in PCC patients (p?=?0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients (p?=?0.05) and 18 and 43 months in PCC patients (p?=?0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients (p?=?0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients (p?=?0.01); the 0–0.25 group did not reach the value. In PCC patients, median survival of 0, 0–0.25, and >0.25 groups of patients were 42, 23, and 11 months (p?=?0.01), respectively.

Conclusions

LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC.     

Surgical Outcome and Prognostic Factors in Intrahepatic Cholangiocarcinoma

BACKGROUND: The clinicopathologic features and surgical outcome of intrahepatic cholangiocarcinoma are not fully understood. METHODS: Fifty-six consecutive patients with intrahepatic cholangiocarcinoma who underwent surgical resection at the National Cancer Center Hospital East between October 1992 and July 2007 were retrospectively analyzed. Intrahepatic cholangiocarcinomas were subdivided into solitary tumors and tumors with intrahepatic metastasis. RESULTS: Complete tumor removal (R0 resection) was performed in 42 patients (75%). The 5-year survival rate for patients with intrahepatic cholangiocarcinoma (n = 56), patients with a solitary tumor (n = 46), and patients with intrahepatic metastasis (n = 10) were 32, 38, and 0%, respectively. There was a significant difference in survival between patients with a solitary tumor and those with intrahepatic metastasis (p < 0.0001). The 5-year survival rate for patients with stage I (n = 3), II (n = 9), III (n = 15), and IV disease (n = 26) was 100, 67, 37, and 0%, respectively. There was a significant difference in survival between stage I and stage IV (p = 0.011), between stage II and stage IV (p = 0.0002), and between stage III and stage IV (p = 0.0015). The most frequent site of recurrence was the liver. Univariate analysis showed that intrahepatic metastasis, portal vein invasion, hepatic duct invasion, lymph node metastasis, perineural invasion, and positive surgical margin (R1) were significantly associated with poor survival. Multivariate analysis confirmed that intrahepatic metastasis was a significant and independent prognostic indicator after surgical resection for intrahepatic cholangiocarcinoma (p = 0.001). No patient with intrahepatic metastasis survived more than 10 months in this study. CONCLUSIONS: Intrahepatic metastasis was the strongest predictor of poor survival in intrahepatic cholangiocarcinoma.     

A Comparison of Prognostic Schemes for Perihilar Cholangiocarcinoma

Introduction

Although widely used, the 7th edition American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (PHC) may be limited. Disease-specific nomograms have been proposed as a better means to predict long-term survival for individual patients. We sought to externally validate a recently proposed nomogram by Memorial Sloan Kettering Cancer Center (MSKCC) for PHC, as well as identify factors to improve the prediction of prognosis for patients with PHC.

Methods

Four hundred seven patients who underwent surgery for PHC between 1988 and 2014 were identified using an international, multi-center database. Standard clinicopathologic and outcome data were collected. The predictive power of the AJCC staging system and nomogram were assessed.

Results

Median survival was 24.4 months; 3- and 5-year survival was 37.2 and 20.8 %, respectively. The AJCC 7th edition staging system (C-index 0.570) and the recently proposed PHC nomogram (C-index 0.587) both performed poorly. A revised nomogram based on age, lymphovascular invasion, perineural invasion, and lymph node metastases performed better (C-index 0.682). The calibration plot of the revised PHC nomogram demonstrated good calibration.

Conclusion

The 7th edition AJCC staging system and the MSKCC nomogram had a poor ability to predict long-term survival for individual patients with PHC. A revised nomogram provided more accurate prediction of survival, but will need to be externally validated.

     

Perineural Invasion Is a Prognostic Factor in Intrahepatic Cholangiocarcinoma

Background  Perineural invasion is commonly observed in biliary tract cancer and is an independent prognostic factor. Since intrahepatic cholangiocarcinoma (ICC) develops from biliary epithelia in the liver, ICC may share the same characteristics in terms of the prognostic implications of perineural invasion. The aim of this study was to evaluate the clinical significance of perineural invasion in ICC. Methods  A total of 59 patients with ICC who underwent hepatectomy were retrospectively reviewed. The numbers of nerves with and without tumor involvement were counted. The perineural invasion index (PNI) was calculated as the number of involved nerves divided by the total number of nerves examined. Predictors for perineural invasion and prognostic factors were analyzed. Results  Perineural invasion was observed in 47 of 59 (80%) patients, and the median PNI was 0.082. The macroscopic tumor appearance and tumor location were significantly associated with perineural invasion (p = 0.013 and 0.032, respectively). Univariate and multivariate analyses (excluding seven in-hospital deaths) revealed that histologic grade, the presence of perineural invasion, nodal metastasis, and intrahepatic metastasis were independent prognostic factors. The survival rate of the patients with (n = 42) or without (n = 10) perineural invasion was 17 and 80% at 3 years; and 17 and 70% at 5 years, respectively (p = 0.001). Conclusion  Perineural invasion is frequently found in patients with ICC and is an independent prognostic factor. ICC is an aggressive tumor similar to other biliary tract cancers. Because perineural invasion is a histologic marker of aggressiveness, it potentially has a role as a determinant of patient selection for adjuvant therapy.