Drugs targeting TGF-ß/Notch interaction attenuate hypertrophic scar formation by optic atrophy 1-mediated mitochondrial fusion.

Hypertrophic scar (HS) formation is a cutaneous fibroproliferative disease that occurs after skin injuries and results in severe functional and esthetic disability. To date, few drugs have shown satisfactory outcomes for the treatment of HS formation. Transforming growth factor-beta (TGF-ß)/Notch interaction via small mothers against decapentaplegic 3 (Smad3) could facilitate HS formation; therefore, targeting TGF-ß/ Notch interaction via Smad3 is a potential therapeutic strategy to attenuate HS formation. In addition, optic atrophy 1 (OPA1)-mediated mitochondrial fusion contributes to fibroblast proliferation, and TGF-ß/Smad3 axis and the Notch1 pathway facilitate OPA1-mediated mitochondrial fusion. Thus, the aim of this study was to investigate whether drugs targeting TGF-ß/Notch interaction via Smad3 suppressed fibroblast proliferation to attenuate HS formation through OPA1-mediated mitochondrial fusion. We found that the TGF-ß pathway, Notch pathway, and TGF-ß/Notch interaction via Smad3 were inhibited by pirfenidone, the gamma- secretase inhibitor DAPT, and SIS3 in human keloid fibroblasts (HKF) and an HS rat model, respectively. Protein interaction was detected by co-immunoprecipitation, and mitochondrial morphology was determined by electron microscopy. Our results indicated that pirfenidone, DAPT, and SIS3 suppressed the proliferation of HKFs and attenuated HS formation in the HS rat model by inhibiting TGF-ß/Notch interaction via Smad3. Moreover, pirfenidone, DAPT, and SIS3 hindered OPA1-mediated mitochondrial fusion through inhibiting TGF-ß/Notch interaction, thereby suppressing the proliferation of HS fibroblasts and HS formation. In summary, these findings investigating the effects of drugs targeting TGF-ß/Notch interaction on HS formation might lead to novel drugs for the treatment of HS formation.

Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma: Validation in a Chinese cohort.

AIM: The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh (C-P) score in predicting prognosis in this study. METHODS: The clinical data of 491 C-P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C-P score in predicting the short- and long-term clinical outcomes were compared. RESULTS: The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months, the 1-year, 3-year, and 5-year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C-P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test. CONCLUSIONS: The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well-designed studies with larger sample sizes are warranted.

Total tumor volume predicts survival following liver resection in patients with hepatocellular carcinoma.

Assessing the prognosis of patients with hepatocellular carcinoma (HCC) by the number and size of tumors is sometimes difficult. The main purpose of the study was to evaluate the prognostic value of total tumor volume (TTV), which combines the two factors, in patients with HCC who underwent liver resection. We retrospectively reviewed 521 HCC patients from January 2001 to December 2008 in our center. Patients were categorized using the tertiles of TTV. The prognostic value of TTV was assessed. With a median follow-up of 116 months, the 1-, 3-, and 5-year overall survival (OS) rates of the patients were 93.1 , 69.9, and 46.3 %, respectively. OS was significantly differed by TTV tertile groups, and higher TTV was associated with shorter OS (P < 0.001). Multivariate analysis revealed that TTV was an independent prognostic factor for OS. Larger TTV was significantly associated with higher alpha-fetoprotein level, presence of macrovascular invasion, multiple tumor lesions, larger tumor size, and advanced tumor stages (all P < 0.05). Within the first and second tertiles of TTV (TTV ≤ 73.5 cm(3)), no significant differences in OS were detected in patients within and beyond Milan criteria (P = 0.183). TTV-based Cancer of the Liver Italian Program (CLIP) score gained the lowest Akaike information criterion value, the highest χ (2) value of likelihood ratio test, and the highest C-index among the tested staging systems. Our results suggested that TTV is a good indicator of tumor burden in patients with HCC. Further studies are warranted to validate the prognostic value of TTV.

Impaction of surgical margin status on the survival outcome after surgical resection of intrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

BACKGROUND: Conflicting results about the prognostic value of surgical margin status in patients with intrahepatic cholangiocarcinoma (ICC) have been reported. We aimed to assess the association between surgical margin status and prognosis in ICC through a meta-analysis. MATERIALS AND METHODS: We conducted a literature search of the articles evaluating the prognostic value of surgical margin status in patients with ICC. The pooled estimation of the hazard ratio (HR) with the 95% confidence interval (CI) was performed to determine the influence of surgical margin status on the survival outcome. RESULTS: A total of 21 studies involving 3201 patients were finally included into the meta-analysis. The percentage of patients with positive surgical margin ranged from 7.2% to 75.9% in the enrolled studies. The pooled estimates showed that patients with positive surgical margin had inferior overall survival (HR: 1.864; 95% CI: 1.542-2.252; P < 0.001) and progression-free survival (HR: 2.033; 95% CI: 1.030-4.011; P = 0.041) than patients with negative ones. The subgroup analyses and sensitivity analyses were consistent with the overall results. CONCLUSIONS: Patients with negative surgical margin had significantly favorable overall survival and progression-free survival after surgical resection for ICC. The notion of achieving the R0 resection should be emphasized.

[Clinicopathological and prognostic analysis of primary clear cell carcinoma of the liver].

OBJECTIVE: To investigate the clinicopathological features and prognostic factors of primary clear cell carcinoma of the liver (PCCCL). METHODS: The clinical data of 41 PCCCL patients who underwent hepatic resection for PCCCL from October 1998 to June 2012 in our department were retrospectively analyzed. There were 31 male and 10 female patients. The median age was 56 years (range, 25 to 80 years), and the diagnosis was confirmed by postoperative pathological examination. The data of 106 well or moderately differentiated non-clear cell hepatocellular carcinoma (HCC) patients and 86 poorly differentiated non-clear cell HCC patients who underwent hepatic resection in the same period in our hospital in the same period were compared. The χ(2) test or Fischer's exact test, as appropriate, was used to compare group frequencies. Survival analysis was estimated by Kaplan-Meier method. Cox proportional hazards model was used in multivariate analysis. RESULTS: The proportion of fibrous capsule formation in the PCCCL tumors (46%, 19/41) was significantly higher than that of the other two groups (P < 0.05), whereas the PCCCL group had a lower rate of intravascular tumor embolus (2/41) and vascular invasion (1/41) (P < 0.05). The median survival time of PCCCL group was 65 months, the 1-, 3-, 5-year survival rates for PCCCL patients were 90.2%, 67.4% and 42.0%, significantly better than that of poor differentiated NCCHCC group's (82.9%, 33.3%, 7.2%, P < 0.01). However, there were no statistic significant differences between PCCCL group and well or moderately differentiated NCCHCC group (84.7%, 55.7%, 34.4%, P > 0.05). Tumor capsule formation was an independent favorable prognostic factor. In contrast, preoperative serum α-fetoprotein (AFP) level and hepatitis B virus infection were independent unfavorable prognostic factors for PCCCL. CONCLUSIONS: PCCCL is a rare, low degree malignant pathological subtype of HCC. Surgical resection may achieve favorable prognosis and even long-term survival.

[Prognosis of hepatocellular carcinoma: a study of 832 cases].

OBJECTIVE: To investigate the prognostic factors of hepatocellular carcinoma. METHODS: The purpose of this study was to retrospectively analyze the surgical outcomes of hepatocellular carcinoma (HCC) in 832 patients who underwent hepatic resection between February 2002 and June 2010 in the Cancer Hospital of Chinese Academy of Medical Sciences. Post-resection prognostic factors were assessed using a univariate Kaplan-Meier analysis and a multivariate Cox proportional hazards model. RESULTS: The overall 1-, 3- and 5-year survival rates were 92.0%, 70.2% and 53.6%, respectively. The disease free survival rates (DFS) were 90.2%, 61.5% and 40.5%, respectively. The univariate analysis showed that a better prognosis for overall survival (OS) was associated with asymptomatic presentation, small tumor, single lesion, high-grade histological differentiation, no vascular tumor embolus, negative serum alpha-fetoprotein (AFP), negative serum alkaline phosphatase (ALP), Child-Pugh class A, no ascites, no/mild cirrhosis, new surgical techniques, no blood transfusion, no regional lymph node metastasis, no major vascular invasion, and no extra-hepatic invasion. The multivariate analysis showed that asymptomatic presentation, small tumor, single lesion, no tumor embolus, negative serum alpha-fetoprotein (AFP), no regional lymph node metastasis, no major vascular invasion, no extra-hepatic invasion, no/mild cirrhosis, and surgical techniques are independent factors for a longer overall survival. CONCLUSIONS: The prognosis of HCC after resection is influenced by a number of factors. Therefore, regularly screening and early diagnosis, applying surgical techniques to minimize the liver injury, and preventing the aggravation of cirrhosis are important measures to improve the overall survival of HCC patients. For those patients with high risk factors of recurrence, routine follow-up is one of the best methods to be recommended.

[Surgical management of nodular hyperplasia tumor-like hepatic lesions: a study of 72 cases].

OBJECTIVE: To explore and improve the diagnosis and treatment of benign hyperplasia tumor-like hepatic lesion. METHODS: The clinical data of 72 patients who had undergone hepatic resection for benign non-cystic hepatic lesions between January 1987 and December 2010 were analyzed retrospectively. There were 46 male and 26 female patients. The median age was 49 years (ranging 15 to 72 years), and diagnosis were confirmed by postoperative pathological examination. Thirty-four cases had symptoms, such as abdominal discomfort in right upper quadrant, fever, fatigue. All the cases had undergone hepatic resection; totally 78 lesions were removed. The surgical procedure including hepatic lobectomy for 13 cases, hepatic segmentectomy for 19 cases and non-anatomy resection for 39 cases. RESULTS: The finally diagnosis included focal nodular hyperplasia in 47 cases, adenomatous hyperplasia in 3 cases, hepatic dysplastic nodule in 3 cases, inflammatory pseudotumor in 3 cases, hepatic granuloma in 4 cases, nodular cirrhosis in 3 cases, hepatitis nodule in 6 cases, nodular regenerative hyperplasia in 1 case, lymphoid hyperplasia in 1 case. The postoperative complication rate was low (19.4%, 14/72). The follow-up period was 6 to 96 months. There was no mortality caused by lesion. One patient developed recurrence after 3 years. CONCLUSIONS: It is suggested that symptomatic lesions, lesions when malignancy cannot be excluded, and lesions which have canceration tendency, just like adenomatous hyperplasia, dysplastic nodule, and nodular cirrhosis regenerative hyperplasia need surgical resection. Operation is not necessary for other nodular hyperplasia lesions if the diagnoses are identified.

Impact of hepatitis B virus infection on outcome following resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Little is known about the prognosis of intrahepatic cholangiocarcinoma (ICC) patients with hepatitis B virus (HBV) infection following surgical resection. METHODS: The clinico-pathological data of 40 consecutive ICC patients including 29 patients with HBV infection were analyzed after surgical resection. RESULTS: Of all 40 ICC patients, the overall 1-, 3-, 5-year survival rates and a median survival for 29 (74.4%) patients with current or previous HBV infection were 78.9%, 42.8%, 35.7%, and 32.0 months, respectively. Twenty-nine (74.4%) patients with HBV infection, represented by HBsAg(+) or anti-HBc(+), had a better prognosis than 10(25%) patients without HBV infection represented by all markers-negative. Compared with 10 (25%) patients without HBV infection, 11 (27.5%) ICC patients with HBsAg(+) had a better prognosis as well. Additionally, lymph node metastasis were identified as an independent predictors of poor overall survival on multivariate analysis in the study of all the 40 patients and 29 patients with HBV infection. CONCLUSIONS: Patients with current or previous HBV infection, represented by HBsAg+ or anti-HBc+, had significantly better prognosis than patients without HBV infection. Patients with HBV infection should be distinguished from other ICC patients, because of their favorable outcome after surgery.

[Peri-operative treatment for hepatocellular carcinoma patients complied with cirrhosis and hypersplenism].

OBJECTIVE: To investigate the influence of combined hepatectomy with splenectomy on safety of operation for hepatocellular carcinoma patients complied with cirrhosis and hypersplenism and the best peri-operative treatment of these patients. METHODS: Clinical data of 177 hepatocellular carcinoma patients complied with cirrhosis and hypersplenism admitted from January 1999 to December 2009 were analyzed retrospectively. Among which, 71 patients received concomitant splenectomy with hepatectomy (splenectomy group), 106 patients only receive a hepatectomy (non-splenectomy group). The safety of operation, complications, liver function and WBC and PLT counts were compared between the two groups. RESULTS: There was no significant difference of general conditions, counts of WBC and PLT between the two groups before operation. The counts of PLT at 1, 10, 30 day after operation were (88.4 ± 23.6) × 109/L, (345.3 ± 98.2) × 109/L and (210.8 ± 92.2) × 109/L respectively in splenectomy group, which were significantly higher than that of non-splenectomy group (P < 0.05). The operation time of splenectomy group was (216 ± 105) min, which was longer than that of non splenectomy group (P < 0.05), but the blood loss and transfusion rate had not significantly difference between the two groups. The complication rates of splenectomy group and non-splenectomy group were 11.3% and 6.6% respectively, there was no significant difference between the two groups. CONCLUSION: Combined hepatectomy with splenectomy will be safe for hepatocellular carcinoma patients complied with cirrhosis and hypersplenism as if the operative indication and increase the ability of peri-operative treatment are strictly obeyed.

Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study.

Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory, but the effect of postoperative transarterial chemoembolization (p-TACE) remains controversial. This multi-center retrospective study was to evaluate the clinical value of p-TACE and identify the selected patients who would benefit from p-TACE. Methods: Data of ICC patients who underwent radical resection with/without p-TACE therapy was obtained from 12 hepatobiliary centers in China between Jan 2014 and Jan 2017. Overall survival (OS) was set as the primary endpoint, which was analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Subgroup analysis was conducted based on the established staging system and survival risk stratification. Results: A total of 335 patients were enrolled in this study, including 39 patients in the p-TACE group and 296 patients in the non-TACE group. Median OS in the p-TACE group was longer than that in the non-TACE group (63.0 months vs. 18.0 months, P=0.041), which was confirmed after 1:1 PSM (P=0.009). According to the 8th TNM staging system, patients with stage II and stage III stage would be benefited from p-TACE (P=0.021). Subgroup analysis stratified by risk factors showed that p-TACE could only benefit patients with risk factors <2 (P=0.027). Conclusion: Patients with ICC should be recommended to receive p-TACE following radical resection, especially for those with stage II, stage III or risk factors <2. However, the conclusion deserved further validation.

[Analysis of prognostic factors influencing the outcome of intrahepatic cholangiocarcinoma].

OBJECTIVE: To analyze the clinicopathologic factors influencing the outcome of surgically treated intrahepatic cholangiocarcinoma (ICC) and to explore the proper treatment choice of ICC. METHODS: The clinicopathological data of 43 surgically treated ICC patients in our hospital were retrospectively analyzed. Of the 43 patients, hepatic resection was performed in 40 patients, ethanol injection in 2, and laparoscopic exploration alone in 1. Kaplan-Meier method and Cox regression model were used for the analysis of factors influencing survival after operation. RESULTS: The accumulative 1-, 3- and 5-year survival rates were 64.4%, 30.9%, 25.8% for the whole group, and 74.7%, 33.3%, 27.8% for the 40 patients with hepatic resection, respectively. Univariate analysis revealed that tumor size, carcinoembryonic antigen (CEA) level, lymph node involvement and TNM stage were factors significantly affecting the survival (P < 0.05). Cox multivariate analysis demonstrated that only tumor size and lymph node involvement were the independent factors significantly affecting the survival (P < 0.05). CONCLUSION: Our results show that tumor size and lymph node involvement are independent factors affecting the survival. CEA level and TNM stage are important prognostic factors for surgical management. Radical resection is still the optimal treatment for patient with intrahepatic cholangiocarcinoma.

A Low Neutrophil to Lymphocyte Ratio Before Preoperative Chemotherapy Predicts Good Outcomes After the Resection of Colorectal Liver Metastases.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is a marker of inflammation and is associated with poor outcomes. We aimed to evaluate the role of the pretreatment NLR in predicting the outcomes after preoperative chemotherapy in patients with colorectal liver metastases (CRLM). METHODS: A retrospective review was performed for 183 patients with CRLM. The NLR was measured before chemotherapy, and a receiver operating characteristic (ROC) curve was used to estimate the cutoff value. Logistic regressions were applied to analyze potential predictors of the pathological response. The Cox proportional hazard method was used to analyze survival. RESULTS: The pre-chemotherapy NLR was 2.4 ± 1.1, whereas the post-chemotherapy NLR was 2.1 ± 1.6 (p < 0.001). The pretreatment NLR of 2.3 was a significant predictive marker for the pathological response. The pathological response rates were 67.1% in the patients with an NLR ≤ 2.3 and 48.1% in patients with an NLR > 2.3 (p = 0.01). Multivariate analysis revealed that the factors independently associated with pathological responses were a low pretreatment NLR (p = 0.043), radiological response to chemotherapy (p < 0.001), first-line chemotherapy (p = 0.001), and targeted therapy (p = 0.002). The median overall survival (OS) and recurrence-free survival (RFS) were worse in the increased NLR cohort than in the low NLR cohort (OS: 31.1 vs. 43.1 months, p = 0.012; RFS: 6.5 vs. 9.4 months, p = 0.06). According to multivariate analyses, a high pretreatment NLR was a significant predictor for both worse OS (HR = 2.43, 95%CI = 1.49-3.94, p < 0.001) and RFS (HR = 1.53, 95%CI = 1.08-2.18, p = 0.017). CONCLUSIONS: An increased pretreatment NLR was a significant predictor of a poor pathological response and worse prognosis after preoperative chemotherapy. The NLR is a simple biomarker for assessing chemotherapy efficacy.

Resectable recurrent colorectal liver metastasis: can radiofrequency ablation replace repeated metastasectomy?

BACKGROUND: Percutaneous radiofrequency ablation (RFA) is used as a first-line treatment for colorectal liver metastases that recur after first liver resection in our institution. We aim to evaluate its therapeutic efficacy compared to repeated surgical resection. METHODS: A retrospective review was performed in 104 patients treated with curative intent for resectable recurrent colorectal liver metastases. RESULTS: Sixty-one patients underwent RFA and 43 patients underwent surgery. The overall recurrence rates were 82% in the RFA group and 65.1% in the resection group (P = 0.05). The local recurrence rate on a lesion-basis was markedly higher after RFA than that after resection (16.7% versus 7.3%, P = 0.04). The difference remained significant in patients with a maximum lesion diameter >3 cm (24.5% versus 7.6%, P = 0.01). RFA treatment was independently associated with recurrence on multivariate analyses (P = 0.01). 69.7% of RFA patients and 42.6% of surgery patients with intrahepatic recurrence were amenable to repeated local treatment (P = 0.05), leading to the equivalent actuarial 3-year progression free survival rates (RFA: 29.1% versus Resection: 33.1%, P = 0.48) and 5-year overall survival rates in the two treatment groups (RFA: 33% versus Resection: 28.4%, P = 0.36). CONCLUSIONS: Surgery remains the treatment of choice for resectable recurrence. RFA may offer similar benefit in selected patients.

Establishment of a sandwich ELISA method for detection of vascular endothelial growth factor in serum samples of hepatocellular carcinoma patients.

OBJECTIVE: To establish a sandwich ELISA method for detecting vascular endothelial growth factor (VEGF) in sera of population and the patients with hepatocellular carcinoma (HCC). METHODS: Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coli in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein G, a sandwich ELISA technique was established. Serum VEGF levels were evaluated in 229 adults and 291 HCC patients. RESULTS: SDS-PAGE displayed that the molecular weights of the expressed full length (His-Trx-VEGF1-165), N-terminal (His-Trx-VEGF1-100) and C-terminal (GST-VEGF100-165) human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R2 = 0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference. CONCLUSION: The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index.

[Diagnosis,treatment, and prognostic of liver sarcoma: analysis of 16 cases].

OBJECTIVE: To explore the diagnosis, treatment, and prognostic factors of liver sarcoma. METHODS: The clinical data of 16 liver sarcoma patients, 9 males and 7 females, aged 46.7 (12-73), treated 1980-2005, were analyzed retrospectively. RESULTS: The most common symptoms were right upper quadrant pain (56.3%) and mass in the right upper abdomen (56.3%). Alpha fetoprotein (AFP) was negative in all the patients. None was correctly diagnosed by imaging examination preoperatively. Fifteen patients underwent surgical treatment, including radical operation in 7 patients (46.7%) and palliative resection/biopsy in 8 patients. 1 patient took transcatheter hepatic arterial chemo-embolization rather than operation because of multifocal tumor. Pathological analysis diagnosed 6 patients (37.5%) as with leiomyosarcoma, 5 patients (31.25%) with angiosarcoma, 2 patients (12.5%) with fibrosarcoma, 1 patient (12.5%) with epithelioid hemangioendothelioma, 1 patient (12.5%) with myxoid liposarcoma, and 1 patient (12.5%) with undifferentiated embryonal sarcoma. The 1-year, 3-year, and 5-year survival rates were 71.4%, 41.7%, and 33.3% respectively. The 1-year, 3-year, and 5-year survival rates of the patients who received R0 were 100.0%, 83.3%, and 66.7% respectively, all significantly higher than those of the patients who did not receive R0 (all P = 0.011). The 1-year, 3-year, and 5-year survival rates of the patients with the tumor size < 5 cm were 100%, 100%, and 75% respectively, all higher than those of the patients with the tumor size > 5 cm, however, not significantly (all P = 0.084). CONCLUSION: Liver sarcoma is difficult to be diagnosed preoperatively. Surgical resection is the mainstay of the treatment of liver sarcoma. R0 and tumor size are of prognostic values.

[Clinical application of anatomic method of separation in hepatectomy].

OBJECTIVE: To investigate the effectiveness of anatomic method of separation in hepatectomy methods of decreasing postoperative complication and mortality for liver cancer patients. METHODS: The clinical data of 398 patients with liver malignant tumors, admitted in our hospital during 2001 to 2007, were retrospectively analyzed. The anatomic method group (group A) included 243 contiguous patients of liver cancer who received hepatectomy by anatomical method of separation, while the traditional method group (group B) included 155 patients of liver cancer who received hepatectomy by traditional method of separation during the same period. Blood loss and transfusion during operation, postoperative liver function, complication and mortality of operation, and postoperative hospital stay were compared between these two groups. RESULTS: In group A, the tumor diameters ranged (6.02 +/- 3.24) cm, the operative blood loss was (445 +/- 240) ml, and 52 patients (24.3%) underwent blood transfusion [range: (520 +/- 280) ml]. No mortality and intraabdominal hemorrhage, liver function failure, or other severe complications were noted. Only 12 patients (4.9%) suffered mild complications. The postoperative hospital stay was (13.4 +/- 4.9) days. In group B, the tumor diameters ranged (5.84 +/- 2.93 cm, the operative blood loss was (1200 +/- 320) ml, and 53 patients (34.2%) underwent transfusion [range: (1400 +/- 623) ml]. Five patients (3.23%) died within 30 days after operation. The total complication morbidity was 16.1% (25/155). Five patients suffered intraabdominal hemorrhage and 5 experienced liver function failure. Postoperative hospital stay was (18.9 +/- 10.3) days. The volume of blood loss and transfusion in group A were significantly less than in group B (P < 0.05). Mortality, severe complications, and total complication morbidity were significantly lower in group A than in group B (P < 0.05, P < 0.01). The postoperative stay was also significantly shorter in group A than in group B (P < 0.05). CONCLUSION: Anatomical method of separation is an effective method of hepatectomy with relatively low complication and mortality.

Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. PATIENTS AND METHODS: This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. RESULTS: The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). CONCLUSION: Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and shortens OS.

Interaction of margin status and tumour burden determines survival after resection of colorectal liver metastases: A retrospective cohort study.

PURPOSE: We sought to determine the impact of surgical margin status on overall survival (OS) and recurrence pattern stratified by tumor burden. MATERIALS AND METHODS: Data were collected from patients undergoing resection for colorectal liver metastases (CRLM). Tumor burden was calculated according to a newly proposed Tumor Burden Score (TBS) system, defined as the distance from the origin on a Cartesian plane that incorporated maximum tumor size and number of liver lesions. Patients were divided into low tumor burden group and high tumor burden group accordingly, and the impact of resection margin on overall survival was examined. RESULTS: A total of 286 patients were available, among which R1 resection was observed in 88 patients. The median TBS for the entire cohort was 3.84. Metastases in the R1 group were characterized by more advanced disease and more complex resections. Compared with a R0 resection, a R1 resection offered an lower 5-year overall survival rate (46.8% vs. 22.1%, p = 0.001). Multivariate analysis identified R1 resection (p = 0.03), high TBS (p = 0.002), lymph nodes metastases (p = 0.003) and lymphovascular invasion (p = 0.03) of the primary colorectal tumor as the factors independently associated with worse survival. The survival benefit associated with negative margins was greater in patients with low TBS (55.7% vs. 21.7%, p = 0.021) than in patients with high TBS (31.8% vs. 24.5%, p = 0.116). R1 resection was associated with an increased true margin recurrence rate in patients with low TBS (32.3% vs. 13.4%; p = 0.014) and an increased risk of new intrahepatic metastases in patients with high TBS (43.9% vs. 26.7%; p = 0.034). CONCLUSIONS: Negative margin is an important determinant of survival. The impact of positive margins is more pronounced in patients with low tumor burden.

Non-response to preoperative chemotherapy is a contraindication to hepatectomy plus radiofrequency ablation in patients with colorectal liver metastases.

The long-term outcome of 228 patients with colorectal liver metastases (CRLM) who underwent preoperative chemotherapy followed by hepatectomy ± RFA were retrospectively analyzed. Stratified by chemotherapy response, patients were divided into responding (n=129) and non-responding groups (n=99). Patients who underwent hepatectomy-RFA had a greater number of metastases (median of 4 vs. 2, p=0.000), a higher incidence of bilobar involvement (66.7% vs. 49.1%, p=0.014) and longer chemotherapy cycles (median of 6 vs. 4, p=0.000). In the responding group, the median overall survival (OS) and recurrence free survival (RFS) of hepatectomy-RFA and the hepatectomy alone subgroups were comparable (38.6 months vs. 43.2 months, p=0.824; 8.2 months vs. 11.4 months, p=0.623). In the non-responding group, the median OS and RFS of patients treated with hepatectomy-RFA were significantly shorter (18.5 months vs. 34.2 months, p=0.000; 5.1 months vs. 5.9 months, p=0.002). RFA was identified as the unfavorable independent factor for both OS (HR=3.60, 95%CI=1.81-7.16, p=0.039) and RFS (HR=1.70, 95%CI=1.00-2.86, p=0.048) in non-responsive patients. Local recurrence rate after hepatectomy-RFA was higher in the non-responding group (48.1% vs. 23.6%, p=0.018). Non-response to preoperative chemotherapy may be a contraindication to hepatectomy-RFA in patients with CRLM.