Preoperative prognostic nutritional index predicts postoperative infectious complications and oncological outcomes after hepatectomy in intrahepatic cholangiocarcinoma.

BACKGROUND: In the surgical treatment of intrahepatic cholangiocarcinoma (ICC), postoperative complications may be predictive of long-term survival. This study aimed to identify an immune-nutritional index (INI) that can be used for preoperative prediction of complications. PATIENTS AND METHODS: Multi-institutional data from 316 patients with ICC who had undergone surgical resection were retrospectively analysed, with a focus on various preoperative INIs. RESULTS: Severe complications (Clavien-Dindo grade III-V) were identified in 66 patients (20.8%), including Grade V complications in 7 patients (2.2%). Comparison of areas under the receiver operating characteristic curve (AUCs) among various INIs identified the prognostic nutritional index (PNI) as offering the highest predictive value for severe complications (AUC = 0.609, cut-off = 50, P = 0.008). Multivariate analysis revealed PNI <  50 (odds ratio [OR] = 2.22, P = 0.013), hilar lesion (OR = 2.46, P = 0.026), and long operation time (OR = 1.003, P = 0.029) as independent risk factors for severe complications. In comparing a high-PNI group (PNI ≥ 50, n = 142) and a low-PNI group (PNI <  50, n = 174), the low-PNI group showed higher rates of both major complications (27% vs. 13.4%; P = 0.003) and infectious complications (14.9% vs. 3.5%; P = 0.0021). Furthermore, median survival time and 1- and 5-year overall survival rates were 34.2 months and 77.4 and 33.8% in the low-PNI group, respectively, and 52.4 months and 89.3 and 47.5% in the high-PNI group, respectively (P = 0.0017). CONCLUSION: Preoperative PNI appears useful as an INI correlating with postoperative severe complications and as a prognostic indicator for ICC.

Prognostic Utility of the Glasgow Prognostic Score for the Long-Term Outcomes After Liver Resection for Intrahepatic Cholangiocarcinoma: A Multi-institutional Study.

OBJECTIVE: The usefulness of the modified Glasgow prognostic score (GPS) as a prognostic tool remains unclear for patients undergoing curative surgery for intrahepatic cholangiocarcinoma (ICC). Therefore, this study investigated the prognostic usefulness of the GPS for patients who underwent ICC surgery. METHOD: All ICC patients who had a curative-intent hepatectomy at 17 institutions between 2000 and 2016 were included. The correlation was assessed between the preoperative GPS and the baseline characteristics of the patients, histopathological parameters, surgical parameters, and the postresection overall survival (OS). RESULT: There were 273 patients who met the eligibility criteria between the years 2000 and 2016. The postoperative OS rates at 1, 3, and 5 years were 83.8%, 56.3%, and 41.5%, respectively (median OS, 47.7 months). A multivariate analysis revealed the factors that were associated with a worse OS, which included an increased GPS (hazard ratio = 1.62; 95% confidence interval [CI]: 1.01-2.53; P = 0.03), an elevated carcinoembryonic antigen level (hazard ratio = 1.60; 95% CI: 1.06-2.41; P = 0.02), an elevated carbohydrate antigen 19-9 level (hazard ratio = 1.55; 95% CI: 1.05-2.30; P = 0.03), undifferentiated carcinoma (hazard ratio = 2.41; 95% CI: 1.56-3.67; P < 0.01), and positive metastasis to the lymph nodes (hazard ratio = 2.54; 95% CI: 1.76-3.67; P < 0.01). In ICC patients after a hepatectomy, an elevated GPS was associated with poorer OS, even if the tumour factors that affected GPS were eliminated by propensity-score matching. CONCLUSION: Preoperative GPS can be useful to predict the postoperative outcomes of ICC patients. Therefore, this relatively simple and inexpensive scoring system can be utilized to further refine patient stratification as well as to predict survival.

Efficacy of surgical management for recurrent intrahepatic cholangiocarcinoma: A multi-institutional study by the Okayama Study Group of HBP surgery.

BACKGROUND: The prognosis of intrahepatic cholangiocarcinoma (ICC) has been poor, because of the high recurrence rate even after curative surgery. This study aimed to evaluate the prognostic impact of surgical resection of recurrent ICC. PATIENTS AND METHODS: A total of 345 cases of ICC who underwent hepatectomy with curative intent in 17 institutions were retrospectively analyzed, focusing on recurrence patterns and treatment modalities for recurrent ICC. RESULTS: Median survival time and overall 5-year recurrence-free survival rate were 17.8 months and 28.5%, respectively. Recurrences (n = 223) were classified as early (recurrence at ≤1 year, n = 131) or late (recurrence at >1 year, n = 92). Median survival time was poorer for early recurrence (16.3 months) than for late recurrence (47.7 months, p<0.0001). Treatment modalities for recurrence comprised surgical resection (n = 28), non-surgical treatment (n = 134), and best supportive care (BSC) (n = 61). Median and overall 1-/5-year survival rates after recurrence were 39.5 months and 84.6%/36.3% for surgical resection, 14.3 months and 62.5%/2.9% for non-surgical treatment, and 3 months and 4.8%/0% for BSC, respectively (p<0.0001). Multivariate analysis identified early recurrence, simultaneous intra- and extrahepatic recurrence, and surgical resection of recurrence as significant prognostic factors. In subgroup analyses, surgical resection may have positive prognostic impacts on intra- and extrahepatic recurrences, and even on early recurrence. However, simultaneous intra- and extrahepatic recurrence may not see any survival benefit from surgical management. CONCLUSION: Surgical resection of recurrent ICC could improve survival after recurrence, especially for patients with intra- or extrahepatic recurrence as resectable oligo-metastases.

Effects of adenoviral-mediated hepatocyte growth factor on liver regeneration after massive hepatectomy in rats.

Resection is the only curative treatment for liver metastasis of colorectal cancers. Despite the supreme regenerative potential of the liver, major hepatectomy sometimes leads to liver failure, and the limitation of resectable liver volumes makes advanced tumors inoperable. This study was attempted to promote liver regeneration using hepatocyte growth factor (HGF) gene transfection by venous-administered adenovirus and to improve the survival of rats after massive hepatectomy. The adenovirus that encodes HGF was administered to rats before 85%-hepatectomy. The administration of HGF gene improved the survival of rats after massive hepatectomy, while the administration of control adenovirus deteriorated their survival. Gene transfection of HGF showed up-regulation of serum HGF, stimulation of hepatocellular proliferation and rapid liver regeneration. Moreover, HGF administration reduced apoptosis of hepatocytes. The administration of HGF gene prevented liver dysfunction after major hepatectomy and may be a new assist for surgery.

Thymidine phosphorylase and dihydropyrimidine dehydrogenase expression levels in tumor and normal tissue specimens of T3 human colorectal carcinoma.

PURPOSE: Thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are important enzymes related to the metabolism of 5-fluorouracil and its derivatives. We evaluated the association between the clinicopathological factors and these enzymes in patients with T3 colorectal carcinoma. METHODS: The TP and DPD expression levels in 15 patients with T3 colorectal carcinomas were measured in tumor and adjacent normal tissue specimens by enzyme-linked immunosorbent assay. Correlations between each enzyme and clinicopathological factors were also statistically evaluated. RESULTS: The TP levels in tumor and normal tissue specimens were 77.9 +/- 33.6 and 24.7 +/- 10.3, respectively (P < 0.001). The DPD levels in tumor and normal tissue specimens were 44.1 +/- 18.2 and 53.1 +/- 24.1, respectively (P = 0.46). The TP/DPD ratios in tumor and normal tissue specimens were 1.84 +/- 0.52 and 0.53 +/- 0.26, respectively (P < 0.001). The tumor/normal ratios of TP level in patients with and without liver metastasis were 1.79 +/- 0.91 and 4.67 +/- 2.51, respectively (P = 0.024). CONCLUSION: The measurement of the enzyme expression levels of TP and DPD is considered to be useful for better understanding the conditions of tumor progression. The mechanisms of regulation of these enzymes thus require further evaluation.

Gefitinib decreases the synthesis of matrix metalloproteinase and the adhesion to extracellular matrix proteins of colon cancer cells.

BACKGROUND: Adhesion to extracellular matrix (ECM) proteins and degradation of basement membranes by matrix metalloproteinase (MMP) play important roles in cancer metastasis. In this study, the effects of gefitinib on the enzymatic activity of MMP and adhesion to ECM proteins in the HT29 colon cancer cell line were investigated. MATERIALS AND METHODS: Microtiter plates, coated with ECM proteins, were used to investigate the adhesion of cancer cells to ECM proteins. The expression of MMPs was examined by zymography and semiquantitative RT-PCR. RESULTS: Gefitinib inhibited MMP-9 and MMP-2 secretion and mRNA expression in HT29 cells. Gefitinib also reduced the ability to adhere to laminin and type IV collagen. These effects were observed at such low doses that gefitinib had neither an antiproliferative effect nor the ability to induce apoptosis. CONCLUSION: Gefitinib decreased the production of MMPs and the adhesion to ECM proteins, important steps associated with cancer metastasis. These results suggest that gefitinib may have antimetastatic activity in colon cancer.

Biliary reconstruction with right hepatic lobectomy due to delayed management of laparoscopic bile duct injuries: a case report.

We report a case requiring biliary reconstruction with right hepatic lobectomy due to biliary strictures caused by continuous cholangitis after laparoscopic bile duct injury. The patient, a 55-year-old woman, underwent laparoscopic cholecystectomy for cholelithiasis at another hospital. Although a bile leakage from the intraabdominal drain was observed several days after the operation, the patient was not given adequate treatment to stop the leakage. Two months after the initial laparoscopic cholecystectomy, she was referred to our hospital. Endoscopic retrograde cholangiopancreatography (ERCP) showed complete obstruction of the common hepatic duct, which was caused by clipping during laparoscopic cholecystectomy. Cholangiography from percutaneous transhepatic biliary drainage (PTBD) catheters revealed that sections of the secondary branches of the right intrahepatic bile duct had become constricted due to persistent cholangitis. Fortunately, the left hepatic duct was judged to be normal by imaging. Therefore, we elected to perform a right hepatic lobectomy and left hepaticojejunostomy, because we felt that performing a hepaticojejunostomy without hepatic resection would put the patient at risk of continuing to suffer from cholangitis. The patient was discharged on the 55 th postoperative day, and, 5 years after reconstructive surgery, is healthy and has remained free from biliary strictures in the remnant liver. Appropriate decision-making is essential in the treatment of biliary injury after laparoscopic cholecystectomy. Surgeons should not hesitate to perform biliary reconstruction with hepatic resection to reduce the risk of cholangitis or biliary strictures of the remnant liver. More importantly, preoperative clear imaging of the biliary tree and suitable management of any biliary injury which might occur are necessary to avoid having to perform reconstructive surgery.

nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation.

The nm23-H1 gene is known as a potential metastasis suppressor gene in various types of carcinomas. However, the role of nm23-H1 in colorectal carcinoma still remains controversial and the cellular mechanisms by which its protein may modulate the metastatic phenotype are not yet known. We transfected nm23-H1 cDNA into the human colon cancer cell line, HT-29, to test the effects and cellular biological mechanism of nm23 protein in colon cancer. We found that nm23-H1 strongly inhibited the liver metastasis of HT-29 cells in nude mice and inhibited the epidermal growth factor (EGF)-induced cell migration in vitro. Furthermore, we clarified the regulation of the myosin light chain (MLC) phosphorylation by nm23-H1, which has been demonstrated as having potential role in cell migration.

The transfection of thymidylate synthase antisense suppresses oncogenic properties of a human colon cancer cell line and augments the antitumor effect of fluorouracil.

5-Fluorouracil (5-FU), a fluoropyrimidine analogue, is one of the most commonly used anticancer drugs for the treatment of gastrointestinal malignancies. Some studies reported that the cytotoxicity of fluoropyrimidines is mediated, in large part, by inhibition of the thymidylate synthase (TS), an essential DNA synthetic enzyme. The aim of this study was to determine if antisense TS technology could augment the chemosensitivity of human cancer cells to 5-FU. The full length coding region of TS cDNA was inversely cloned into the eukaryotic expression vector pCDL81 and transfected into DLD-1 cells. The expression and activity of TS were significantly suppressed in the antisense TS transfected cells. Interestingly, the transfection of antisense TS alone inhibited the cellular growth in vitro. The chemosensitivity to 5-FU was significantly increased in the transfected cells. The 50% inhibition values of 5-FU on DLD-1/anti-TS were approximately one forth that on parental cells. The augmentation of chemosensitivity to 5-FU was also confirmed in a nude mice model. The tumor growth of DLD-1/anti-TS cells was suppressed significantly more than that of DLD-1 cells by the 5-FU. The expression and activity of TS in human colon cancer cells were effectively inhibited by TS antisense treatment and the effect of 5-FU to cancer cells can be augmented. The antisense TS technology could be promising for treatments of gastrointestinal cancers.

Primary adenosquamous carcinoma of the liver: case report.

We describe a case of adenosquamous carcinoma of the liver, including treatment for the recurrence. A 67-year-old man with prolonged high fever was diagnosed with a mass lesion in the left lobe of the liver seen by imaging studies. That mass lesion was histologically diagnosed as cholangiocarcinoma by needle biopsy. Left hepatic lobectomy was performed, and a tumor was found that measured 8.0 x 7.0 x 6.0 cm. It was a yellowish white solid mass without macroscopic invasion of the intrahepatic bile duct. Histological examination of the resected specimen revealed both adenocarcinoma and squamous cell carcinoma. The postoperative course was uneventful, but abdominal computed tomography 3 months after operation revealed seven masses in the remnant liver. We diagnosed recurrence of the tumor, and intrahepatic arterial infusion of cisplatin and 5-fluorouracil was begun. A partial remission resulted. Progression-free survival after chemotherapy lasted 2 months. However, the tumor markers and remnant tumor size increased gradually 9 months after the operation, and he died 14 months after surgery. We also review 41 cases of adenosquamous carcinoma of the liver reported in the Japanese and English language literature, including the present case.