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Biomedical subjects

K L King

Publications and source records attributed to K L King.

At least 37 records · Page 2Linked to original sources
PubMed1999

Evaluation of a simplified staging system for prognosis of hepatocellular carcinoma.

The current TNM (tumor, nodes, metastases) staging system for human hepatocellular carcinoma (HCC) has been challenged since a new T staging system was proposed to correlate the staging group with patient outcome after curative liver resection. The new T staging system proposed T1 as no vascular invasion, small size (< or = 5 cm), and solitary tumor. T2 was defined as the presence of one of the following factors: size greater than 5 cm, vascular invasion, or multiple tumors; T3 as the presence of two of the above three factors; and T4, the presence of all three factors. A total of 323 patients undergoing curative partial hepatectomy for HCC were studied. Kaplan-Meier survival analysis was used to evaluate the postoperative outcome. The new T staging showed good correlation between the staging group and patient outcome. The 1-year disease-free survival (DFS) rate and overall survival (OS) rate were 80.0% and 87.8% for stage 1 (n = 115), 67.6% and 81.6% for stage 2 (n = 136), 40.0% and 58.0% for stage 3 (n = 58), and 21.4% and 42.8% for stage 4 (n = 14), respectively. The 3-year DFS rate and OS rate were 61.0% and 64.5% for stage 1, 37.8% and 50.7% for stage 2, 21.4% and 29.8% for stage 3, and 21.4% and 34.3% for stage 4, respectively. When analyzed using the current International Union Against Cancer (UICC) pathologic (p) TNM staging system, the 1-year and 3-year DFS rates were 86.2% and 64.0% for stage 1 (n = 30), 73.9% and 50.0% for stage 2 (n = 182), and 46.8% and 22.3% for stage 3 (n = 111), respectively. Our results showed that, while both staging systems allow clear stratification of patients into prognostic groups, the modified TNM system is not superior to the UICCpTNM system in predicting survival of HCC patients after curative partial hepatectomy. A larger scale, multicenter study may be needed to test the revised TNM system.

Carcinoma, Hepatocellular↗
PubMed1998

Temporal inhibition of calmodulin in the nucleus.

Calmodulin (CaM) acts as a primary mediator of calcium signaling by interacting with target proteins. We have previously shown that nuclear CaM is critical for cell cycle progression using a transgene containing four repeats of a CaM inhibitor peptide and nuclear targeting signals (J. Wang et al., J. Biol. Chem. 270 (1995) 30245 30248; Biochim. Biophys. Acta 1313 (1996) 223-228). To evaluate the role of CaM in the nucleus specifically during S phase of the cell cycle, a motif which stabilizes the mRNA only during S phase was included in the transgene. The CaM inhibitor mRNA transcript contains a self-annealing stem-loop derived from histone H2B at the 3' end. This structure provides stability of the mRNA only during S phase, thereby restricting CaM inhibitor expression to S phase. The inhibitor accumulates in the nucleus, particularly in the nucleoli. Flow cytometric analysis demonstrated that the CaM inhibitor is expressed in S and G2. Transfected cells show growth inhibition and a reduction in DNA synthesis. The CaM inhibitor peptide is a versatile reagent that allows spatial as well as temporal dissection of calmodulin function.

Amino Acid Sequence↗
PubMed1998

Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses.

Herein we report the generation of mice lacking the ubiquitously expressed Janus kinase, Jak1. Jak1-/- mice are runted at birth, fail to nurse, and die perinatally. Although Jak1-/- cells are responsive to many cytokines, they fail to manifest biologic responses to cytokines that bind to three distinct families of cytokine receptors. These include all class II cytokine receptors, cytokine receptors that utilize the gamma(c) subunit for signaling, and the family of cytokine receptors that depend on the gp130 subunit for signaling. Our results thus demonstrate that Jak1 plays an essential and nonredundant role in promoting biologic responses induced by a select subset of cytokine receptors, including those in which Jak utilization was thought to be nonspecific.

Animals↗
PubMed1998

An integrated approach to proteome analysis: identification of proteins associated with cardiac hypertrophy.

Hypertrophy of cardiac myocytes is a primary response of the heart to overload, and is an independent predictor of heart failure and death. Distinct cellular phenotypes are associated with hypertrophy resulting from different causes. These phenotypes have been described by others at the molecular level by analysis of gene transcription patterns. An alternative approach is the analysis of large-scale protein expression patterns (the proteome) by two-dimensional polyacrylamide gel electrophoresis. Realization of this goal requires the ability to rigorously analyze complex 2D gel images, efficiently digest individual gel isolated proteins (especially those expressed at low levels), and analyze the resulting peptides with high sensitivity for rapid database searches. We have undertaken to improve the technology and experimental approaches to these challenges in order to effectively study a cell culture model for cardiac hypertrophy. The 2D gel patterns for cell lysates from multiple samples of cardiac myocytes with or without phenylephrine-induced hypertrophy were analyzed and spots which changed in abundance with statistical significance were located. Eleven such spots were identified using improved procedures for in-gel digestion of silver-stained proteins and high-sensitivity mass spectrometry. The incorporation of low levels of sodium dodecyl sulfate into the digestion buffer improved peptide recovery. The combination of matrix-assisted laser desorption mass spectrometry for initial measurements and capillary liquid chromatography-ion trap mass spectrometry for peptide sequence determination yielded efficient protein identification. The integration of 2D gel image analysis and routine identification of proteins present in gels at the subpicomole level represents a general model for proteome studies relating genomic sequence with protein expression patterns.

Amino Acid Sequence↗
PubMed1998

Detection of serum hepatitis B, C, and D viral nucleic acids and its implications in hepatocellular carcinoma patients.

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.

Adult↗
PubMed1998

Surgical treatment and outcome in patients with a hepatocellular carcinoma greater than 10 cm in diameter.

BACKGROUND: Hepatocellular carcinoma (HCC) over 10 cm in diameter at the time of diagnosis continues to account for a number of patients undergoing hepatic resection. This study evaluated the clinicopathological features and outcome following surgery for large HCC. METHODS: Forty patients with a large HCC (greater than 10 cm) (group 1) resected between 1991 and 1996 were studied retrospectively. They were compared with 245 patients who had smaller HCCs (10 cm or less) (group 2). RESULTS: No patient in group 1 had hepatitis C infection compared with 22.9 per cent in group 2 (P=0.001). Patients in group 1 were significantly younger, had higher alpha-fetoprotein levels (16750 versus 1864 ng/ml; P < 0.001), better liver function, a higher incidence of multiple tumours (27 of 40 versus 42.0 per cent; P=0.003) and venous invasion (35 of 40 versus 52.2 per cent; P < 0.001), and underwent more major resections (37 of 40 versus 26.5 per cent; P < 0.001) than those in group 2. Morbidity and mortality rates and hospital stay were comparable in the two groups. For group 1, the 1-, 3- and 5-year disease-free survival rates were 42, 30 and 28 per cent respectively. Multiple tumours, venous invasion and impaired liver function were factors associated with recurrence. CONCLUSION: Large HCC had specific clinicopathological features. In selected patients, resection is safe and offers the chance of long-term disease-free survival.

Adult↗
PubMed1998

Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma.

Ki-67 expression in tumours has been shown to be associated with prognosis in patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples were obtained from 67 patients undergoing surgical resection. None of these patients had been subjected previously to any other form of therapy, such as arterial embolization or chemotherapy. Histologically normal liver tissues from liver resection for metastatic colon cancer were taken as controls (n = 8). Monoclonal antibody against Ki-67 was used for immunostaining and flow cytometry was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage of Ki-67-positive cells) of the HCC (26 +/- 22%; range 0.1-89%) was significantly higher than that of the normal controls (39 +/- 0.8%, P < 0.05). The mean Ki-67 labelling index (19 +/- 15%; n = 28) of the tumours with diploid DNA pattern was significantly lower than those with aneuploid DNA pattern (32 +/- 25%, n = 39; P = 0.01). Hepatocellular carcinoma patients (n = 47) with Ki-67 index > 10% had a significantly lower disease-free and overall survival than those (n = 20) with Ki-67 index < or = 10% (P = 0.0009 and P = 0.02, respectively). Multivariate analysis showed that Ki-67 expression and tumour node metastasis stage were two independent prognostic factors for disease-free and overall survival rates. Our results suggest that the expression of Ki-67 is an independent prognostic indicator for patients with HCC after resection and could be of assistance in the decision-making of adjuvant therapy.

Aged↗
PubMed1998

Cell cycle regulation and apoptosis.

Tissue homeostasis requires a balance between cell proliferation and death. Apoptosis and proliferation are linked by cell cycle regulators, and apoptotic stimuli affect both cell proliferation and death. Glucocorticoids induce G1 arrest and apoptosis in transformed lymphoid cells. Decreased expression of the cell cycle components c-myc and cyclin D3 is essential for glucocorticoid-induced growth arrest and death in dividing cells. Other G1 regulators, such as p53, pRb, and E2F, have also been implicated in apoptosis. Mice lacking either p53 or E2F display aberrant cell proliferation and tumor formation, suggesting that these proteins are involved in the elimination of abnormal cells through apoptosis. In contrast, pRb induces G1 arrest and suppresses apoptosis in cultured cells. Mice that lack pRb are nonviable and show ectopic mitosis and massive cell death, suggesting that pRb is an apoptotic suppressor. Further analysis of common components of apoptotic and cell cycle machinery may provide insight into the coordinated regulation of these antagonistic processes.

Animals↗
PubMed1998

Biological response to ErbB ligands in nontransformed cell lines correlates with a specific pattern of receptor expression.

The human epidermal growth factor receptor (HER or ErbB) family consists of four distinct members, including the epidermal growth factor (EGF) receptor (EGFR, HER1, or ErbB1), ErbB2 (HER2 or neu), ErbB3 (HER3), and ErbB4 (HER4). Activation of these receptors plays an important role in the regulation of cell proliferation, differentiation, and survival in several different tissues. Binding of a specific ligand to one of the ErbB receptors triggers the formation of specific receptor homo- and heterodimers, with ErbB2 being the preferred signaling partner. We analyzed the levels of various ErbB receptor messenger RNAs in a series of nontransformed cell lines by real time quantitative RT-PCR. The cell lines chosen were derived from a variety of tissues, including pancreas, lung, heart, and nervous system. Further, we measured biological responses in these cell lines upon treatment with EGF, betacellulin, and two types of neuregulins, heregulin and sensory and motor neuron-derived factor. All cell lines examined expressed detectable levels of ErbB2. High levels of expression of ErbB3 were correlated with responsiveness to heregulin and sensory and motor neuron-derived factor, whereas high levels of EGFR expression were correlated with responsiveness to EGF and betacellulin. Moreover, the sensitivity of a cell line to ErbB ligands was also correlated with the levels of expression of the appropriate ErbB receptors in that cell line. These results are consistent with our hypothesis that appropriate biological responsiveness to ErbB ligands is determined by the levels of expression of specific ErbB receptor combinations within a given tissue.

Animals↗
PubMed1998

Phenylephrine, endothelin, prostaglandin F2alpha' and leukemia inhibitory factor induce different cardiac hypertrophy phenotypes in vitro.

In these studies, we show that endothelin (ET), leukemia inhibitory factor (LIF), phenylephrine (PE), and prostaglandin F2alpha (PGF2alpha), which are all hypertrophic for neonatal rat cardiac myocytes in culture, induce distinct morphological, physiological, and genetic changes after a 48-h treatment. Transmission electron microscopy revealed differences in myofibril organization, with ET-treated cells containing the most mature-looking myofibrils and PGF2alpha- and LIF-treated cells the least. ET- and PE-treated cultures contained the same number of beating cells as control, but LIF and PGF2alpha treatment increased the number of beating cells 180%. Treatment with LIF, PE, and PGF2alpha increased the beat rate to 3.3 times that of control. After exposure to the beta-adrenergic agonist isoproterenol, the beat rate increased 50% for PGF2alpha' 54% for PE, 84% for LIF, and 125% for control. ET treatment did not increase the beat rate, nor did these cells respond to isoproterenol. ET, LIF, and PE increased the production of atrial natriuretic peptide (ANP) by three-fold and PGF2alpha by 18-fold over nontreated cells. Brain natriuretic peptide (BNP) was increased fourfold by ET and PE, 16-fold by LIF, and 29-fold by PGF2alpha. Interestingly, on a pmol/L basis, only LIF induced more BNP than ANP. Treatment with all agents led to a similar pattern of gene induction: increased expression of the embryonic genes for ANP and skeletal alpha-actin, and less than a twofold change in the constitutively expressed gene myosin light chain-2, with the exception that LIF did not induce skeletal alpha-actin. Each agent, however, induced ANP mRNA with a different time-course. We conclude that at least four distinct cardiac myocyte hypertrophy response programs can be induced in vitro. Further studies are necessary to determine whether these correlate to the different types of cardiac hypertrophy seen in vivo.

Actins↗
PubMed1997

Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases.

Microsatellite instability (MSI) is intrinsic to most colorectal carcinomas (CRC) from patients with hereditary nonpolyposis colorectal cancer (HNPCC), reflecting germline mutations in the mismatch-repair (MMR) genes. Its occurrence and chronological sequence of development in sporadic CRC appears less well defined. To explore the time sequence in acquisition of MSI, and the role it plays during tumor progression in sporadic CRC, we compared the incidence of MSI in tissue samples from 40 Dukes'-B and 30 Dukes'-D CRC patients with liver metastases, at 4 different microsatellite loci, representing sites on the APC, DCC and p53 genes respectively as well as the D2S123 site. Among the 30 patients with hepatic metastases, MSI was found in 9 (30%) of the primary, and 13 (43.3%) of the metastatic tumors. In comparison, among the 40 Dukes'-B CRC, MSI was found in only 8 cases (20%). CRC with MSI were more frequently located in the right colon, less frequently on the left side, and seldom in the rectum. Tumor ploidy analysis shows that 46.2% of Dukes'-D primary tumors with MSI are diploid (chi2 = 4.46, p = 0.035). With a mean follow-up time of 4.2 years for the Dukes'-B CRC, there were no recurrences in the 8 patients with MSI, whilst 6 (18.8%) relapses occurred amongst the 32 patients without MSI, average time to recurrence being 15 months. In Dukes'-D CRC, mean survival time for patients with MSI was 37 months (95% CI, 24 to 51 months), for those without MSI 26 months (95% CI, 18 to 35 months), although this was not statistically significant. Our data suggest that tumor progression may involve increased genetic instability.

Aged↗
PubMed1997

Prognostic significance of surgical margin in hepatocellular carcinoma resection: an analysis of 165 Childs' A patients.

BACKGROUND AND OBJECTIVES: The clinical significance of the width of the surgical margin in the resection of hepatocellular carcinoma (HCC) has yet to be clarified. METHODS: Childs' A patients (165) who underwent resections of HCC were studied. Patients were divided into a wide margin group (1.0 cm or more, group W, n = 85), and a narrow margin group (< 1.0 cm, group N, n = 80). RESULTS: Multivariate analysis showed that preoperative alpha-fetoprotein level (P = 0.0202), venous invasion (P = 0.0226), surgical margin (P = 0.0012), and TNM stage (P = 0.0023) were significant predictors of disease-free survival. By the log-rank test, the disease-free survival rate of the group W patients was significantly higher than that of the group N patients (P = 0.0007). Group N had a higher percentage of patients undergoing minor resection (wedge resection or subsegmentectomy) (44% vs. 26%, P = 0.016) and had a higher percentage of patients with centrally located tumor (62% vs. 29%, P = 0.000) than group W. CONCLUSIONS: The results of this study indicated the significant influence of surgical margin on HCC recurrence after resection. Minor resection and centrally located tumor are factors related to a narrow surgical margin.

Adult↗
PubMed1997

Randomized trial of three types of gastrojejunostomy in unresectable periampullary cancer.

BACKGROUND: A gastrojejunostomy with duodenal partition was designed to clarify whether so-called circulus vomiting exists and, if so, its clinical significance, by comparing it with two other types of gastrojejunostomy commonly used for gastric bypass in unresectable periampullary cancer. METHODS: Forty-five patients with unresectable periampullary cancer complicated by gastric outlet obstruction (GOO) were recruited into this study between May 1992 and November 1995. They were randomized to receive one of the three types of gastrojejunostomy. The anastomosis in type I gastrojejunostomy was performed at the jejunum 20 cm distal to the ligament of Treitz. Type II was similar to type I except that in type II a duodenum partition was done by linear stapler 1 cm beyond the pylorus. Type III gastrojejunostomy was performed at the Roux-limb jejunum 60 cm distal to biliojejunostomy. RESULTS: "Food reentry" was noted in three (21%) of the type I patients, as determined by upper gastrointestinal (UGI) study. Of the three, one patient had severe circulus vomiting, one had anorexia, and one had no major symptoms. When patients were evaluated immediately after oral diet intake resumed, the incidence (27%) of clinical GOO symptoms and mean value of gastric emptying time (GET1/2, 118.1 +/- 39.2 min) were significantly lower in type II patients than in types I and III patients. When evaluated I month after operation, the incidence (7% and 17%, respectively) of clinical symptoms of GOO and mean value of GET1/2 (42.0 +/- 23.0 and 35.6 +/- 5.4 min, respectively) were significantly lower in both type II and type III patients than in type I patients. The type II patients resumed oral diet after operation 3.5 days earlier than type I patients, p < 0.05. CONCLUSIONS: Circulus vomiting induced by food reentry does exist if the gastrojejunostomy is performed as the type I gastrojejunostomy in this study. The newly designed type II gastrojejunostomy with duodenal partition is an easy, safe, and effective gastric bypass and avoids the problem of food reentry.

Aged↗
PubMed1997

Clinicopathological comparison of resectable hepatocellular carcinoma between the young and the elderly patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in many parts of the world. In Taiwan it is the leading cause of death in male cancer patients. The peak age of onset of HCC varies according to geographic barriers, which indicates different hepatocarcinogenesis among different age groups. This study aims to evaluate whether there exists significantly different clinicopathological features between young and elderly HCC patients. METHODS: During a six-year period, a total of 248 patients with HCC underwent liver curative resection at Veterans General Hospital-Taipei, Taiwan. Among them, 22 patients were younger than 40 years of age, and 43 patients were older than 70 years of age. Important clinicopathological characteristics of the patients (including sex, family history of HCC, smoking habits and alcohol consumption patterns, hepatitis B or C infection, indocyanine-green retention rate at 15 minutes (ICGR-15), serum alpha-fetoprotein value, tumor size, tumor number, tumor venous invasion, capsular formation, tumor staging, cirrhosis, and tumor DNA ploidy) and postresectional prognosis were compared between young and elderly HCC patients. RESULTS: The frequency of presence of family history (22.7% versus 4.7%), hepatitis B surface antigen carrier rate (81.8% versus 48.8%), and patients with large-sized tumors (31.8% versus 7.0%) were significantly higher in young patients than in elderly patients. The male:female ratio (4.5:1 versus 42:1), degree of liver damage (reflected by the ICGR-15 value, 5.6 +/- 5.0% versus 13.1 +/- 8.8%) and the incidences of liver cirrhosis (18.2% versus 48.8%) were significantly lower in young patients than in elderly patients. However, there were no significant differences in postresectional survival rates between these two groups. CONCLUSIONS: There are age-related differences in clinicopathological characteristics of HCC patients. Accordingly, different mechanisms of hepatocarcinogenesis may exist between young and elderly HCC patients.

Adolescent↗
PubMed1996

Glycerophosphorylethanolamine (GPEA) identified as an hepatocyte growth stimulator in liver extracts.

Extracts from weanling pig liver were found to act synergistically with growth factors such as hepatocyte growth factor and transforming growth factor-alpha to stimulate hepatocyte growth in serum-free cultures. In the absence of added growth factors, the extracts had no activity. The compound responsible for this activity was isolated by passing heat-treated liver extract through anion-exchange and heparin columns followed by gel filtration at neutral and low pH, reversed-phase HPLC, and a final gel filtration column at low pH. The activity was followed throughout the purification by its ability to increase substantially the incorporation of [3H]thymidine into primary rat hepatocytes cultured serum-free in the presence of hepatocyte growth factor. The active compound was identified by NMR and mass spectrometry as glycerophosphorylethanolamine (GPEA), a breakdown product of the phospholipid phosphatidylethanolamine. The ethanolamine portion of the molecule was critical for the observed activity, whereas the glycerol phosphate portion was not necessary. In the absence of added growth factors, neither GPEA nor ethanolamine had any stimulatory effect on the cells. These results demonstrate that hepatocytes grown in culture, and especially those grown in serum-free media, require a supplement of ethanolamine and/or GPEA. In the absence of these compounds, their response to growth stimuli is greatly reduced.

Animals↗
PubMed1996

Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s).

Primary hepatocellular carcinoma (HCC) extending to the adjacent organ(s) is sometimes encountered in patients with large, peripherally located tumours. Over a 4-year period, a total of 151 patients received curative resection of HCC at the Surgical Department of Veterans General Hospital-Taipei, Taiwan. Of these patients, 21 underwent hepatic resection combined with en-bloc resection of the adjacent organ(s) because tumour extension was found during operation. Subsequent histological examination of the resected specimens found evidence of HCC invasion into the resected adjacent organ(s) in only nine patients (group I), and the remaining 12 patients showed no evidence of extrahepatic HCC invasion (group II). Twenty-seven HCC patients with clinico-pathologically matched tumours but without extrahepatic extension were selected as controls (group III). One patient in group I died of hepatic failure after the operation. The morbidity rate was 48% in group I and group II patients, and 30% in group III patients. The difference was not statistically significant. On evaluating the clinico-pathological factors, including DNA ploidy status of the tumours, there were no significant differences between tumours with and without extrahepatic invasion. Patients with locally invasive HCC (group I) had disease-free and overall survival rates comparable with those of the patients without local tumour invasion (group II and III). We conclude that HCC with invasion to the adjacent organ(s) does not seem to be directly related to the 'aggressiveness' of the tumour, and extrahepatic infiltration of the tumour does not preclude a chance of cure. Our results underscore the need for en-bloc resection as treatment of choice for these patients.

Carcinoma, Hepatocellular↗
PubMed1996

Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma.

UNLABELLED: OBJECTIVE; Morbidity and mortality involved in the resection of hilar cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and laboratory parameters that might influence the patient's survival also were re-evaluated. SUMMARY BACKGROUND DATA: Although much progress has been made in the diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most patients remains poor. Surgical resection is usually prohibited because of its local invasiveness, and most patients can only be managed by palliative drainage. Recently, many surgeons have adopted a more aggressive resection with varying degrees of success. Several prognostic factors in bile duct carcinoma have been proposed; however, no reports have specifically focused on resected hilar cholangiocarcinoma and its prognostic survival factors using multivariate analysis. METHODS: The clinical records and pathologic slides of 49 cases with resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical and laboratory parameters were evaluated for their correlation with postoperative morbidity and mortality, whereas 31 variables were evaluated for their significance with postoperative survival. Variables showing statistical significance in the first univariate analysis were included in the following multivariate analysis using stepwise logistic regression test for factors affecting morbidity and mortality and Cox stepwise proportional hazard model for factors influencing survival. RESULTS: There were 5 in-hospital deaths, and the cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a median survival of 14.0 months. Multivariate analysis disclosed that co-existent hepatolithiasis and lower serum asparate aminotransferase levels (<90 U/L) had a significant low incidence of postoperative morbidity, whereas a serum albumin of less than 3 g/dL was the only significant factor affecting mortality. Regarding survival, univariate analysis identified eight significant factors: 1) total bilirubin > or = 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal resected margin, and 8) positive surgical margin. However, multivariate analysis disclosed total bilirubin > or = 10 mg/dL, curative resection, and histologic type as the three most significant independent variables. CONCLUSIONS: Surgical resection provides the best survival for hilar cholangiocarcinoma. An adequate nutritional support to increase serum albumin over 3 g/dL is the most important factor to decrease postoperative mortality. Moreover, preoperative biliary drainage to decrease jaundice and a curative resection with adequate surgical margin are recommended if longer survival is anticipated. Patients with well-differentiated adenocarcinoma seem to survive longer compared to those with moderately or poorly differentiated tumors.

Adult↗