HER2 immunohistochemical scores provide prognostic information for patients with HER2-type invasive breast cancer.

AIMS: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in-situ hybridisation (ISH) positivity are suitable for anti-HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. METHODS AND RESULTS: We analysed the clinicopathological information of 886 consecutive cases of HER2-positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti-HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut-off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. CONCLUSION: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2-positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis.

Prognostic factors of primary resected retroperitoneal soft tissue sarcoma: Analysis from a single asian tertiary center and external validation of gronchi's nomogram.

BACKGROUND: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. METHODS: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July 30th, 2011. The prognostic influence of clinicopathological characteristics as well as treatments on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were examined by univariate and multivariate analyses. A histology-specific nomogram developed by Gronchi et al was used for validation. RESULTS: Liposarcoma, leiomyosarcoma, and malignant peripheral sheath tumor (MPNST) were the most common histologies (70%). Multivariate analysis revealed FNCLCC tumor grade was the most significant prognostic factor for OS (P = 0.001) and DMFS (P < 0.001) and complete resection was the only significant prognostic factor for LRFS (P = 0.043). Incomplete resection of grade 3 tumor was significantly associated with a worse OS. Despite some differences in characteristics between our patients and Gronchi's cohort, external validation of Gronchi's nomogram demonstrated excellent concordance in predicting survival. CONCLUSIONS: Our study demonstrated tumor grade and surgical margins had significant prognostic influence and the Gronchi's nomogram has an excellent applicability in predicting survival of STS patients. J. Surg. Oncol. 2016;113:355-360. © 2016 Wiley Periodicals, Inc.

Thyroid metastasis from breast cancer presenting with diffuse microcalcifications on sonography: a case report.

Microcalcifications are frequently associated with papillary thyroid cancers. Metastatic nodules from extrathyroid malignancies may mimic primary thyroid neoplasm on sonography, but do not present with microcalcifications. We report the case of a 45-year-old woman with a history of invasive ductal carcinomas of bilateral breasts, status post surgery and neoadjuvant chemotherapy. Four years after surgery, thyroid sonography revealed diffuse microcalcifications without nodular component. Core needle biopsy confirmed thyroid metastasis from primary breast cancer.

Significance of incorporation of model for end-stage liver disease score with TNM staging in patients with hepatocellular carcinoma undergoing hepatic resection.

BACKGROUND/AIMS: Currently, the tumor-node-metastasis (TNM) system is used in hepatectomy patients for tumor staging of HCC patients. However this can only evaluate the histopathological factor. MELD score is an objective measure for liver function widely used as a severity index for priority on the waiting list for liver transplantation. Here we suggest a modified TNM staging system based on the MELD score and test its relation with post-operative outcome of HCC. METHODOLOGY: We retrospectively collected 922 HCC patients undergoing hepatic resection, with TNM stage I (n=239), stage II (n=375) and stage III (n=308); giving points 0 to 2 for each stage (from I to III). Pre-operative MELD score was calculated and assigned 0 points for MELD <6; 1 for 6-8; 2 for >8. The two scores were added together to form a modified MELD-base TNM stage score and tested the correlation of this new scoring system with outcome after liver resection. RESULTS: The modified MELD-base TNM stage score resulted in score 0 (n=114), score 1 (n=247), score 2 (n=335), score 3 (n=164), and score 4 (n=62). The disease-free survival in each group showed significant difference (p<0.05), the lower the score, the better the outcome. CONCLUSIONS: The MELD-based TNM staging system reliably separates patients with HCC into homogeneous groups with respect to post-resectional prognosis. Further prospective validation studies are required to confirm the feasibility of this strategy.

Isolation and identification of Acanthamoeba species from thermal spring environments in southern Taiwan.

Acanthamoeba species are free-living amoebae found in a range of environments. Within this genus, a number of species are recognized as human pathogens, potentially causing Acanthamoeba keratitis, granulomatous amoebic encephalitis, and chronic granulomatous lesions. In this study, 60 water samples were taken from four thermal spring recreation areas in southern Taiwan. We detected living Acanthamoeba spp. based on culture-confirmed detection combined with the molecular taxonomic identification method. Living Acanthamoeba spp. were detected in nine (15%) samples. The presence or absence of Acanthamoeba spp. in the water samples depended significantly on the pH value. The most frequently identified living Acanthamoeba genotype was T15 followed by T4, Acanthamoeba spp., and T2. Genotypes T2, T4, and T15 of Acanthamoeba, are responsible for Acanthamoeba keratitis as well as granulomatous amoebic encephalitis, and should therefore be considered a potential health risk associated with human activities in thermal spring environments.

Clinicopathological characteristics and treatment outcomes of luminal B1 breast cancer in Taiwan.

BACKGROUND: Hormone receptor-positive, human epidermal growth factor receptor II (HER2)-negative luminal B1 breast cancer is associated with a higher risk of disease relapse than luminal A breast cancer. Therefore, we assessed and compared the distant metastasis pattern and clinical outcomes associated with luminal B1 and luminal A breast cancer in an Asian population. METHODS: In this observational study, we assessed patients with estrogen receptor-positive, HER2-negative breast cancer who underwent surgery from 2009 to 2016. Patients were classified into luminal A or luminal B1 subsets via immunohistochemical analysis. Disease-free survival, post-metastasis survival, and overall survival were estimated; time to disease relapse and patterns of distant metastasis were compared. Risk of relapse and mortality were assessed using Cox proportional hazards model. RESULTS: Patients with luminal B1 breast cancer (n = 677) were significantly younger and had larger tumors and a higher degree of affected axillary lymph nodes, lymphovascular invasion, and tumor necrosis than those with luminal A breast cancer (n = 630). Higher rates of local recurrence and distant metastasis were observed for luminal B1 (both p < 0.05); however, no difference was observed in the specific distant metastatic sites. We observed a significant increase in disease relapse risk in luminal B1 patients compared with that in luminal A (hazard ratio: 2.157, 95% CI: 1.340-3.473, p < 0.05). Patient age, tumor size, stage, lymphovascular invasion, and receiving chemotherapy and hormone therapy were independent risk factors for metastasis and recurrence. Only the luminal B1 subtype (hazard ratio: 5.653, 95% CI: 1.166-27.409, p < 0.05) and stage (hazard ratio: 3.400, 95% CI: 1.512-7.649, p < 0.05) were identified as independent risk factors for post metastatic mortality. CONCLUSION: Luminal B1 breast cancer has aggressive tumor biology compared with luminal A breast cancer in the follow-up period. However, there was no significant difference in the disease relapse pattern between the groups.

Adjuvant oxaliplatin- or irinotecan-containing chemotherapy improves overall survival following resection of metachronous colorectal liver metastases.

PURPOSE: Adjuvant systemic 5-fluorouracil (5-FU)-based chemotherapy improves survival after resection of synchronous colorectal liver metastases (CLMs), but not metachronous. We retrospectively examined if adjuvant chemotherapy with new regimen containing oxaliplatin or irinotecan improved survivals after resection of metachronous CLMs. METHODS: Between 2000 and 2007, 52 patients having undertaken resection of metachronous CLMs with curative intent were identified from Taipei Veterans General Hospital hospitalization registry. One patient with perioperative mortality and another being lost to follow-up within 3 months after metastasectomy were excluded. Thirty-one patients experienced six to 12 cycles of FOLFOX or FOLFIRI chemotherapy while 19 patients with 5-FU/leucovorin (LV)-based chemotherapy following CLM resection. The primary end point was disease-free survival (DFS) and secondary end point, overall survival (OS). RESULTS: By the univariate analysis, median DFS was 34.3 months in the FOLFOX/FOLFIRI group vs 14.2 months in the 5-FU/LV group (P = 0.022). The median OS and 5-year survival rates were longer than 57.7 months (not reached, with median follow-up of 35.5 months) and 54.0%, respectively, in the FOLFOX/FOLFIRI group compared to 49 months and 34.6% in the 5-FU/LV group (P = 0.027). FOLFOX/FOLFIRI chemotherapy was shown by multivariate analyses to be an independent factor predicting a better DFS (hazard ratio [HR] = 0.37; 95% CI: 0.15-0.94; P = 0.036) and a better OS (HR = 0.27; 95% CI: 0.083-0.86, P = 0.026) than 5-FU/LV-based. CONCLUSIONS: Adjuvant FOLFOX/FOLFIRI chemotherapy following resection of metachronous CLMs is demonstrated to have better DFS and OS than 5-FU/LV chemotherapy.

Predicting morbidity and mortality after hepatic resection in patients with hepatocellular carcinoma: the role of Model for End-Stage Liver Disease score.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is currently used as a disease severity index of cirrhotic patients awaiting liver transplantation. This study evaluated the usefulness of the MELD score in predicting mortality and morbidity of patients with hepatocellular carcinoma (HCC) undergoing hepatic resection. METHODS: The study cohort consisted of 1,017 patients who underwent hepatic resection for HCC between 1991 and 2005. Patient variables were examined by univariate and multivariate analyses to identify risk factors for morbidity and mortality. Accuracy in predicting mortality was assessed with the area under the receiver operator characteristic curve (AUC) analysis. RESULTS: The morbidity and mortality rates were 30.7% and 1.9%, respectively. Age, liver cirrhosis, operation time, and MELD score were risk factors for mortality, whereas indocyanine green retention rate at 15-min value, operation time, blood loss, and Child-Turcotte-Pugh score were risk factors for morbidity. Patients with MELD score >8 had higher mortality (4.0% vs. 0.6%, p = 0.004) and higher liver-related morbidities (16.1% vs. 4.3%, p < 0.001), including massive ascites, intra-abdominal hemorrhage, and hepatic failure, compared with patients with MELD score <6. High MELD score also was related to longer postoperative hospital stay (score >8, 14.5 days vs. score <6, 12.6 days, p = 0.015). The AUC for MELD score as a predictor of mortality was 0.718, indicating high clinical usefulness. CONCLUSIONS: The MELD score relates with mortality and liver-related morbidities in HCC patients who undergo hepatic resection. A MELD score >8 represents the trigger for intensive treatment to improve patient outcome.

Prognostic value and clinical relevance of the 6th Edition 2002 American Joint Committee on Cancer staging system in patients with resectable hepatocellular carcinoma.

BACKGROUND: A simplified American Joint Committee on Cancer (AJCC) TNM staging system for hepatocellular carcinoma (HCC) (the 6th edition) was proposed in 2002. In this study, we validated the prognostic value of the staging system in a patient cohort undergoing hepatic resection with longterm followup. STUDY DESIGN: From a prospective database, the study cohort consisted of 440 patients who underwent curative hepatic resection for HCC between July 1991 and January 1999. Median followup time was 66 months. Multivariate analysis was performed to identify the independent prognostic factors related to postoperative survival. Patients were staged according to both the 5th edition (TNM-5) and 6th edition (TNM-6) AJCC TNM staging criteria. RESULTS: The independent prognostic factors included major vascular invasion, microvascular invasion, surgical margin < 1 cm, indocyanine green retention rate at 15 minutes > 10%, multiple tumors, tumor rupture, male, and serum aspartate aminotransferase > 90 U/L. The breakdown by TNM-5 staging: I, 27 (6.1%); II, 108 (24.5%); III, 218 (49.5%); and IVA, 87 (19.8%) and by TNM-6 staging: I, 120 (27.3%); II, 170 (38.6%); and III, 150 (34.1%). When stratified according to the TNM-5 system, difference in survival was notable between stages II and IIIA (p < 0.001), between stages IIIA and IVA (p < 0.001), but not between stages I and II (p > 0.05). When stratified according to the TNM-6 system, difference in survival was considerable between stages I and II (p < 0.01), stages II and III (p < 0.001), and stages I and III (p < 0.001). CONCLUSIONS: Overall, the TNM-6 staging system appears to provide a reliable prognostic classification of HCC patients and is simpler to use than the TNM-5 staging system.

Risk factors associated with bile leakage after hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: Bile leakage after hepatic resection can cause septic complications and mortality. This study evaluated the risk factors associated with postoperative bile leakage in hepatocellular carcinoma patients. METHODOLOGY: Between July 1991 and December 2000, 605 consecutive hepatocellular carcinoma patients who underwent hepatic resection were enrolled. Risk factors associated with postoperative bile leakage were examined, with 38 clinicopathological variables being analyzed. Data were collected prospectively and analyzed retrospectively. RESULTS: Bile leakage developed in 35 (5.8%) of 605 patients. When compared with patients without bile leakage, those with bile leakage had higher risk for concomitant morbidities (54.3% vs. 29.2%, P=0.002), postoperative mortality (8.6% vs. 2.6%, P=0.045), and a prolonged postoperative hospital stay (29 days vs. 14 days, P<0.001). The bile leakage rate of centrally located tumors (9.4%) was significantly higher than that of peripherally located tumors (3.5%; P=0.002). The bile leakage rate of patients with preoperative chemoembolization (13.8%) was significantly higher than those without chemoembolization (4.9%; P=0.004). Stepwise logistic regression analysis identified preoperative chemoembolization (OR=3.274, P=0.005) and tumor(s) being centrally located (OR=2.927, P=0.003) as the independent predictors of development of bile leakage. CONCLUSIONS: For HCC patients, preoperative chemoembolization and tumor(s) with central location are risk factors for post-hepatectomy bile leakage. As bile leakage can cause septic complications and liver failure, careful surgical procedures and use of preventive measures are necessary, especially in patients with high risk factors.

Hepatocellular carcinoma confined to Couinaud segment VIII: experience with extensive or limited resection.

BACKGROUND/AIMS: Surgical treatment of hepatocellular carcinoma (HCC) confined to Couinaud segment VIII has been regarded as difficult. This study evaluates surgical and oncological results after extensive or limited resection of the tumor(s). METHODOLOGY: Of the 399 HCC patients that underwent hepatic resection, 36 patients had the tumor(s) confined to segment VIII. These 36 patients were divided into group 1 (extensive resection) (n=15) (three right hepatectomies, 12 anterior segmentectomies) and group 2 (limited resection) (n=21) (11 subsegmentectomies, 10 wedge resections). Data were collected prospectively and analyzed retrospectively. RESULTS: Hospital mortality and morbidity were 0% and 20% in group 1, 9.5%, and 38% in group 2 (P>0.05). Group 1 patients had larger tumor (4.0cm vs. 2.8cm; P=0.01), heavier resected specimen (380g vs. 118g; P<0.01), and a higher incidence of wide surgical margin (> or =1cm) (67% vs. 29%; P=0.041) than those in group 2. The percentage of patients in whom the a-fetoprotein levels returned to the normal range after resection was higher in group 1 (75.0%, 6 of 8 patients) than in group 2 (26.7%, 4 of 15 patients) (P=0.037). The 1-, 3-, and 5-year disease-free survival in group 1 (93%, 79% and 52%) were significantly better than those of group 2 (67%, 38% and 22%) (P=0.021). CONCLUSIONS: In selected patients, extensive resection of HCC located in segment VIII correlates with better survival.

Mitochondrial DNA alterations correlate with the pathological status and the immunological ER, PR, HER-2/neu, p53 and Ki-67 expression in breast invasive ductal carcinoma.

We analyzed the changes in mitochondrial DNA (mtDNA) copy numbers and the shifting of mtDNA D310 sequence variations (D310 mutation) with their relationships to pathological status and the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2/neu), tumor-suppressor protein p53 and cellular proliferation protein Ki-67 in breast invasive ductal carcinoma (BIDC), respectively. Fifty-one paraffin-embedded BIDCs and their paired non-cancerous breast tissues were dissected for DNA extraction. The mtDNA copy number and mtDNA D310 sequence variations were determined by quantitative real-time polymerase chain reaction (q-PCR) and PCR-based direct sequencing, respectively. The expression levels of ER, PR, HER-2/neu, p53 and Ki-67 were determined by immunohistochemical (IHC) staining. Compared to the paired non-cancerous breast tissues, 24 (47.1%) BIDCs had elevated mtDNA copy numbers and 29 (56.9%) harbored mtDNA D310 mutations. Advanced T-status (p=0.056), negative-ER (p=0.005), negative-PR (p=0.007), positive-p53 (p=0.050) and higher Ki-67 (p=0.004) expressions were related to a higher mtDNA copy ratio. In addition, advanced T-status (p=0.019) and negative-HER-2/neu expression (p=0.061) were associated with mtDNA D310 mutations. In conclusion, higher mtDNA copy ratio and D310 mutations may be relevant biomarkers correlated with pathological T-status and the expression levels of ER, PR, HER-2/neu, p53 and Ki-67 in BIDCs.

Elevation of soluble guanylate cyclase suppresses proliferation and survival of human breast cancer cells.

Nitric oxide (NO) is an essential signaling molecule in biological systems. Soluble guanylate cyclase (sGC), composing of α1 and ß1 subunit, is the receptor for NO. Using radioimmunoassay, we discovered that activation of sGC by treatment with bradykinin or sodium nitroprusside (SNP) is impaired in MCF-7 and MDA-MB-231 breast cancer cells as compared to normal breast epithelial 184A1 cells. The 184A1 cells expressed both sGC α1 and sGCß1 mRNAs. However, levels of sGCß1 mRNAs were relatively lower in MCF-7 cells while both mRNA of sGC subunits were absent in MDA-MB-231 cells. Treatment with DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) increased mRNA levels of both sGCα1 and sGCß1 in MDA-MB-231 cells but only sGCß1 mRNAs in MCF-7 cells. The 5-aza-dC treatment increased the SNP-induced cGMP production in MCF-7 and MDA-MB-231, but not in 184A1 cells. Bisulfite sequencing revealed that the promoter of sGCα1 in MDA-MB-231 cells and promoter of sGCß1 in MCF-7 cells were methylated. Promoter hypermethylation of sGCα1 and sGCß1 was found in 1 out of 10 breast cancer patients. Over-expression of both sGC subunits in MDA-MB-231 cells induced apoptosis and growth inhibition in vitro as well as reduced tumor incidence and tumor growth rate of MDA-MB-231 xenografts in nude mice. Elevation of sGC reduced protein abundance of Bcl-2, Bcl-xL, Cdc2, Cdc25A, Cyclin B1, Cyclin D1, Cdk6, c-Myc, and Skp2 while increased protein expression of p53. Our study demonstrated that down-regulation of sGC, partially due to promoter methylation, provides growth and survival advantage in human breast cancer cells.

Long-term results of hepatic resection for hepatocellular carcinoma originating from the noncirrhotic liver.

HYPOTHESIS: In patients with hepatocellular carcinoma who do not have cirrhosis, the clinicopathologic characteristics and long-term postresectional outcomes must be clarified and liver transplantation may also have a role in future treatment strategy. DESIGN: Case series. The mean (SD) follow-up time was 52.4 (33.8) months. SETTING: A tertiary care medical center. PATIENTS: From a prospective database, 445 patients with hepatocellular carcinoma who underwent hepatectomy were classified into 2 groups-those without cirrhosis (n = 223) and those with cirrhosis (n = 222). Clinicopathologic factors and postresectional outcomes were compared between these groups based on the new American Joint Committee on Cancer/Union Internationale Contre le Cancer TNM (sixth edition) staging system and the patient selection criteria for undergoing transplantation. MAIN OUTCOME MEASURES: Postresectional disease-free and overall survival rates. RESULTS: Compared with patients with cirrhosis, patients without cirrhosis were younger, had a lower rate of viral hepatitis type C infection, and had more advanced TNM stage III disease. Also more of the patients who did not have cirrhosis had undergone major resection. The tumor recurrence rate was significantly lower in the noncirrhotic group than in the cirrhotic group (59.5% vs 69.5%, P =.03). The 5- and 10-year disease-free and overall survival rates of the noncirrhotic group were 36.8% and 25.7%, and 53.0% and 36.9%, respectively. The survival of the members of the noncirrhotic group was better than the survival of the members of the cirrhotic group for patients with early stage (TNM stage I or transplantable) diseases. The 5-year disease-free and overall survival rates in patients without cirrhosis with transplantable diseases were 54.8% and 70.0%, respectively. CONCLUSIONS: In early stage diseases, patients without cirrhosis had significantly better survival rates than patients with cirrhosis. For a small hepatocellular carcinoma originating in a noncirrhotic liver, hepatic resection is a reasonable first-line treatment. Liver transplantation can be reserved as salvage treatment for patients with recurrent disease after hepatic resection.

Tacrolimus-associated hemolytic uremic syndrome: a case analysis.

BACKGROUND: Tacrolimus is an effective organ transplantation immunosuppressant. Hemolytic uremic syndrome (HUS) is a rare but severe complication of tacrolimus. METHODS: We report a case of tacrolimus-associated HUS and review the 15 previously reported cases. RESULTS: The results of the 16 cases indicated that tacrolimus-associated HUS is more frequent in females (56.3%), with the mean age at onset of 41.3 years. Forty-four percent of cases received renal transplantations. The average time from the first tacrolimus dose to HUS onset was 7.1 months. Prevalence was between 0.14.7%. The tacrolimus trough level did not predict the prognosis. Seven patients (43.7%) had improved graft function after treatment, including anticoagulation and antiplatelet therapy, reduction or discontinuation of tacrolimus, switch to cyclosporine (CyA), plasma exchange (PE) and dialysis. Five patients (31.3%) died and four patients (25%) lost their graft in spite of the above treatment. Mortality risk factors for transplant recipients with tacrolimus-associated HUS included: (1) non-renal transplant recipients (100% vs. 36.4%, p = 0.034); (2) lower peak serum Cr (2.58 +/- 1.23 vs. 6.16 +/- 1.96, p < 0.002); (3) liver dysfunction (60% vs. 0, p < 0.02); (4) higher serum lactate dehydrogenase (LDH) level (3119 +/- 1019 vs. 982 +/- 522, p < 0.001). A lower platelet count carried borderline mortality risk (29500 +/- 14480 vs. 59625 +/- 25584, p = 0.057). CONCLUSIONS: HUS should be included in the differential diagnosis of renal function deterioration in patients on tacrolimus post-organ transplantation. Frequent renal function monitoring and appropriate treatment should be performed aggressively to decrease morbidity and mortality, especially in patients with risk factors.

Factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. The surgeon's role in the managed care era.

BACKGROUND/AIMS: Length of stay is an important marker of medical resource consumption. In the modern managed care era physicians are driven to deliver the highest quality of care while using fewest resources. Hepatectomy represents a technically challenging and resource-intensive procedure, particularly in the setting of hepatic malignancy and liver cirrhosis. For improving quality of surgical management in such cases, we aimed to identify the factors affecting length of stay after hepatectomy for patients with hepatocellular carcinoma. METHODOLOGY: A total of 375 consecutive surgical hepatocellular carcinoma patients at a tertiary referral center during a 7-year period were reviewed. Length of stay after hepatectomy longer than 14 days was defined as prolonged length of stay. Patients were divided into two groups according to their length of stay. Patients with length of stay less than or equal to 14 days were in Group A and those with length of stay longer than 14 days were in Group B. Data for comparative analysis between both groups were categorized according to preoperative patients' clinical demographic factors, operation-related factors, and pathological factors. The significant univariate factors were used for subsequent multivariate analysis. RESULTS: The significant independent factors were patients' preoperative prothrombin activity, intraoperative blood transfusion, surgical complication, and the time to abdominal drain removal. Among these independent factors, surgical complication (p < 0.001, relative risk 7.01, and 95% confidence interval 3.46 to 14.18) was the most powerful factor for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma. CONCLUSIONS: Most of the independent factors for prolonged length of stay after elective hepatectomy for hepatocellular carcinoma patients are operation-related and surgeon-dependent. The surgeon plays a key role in determining length of stay. By minimizing blood transfusion, surgical complication, and the time to abdominal drain removal, length of stay can be significantly decreased in hepatocellular carcinoma patients undergoing hepatectomy.

Clinical characteristics of patients undergoing surgical resection of benign liver tumors in Taiwan, an endemic area for hepatocellular carcinoma.

BACKGROUND AND PURPOSE: The management of benign liver tumors in Asian countries endemic for hepatocellular carcinoma (HCC) may be different from that in western countries with a lower prevalence of HCC. The aim of this study was to investigate the characteristics of surgically treated benign liver tumors in a liver disease treatment center in Taiwan, an area prevalent for HCC. METHODS: Between January 1991 and June 2001, 57 patients with benign liver tumors underwent liver resection. The demographic data, radiologic diagnosis, and postoperative pathologic diagnosis of these patients were reviewed and analyzed. RESULTS: Cavernous hemangioma (n = 15), focal nodular hyperplasia (n = 12), and macro-regenerative nodule (n = 9) were the most frequent pathologic diagnoses of the resected liver tumors. HCC was the most frequent preoperative radiologic diagnosis (27/57, 47%). Four of the 9 macro-regenerative nodules had associated focal dysplastic change. All of the patients with macro-regenerative nodule had a preoperative imaging diagnosis of HCC. Only 1 liver biopsy was performed among the 57 patients. CONCLUSIONS: HCC was the most frequent preoperative radiologic diagnosis for benign liver tumors undergoing liver resection at a tertiary referral center in Taiwan. Macro-regenerative nodule of liver was commonly misdiagnosed as HCC by radiology alone in this study. In order to avoid unnecessary surgery, aspiration cytology should be performed for all patients without elevated serum alpha-fetoprotein and typical radiologic features of HCC. Patients with macro-regenerative nodules without atypical hepatocytes can be followed safely without surgical intervention, but when a macro-regenerative nodule with dysplastic change is found, it should be treated either by surgical resection or local ablation.

Risk factors associated with intra-operative major blood loss in patients with hepatocellular carcinoma who underwent hepatic resection.

BACKGROUND: Minimizing intraoperative blood loss during hepatectomy for hepatocellular carcinoma (HCC) decreases the need for blood transfusion. The purpose of this study was to investigate the risk factors associated with major blood loss in performing liver resection for HCC. METHODS: A total of 643 consecutive patients who underwent hepatic resection for HCC were included in this retrospective study. Patients were divided into groups according to the intraoperative blood loss. Blood loss more than 1,000 mL was defined as major blood loss. Twenty-eight variables were analyzed. RESULTS: As compared with patients with blood loss < 1,000 mL, patients with major blood loss had worse disease-free and overall survival rates (p < 0.001). Patients with major blood loss had higher surgical morbidity, mortality and prolonged hospital stay (p < 0.001). Multivariate analysis shows that independent risk factors associated with major blood loss include: male gender, alanine aminotrasferase > 55U/dL, prothrombin time < 95%, resection more than 3 Couinaud segments, en bloc resection, surgeon with low case volume (< 65 cases) and tumor with central location. CONCLUSIONS: Hemorrhage control is the main problem in liver resection for HCC. In patients with risk factors of major bleeding, it is essential to take effective measure in order to minimize intraoperative blood loss in hepatectomy for patients with HCC.

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

BACKGROUND: To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. METHODS: Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. RESULTS: The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. CONCLUSIONS: Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

BACKGROUND: Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. PATIENTS AND METHODS: We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. RESULTS: Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. CONCLUSIONS: Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.