Is There Really a Difference in Outcomes between Men and Women with Hepatocellular Cancer?

Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)-only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options-likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.

Palliative care reduces emergency room visits and total hospital days among patients with metastatic HPB and GI cancers.

Palliative care services (PCS) have improved quality of life for patients across various cancer subtypes. Minimal data exists regarding PCSfor metastatic hepatopancreaticobiliary (HPB) and gastrointestinal (GI) cancers. We assessed the impact of PCS on emergency department visits, hospital admissions, and survival among these patients. Patients with metastatic HPB and GI cancer referred to outpatient PCS between 2014 and 2018 at a single institution were included. We compared the demographics, outcomes, and end-of-life indicators between those who did and did not receive PCS. The study included 183 patients, with 118 (64.5%) having received PCS. There were no significant differences in age, gender, race, marital status, or insurance. Those receiving PCS were more likely to have colorectal cancer (p = 0.0082) and receive chemotherapy (p = 0.0098). On multivariate analysis, PCS was associated with fewer ED visits (p = 0.0319), hospital admissions (p = 0.0002), and total inpatient hospital days (p < 0.0001) per 30 days of life. Overall survival was greater among patients receiving PCS (HR: 0.65 (0.46-0.92)). Outpatient PCS for patients with metastatic HPB and GI cancer is associated with fewer emergency department visits, hospital admissions, and inpatient hospital days, and improved overall survival.

Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma.

BACKGROUND: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS. METHODS: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro. RESULTS: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR. CONCLUSIONS: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS.

Outcomes of Breast-Conserving Surgery Plus Radiation vs Mastectomy for All Subtypes of Early-Stage Breast Cancer: Analysis of More Than 200,000 Women.

BACKGROUND: Recent large retrospective studies suggest that breast-conserving therapy (BCT) plus radiation yielded better outcomes than mastectomy (MST) for women with early-stage breast cancer (ESBC). Whether this is applicable to the different subtypes is unknown. We hypothesize that BCT yielded better outcomes than MST, regardless of subtypes of ESBC. STUDY DESIGN: Data on women diagnosed with first primary stage I to II breast cancer between 2010 and 2017 who underwent either BCT or MST were from the population-based 18 Surveillance, Epidemiology, and End Results cancer registries. The Kaplan-Meier method was used to estimate unadjusted 5-year overall survival and cause-specific survival. Univariable and multivariable Cox proportional regression models were used to determine the impact of surgical approaches on the hazard ratios adjusted for relevant demographic and clinical variables for molecular subtype (luminal A, luminal B, triple-negative, and HER2 enriched). RESULTS: Of the 214,128 patients with breast cancer, 41.6% received MST. For the different subtypes, BCT yielded better 5-year overall survival and cause-specific survival than MST. After adjusting for demographic and clinical factors, the risk of overall survival and cause-specific survival was still statistically significantly higher among MST recipients than BCT recipients for all subtypes. CONCLUSIONS: BCT yielded better survival rates than mastectomy for women with all subtypes of ESBC. The role of mastectomy for women with ESBC should be reassessed in future clinical trials.

Trends in hepatocellular carcinoma in Louisiana, 2005-2015.

Introduction: Louisiana has one of the highest incidence and mortality rates of hepatocellular carcinoma (HCC) in the nation. The aim of this study was to analyze the trends in HCC incidence and relative survival rates in Louisiana and compare them with corresponding national rates, which can be used to formulate strategies to improve Louisiana HCC outcomes. Methods: Data on primary invasive HCC diagnosed in patients 20 years or older between 2005 and 2015 were obtained from the Surveillance, Epidemiology and End Results (SEER) program and Louisiana Tumor Registry. Time trends in HCC incidence and 12-month relative survival were analyzed using Joinpoint regression. Case characteristics were compared on 2 time periods (2005-2009 and 2010-2015) using Chi-squared tests. Cause-specific survival was analyzed via log-rank and multivariable Cox proportional hazard model. Results: Over the study period, the average annual percent change (AAPC) in age-adjusted HCC incidence in Louisiana was nearly double that of the national estimate, 6% (95% CI: 4.7, 7.3) compared to 3.1% (95% CI: 2.4, 3.7). 12-month relative survival among HCC patients in Louisiana was 40.7% (95% CI: 38.9, 42.4) which was significantly less than the US rate of 48.2% (95% CI: 47.8, 48.6). Relative survival did improve in Louisiana from 2000 to 2015 at a rate similar to that of the US (AAPC (95% CI): 2.9 (0.7, 5.2) vs. 2.7 (2.3, 3.1), p = 0.8). In multivariable survival analysis, factors amongst Louisianans associated with worse survival were older age at diagnosis, advanced stage of disease, and lack of surgical therapy. Conclusion: The incidence of HCC continues to rise more dramatically in Louisiana than in the US. While some modest improvements in HCC survival have been realized, outcomes remain dismal. Future work identifying the most at-risk populations are needed to inform statewide public health initiatives.

10-Year Survival after Breast-Conserving Surgery Compared with Mastectomy in Louisiana Women with Early-Stage Breast Cancer: A Population-Based Study.

BACKGROUND: Louisiana has the third highest breast cancer mortality in the US, despite ranking 30th in incidence. Whether surgical approach contributes to such a poor outcome is unknown. We compared outcomes of breast-conserving surgery plus radiation (BCT) vs mastectomy (MST) for Louisiana women with early-stage breast cancer. STUDY DESIGN: Data on women diagnosed with Stage I-II breast cancer from 2004 to 2016 were analyzed from the Louisiana Tumor Registry. Overall survival (OS) and breast cancer-specific survival (CSS) were compared between BCT and MST. Kaplan-Meier method and log-rank test were used to compare survival curves, and logistic regression was used to examine the association of sociodemographic and clinical factors with the type of breast cancer surgery. Values of p < 0.05 were considered significant. RESULTS: Of the 18,260 patients, 9,968 patients (54.6%) had BCT and 8,292 patients (45.4%) had MST. Compared with BCT, the MST group tended to be underinsured/Medicare/Medicaid, more impoverished, had higher stage 2 disease, were more likely to reside in rural regions, travel ≥25 miles to radiation treatment facility, be treated at low volume centers, and have T3, node positive, and poorly differentiated tumors. Ten-year OS and CSS were significantly better among those who had BCT (OS: 80.0%; 95% CI: 79.0%-81.1%; CSS: 92.7%; 95% CI: 92.1%-93.4%) than those having MST (OS: 69.3%; 95% CI: 68.0%-70.5%; CSS: 88.8%:95% CI: 87.9%-89.7%) (p < 0.05). Even after controlling for sociodemographic and clinical variables, MST was associated with a 28.6% increased risk of death from all causes (hazard ratio [HR]:1.286; 95% CI:1.197-1.380) and a 29.8% increased risk of breast-cancer specific death (HR:1.298; 95% CI: 1.150-1.465). CONCLUSIONS: Surgical approach, a factor that is within the control of the surgeon, has an impact on mortality for Louisiana women with early-stage breast cancer.

Positive impact of the Patient Protection and Affordable Care Act Medicaid expansion on Louisiana women with breast cancer.

BACKGROUND: Louisiana is one of the few Southern states that enacted the Medicaid expansion of the Patient Protection and Affordable Care Act (ACA). To the authors' knowledge, the issue of how this has affected the breast cancer landscape in Louisiana is unknown. The authors have postulated that ACA expansion had a positive impact for Louisiana women diagnosed with breast cancer. METHODS: Data from the Louisiana Tumor Registry regarding 14,640 women aged 20 to 64 years who resided in Louisiana and were diagnosed with American Joint Committee on Cancer stage 0 to stage IV breast cancer between 2012 and 2018 were analyzed. The study period was divided into 2 groups: 1) before ACA expansion (January 1, 2012-May 31, 2016); and 2) after ACA expansion (June 1, 2016-December 31, 2018). The chi-square test and multivariable logistic regression models were used to assess the impact of ACA expansion. A P value <.05 was considered statistically significant. RESULTS: After ACA expansion, the rate of uninsured patients decreased from 5.4% to 3.0% (P < .0001), and the rate of Medicaid recipients increased from 11.6% to 17.7% (P < .0001). The diagnosis of stage I breast cancer increased from 36.8% to 44.7% (P < .0001), whereas the diagnosis of stage III breast cancer decreased from 10.7% to 8.5% (P < .0001). The receipt of radiotherapy after breast-conserving surgery increased from 81.2% to 84.0% (P = .0035), and the receipt of radiotherapy within 90 days increased from 57.2% to 61.7% (P = .0012). After adjustment for sociodemographic and clinical variables, the models demonstrated that ACA expansion decreased the uninsured rate by 48% (odds ratio [OR], 0.52; 95% CI, 0.43-0.63), increased the diagnosis of early-stage disease (stage0 to stage II) by 27% (OR, 1.27; 95% CI, 1.15-1.41), increased receipt of radiotherapy after breast-conserving surgery by 19% (OR, 1.19; 95% CI, 1.03-1.37), and reduced the delay of receipt of radiotherapy by 16% (OR, 0.84; 95% CI, 0.74-0.95). CONCLUSIONS: ACA expansion in Louisiana reduced the uninsured rate, increased the diagnosis of early-stage disease, and increased access to treatment.

Operative procedures for unresectable pancreatic cancer: does operative bypass decrease requirements for postoperative procedures and in-hospital days?

BACKGROUND: The optimal surgical management of patients found to have unresectable pancreatic cancer at open exploration remains unknown. METHODS: Records of patients who underwent non-therapeutic laparotomy for pancreatic cancer during 2000-2009 and were followed until death at Memorial Sloan-Kettering Cancer Center, New York, were reviewed. RESULTS: Over the 10-year study period, 157 patients underwent non-therapeutic laparotomy. Laparotomy alone was performed in 21% of patients; duodenal bypass, biliary bypass and double bypass were performed in 11%, 30% and 38% of patients, respectively. Complications occurred in 44 (28%) patients. Three (2%) patients died perioperatively. Postoperative interventions were required in 72 (46%) patients following exploration. The median number of inpatient days prior to death was 16 (interquartile range: 8-32 days). Proportions of patients requiring interventions were similar regardless of the procedure performed at the initial operation, as were the total number of inpatient days prior to death. Patients undergoing gastrojejunostomy required fewer postoperative duodenal stents and those undergoing operative biliary drainage required fewer postoperative biliary stents. CONCLUSIONS: In this study, duodenal, biliary and double bypasses in unresectable patients were not associated with fewer invasive procedures following non-therapeutic laparotomy and did not appear to reduce the total number of inpatient hospital days prior to death. Continued effort to identify unresectability prior to operation is justified.

Axillary node staging for microinvasive breast cancer: is it justified?

BACKGROUND: The natural history and role of axillary staging in microinvasive breast cancer (DCISM) remains controversial. We report clinical characteristics and outcome in patients with DCISM, focusing on the role of sentinel lymph node (SLN) biopsy. METHODS: From our prospective database we retrospectively identified 112 patients with DCISM who underwent SLN biopsy between 1996 and 2004 at our institution. Median follow-up was 6 years. RESULTS: We found positive SLN in 12% of patients (14 of 112): macrometastasis in 2.7% (3 of 112) and micrometastases or isolated tumor cells (ITC) in 10% (11 of 112). We performed axillary dissection (ALND) in all patients with macrometastasis (3 of 3), finding additional positive nodes in 66% (2 of 3), and in 27% of those with micrometastases/ITCs (3 of 11), finding no additional positive nodes. Among 98 patients with negative SLN (38% of whom received systemic therapy), there were 5 locoregional recurrences (1 in the ipsilateral axilla, 4 in the ipsilateral breast, all DCIS) and 4 contralateral second primary cancers. Among 14 patients with positive SLN (82 % of whom received systemic adjuvant therapy), there were no locoregional or distant recurrences. CONCLUSIONS: Our results suggest that SLN biopsy may be justified for DCISM, but is clearly most beneficial to identify a very small subset of DCISM patients (2.7%, with SLN macrometastasis) who could benefit from systemic adjuvant therapy. The benefit of SLN biopsy for patients with SLN micrometastases/ITCs (pN0mi or pN0(i+)) is uncertain, and in these cases ALND does not appear to be warranted. We suggest a wider reappraisal of routine SLN biopsy for DCISM.

Hypothermia: an unusual indication for gastric lavage.

BACKGROUND: Previous reports suggest that gastric lavage holds many risks and is not routinely indicated for decontamination of the overdose patient. OBJECTIVE: To present a case of overdose with concurrent accidental hypothermia where gastric decontamination was utilized. CASE REPORT: A 50-year-old hypothermic, comatose patient was transported to the Emergency Department with a concurrent, massive medication ingestion diagnosed incidentally on a routine abdominal computed tomography scan. Both active and passive rewarming measures, in conjunction with gastric lavage and retrieval of multiple pill fragments, were performed, and the patient survived to hospital discharge without sequelae. Interestingly, the patient admitted to an intentional ingestion of both labetalol and lorazepam. CONCLUSION: Due to hypothermia-mediated changes in metabolism, including gastric atony and decreased hepatic metabolism, gastric lavage may provide additional benefit in the management of severely hypothermic patients with potentially lethal, massive pill ingestions.

The role of VEGF pathways in human physiologic and pathologic angiogenesis.

BACKGROUND: In preclinical models, VEGF is a potent stimulant of both physiologic and pathologic angiogenesis. Conversely, anti-VEGF regimens have successfully inhibited angiogenesis both in vitro and in vivo. We hypothesized that VEGF would stimulate both physiologic and pathologic angiogenesis in a human-based fibrin-thrombin clot angiogenesis assay. We further speculated that anti-VEGF regimens would inhibit angiogenesis in this assay. METHODS: To test these hypotheses, discs of human placental veins (physiologic model) and fragments of human tumors (pathologic model) were embedded in fibrin-thrombin clots and treated with either VEGF-A165 (VEGF) or anti-VEGF pathway reagents including bevacizumab, IMC-18F1, IMC-1121, and PTK787 (n=30 wells per treatment group, multiple concentrations tested in each specimen). Angiogenic responses were assessed visually using a previously validated grading scheme. The percent of tissue explants that developed angiogenic invasion into the clot (% I) as well as the extent of angiogenic growth (AI) via a semi-quantitative scale were assessed at set intervals. RESULTS: VEGF failed to stimulate angiogenesis in both the physiologic and the pathologic model. While anti-VEGF reagents that targeted only one element of the VEGF pathway failed to consistently inhibit angiogenesis, PTK787, a receptor tyrosine kinase inhibitor that targets multiple VEGF and non-VEGF receptors, profoundly inhibited both physiologic and pathologic angiogenesis. CONCLUSION: These results suggest that VEGF-related pathways may not be solely responsible for stimulating angiogenesis in humans. Targeting the VEGF pathway in combination with elements of other growth factor pathways may provide a more effective means of inhibiting angiogenesis than targeting VEGF alone.

Medical malpractice matters: medical record M & Ms.

Accurate and thorough chart documentation is extremely important not only for patient continuity of care but also for medical legal risk reduction. It is common knowledge that a large percentage of court cases involving health care practitioners rely substantially on the chart documentation to determine outcomes. In this article, the authors have outlined particular court cases that illustrate the dramatic influence medical documentation has had in case law.

In vitro chemoresistance testing in well-differentiated carcinoid tumors.

BACKGROUND: Well-differentiated, "typical" carcinoid tumors traditionally have a very poor response to chemotherapy. We hypothesized that tumor specimens from well-differentiated carcinoid tumors would be highly resistant to the effects of chemotherapy when tested against a variety of antineoplastic agents in vitro. METHODS: Ninety-eight typical carcinoid specimens were surgically harvested, cultured, and tested against antineoplastics in vitro. (3)H-Thymidine incorporation was used to assess the percentage of cell-growth inhibition (PCI) of tested specimens. PCI was used to determine if specimens had extreme drug resistance (EDR), intermediate drug resistance (IDR), or low drug resistance (LDR) to each reagent against which they were tested. RESULTS: Seventy specimens generated results. Each was tested with an average of six drugs. The mean proportions of drugs classified as LDR, IDR, and EDR were 0.48 (range 0-1), 0.34 (range 0-1), and 0.18 (range 0-0.80), respectively. The mean numbers of drugs per specimen exhibiting LDR, IDR, and EDR chemoresistance were 2.7, 2.1, and 1.2, respectively. 57 of 70 specimens (81%) had LDR to at least two drugs. 5-FU had the highest frequency of low chemoresistance at 69%, followed by doxorubicin at 67%. Low in vitro resistance to chemotherapeutics was prevalent among typical carcinoids, while EDR was comparatively infrequent. CONCLUSIONS: This implies that there may be less clinical chemoresistance and more chemosensitivity among typical carcinoid tumors than clinical trials have previously revealed. These findings warrant additional investigations assessing the response of carcinoid tumors to assay-guided chemotherapy regimens.

A novel assay to assess the effectiveness of antiangiogenic drugs in human breast cancer.

BACKGROUND: Many cytotoxic drugs maintain antiangiogenic properties, but there are no human, tumor-based assays to evaluate their antiangiogenic potential. We used a fibrin-thrombin clot-based angiogenesis model to evaluate the angiogenic response of human breast cancer to various cytotoxic agents commonly used in its treatment. METHODS: Fragments of freshly harvested human breast tumors were embedded in fibrin-thrombin clots and treated with five drugs: adriamycin, taxol, 5-fluorouracil (5-FU), methotrexate, and vincristine. Each treatment group included a mean of 28 fragments (range 16-60). A total of four tumors were tested. Tumor fragments were tested with a single dose of each reagent. Angiogenic initiation, angiogenic growth, and overall angiogenic effect were determined for each treatment group using a previously validated scale. RESULTS: All four breast cancer specimens tested developed an angiogenic response, sprouting neovessels in vitro in a time-dependent fashion (r = 0.84, P = 0.0007). Taxol statistically inhibited angiogenesis in all four specimens with decreases in the mean angiogenic initiation, angiogenic growth, and overall effect that were 69%, 81%, and 94% of control values, respectively. Vincristine and 5-FU inhibited the mean overall angiogenic effect by 89% and 82% compared with control, respectively. Adriamycin inhibited overall effect 49%. Methotrexate was less effective. CONCLUSION: Freshly harvested breast cancer specimens develop an angiogenic response in a fibrin-thrombin clot-based angiogenesis model and respond to treatment with antineoplastic/antiangiogenic drugs. The antiangiogenic potential of commonly used breast cancer drugs varied among individual tumors. Data obtained from this model is unique and might potentially be used to further enhance the efficacy of cytotoxic regimens and individualize patient therapy.