MicroRNA-203 predicts human survival after resection of colorectal liver metastasis.

BackgroundResection of colorectal liver metastasis (CRLM) can be curative. Predicting which patients may benefit from resection, however, remains challenging. Some microRNAs (miRNAs) become deregulated in cancers and contribute to cancer progression. We hypothesized that miRNA expression can serve as a prognostic marker of survival after CRLM resection.ResultsMiR-203 was significantly overexpressed in tumors of short-term survivors compared to long-term survivors. R1/R2 margin status and high clinical risk score (CRS) were also significantly associated with short-term survival (both p = 0.001). After adjusting for these variables, higher miR-203 expression remained an independent predictor of shorter survival (p = 0.010). In the serum cohort, high CRS and KRAS mutation were significantly associated with short-term survival (p = 0.005 and p = 0.026, respectively). After adjusting for CRS and KRAS status, short-term survivors were found to have significantly higher miR-203 levels (p = 0.016 and p = 0.033, respectively).Materials and methodsWe employed next-generation sequencing of small-RNAs to profile miRNAs in solid tumors obtained from 38 patients who underwent hepatectomy for CRLM. To validate, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed on 91 tumor samples and 46 preoperative serum samples.ConclusionsAfter CRLM resection, short-term survivors exhibited significantly higher miR-203 levels relative to long-term survivors. MiR-203 may serve as a prognostic biomarker and its prognostic capacity warrants further investigation

Image-guided liver surgery: intraoperative projection of computed tomography images utilizing tracked ultrasound

AbstractBackgroundUltrasound (US) is the most commonly used form of image guidance during liver surgery. However, the use of navigation systems that incorporate instrument tracking and three-dimensional visualization of preoperative tomography is increasing. This report describes an initial experience using an image-guidance system with navigated US.MethodsAn image-guidance system was used in a total of 50 open liver procedures to aid in localization and targeting of liver lesions. An optical tracking system was employed to localize surgical instruments. Customized hardware and calibration of the US transducer were required. The results of three procedures are highlighted in order to illustrate specific navigation techniques that proved useful in the broader patient cohort.ResultsOver a 7-month span, the navigation system assisted in completing 21 (42%) of the procedures, and tracked US alone provided additional information required to perform resection or ablation in six procedures (12%). Average registration time during the three illustrative procedures was <1min. Average set-up time was approximately 5min per procedure.ConclusionsThe Explorer™ Liver guidance system represents novel technology that continues to evolve. This initial experience indicates that image guidance is valuable in certain procedures, specifically in cases in which difficult anatomy or tumour location or echogenicity limit the usefulness of traditional guidance methods

Prognostic significance of early recurrence: a conditional survival analysis in patients with resected colorectal liver metastasis

AbstractBackgroundFor patients undergoing liver resection for colorectal metastases, specific clinico‐pathological variables have been shown to be prognostic at baseline. This study analyses how the prognostic capability of these variables changes in a conditional survival model.MethodsRetrospective review of a prospectively maintained database of patients who underwent an R0 resection of colorectal liver metastases from 1994 to 2004 at a single institution.ResultsIn total, 807 patients were identified, with an 87‐month median follow‐up for survivors. Five‐ and 10‐year disease‐specific survivals (DSS) were 68% and 55%, respectively. The probability of further survival increased as the survival time increased. For 3‐year survivors (n = 504), DSS were no longer significantly different between patients with a low (0–2) or high (3–5) clinical risk score (CRS, P = 0.19). On multivariate analysis, independent predictors of DSS for 3‐year survivors were recurrence within the first 3 years after a liver resection, a pre‐operative carcinoembryonic antigen (CEA) >200 ng/ml and disease‐free interval <12 months prior to the diagnosis of liver metastasis. However, for those patients who were recurrence free at 1 year, no clinico‐pathological variables retained prognostic significance.DiscussionAfter 3 years of DSS and 1 year of recurrence‐free survival, baseline clinico‐pathological variables have a limited ability to predict future survival. Early post‐operative recurrence appears to be the most useful single clinical feature in estimating conditional DSS

Mutation location on the RAS oncogene affects pathologic features and survival after resection of colorectal liver metastases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136316/1/cncr30351_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136316/2/cncr30351.pd

The association between green space and cause-specific mortality in urban New Zealand: an ecological analysis of green space utility

&lt;b&gt;Background:&lt;/b&gt; There is mounting international evidence that exposure to green environments is associated with health benefits, including lower mortality rates. Consequently, it has been suggested that the uneven distribution of such environments may contribute to health inequalities. Possible causative mechanisms behind the green space and health relationship include the provision of physical activity opportunities, facilitation of social contact and the restorative effects of nature. In the New Zealand context we investigated whether there was a socioeconomic gradient in green space exposure and whether green space exposure was associated with cause-specific mortality (cardiovascular disease and lung cancer). We subsequently asked what is the mechanism(s) by which green space availability may influence mortality outcomes, by contrasting health associations for different types of green space. &lt;b&gt;Methods:&lt;/b&gt; This was an observational study on a population of 1,546,405 living in 1009 small urban areas in New Zealand. A neighbourhood-level classification was developed to distinguish between usable (i.e., visitable) and non-usable green space (i.e., visible but not visitable) in the urban areas. Negative binomial regression models were fitted to examine the association between quartiles of area-level green space availability and risk of mortality from cardiovascular disease (n = 9,484; 1996 - 2005) and from lung cancer (n = 2,603; 1996 - 2005), after control for age, sex, socio-economic deprivation, smoking, air pollution and population density. &lt;b&gt;Results:&lt;/b&gt; Deprived neighbourhoods were relatively disadvantaged in total green space availability (11% less total green space for a one standard deviation increase in NZDep2001 deprivation score, p &#60; 0.001), but had marginally more usable green space (2% more for a one standard deviation increase in deprivation score, p = 0.002). No significant associations between usable or total green space and mortality were observed after adjustment for confounders. &lt;b&gt;Conclusion&lt;/b&gt; Contrary to expectations we found no evidence that green space influenced cardiovascular disease mortality in New Zealand, suggesting that green space and health relationships may vary according to national, societal or environmental context. Hence we were unable to infer the mechanism in the relationship. Our inability to adjust for individual-level factors with a significant influence on cardiovascular disease and lung cancer mortality risk (e.g., diet and alcohol consumption) will have limited the ability of the analyses to detect green space effects, if present. Additionally, green space variation may have lesser relevance for health in New Zealand because green space is generally more abundant and there is less social and spatial variation in its availability than found in other contexts

Translation and psychometric assessment of the mastectomy module of the BREAST-Q questionnaire for use in Nigeria

Background: The majority of non-metastatic breast cancer patients in sub-Saharan Africa are recommended to have mastectomy. The impact of mastectomy on a predominantly young African patient population requires evaluation. The BREAST-Q is a validated patient-reported outcome measure of quality-of-life following breast surgery that has been translated into 30 languages-none in Africa. This study aimed to translate and assess the psychometric properties of the mastectomy module of the BREAST-Q for use in Nigeria. Methods: The BREAST-Q mastectomy module was translated from English to Yoruba and its psychometric properties assessed using best practice guidelines. Translation was performed in 4 steps: forward translation (x2), back translation, back translation review, and cognitive interviews with post-mastectomy patients. The translated BREAST-Q instrument was administered to post-mastectomy patients (n = 21) alongside the EORTC-QLQ BR23 to evaluate construct validity. Test-retest reliability was evaluated using intraclass correlation coefficients (ICC); surveys were re-administered 4 weeks apart. Results: The translation process identified English phrases not amenable to direct translation, including “emotionally healthy” and descriptions of pain (“nagging,” “throbbing,” “sharp”). Translations were amended to reflect local context and question intent. During cognitive interviews, patients provided suggestions to simplify complex phrases, e.g. “discomfort in your breast area.”. Internal consistency within scales was over 0.70 for psychosocial wellbeing (α = 0.84–0.87), sexual wellbeing (α = 0.98–0.99), physical wellbeing in chest (α = 0.84–0.86), and satisfaction with care (α = 0.89–0.93). ICC for test-retest reliability was moderate (0.46–0.63). Conclusions: The Yoruba version of the BREAST-Q mastectomy module presents a unique opportunity to adequately capture the experiences of Nigerian women post mastectomy. This instrument is being used in a pilot study of Nigerian patients to identify targets for intervention to improve the patient experience and compliance with breast cancer surgery

Percutaneous Preoperative Biliary Drainage for Resectable Perihilar Cholangiocarcinoma: No Association with Survival and No Increase in Seeding Metastases

Background: Endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) are both used to resolve jaundice before surgery for perihilar cholangiocarcinoma (PHC). PTBD has been associated with seeding metastases. The aim of this study was to compare overall survival (OS) and the incidence of initial seeding metastases that potentially influence survival in patients with preoperative PTBD versus EBD. Methods: Between 1991 and 2012, a total of 278 patients underwent preoperative biliary drainage and resection of PHC at 2 institutions in the Netherlands and the United States. Of these, 33 patients were excluded for postoperative mortality. Among the 245 included patients, 88 patients who underwent preoperative PTBD (with or without previous EBD) were compared to 157 patients who underwent EBD only. Survival analysis was done with Kaplan–Meier and Cox regression with propensity score adjustment. Results: Unadjusted median OS was comparable between the PTBD group (35 months) and EBD-only group (41 months; P = 0.26). After adjustment for propensity score, OS between the PTBD group and EBD-only group was similar (hazard ratio, 1.05; 95 % confidence interval, 0.74–1.49; P = 0.80). Seeding metastases in the laparotomy scar occurred as initial recurrence in 7 patients, including 3 patients (3.4 %) in the PTBD group and 4 patients (2.7 %) in the EBD-only group (P = 0.71). No patient had an initial recurrence in percutaneous catheter tracts. Conclusions: The present study found no effect of PTBD on survival compared to patients with EBD and no increase in seeding metastases that developed as initial recurrence. These data suggest that PTBD can safely be used in preoperative management of PHC

Gemcitabine with Cisplatin Versus Hepatic Arterial Infusion Pump Chemotherapy for Liver-Confined Unresectable Intrahepatic Cholangiocarcinoma

Background: A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA. Methods: We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center. Results: In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p &lt; 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0–13.6%) in the gem-cis group versus 34.3% (95% CI 28.1–41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19–0.39). Conclusions: This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.</p

Cancer disparities in Southeast Asia: intersectionality and a call to action.

Southeast Asia has a population of over 680 million people—approximately half the population of India and twice the population of the United States—and is a region marked by rich and complex histories and cultures, dynamic growth, and unique and evolving health challenges.1 Despite the momentum of economic development, health inequalities persist. These inequities have been aggravated since the COVID-19 pandemic, which pushed millions further into poverty, possibly exacerbating health disparities, especially among populations who suffer vulnerabilities.2 Particularly salient are the challenges associated with providing adequate care for people with cancer, a leading cause of morbidity and mortality in the region.1,2 Cancer incidence and mortality in the region are projected to rise in the coming decades, given population growth and rapidly changing socioeconomic and geopolitical factors, as well as a host of interrelated and dynamic environmental, behavioral, and occupational risk factors.1, 2, 3 Large epidemiologic studies have demonstrated differences among Southeast Asian countries in terms of cancer incidence and mortality.3 Epidemiologic patterns can be attributed to variations in complex risk factors, access to screening and cancer care, and likely genetic predisposition.1, 2, 3 However, these differences also underscore that within each country exist richly diverse populations that experience disparities in cancer risk, screening, care access, outcomes, and survivorship in ways that require further examination. We draw attention to disparities in cancer in Southeast Asian countries. We highlight the need to study cancer disparities affecting minoritised groups in Southeast Asia—not only along lines of race/ethnicity, but also people minoritised along lines of sex/gender, socioeconomic status, religion, geography, and others. We highlight the intersectionality of elements of an individual's identity. Intersectionality, developed by critical race theorist Professor Kimberlé Crenshaw in 1989, is an analytic framework borne out of Black American feminist scholarship, that examines how a person's sociopolitical identities lead to disparate balances of privilege and discrimination.4 An intersectional approach would demonstrate that an individual or a community does not only experience economic poverty as the sole barrier to improved health; such an approach would examine how other identities such as religion or immigration status affect access to care. These different social determinants of health are not mutually exclusive; their interrelationships are complex, with consequences for health.5 We leverage the intersectional approach, which parallels the inherently syncretic cultures and histories of Southeast Asian nations, and explore how these identities impact access to cancer care. Meaningful cancer research focusing on peoples of Southeast Asia could present many opportunities for intervention and improvement