HLA DRB1, DQA1, DQB1 and DPB1 polymorphisms in Namibian Khoi and San and in the Xhosa and South African mixed-ancestry population

We have analysed the HLA allele distributions in unrelated Namibian Khoi and San and South African Xhosa and mixed-ancestry (so-called Cape coloured) populations. The allelic specificities of the DRB1, DQA1, DQB1 and DPB1 loci were determined. We found loss of allelic diversity and predominance of certain alleles to be more pronounced in the San than in the Khoi. By contrast, the Xhosa indicated wide allelic diversity especially at the DRB1 and DPB1 loci. We found evidence that the Caucasoids may have been derived from an early migration wave, whereas African blacks arose from a later migration wave of an ancestral population pre-dating ethnic diversity. Frequencies in the Xhosa for the DRB10302, 1101, 1302 and 1304 alleles revealed clinal variation in a north-south direction across the African continent. For the DRB1, DQA1, DQB1 haplotypes there was greater variation in the Khoi than in the San, in whom certain haplotypes predominated. We found 13 previously unreported haplotypes. In Xhosa we found 30 different DRB1, DQA1, DQB1 haplotypes. Allele and haplotype characteristics and frequencies in the South African mixed-ancestry population were mostly intermediate between those found in Xhosa and reported for Caucasoids, and three possible ancestral southern African DRB1, DQB1, DPB1 haplotypes were found. We discuss the implications of our findings for organ donor transplantation in Xhosa and in the South African mixed-ancestry population

Effects of stocking density and immersion time on the performance of oysters in intertidal off-bottom culture

Intertidal culture in meshed bags on trestles is worldwide the most established culture method for oysters. Culturists can affect oyster performance by adjusting stocking density and immersion time, and it can be expected that these factors are not independent. The combined effect of stocking density and immersion time on survival, growth and condition of oysters was investigated on a culture site, where oysters are usually stocked at 8 kg bag−1. Half-grownoysters were stocked in three biomass densities: 4, 8 and 12 kg bag−1, nested within three immersion times (87%, 76% and 73% of tidal cycle). Chlorophyll-a concentration peaked in summer (~ 3–10 μg l−1) and was low in autumn (~ 1 μg l−1), and high chlorophyll-a levels coincided with oyster spawning period. Survival was not affected by density or immersion time. Shell growth per oyster and biomass production per bag were density dependent—higher at 4 than at 12 kg bag−1—but neither were different from 8 kg bag−1. Growth rates werenegativity related with immersion over the spawning period but showed a (non-significant) positive trend over other periods. At harvest, condition per oyster decreased with stocking density and increased with immersion. There was no interaction between density and immersion. Treatments had a more pronounced effect on meat content than on biomass production. Hence, oysters might be kept at higher stocking densities to increase biomass production during most of the growth cycle but restocked in lower densities, with longer immersion timesprior to harvest to maximize meat content at harvest

Beyond Median Overall Survival: Estimating Trends for Multiple Survival Scenarios in Patients With Metastatic Esophagogastric Cancer

Background: In recent years, clinical trials have shown improved survival of patients with metastatic esophageal or gastric cancer. The number of patients participating in clinical trials is limited, and survival improvements observed from clinical trials are unrepresentative for the full population. The aim of our study was to assess trends in survival for the best-case, typical, and worst-case scenarios in patients with metastatic esophageal or gastric cancer. Methods: We selected patients with metastatic esophageal or gastric cancer diagnosed between 2006 and 2020 fromthe nationwideNetherlands Cancer Registry. Survival was calculated for different percentiles of the survival curve for each incidence year (eg, the 10th percentile [p10] represents the top 10% of patients with the best survival): p10 (best-case), p25 (upper-typical), p50 (median), p75 (lower-typical), and p90 (worstcase). Weighted linear regression analyses were performed to test whether changes in survival were significant. Results: The overall median survival between 2006 and 2020 remained unchanged for patients with esophageal cancer (n510,448; from 5.2 to 5.2 months, respectively; P5.06) and improved for patients with gastric cancer (n510,512; from 3.5 to 4.3 months, respectively; P5.001). For patients with esophageal cancer, survival for the best-case scenario (p10; best 10% of patients) significantly improved from 17.2 to 21.0 months (P5.006). For patients with gastric cancer, survival significantly improved for the best-case scenario (p10) from 15.9 to 23.5 months (P,.001) and the upper-typical scenario (p25) scenario improved from 7.9 to 9.9 months (P,.001). Conclusions: Despite significant survival improvements in clinical trials, survival improvements were not observed for the majority of patients treated in daily clinical practice. An increase in survival was only observed for patients with the best prognosis

Implementation of a regional video multidisciplinary team meeting is associated with an improved prognosis for patients with oesophageal cancer A mixed methods approach

Background: Studies have shown that multidisciplinary team meetings (MDTM) improve diagnostic work-up and treatment-decisions. This study aims to evaluate the influence of implementing a regional-video-Upper-GI-MDTM (uMDTM) for oesophageal cancer (OC) on the number of patients discussed, treatment-decisions, perspectives of involved clinicians and overall survival (OS) in the Eindhoven Upper-GI Network consisting of 1 resection hospital and 5 referring hospitals. Methods: Between 2012 and 2018, patients diagnosed with OC within this region, were selected from the Netherlands Cancer Registry(n = 1119). From 2014, an uMDTM was gradually implemented and a mixed-method quantitative and qualitative design was used to analyse changes. Quantitative outcomes were described before and after implementation of the uMDTM. Clinicians were interviewed to assess their perspectives regarding the uMDTM. Results: After participation in the uMDTM more patients were discussed in an MDTM (80%–89%,p < 0.0001) and involvement of a resection centre during the uMDTM increased (43%–82%,p < 0.0001). The proportion of patients diagnosed with potentially curable OC (cT1-4a-x, any cN, cM0) remained stable (59%–61%, p = 0.452). Endoscopic or surgical resections were performed more often (28%–34%,p = 0.034) and the use of best supportive care decreased (21%–15%,p = 0.018). In the qualitative part an improved knowledge, collaboration and discussion was perceived due to implementation of the uMDTM. Three-year OS for all OC patients increased after the implementation of the uMDTM (24%–30%,p = 0.025). Conclusions: Implementation of a regional Upper-GI MDTM was associated with an increase in patients discussed with a resection centre, more curative resections and a better OS. It remains to be elucidated which factors in the clinical pathway explain this observed improved survival

Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease

BACKGROUND: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. METHODS: From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. RESULTS: The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P <0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. CONCLUSIONS: Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].

Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial.

Contains fulltext : 81805.pdf (publisher's version ) (Closed access)BACKGROUND: Little is known about the longitudinal course of health-related quality of life (HRQoL) in patients with Hodgkin's lymphoma during their post-treatment follow-up and re-adaptation to normal life. We report on the HRQoL of patients treated in the randomised H8 trial of the European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). We aimed to assess HRQoL and fatigue following treatment, to analyse relations with treatment, and to identify factors that predict persistent fatigue. METHODS: Patients received HRQoL questionnaires at the end of primary therapy and during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analysed with mixed models. Multiple polytomic nominal logistic regression was done to identify independent baseline predictors of fatigue within MFI-20 dimensions. Analyses were done on an intention-to-treat basis. This study is registered with www.ClinicalTrials.gov, number NCT00379041. FINDINGS: 2666 assessments from 935 patients were analysed. Mean follow-up was 90 months (range 52-118). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms; improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end of treatment was the only predictive variable for persistent fatigue, with odds ratios varying from 2.58 (95% CI 1.00-6.67) to 41.51 (12.02-143.33; p</=0.0001). Sensitivity analyses adjusting for missing data were much the same as the main results. INTERPRETATION: HRQoL data after treatment for early-stage Hodgkin's lymphoma show that patients experience strain and limitations in all subdomains apart from cognitive functioning (QLQ-C30), and also have reduced motivation (MFI-20). Differences in HRQoL improvement with time were linked to age and sex, but not type of treatment. Fatigue status at the end of treatment seems to predict subsequent HRQoL. FUNDING: French Ministry of Health, Programme Hospitalier de Recherche Clinique 1994, and French National League Against Cancer

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial

Background: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer. Methods: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0–2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m2) for 30 min at 42°C, delivered simultaneously or within 5–8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086. Findings: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3–88·5] for the experimental group vs 76·2% [68·0–84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis. Interpretation: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial. Funding: Organization for Health Research and Development and the Dutch Cancer Society