Prostate Specific Antigen and Biopsy Contamination in the Göteborg-1 Randomized, Population-Based, Prostate Cancer Screening Trial.

PURPOSE: Even when a screening study has demonstrated a mortality reduction, the degree of pre-testing and contamination is of importance as it can dilute the "true" effect of screening. Our object was to describe the level of pre-testing and contamination in the Göteborg-1 prostate cancer screening trial. MATERIALS AND METHODS: A total of 20,000 men, 50-64 years old, were invited in 1994 and randomized to either a screening group (offered prostate specific antigen testing every 2 years) or to a control group. Follow-up was through December 31, 2014. Outcome measurement was overall testing in the screening group and control group. A positive prostate specific antigen test was defined as a prostate specific antigen ≥3 ng/ml. RESULTS: In the study, 4.2% in the screening group and 4.6% men in the control group were tested before study start. During follow-up, 72% in the control group took at least 1 prostate specific antigen test (contamination) compared to 87% of men in the screening group. Of all prostate specific antigens, 24% in the screening group and 39% in the control group were above threshold. In total, 66% of the men underwent prostate biopsy within 12 months from a raised prostate specific antigen in the screening group and 28% in the control group. CONCLUSIONS: Similar proportions of men were prostate specific antigen-tested in both the screening group and control group, yet only a minority of contamination prostate specific antigens led to biopsy. Also, men in the screening group started screening at a younger age. These could both be explanations for our result that organized screening is more effective in reducing prostate cancer mortality than non-organized testing. When carried out properly and compared to an unscreened population, the effects of organized screening are likely even greater than previously shown in the Göteborg screening trial.

C-reactive protein identifies patients at risk of postpancreatectomy hemorrhage.

BACKGROUND: Postpancreatectomy hemorrhage grade C (PPH C) is a dreaded complication after pancreaticoduodenectomy (PD) with high mortality rate. Concurrent risk factors for PPH C have been difficult to recognize. Connection between postoperative pancreatic fistulas (POPF) and PPH C is well known, but POPF is often unknown prior to the PPH. The aim of this retrospective study was to define potential predictive factors for PPH C. METHODS: Retrospectively, 517 patients who underwent PD between 2003 and 2018 were included in the study. Twenty-three patients with PPH C were identified, and a matched control group of 92 patients was randomly selected. Preoperative data (body mass index, cardiovascular disease, history of abdominal surgery, biliary stent, C-reactive protein (CRP), ASA-score), perioperative data (bleeding, pancreatic anastomosis, operation time), and postoperative data (CRP, drain amylase, POPF, biliary fistula) were analyzed as potential predictors of PPH C. RESULTS: High postoperative CRP (median 140 mg/L on day 5 or 6) correlated with the development of PPH C (p < 0.05). Postoperative drain amylase levels were not clinically relevant for occurrence of PPH C. Grade C POPF or biliary leak was observed in the majority of the PPH C patients, but the leaking anastomoses were not detected before the bleeding started. DISCUSSION: High postoperative CRP levels are related to an increased risk of PPH C.

Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. PURPOSE: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. MATERIAL AND METHODS: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. RESULTS: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. CONCLUSIONS: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.

Patterns and resectability of colorectal cancer recurrences: outcome study within the COLOFOL trial.

BACKGROUND: Improvements in surgery, imaging, adjuvant treatment, and management of metastatic disease have led to modification of previous approaches regarding the risk of recurrence and prognosis in colorectal cancer. The aims of this study were to map patterns, risk factors, and the possibility of curative treatment of recurrent colorectal cancer in a multimodal setting. METHODS: This was a cohort study based on the COLOFOL trial population of patients who underwent radical resection of stage II or III colorectal cancer. The medical files of all patients with recurrence within 5 years after resection of the primary tumour were scrutinized. Follow-up time was 5 years after the first recurrence. Primary endpoints were cumulative incidence, site, timing, and risk factors for recurrence, and rate of potentially curative treatment. A secondary endpoint was survival. RESULTS: Of 2442 patients, 471 developed recurrences. The 5-year cumulative incidence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. The median time to detection was 1.1 years after surgery and 87.3 per cent were detected within 3 years. Some 98.2 per cent of patients who had potentially curative treatment were assessed by a multidisciplinary tumour board. A total of 47.8 per cent of the recurrences were potentially curatively treated. The 5-year overall survival rate after detection was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent for all patients with recurrence, 58.6 (51.9 to 64.7) per cent in the potentially curatively treated group and 7.7 (4.8 to 11.5) per cent in the palliatively treated group. CONCLUSION: Time to recurrence was similar to previous results, whereas the 21.4 per cent risk of recurrence was somewhat lower. The high proportion of patients who received potentially curative treatment, linked to a 5-year overall survival rate of 58.6 per cent, indicates that it is possible to achieve good results in recurrent colorectal cancer following multidisciplinary assessment.

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study.

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003-2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P<0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P=0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P=0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.

Determinants of energy drink consumption in adolescents: identification of sex-specific patterns.

OBJECTIVES: To investigate sex differences in sociodemographic and lifestyle correlates of frequent energy drink (ED) consumption in adolescents. STUDY DESIGN: This study was based on data collected among French-speaking Belgian adolescents aged 11-20 years (n = 8137) within the 2018 Health Behaviour in School-aged Children study. METHODS: Multiple logistic analyses stratified by sex were performed to estimate the associations between consuming EDs more than once a week, and various sociodemographic and lifestyle characteristics. RESULTS: Overall, 14.0% of boys and 7.6% of girls consumed ED more than once a week. For both genders, the likelihood of consuming ED more than once a week was higher among adolescents consuming soft drinks daily (vs. < daily), alcohol weekly (vs. < weekly), spending at least 5 h/day in front of screens (vs. < 5 h/day), and going to bed later than 11:30 PM (vs. ≤ 10:00 PM). Among boys, adolescents reporting at least 1 h of moderate-to-vigorous physical activity (MVPA) daily (vs. < 1 h/day MVPA) were more likely to consume ED more than once a week (adjusted odd ratio (aOR) = 1.49 (95% confidence interval [CI] 1.11-2.01)). Among girls, adolescents from low affluence families (vs. high affluence) (aOR = 2.03 (95% CI 1.19-3.48)) and immigrants (vs. natives) (2nd generation: aOR = 1.75 (95% CI 1.31-2.32); 1st generation: aOR = 1.90 (95% CI 1.20-3.03)) were more likely to consume ED more than once a week. CONCLUSIONS: We identified different patterns of ED consumption in boys and girls. These results suggest that sex-tailored interventions could be relevant to reduce ED consumption in adolescents.

Influence of primary tumour and patient factors on survival in patients undergoing curative resection and treatment for liver metastases from colorectal cancer.

BACKGROUND: Resection of the primary tumour is a prerequisite for cure in patients with colorectal cancer, but hepatic metastasectomy has been used increasingly with curative intent. This national registry study examined prognostic factors for radically treated primary tumours, including the subgroup of patients undergoing liver metastasectomy. METHODS: Patients who had radical resection of primary colorectal cancer in 2009-2013 were identified in a population-based Swedish colorectal registry and cross-checked in a registry of liver tumours. Data on primary tumour and patient characteristics were extracted and prognostic impact was analysed. RESULTS: Radical resection was registered in 20 853 patients; in 38·7 per cent of those registered with liver metastases, surgery or ablation was performed. The age-standardized relative 5-year survival rate after radical resection of colorectal cancer was 80·9 (95 per cent c.i. 80·2 to 81·6) per cent, and the rate after surgery for colorectal liver metastases was 49·6 (46·0 to 53·2) per cent. Multivariable analysis identified lymph node status, multiple sites of metastasis, high ASA grade and postoperative complications after resection of the primary tumour as strong risk factors after primary resection and following subsequent liver resection or ablation. Age, sex and primary tumour location had no prognostic impact on mortality after liver resection. CONCLUSION: Lymph node status and complications have a negative impact on outcome after both primary resection and liver surgery. Older age and female sex were underrepresented in the liver surgical cohort, but these factors did not influence prognosis significantly.

ANTECEDENTES: Para curar el cáncer colorrectal es necesaria la resección del tumor primario, pero cada día es más frecuente la realización de una metastasectomía hepática con intención curativa. Este estudio basado en un registro nacional analizó los factores pronósticos para los tumores primarios tratados con intención curativa, incluido un subgrupo de pacientes a los que se realizó una metastasectomía hepática. MÉTODOS: En el registro poblacional sueco de cáncer colorrectal se identificaron los pacientes a los que se realizó una resección primaria radical entre 2009-2013 y se cotejaron con un registro de tumores hepáticos. Se obtuvieron los datos sobre el tumor primario y las características del paciente, y se analizó su influencia en el pronóstico. RESULTADOS: Se identificaron 20.853 pacientes con resección radical, de los que en un 38,9% se realizó la resección o ablación de metástasis hepáticas. La supervivencia relativa a 5 años, estandarizada por edad, después de la resección radical del cáncer colorrectal y después de la cirugía de las metástasis hepáticas colorrectales fue del 80,6% (i.c. del 95% 79,8-81,3) y del 49,6% (i.c. del 95%: 46,0-53,2), respectivamente. El análisis multivariable identificó la invasión ganglionar, las metástasis en varias localizaciones, una puntuación ASA alta y las complicaciones postoperatorias después de la resección del tumor primario como factores de riesgo tanto de la resección primaria como de la resección o ablación hepática. No tuvieron influencia sobre la mortalidad tras de la resección hepática ni la edad, el sexo o la ubicación del tumor primario. CONCLUSIÓN: El grado de invasión linfática y las complicaciones después de la resección primaria tuvieron un impacto negativo en los resultados tanto de la cirugía primaria, como de la cirugía hepática. Si bien la edad avanzada y el sexo femenino estaban infrarrepresentados en la cohorte de cirugía hepática, estos factores no influyeron significativamente en el pronóstico.

The impact of increased immigration to Sweden on the incidence and treatment of patients with HCC and underlying liver disease.

Background: Sweden has traditionally been considered a country with a low incidence of hepatocellular carcinoma (HCC). However, the increasing number of immigrants from areas with a high incidence of HCC might affect the number of HCC patients in Sweden. Aim: To examine trends in the incidence, treatment and overall survival of patients with HCC and an underlying liver disease (ULD) from a restricted, well-defined region of Sweden, between 2000 and 2014. Patients and methods: Nine hundred and eight patients with HCC were identified. Subjects were grouped into 5-year periods, and analysed for HCC diagnosis, ULD, staging and treatment selection in populations born outside Sweden versus non-immigrants and patient survival. The regions were Africa, Asia, EU-28 together with America and the Nordic countries, eastern Europe and Sweden. Results: Over the time periods, the patients with HCC and ULD increased. More patients from Africa had HCC and ULD than what would have been expected based on the number of immigrants from this region and they were also significantly younger than Sweden-born patients. For patients from Africa, Asia and eastern Europe; viral hepatitis was dominating ULDs. Patients from Africa, Asia and eastern Europe were subjected to liver transplantation (LT) in higher proportions than patients from Sweden. The survival rate for patients from eastern Europe was significantly better. Conclusions: Immigration increased the incidence of HCC and the need for active treatment such as LT. This fact raises the question of whether immigrants from regions with a high incidence of HCC ought to be subjected to mandatory hepatitis B and C virus (HBV and HCV) diagnosis and consequent liver ultrasounds for diagnosis of occult HCC. With such strategies, the morbidity and mortality of HCC could be reduced.

Allopregnanolone involvement in feeding regulation, overeating and obesity.

Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABAA receptors (primarily with α3 and α2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABAA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABAA receptor (with compensatory >12-, >5- and >1.5-fold increases in α4, γ2, and α1, α3 subunits), and increases in the α4, ßx, δ receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.

Risk factors for lymph node metastases in women with endometrial cancer: A population-based, nation-wide register study-On behalf of the Swedish Gynecological Cancer Group.

The role of lymphadenectomy in the management of early endometrial cancer remains controversial. In the recent ESMO-ESGO-ESTRO guidelines, lymphadenectomy is recommended for patients with endometrioid adenocarcinoma Grade 3 with deep myometrial invasion, but complete agreement was not achieved. In Sweden, DNA aneuploidy has been included as a high-risk factor. The aim of our study was to evaluate the impact of tumor histology, FIGO grade, DNA ploidy and myometrial invasion (MI) on occurrence of lymph node metastasis (LNM) in patients with endometrial cancer. The study design is a retrospective cohort study based on prospectively recorded register data. Endometrial cancer patients registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2015 with FIGO Stages I-III and verified nodal status were included. Data on DNA ploidy, histology, FIGO grade and MI were included in multivariable log-binomial regression analyses with LNM as dependent variable. 1,165 cases fulfilled the inclusion criteria. The multivariable analyses revealed increased risk of LNM in patients with tumors with MI ≥ 50% (risk ratio [RR] = 4.1; 95% confidence interval [CI] 3.0-5.6), nonendometrioid compared to endometrioid histology (RR 1.8; CI 1.4-2.4) and FIGO Grade 3 compared to Grade 1-2 tumors (RR 1.5; CI 1.1-2.0). No statistically significant association between DNA ploidy status and LNM was detected. This population-based, nation-wide study in women with endometrial cancer confirms a strong association between MI ≥ 50%, nonendometrioid histology and FIGO Grade 3, respectively, and LNM. DNA ploidy should not be included in the preoperative decision making of removing nodes or not.

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial, SweBCG 91 RT.

BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients. PATIENTS AND METHODS: A total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program. RESULTS: After 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P<0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P=0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P=0.68, nor was breast cancer-specific mortality significantly higher. CONCLUSIONS: RT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

STUDY DESIGN: This is a randomized controlled prospective trial with two parallel groups. OBJECTIVES: The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. SETTING: This study was conducted in SCS Research Center in Colorado, USA. METHODS: A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). RESULTS: Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. CONCLUSION: TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study.

BACKGROUND: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. PATIENTS AND METHODS: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, postmastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. RESULTS: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. CONCLUSION: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet.

Ingestion of energy rich high fat diets is one of the determining factors associated with the obesity epidemic. Therefore, much can be learned from studies of obesity-related substances given to animals fed a high fat diet. The progesterone metabolite allopregnanolone is a potent positive modulator of the gamma-aminobutyric acid (GABA)A-receptor, and both allopregnanolone and GABA have been implicated in evoking hyperphagia. In this study, food intake and body weight gain were investigated during repeated allopregnanolone exposure. Male Wistar rats were studied when fed chow ad libitum, with chow access for 4h per day or with 45% high fat pellets for 4h per day. Rats on the high fat diet were separated into obesity prone and obesity resistant individuals. Subcutaneous injections of allopregnanolone were given once daily over five consecutive days. Repeated exposure to allopregnanolone lead to increased weight gain, significantly so in schedule fed rats on a high fat diet. The increased weight gain was correlated to an increased energy intake. Both obesity resistant and obesity prone rats responded to allopregnanolone with increased weight gain. Obesity resistant rats treated with allopregnanolone increased their energy intake and ate as much as vehicle treated obesity prone rats. Their weight gain was also increased to the level of obesity prone rats injected with just the vehicle carrier oil. Thus, it appears that allopregnanolone may be one of the endogenous factors involved in weight gain, especially when the diet is rich in fat.

Allopregnanolone induces a diurnally dependent hyperphagic effect and alters feeding latency and duration in male Wistar rats.

AIM: Gamma-aminobutyric acid (GABA)-ergic transmission from the hypothalamus is essential for normal feeding regulation, and hyperphagia can be induced by local application of GABAA -receptor agonists to different feeding-associated brain areas. The food intake in rats varies diurnally and that may influence the effect of GABAA -receptor active compounds. The progesterone metabolite allopregnanolone is a highly potent endogenous positive modulator of the GABAA receptor. Therefore, it is easy to envisage that allopregnanolone would have a hyperphagic effect, but earlier reports in rat have given ambiguous results. However, a contributing factor for the discrepancy may be the time point of the diurnal cycle in which the experiments were performed. The aim of this study was to investigate the effect of allopregnanolone on intake of standard chow in male Wistar rats at different time points of the day. METHODS: Chow intake was measured after acute administration of allopregnanolone, and feeding behaviour was analysed to detect meal patterns. RESULTS: We found that allopregnanolone increased chow intake by up to four times in the dark part of the 24-h cycle. The rats ate significantly more, and the effect of allopregnanolone was more prominent in the active (dark) compared with the inactive (light) period. Allopregnanolone also reduced feeding latency and prolonged the meal duration compared with vehicle. CONCLUSION: Allopregnanolone seems to act at several levels of feeding regulation, that is, to initiate feeding and to prolong the duration of a meal, thereby increasing the meal size, especially in the dark period of the 24-h cycle.

Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy.

Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.

Heavy drinking in early adulthood and outcomes at mid life.

BACKGROUND: Heavy drinking in early adulthood among Blacks, but not Whites, has been found to be associated with more deleterious health outcomes, lower labor market success and lower educational attainment at mid-life. This study analysed psychosocial pathways underlying racial differences in the impact of early heavy alcohol use on occupational and educational attainment at mid-life. METHODS: Outcomes in labor market participation, occupational prestige and educational attainment were measured in early and mid-adulthood. A mixture model was used to identify psychosocial classes that explain how race-specific differences in the relationship between drinking in early adulthood and occupational outcomes in mid-life operate. Data came from Coronary Artery Risk Development in Young Adults, a longitudinal epidemiologic study. RESULTS: Especially for Blacks, heavy drinking in early adulthood was associated with a lower probability of being employed in mid-life. Among employed persons, there was a link between heavy drinking for both Whites and Blacks and decreased occupational attainment at mid-life. We grouped individuals into three distinct distress classes based on external stressors and indicators of internally generated stress. Blacks were more likely to belong to the higher distressed classes as were heavy drinkers in early adulthood. Stratifying the data by distress class, relationships between heavy drinking, race and heavy drinking-race interactions were overall weaker than in the pooled analysis. CONCLUSIONS: Disproportionate intensification of life stresses in Blacks renders them more vulnerable to long-term effects of heavy drinking.

Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC: satellite--a phase II study from the Swedish Lung Cancer Study Group.

BACKGROUND: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. METHODS: Between February 2006 and August 2007 75 patients in stage III NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1>1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m² and cisplatin 75 mg/m² with 3 weeks interval. An initial dose of cetuximab 400 mg/m² was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m². TOXICITY was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. RESULTS: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. HISTOLOGY: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss>5%. TOXICITY: esophagitis grade 1-2: 72%; grade 3: 1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5: 1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. CONCLUSION: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. TOXICITY, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.

Rectal washout and local recurrence of cancer after anterior resection.

BACKGROUND: Adenocarcinomas of the rectum shed viable cells, which have the ability to implant. Intraoperative rectal washout decreases the amount and viability of these cells, but there is no conclusive evidence of the effect of rectal washout on local recurrence after rectal cancer surgery. METHODS: Data were analysed from a population-based registry of patients who had anterior resection from 1995 to 2002 and were followed for 5 years. Rectal washout was performed at the discretion of the surgeon. National inclusion of patients with rectal cancer and follow-up was near complete (approximately 97 and 98 per cent respectively). RESULTS: A total of 4677 patients were analysed (3749 who had washout, 851 no washout and 77 with information missing); 52.0 per cent of patients in the washout group and 41.4 per cent in the no-washout group had preoperative radiotherapy (P < 0.001). Local recurrence rates were 6.0 and 10.2 per cent respectively (P < 0.001). Univariable and multivariable logistic regression analyses produced odds ratios that favoured washout: 0.56 (95 per cent confidence interval (c.i.) 0.43 to 0.72) and 0.61 (0.46 to 0.80) respectively (both P < 0.001). In multivariable analysis restricted to patients who had curative surgery, the odds ratio was 0.59 (95 per cent c.i. 0.44 to 0.78; P < 0.001). CONCLUSION: There was a more favourable outcome in patients after rectal washout than without.

Regional differences in local recurrence rates after rectal cancer surgery.

AIM: To analyse a substantial regional difference in local failure rate after rectal cancer surgery focusing on management. METHOD: National, population-based, prospective registry data were used, including comprehensive 5-year follow up of 3783 patients operated on in the period 1998-2000. Local recurrence rates were compared using crude rate, Kaplan-Meier estimates and competing risk methodology. Resected patients (651 regional and 3132 national) were analysed and subgroup comparisons of management were performed. RESULTS: The crude local recurrence rate was 13.7% in the regional cohort and 7.1% in the national cohort. The absolute difference of 6.6% may partly be explained by systematic errors of underreporting (≤ 1.4%), differences in patient populations and indications for surgery. A significant difference in the use of neoadjuvant radiotherapy (explaining ≤ 1.0%) and some aspects of surgical strategy were also observed. CONCLUSIONS: We conclude that some of the difference in the registered incidence of local recurrence between the regional and the national cohorts remains unexplained and may depend on surgical technique in terms of lack of radicality in removing tumour tissue.