Background: In the past three decades, the incidence of colorectal cancer (CRC) in Norway has doubled, surpassing all other Nordic countries for both men and women to become the most frequently ...diagnosed cancer. A small-scale, randomized study on flexible sigmoidoscopy (FS) screening in Telemark, Norway, has shown a reduction in accumulated CRC incidence after 13 years. The aim of our study was to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions (polypectomy), and to test out the management and organization mimicking a countrywide screening service. A total of 13,823 men and women (1:1), age 55-64 years, were drawn randomly from the population registries in Oslo (urban) and the county of Telemark (mixed urban and rural) and invited to have a screening examination. The rest of the relevant age cohorts constituted the control groups. In the screening group, 535 individuals were excluded according to exclusion criteria, rendering 13,288 individuals eligible for screening examination. Methods: A once only screening model was used. In the screening group, individuals were randomized to have a once only FS or a combination of FS and faecal occult blood test (FOBT). Results: The overall attendance rate was 8,849 out of 13,288 (67%); 73% in Telemark and 60% in Oslo. Attendance for FS only was 68% and 65% for combined FS&FOBT. Conclusions: The present FS/FS&FOBT screening study obtained a high acceptance rate for both screening modalities. The attendance rate was stable throughout the trial, suggesting an acceptable model for management of future countrywide screening.
To examine the relationship between body mass index (BMI) and semen quality among young men from the general population.
Cross-sectional study.
Danish young men were approached when they attended a ...compulsory physical examination to determine their fitness for military service.
From 1996-1998, 1,558 (19%) young men (mean age 19 years) volunteered.
Semen volume (in milliliters), sperm concentration (in million per milliliter), percentage of motile spermatozoa, percentage of spermatozoa with normal morphology, total sperm count (in million), and testis size (in milliliters). In addition, serum reproductive hormones were measured.
Serum T, sex hormone-binding globulin (SHBG), and inhibin B all decreased with increasing BMI, whereas free androgen index and E(2) increased with increasing BMI. Serum FSH was higher among slim men. After control for confounders, men with a BMI <20 kg/m(2) had a reduction in sperm concentration and total sperm count of 28.1% (95% confidence interval CI 8.3%-47.9%) and 36.4% (95% CI 14.6%-58.3%), respectively, and men with a BMI >25 kg/m(2) had a reduction in sperm concentration and total sperm count of 21.6% (95% CI 4.0%-39.4%) and 23.9% (95% CI 4.7%-43.2%), respectively, compared to men with BMI between 20-25 kg/m(2). Percentages of normal spermatozoa were reduced, although not significantly, among men with high or low BMI. Semen volume and percentage of motile spermatozoa were not affected by BMI.
High or low BMI was associated with reduced semen quality. It remains to be seen whether the increasing occurrence of obesity in the Western world may contribute to an epidemic of poor semen quality registered in some of the same countries. If so, some cases of subfertility may be preventable.
Abstract
Background
To support the implementation of high-throughput pipelines suitable for SARS-CoV-2 sequencing and analysis in a clinical laboratory, we developed an automated sample preparation ...and analysis workflow.
Methods
We used the established ARTIC protocol with approximately 400 bp amplicons sequenced on Oxford Nanopore’s MinION. Sequences were analyzed using Nextclade, assigning both a clade and quality score to each sample.
Results
A total of 2179 samples on twenty-five 96-well plates were sequenced. Plates of purified RNA were processed within 12 h, sequencing required up to 24 h, and analysis of each pooled plate required 1 h. The use of samples with known threshold cycle (Ct) values enabled normalization, acted as a quality control check, and revealed a strong correlation between sample Ct values and successful analysis, with 85% of samples with Ct < 30 achieving a “good” Nextclade score. Less abundant samples responded to enrichment with the fraction of Ct > 30 samples achieving a “good” classification rising by 60% after addition of a post-ARTIC PCR normalization. Serial dilutions of 3 variant of concern samples, diluted from approximately Ct = 16 to approximately Ct = 50, demonstrated successful sequencing to Ct = 37. The sample set contained a median of 24 mutations per sample and a total of 1281 unique mutations with reduced sequence read coverage noted in some regions of some samples. A total of 10 separate strains were observed in the sample set, including 3 variants of concern prevalent in British Columbia in the spring of 2021.
Conclusions
We demonstrated a robust automated sequencing pipeline that takes advantage of input Ct values to improve reliability.
Background. The aim of this study was to determine whether there exists a correlation between anal incontinence, occult sphincter injuries, anal manometry values, and delivery variables in ...primiparous women after first time vaginal delivery.
Methods. Eighty‐six primigravida women were recruited for this study. Transanal ultrasonography (TAUS) and vector volume manometry (VVM) was performed and bowel symptoms were recorded at 25 weeks of pregnancy and 5 months after labor. Incontinent women at 5 months after vaginal delivery were interviewed again at 12 months.
Results. Nineteen women (25%) experienced flatus incontinence postpartum. After 12 months, only one‐third of the women were still incontinent. Fourteen women (19%) showed abnormal TAUS of the anal sphincter. Of the delivery variables, only baby head circumference was significantly associated with flatus incontinence (p = 0.01). There was no correlation between flatus incontinence or delivery variables and anal sphincter injuries; VVM values were not associated with either anal sphincter injuries or flatus incontinence at 5 months, but VVM values were negatively associated with flatus incontinence at 12 months after labor.
Conclusions. At 5 months after labor, flatus incontinence is relatively common, and is not associated with reduced VVM values. Two‐thirds of women recover from flatus incontinence during the first year. Women who had flatus incontinence persisting for a minimum of 1 year had reduced VVM values. Anal sphincter injuries as seen by TAUS are not associated with either VVM values or any delivery variable. Baby head circumference is the only delivery variable significantly associated with flatus incontinence.
Background and Aims:
The main aim was to examine constipation and anal incontinence in patients before and after resection for external rectal prolapse.
Material and Methods:
Twenty patients had ...ligament preserving suture rectopexy and sigmoid resection (resection rectopexy) for external rectal prolapse by laparoscopic (n = 15) or open (n = 5) technique during 2001–2005. They were prospectively evaluated for constipation and anal incontinence using validated incontinence and KESS-constipation scores.
Results and Conclusions:
Constipation score was significantly reduced from mean 7.7 (5.4–9.9) to 4.5 (2.5–6.4) after median 4 months (1–19) and to 4.3 (2.2–6.3) after median 17 months (4–51). Six and four patients were constipated preoperatively and 17 months postoperatively, respectively. The four symptoms feeling incomplete evacuation of stool, minutes in lavatory per attempt, use of enemas/digitation and painful evacuation effort were significantly reduced, whilst stool consistency increased. Fourteen patiens (70%) had anal incontinence. Corresponding and significant reduction in their scores were from mean 12.5 (9.4–15.5) to 5.1 (2.1–8.1) and to 3.6 (1.3–5.9). Incontinence was improved in 13 and unaltered in one patient(s). Two patients with worse outcome had increased stool consistency and constipation scores. Resection rectopexy for rectal prolapse reduced anal incontinence and constipation.
Rectal cancer surgery has been characterized by a high incidence of local recurrence, an occurrence which influences survival negatively. In Norway there was a growing recognition that local ...recurrence rates were related to surgeon performance and that surgeons applying a standardized surgical technique in the form of total mesorectal excision could achieve better results. This contrasts with the prevailing argument voiced by many opinion leaders that local recurrence rates and possibly survival rates can only be improved by adjuvant or neoadjuvant treatment strategies. The Norwegian Rectal Cancer Project-initiated in 1993-aimed at improving the outcome of patients with rectal cancer by implementing total mesorectal excision as the standard rectal resection technique.
This observational national cohort study covers all new patients (3,319) with rectal cancer from a population of 4.5 million treated between November 1993 and August 1997. The main outcome measures were local recurrence, survival, and postoperative mortality and morbidity rates. The technique of total mesorectal excision was compared with conventional surgery.
The proportion of patients undergoing total mesorectal excision was 78 percent in 1994, increasing to 92 percent in 1997. The observed local recurrence rate for patients undergoing a curative resection was 6 percent in the group treated by total mesorectal excision and 12 percent in the conventional surgery group. Four-year survival rate was 73 percent after total mesorectal excision and 60 percent after conventional surgery. Postoperative mortality rate was 3 percent and the anastomotic dehiscence rate was 10 percent. Radiotherapy was given to 5 percent and chemotherapy to 3 percent of the patients in the curative resection group.
A refinement of the surgical resection technique for rectal cancer can be achieved on a national level, the technique of total mesorectal excision can be widely distributed, and surgery alone can give good results.
Inhibin B is a testicular glycoprotein that is secreted from the Sertoli cells and believed to play a role in FSH secretion. We characterized the diurnal profile of serum inhibin B and the relation ...to gonadotropins and testicular steroids. Serum inhibin B was measured in 13 healthy normal male volunteers (median age, 30 yr) by continuous blood drawing, with sampling every 30 min for 24 h. Blood samples were also analyzed for FSH, LH, testosterone, estradiol, and sex hormone-binding globulin. We found a significant diurnal variation in inhibin B, with peak values in the early morning and nadirs in the late afternoon, followed by gradual increasing nocturnal values. An average decline of 3%/h from 0900 until 1700 h was calculated. Significant cross-correlation was found between inhibin B and testosterone as well as estradiol, whereas no cross-correlation was found between inhibin B and FSH. Two-dimensional time-series analyses revealed a statistically significant influence of testosterone on inhibin B. In addition, estradiol and inhibin B had a significant influence on one another. In conclusion, we found a significant diurnal variation in inhibin B levels in normal men, with a pattern of higher values in the early morning hours and lower values in the late afternoon and evening. We did not find evidence for a role of FSH in this diurnal variation of inhibin B. However, covariation with serum levels of testosterone and estradiol suggested that these hormones might play a role in the diurnal rhythm of inhibin B, although some other common influence could not be excluded.
OBJECTIVE--To investigate whether semen quality has changed during the past 50 years. DESIGN--Review of publications on semen quality in men without a history of infertility selected by means of ...Cumulated Index Medicus and Current List (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS--14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN OUTCOME MEASURES--Mean sperm density and mean seminal volume. RESULTS--Linear regression of data weighted by number of men in each study showed a significant decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990 (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027), indicating an even more pronounced decrease in sperm production than expressed by the decline in sperm density. CONCLUSIONS--There has been a genuine decline in semen quality over the past 50 years. As male fertility is to some extent correlated with sperm count the results may reflect an overall reduction in male fertility. The biological significance of these changes is emphasised by a concomitant increase in the incidence of genitourinary abnormalities such as testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a growing impact of factors with serious effects on male gonadal function.
The incidence of testicular cancer is rising. Despite a high cure rate, efforts should be made to obtain diagnosis at the pre-invasive intratubular carcinoma in situ (CIS) stage, as the disease is ...potentially lethal and treatment has severe side-effects, especially regarding reproductive function. CIS diagnosis is presently only possible by a surgical biopsy of the testis. Immunocytological staining for transcription factor activator protein (AP-2γ), previously identified as a marker for neoplastic germ cells, was performed in centrifuged samples of ejaculates obtained from 104 andrological patients, including patients with testicular cancer and subfertility. Cells positive for AP-2γ were found only in semen samples from patients diagnosed a priori with testicular neoplasms and, surprisingly, in a 23 year old control subject with oligozoospermia and no symptoms of a germ cell tumour. Testicular biopsies performed during the follow-up of this patient revealed widespread CIS in one testicle, thus proving a potential diagnostic value of the new marker. For the first time, a patient without clinical symptoms of testicular neoplasia was diagnosed at the pre-invasive CIS stage using a new, simple method based on immunocytological staining of a semen sample for AP-2γ, a novel marker for CIS. The value of this method for diagnostic use in the clinic requires further careful validation in a large series of patients and controls, but the preliminary results are promising.
Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic ...(GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.
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