High risk of permanent stoma after anastomotic leakage in anterior resection for rectal cancer.

AIM: This study investigates how often bowel continuity was restored after anastomotic leakage in anterior resection for rectal cancer and assesses the clinical factors associated with permanent stoma. METHOD: The Swedish Colorectal Cancer Registry was used to identify cases of anastomotic leakage registered in southern Sweden between January 2001 and December 2011. Patient characteristics, surgical details and clinical information about the anastomotic leakages were retrieved from medical records. RESULTS: Of the 1442 patients operated on with anterior resection in 11 hospitals, 144 (10%) were diagnosed with anastomotic leakage after anterior resection for rectal cancer. After a median follow-up of 87 months (range 21-165), the overall rate of permanent stoma among patients with anastomotic leakage was 65%. Age ≥ 70 years (P = 0.02) and re-laparotomy (P < 0.001) were independently related to permanent stoma. Compared with nondefunctioned patients with anastomotic leakage, defunctioned patients with anastomotic leakage at the index procedure less often required re-laparotomy at some point during the entire clinical course (P < 0.001), but nondefunctioned and defunctioned patients with anastomotic leakage both had permanent stoma to the same extent (67% and 62%, respectively). CONCLUSION: Anastomotic leakage is highly associated with permanent stoma after anterior resection, especially in patients aged ≥ 70 years. In this cohort of patients with anastomotic leakage, 65% had permanent stoma at long-term follow-up. A defunctioning stoma ameliorates the clinical course but does not affect the end result of bowel continuity in established anastomotic leakage after anterior resection.

Late leakage after anterior resection: a defunctioning stoma alters the clinical course of anastomotic leakage.

AIM: Anastomotic leakage (AL) is common after anterior resection (AR). Long term clinical outcomes of AL including late presenting leakage (LL) are not well studied. This study was undertaken to assess clinical features of LL with respect to incidence, association with predisposing factors and need for re-intervention. METHODS: The Swedish Colorectal Cancer Registry (SCRCR) was explored for AL cases after AR for rectal cancer in patients operated in the south of Sweden from 1 January 2001 to 31 December 2011. Demographic data, surgical technical details, number of postoperative days (POD) until diagnosis of AL, presenting symptoms, methods of diagnosis and treatment were retrieved from medical records. LL was defined according to different cut-offs as leakages occurring after hospital discharge (LLAHD), after 30 POD (LL ≥ POD 30) and after 90 POD (LL ≥ POD 90). RESULTS: In total, 1442 patients were operated on with AR of whom 144 cases of AL (10%) were identified. Median time from operation to follow-up was 87 months (range 21-162). LLAHD, LL ≥ POD 30 and LL ≥ POD 90 were present in 51%, 24% and 9% respectively. All categories of LL were associated with a defunctioning stoma. Relaparotomy was significantly less often employed in LLAHD, but not in other categories of LL. CONCLUSION: LL constitutes a substantial portion of all AL after AR for rectal cancer. The large proportion of LLAHD calls for awareness in the outpatient setting.

The importance of rectal washout for the oncological outcome after Hartmann's procedure for rectal cancer: analysis of population-based data from the Swedish Colorectal Cancer Registry.

BACKGROUND: During rectal cancer surgery the bowel may contain viable, exfoliated cancer cells, a potential source for local recurrence (LR). The amount and viability of these cells can be reduced using intraoperative rectal washout, a procedure that reduces the LR risk after anterior resection. The aim of this study was to analyse the impact of washout on oncological outcome when performed in Hartmann's procedure (HP) for rectal cancer. METHODS: A national cohort study on data for patients registered from 1995 to 2007 in the Swedish Colorectal Cancer Registry was carried out. The final analysis included patients belonging to TNM stages I-III who had undergone R0 HP with a registered 5-year follow-up. Multivariate analysis was performed. RESULTS: A total of 1188 patients were analysed (686 washout and 502 no washout). No differences were detected between the washout group and the no washout group concerning rates of LR [7% (49/686) vs. 10% (49/502); p = 0.13], distant metastasis (DM) [17% (119/686) vs. 18% (93/502); p = 0.65], and overall recurrence (OAR) [21% (145/686) vs. 24% (120/502); p = 0.29]. For both groups, the 5-year cancer-specific survival was below 50%. In multivariate analysis, washout neither decreased the risk of LR, DM, or OAR nor increased overall or the cancer-specific 5-year survival. CONCLUSIONS: The oncological outcome did not improve when washout was performed in HP for rectal cancer.

Time trends, improvements and national auditing of rectal cancer management over an 18-year period.

AIM: The main aims were to explore time trends in the management and outcome of patients with rectal cancer in a national cohort and to evaluate the possible impact of national auditing on overall outcomes. A secondary aim was to provide population-based data for appraisal of external validity in selected patient series. METHOD: Data from the Swedish ColoRectal Cancer Registry with virtually complete national coverage were utilized in this cohort study on 29 925 patients with rectal cancer diagnosed between 1995 and 2012. Of eligible patients, nine were excluded. RESULTS: During the study period, overall, relative and disease-free survival increased. Postoperative mortality after 30 and 90 days decreased to 1.7% and 2.9%. The 5-year local recurrence rate dropped to 5.0%. Resection margins improved, as did peri-operative blood loss despite more multivisceral resections being performed. Fewer patients underwent palliative resection and the proportion of non-operated patients increased. The proportions of temporary and permanent stoma formation increased. Preoperative radiotherapy and chemoradiotherapy became more common as did multidisciplinary team conferences. Variability in rectal cancer management between healthcare regions diminished over time when new aspects of patient care were audited. CONCLUSION: There have been substantial changes over time in the management of patients with rectal cancer, reflected in improved outcome. Much indirect evidence indicates that auditing matters, but without a control group it is not possible to draw firm conclusions regarding the possible impact of a quality control registry on faster shifts in time trends, decreased variability and improvements. Registry data were made available for reference.

Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer.

BACKGROUND: A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery. METHODS: Lymph nodes of pTNM stage I-IV CRC- (166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT-PCR. RESULTS: Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8). CONCLUSION: In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence.

Anastomotic leakage after surgery for rectal cancer: a risk factor for local recurrence, distant metastasis and reduced cancer-specific survival?

AIM: The impact of anastomic leakage (AL) on the oncological outcome after anterior resection (AR) for rectal cancer is still controversial. We explored the impact of AL regarding local recurrence (LR), distant metastasis and overall recurrence (OAR). Overall and cancer-specific survival was analysed. METHOD: Patients undergoing AR for rectal cancer with a registered AL between 1995 and 1997 and a control group were identified in the Swedish Rectal Cancer Registry. The medical records were retrieved for additional data and validation. Differences in the oncological outcome at 5-year follow-up were analysed with multivariate methods. RESULTS: After validation, 114 patients with AL and 136 control patients with locally radical surgery for tumours in tumour-node-metastasis stages I-III were analysed. There was no difference detected between patients with AL and control patients regarding rates of LR [8% (9 of 114) vs 9% (12 of 136); P = 0.97], distant metastasis [18% (20 of 114) vs 23% (31 of 136); P = 0.37] and OAR [19% (22 of 114) vs 28% (38 of 136); P = 0.15]. The 5-year cancer-specific survival was almost 80% in both groups. In multivariate analysis, AL was not a risk factor of LR, distant metastasis or OAR and had no impact on 5-year overall or 5-year cancer-specific survival. Irrespective of the occurrence of AL, preoperative radiotherapy (P = 0.055) and rectal washout (P = 0.046) reduced the LR rate, but did not influence survival. CONCLUSION: Anastomotic leakage was not proved to be a risk factor of worse oncological outcome. Hence, additional adjuvant treatment or extended follow-up on the basis of the occurrence of AL after AR might not be justified.

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.

Risk factors of rectal cancer local recurrence: population-based survey and validation of the Swedish rectal cancer registry.

AIM: Despite advances in rectal cancer treatment, local recurrence (LR) remains a significant problem. To select high-risk patients for different treatment options aimed at reducing LR, it is essential to identify LR risk factors. METHOD: Local recurrence and survival rates of 4153 patients registered 1995-1997 in the Swedish Rectal Cancer Registry were analysed. LR risk factors were analysed by multivariate methods. For LR patients the registry was validated and additional data retrieved. RESULTS: The 5-year overall and cancer-specific survival rates were 45% and 62% respectively. LR was registered in 326 (8%) patients. After R0-resections for tumours in TNM stages I-III, LR developed in 10% of tumours at 0-5 cm, 8% at 6-10 cm and 6% at 11-15 cm above the anal verge. Preoperative radiotherapy (RT) reduced the LR rate irrespective of height [0-5 cm: OR 0.50 (0.30-0.83), 6-10 cm: OR 0.42 (0.25-0.71), and 11-15 cm: OR 0.29 (0.13-0.64)]. Patients without preoperative RT had significantly higher LR risk after rectal perforation [OR 2.50 (1.48-4.24)], and almost significantly decreased LR risk when rectal washout was performed [OR 0.65 (0.43-1.00)]. Preoperative RT prolonged time to LR but did not significantly influence the survival among LR patients. LR was an isolated tumour manifestation in 103 (39%) patients with validated LR. CONCLUSION: Preoperative RT should be considered for rectal cancer also in the upper third of the rectum. Intraoperative perforation should be avoided, and rectal washout is indicated as valuable. Follow-up for the detection of isolated LR is important. Extended follow up should be considered for patients treated with RT.

The Swedish rectal cancer registry.

BACKGROUND: An audit of all patients with rectal cancer in Sweden was launched in 1995. This is the first report from the Swedish Rectal Cancer Registry (SRCR). METHODS: Between 1995 and 2003, 13 434 patients treated for adenocarcinoma of the rectum were registered with the SRCR; there were approximately 1500 new patients annually. RESULTS: Approximately half had an anterior resection, a quarter an abdominoperineal resection and 15 per cent a Hartmann's procedure. The median 30-day postoperative mortality rate was 2.4 per cent and the overall postoperative morbidity rate was 35.0 per cent. The 5-year cancer-specific survival rate was 62.3 per cent. The 5-year relative survival rate was 70.1 per cent after anterior resection, 59.8 per cent after abdominoperineal resection and 39.8 per cent after a Hartmann's procedure. The crude 5-year local recurrence rate was 9.5 per cent overall, 6.1 per cent after preoperative radiotherapy and 11.4 per cent after surgery alone. For 3868 patients who had a locally curative procedure the local recurrence rate was 7.4 per cent overall, 5.9 per cent for those who had radiotherapy and 10.2 per cent for those who did not. The local recurrence rate was 2.9 per cent (28 of 968) for stage I disease, 7.9 per cent (112 of 1418) for stage II, 13.9 per cent (188 of 1357) for stage III and 8.5 per cent (45 of 532) for stage IV. CONCLUSION: These good population-based results are due, in part, to the nationwide prospective quality assurance registration.

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR.

Accurate identification of lymph node involvement is critical for successful treatment of patients with colorectal carcinoma (CRC). Real-time quantitative RT-PCR with a specific probe and RNA copy standard for biomarker mRNA has proven very powerful for detection of disseminated tumour cells. Which properties of biomarker mRNAs are important for identification of disseminated CRC cells? Seven biomarker candidates, CEA, CEACAM1-S/L, CEACAM6, CEACAM7-1/2, MUC2, MMP7 and CK20, were compared in a test-set of lymph nodes from 51 CRC patients (Dukes' A-D) and 10 controls. Normal colon epithelial cells, primary tumours, and different immune cells were also analysed. The biomarkers were ranked according to: (1) detection of haematoxylin/eosin positive nodes, (2) detection of Dukes' A and B patients, who developed metastases during a 54 months follow-up period and (3) identification of patients with Dukes' C and D tumours using the highest value of control nodes as cutoff. The following properties appear to be of importance; (a) no expression in immune cells, (b) relatively high and constant expression in tumour tissue irrespective of Dukes' stage and (c) no or weak downregulation in tumours compared to normal tissue. CEA fulfilled these criteria best, followed by CK20 and MUC2.

Germline mutations in the MYH gene in Swedish familial and sporadic colorectal cancer.

Biallelic germline mutations in the base excision repair gene MYH have been shown to predispose to a proportion of multiple colorectal adenomas and cancer. To evaluate the contribution of MYH mutations to non- FAP, non-HNPCC familial colorectal cancer, 84 unrelated Swedish individuals affected with colorectal cancer from such families were screened for germline mutations in the coding sequence of the gene. None of the cases was found to carry any pathogenic sequence change. We then determined the prevalence of the two most common pathogenic MYH mutations found in Caucasians, Y165C and G382D, in 450 Swedish sporadic colorectal cancer cases and 480 Swedish healthy controls. The frequency of both variants in Swedish cases and controls was similar to those previously reported. In addition, we found that previously unknown sequence variations at the position of amino acid 423 (R423Q, R423P, and R423R) appear to occur more frequently in cases than in controls (p = 0.02), a finding that warrants future studies.

Field efficiency of syphilis screening in antenatal care: lessons from Gutu District in Zimbabwe.

OBJECTIVES: To determine coverage for antenatal syphilis screening in a rural area and evaluate the accuracy of on-site Rapid Plasma Reagin (RPR) tests performed by nurse-midwives. DESIGN: Descriptive cross sectional. SETTING: Rural Health Centres (n = 23) in the Gutu District of Zimbabwe. SUBJECTS: Women booking for antenatal care in the district were used to determine coverage of screening. Results from women who had an RPR test performed during a nine week period were used in assessing the accuracy of tests performed by nurse-midwives. INTERVENTION: On-site antenatal screening for syphilis using an RPR kit with immediate results and treatment for women who tested positive. MAIN OUTCOME MEASURES: Prevalence of syphilis (positive RPR) at booking and the level of agreement between three observers (RHC nurse-midwife, medical practitioner under field conditions and medical laboratory technologist). RESULTS: Eighty five percent of women were screened for syphilis at the first antenatal visit and 11% had a positive RPR. Almost all (97.3%) women with a positive RPR test result were treated. The accuracy of tests performed by RHC staff was poor with a sensitivity of 40% (95% CI 21.8 to 61.1) when compared to those done by the medical practitioner and 8.7% (95% CI 1.5 to 29.5) when compared to those done in a laboratory. The predictive value of a positive test was 22.7% and that of a negative test was 94.9%. CONCLUSION: The coverage of screening for syphilis in pregnant women in Gutu District was good but the results were unreliable. There is need for nurse-midwives, who perform the majority of RPR tests in the RHC, to receive adequate training to ensure competence in testing and to strengthen quality control procedures.

Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors.

BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction. MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification). RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68. CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

Anaemia in women of reproductive age in Dar-es-Salaam, Tanzania.

BACKGROUND: Anaemia is among the greatest health problems in reproductive age women in developing countries. OBJECTIVES: To estimate the prevalence of anaemia among non-pregnant parous women, and to investigate the main underlying cause for the anaemia. SETTING: A sub-urban Maternal and Child Health Clinic (MCH) in Dar es Salaam. DESIGN: Cross-sectional. METHODS: Consecutive parous non-pregnant women who had brought their children for vaccination and/or had come for family planning to Mbagala MCH clinic were invited to participate in the study. Obstetric and social history was recorded, and their height and weight were checked. Haemoglobin was measured using HemoCue hemoglobinometer. Anaemic women were further investigated to determine the cause of anaemia by haematological and biochemical tests. RESULTS: Five hundred and four parous non-pregnant women were screened, 49% were anaemic (Hb <12 g/dl) and 1.6% severely anaemic (Hb <7 g/dl). Anaemia was not related to socio-demographic and obstetric history characteristics, but decreased significantly with increasing Body Mass Index (BMI) (p=0.042). The prevalence of anaemia was significantly lower in women using hormonal contraceptives, compared to non-users (36% vs 54%) (p=0.04). Eighty-seven percent of the anaemic women were iron deficient and 8.7% had elevated serum C-reactive protein indicating undiagnosed infections. CONCLUSION: Nutritional deficiencies in women have to be corrected before and between pregnancies and all contacts women have with the health system should be utilised for anaemia control interventions, in addition to long-term community approaches. To improve maternal health calls for a broader agenda and a change of approach in the MCH-clinics.

Iron status and iron deficiency anaemia in adolescents in a Tanzanian suburban area.

OBJECTIVES: To assess the extent and degree of anaemia in adolescents in a Tanzanian suburban area, to estimate the contribution of iron deficiency, using serum (S)-ferritin and soluble transferrin receptor (sTfR) as markers of iron deficiency. MATERIALS: Consecutive primigravidae at booking for antenatal care (n = 76), primary school boys (n = 101) and postmenarchal girls (n = 130) age >or=12 years were investigated. METHODS: Weight and height were measured; venous blood was drawn for haematological analyses, malaria screening, S-ferritin, sTfR, and C-reactive protein. Stool specimens were analysed for intestinal parasites. RESULTS: Anaemia (Hb <105 g/l) was highly prevalent in adolescent primigravidae (75.5%). Adolescent girls were more anaemic (Hb <120 g/l) than boys (14.5 vs. 7.9%). Iron deficiency and hookworm infestation were predominant in both groups of adolescents, however, malaria contributed more to anaemia in the primigravidae. Nearly 40% of the anaemic primigravidae had indication of infection, and S-ferritin was less useful as a marker of iron deficiency in this group. sTfR identified iron deficiency in both pregnant and non-pregnant adolescents.

COL11A1 in FAP polyps and in sporadic colorectal tumors.

BACKGROUND: We previously reported that the alpha-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of beta-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/beta-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/beta-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer.

A germline E-cadherin mutation in a family with gastric and colon cancer.

Inactivating mutations have been found in the cell-cell adhesion molecule E-cadherin (CDH1), which acts as a tumor suppressor gene in different kinds of cancers, e.g. primarily diffuse gastric cancer and lobular breast cancer. In this study, we screened for germline alterations in familial gastric and colon cancer cases. In total, 20 gastric and 18 colon cancer patients with both familial gastric and colon cancer were tested for germline E-cadherin alterations by using PCR/SSCP, specific restriction digestion test and sequencing. No pathogenic mutations were identified in the gastric cancer patients. In two colon cancer patients, a missense mutation in exon 12, codon 592 (Ala592Thr) was found. This alteration segregated with diffuse gastric cancer and colon cancer in one of the families. The prevalence of this alteration in the general population and colon cancer cases was almost the same. However, the fact that this alteration (Ala592Thr) segregated with colon cancer and diffuse gastric cancer in one big family, suggests that this E-cadherin missense alteration, beside predisposing to diffuse gastric cancer, also may play a role in colorectal carcinogenesis.

Serum anti-p53 in relation to mutations across the entire translated p53 gene in colorectal carcinomas.

Previous reports have claimed that antibodies to mutated p53 protein indicate poor outcome in malignant disease. The mechanism behind this highly specific process is unclear, although it has been claimed that certain DNA alterations are prone to induction of immune response, since wild-type p53 is almost never immunogenic. The aim of the present analysis was to evaluate whether the presence of anti-p53 was statistically significantly related to any certain DNA alterations in the entirely expressed p53 gene in primary tumors of colorectal cancer. P53 serum antibodies were determined by an enzyme linked immunosorbant assay (ELISA). P53 antibodies were detected in serum of 24 of 88 patients (27%). Twenty-two of 24 (92%) sero-positive patients had mutations in their p53 gene while only 22 of 64 (34%) sero-negative patients had p53 mutations (p<0.01). Mutations were mainly missense with a trend to significantly higher frequency of deletions in sero-negative patients compared to sero-positive subjects (8/25, 32% and 2/22, 9% respectively, p<0.08). Mutations in sero-positive patients were mainly located in exon 5 and 7 and within conserved regions (17 of 22 mutations). In sero-negative patients missense mutations were usually located in exon 5, 7 and 8 being also most frequently located within conserved regions. Most of the p53 deletions in sero-negative patients were however located outside conserved regions (seven of eight deletions). There was no statistical difference between sero-positive and negative patients concerning the spectrum of mutations along the expressed gene. Our study demonstrates that p53 antibodies are usually related to p53 gene mutations but a mutational event is not sufficient to elicit self-immunization. Cellular protein binding to p53 or individual differences of major histocompatibility complex based presentation of p53 protein sequences by immune cells is therefore the most likely explanation between sero-negative and sero-positive patients.

Symptoms across pregnancy in relation to psychosocial and biomedical factors.

BACKGROUND: There is current interest in symptoms during pregnancy, but yet little is known about their prevalence and how often they are experienced across pregnancy. The reasons why some women experience more symptoms or experience them more often than others has received limited research attention. OBJECTIVE: To document the prevalence and frequency of 27 pregnancy symptoms and to systematically investigate, cross-sectionally and prospectively, the effect of psychosocial factors on the prevalence and frequency of these symptoms, while controlling for biomedical factors. METHODS: Four hundred and seventy-six nulliparous Scandinavian women who attended routine prenatal care in Uppsala county, Sweden, were studied six times during pregnancy (gestational weeks 10, 12, 20, 28, 32, and 36). RESULTS: The prevalence of symptoms was high, but only a smaller portion of these symptoms were experienced frequently. Psychological stress particularly contributed to the prevalence and frequency of concurrent symptoms and predicted symptoms up to 16 weeks later, independent of medical risk, smoking, and weight gain. CONCLUSIONS: Prevalence rates may be inflated, because many symptoms were experienced only 'occasionally' during each of the 4-week periods we sampled. By examining how frequently symptoms were experienced, we gained an indication of which symptoms are more likely to be bothersome or intrude upon daily activities. Psychosocial variables accounted for individual differences in symptom reports after taking biomedical factors into account. Attention to psychosocial variables in future studies will aid in our understanding of the etiology of pregnancy symptoms.

Perinatal deaths and insufficient antenatal care in Latvia.

OBJECTIVE: A national audit on perinatal deaths was performed to assess the quality of antenatal care, and to suggest measures for improved antenatal care. MATERIAL AND METHODS: Medical records of all the perinatal deaths in Latvia in the years 1995-1996 have been studied. Non-attenders and attenders of antenatal care were characterized by socio-economic and medical variables: maternal age, parity, history of perinatal outcome, health status and behavioral hazards during the index pregnancy, length of gestation and birth weight. The Nordic-Baltic perinatal death classification was used. RESULTS: In 85 of 442 cases (19%) of perinatal deaths women had not taken advantage of antenatal care provided for them. Non-attenders were more likely to be smokers (p<0.001) and alcohol abusers (p<0.005), above 35 years of age (p<0.005), and had higher parity (p<0.001). Non-attenders more often had systemic diseases and pregnancy complications. Neonatal complications, such as congenital syphilis (p<0.05) and other infections (p<0.05), were more common among non-attenders. There was no difference in rates of preterm birth and low birth weight between attenders and non-attenders. CONCLUSIONS: One fifth of mothers with perinatal death did not attend ANC, and in some women who attended ANC, lack of intervention was related to the perinatal death.