Metastatic spread pattern after curative colorectal cancer surgery. A retrospective, longitudinal analysis.

OBJECTIVE: The most common sites of colorectal cancer (CRC) recurrence are the local tissues, liver or lungs. The objective was to identify risk factors associated with the primary CRC tumor and cancer recurrence in these anatomical sites. METHODS: Retrospective, longitudinal analyses of data on CRC survivors. Multivariable Cox regression analysis was performed to examine the association between possible cofounders with recurrence to various anatomical sites. RESULTS: Data for 10,398CRC survivors (tumor location right colon=3870, left colon=2898, high rectum=2569, low rectum=1061) were analyzed; follow up time was up to five years. Mean age at curative surgery was 71.5 (SD 11.8) years, 20.2% received radio-chemotherapy, stage T3 (64.4%) and N0 (65.1%) were most common. Overall 1632 (15.7%) had cancer recurrence (Isolated liver n=412, 3,8%; isolated lung n=252, 2,4%; isolated local n=223, 2.1%). Risk factors associated with recurrent CRC were identified, i.e. isolated liver metastases (male: Adjusted Hazard Ratio (AHR) 1,45; colon left: AHR 1,63; N2 disease: AHR 3,35; T2 disease: AHR 2,82), isolated lung metastases (colon left: AHR 1,53; rectum high: AHR 2,48; rectum low: AHR 2,65; N2 disease 3,76), and local recurrence (glands examined<12: AHR 1,51; CRM <3mm: AHR 1,60; rectum high: AHR 2,15; N2 disease: AHR 2,58) (all p values <0001). CONCLUSION: Our study finds that the site of the primary CRC tumor is associated with location of subsequent metastasis. Left sided colon cancers have increased risk of metastatic spread to the liver, whereas rectal cancers have increased risk of local recurrence and metastatic spread to the lungs. These results, in combination with other risk factors for CRC recurrence, should be taken into consideration when designing risk adapted post-treatment CRC surveillance programs.

Epidemiologic and clinical features of HIV-infected and HIV-uninfected Ugandan children younger than 18 months.

METHODS: Groups of HIV-infected and HIV-uninfected infants younger than 18 months (mainly younger than 6 months) were compared to identify clinical features that could differentiate the two groups. The HIV-infected group also was compared with HIV-infected children older than 18 months. Recruitment was as follows for the group younger than 18 months: 708 children admitted with sepsis and clinical features suggestive of HIV infection were screened for HIV1 and HIV2 by HIV enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) was undertaken on all ELISA-seropositive blood samples (270). HIV infection was confirmed in 136 (19.2%), 438 (61.9%) were HIV-seronegative, 27 (3.8%) were HIV seroreverters, 36 (5.1%) were HIV-seropositive but PCR negative (uninfected), and 71 (10.0%) were indeterminate. One hundred thirty-six HIV-infected children were compared with 501 uninfected children. Confirmed HIV-infected children older than 18 months attending the pediatric HIV clinic were compared with the 136 HIV-infected children younger than 18 months. RESULTS: Under 18 months, the median age of HIV-infected children (n = 136) was 4.0 months (range, 3 d -18 mo ) and the median age of the uninfected children (n = 501) was 1.0 month (range, 3 d -18 mo ). HIV-infected children were more likely to have had injections, chloroquine, and nystatin, and to have attended a health center or hospital (p <.001). In the HIV-infected group, the Z score for weight-for-age was -1.75, length-for-age -0.78, and weight-for-length 1.86, significantly lower scores than those of the uninfected group, which were -0.60, -0.23, and 3.05, respectively (p <.05). The mean head circumference was below the third percentile in 40% of HIV-infected compared with 22% of uninfected children (p <.001). Overall, 56 (8%) children had marasmus, 6 (0.8%) kwashiorkor, and 3 (0.4%) marasmic kwashiorkor. Sixteen percent of the HIV-infected and 7% of uninfected children had marasmus (p <.05). The 1989 revised World Health Organization clinical criteria for diagnosis of AIDS had sensitivity, specificity, and positive predictive values of 28%, 98%, and 93%, respectively. Older than 18 months (n = 109), the median age was 24 months (range, 18-60 mo ). The following were significantly more common in HIV-infected children older than 18 months than in those younger than 18 months: bacille Calmette-Guérin vaccination scar, parotid enlargement, nonspecific generalized dermatitis, and chronic diarrhea ( p <.001). Oral candidiasis was more common in the group younger than 18 months (p <.001). In infants examined in the hospital for infective conditions, oropharyngeal candidiasis, ear discharge, dermatologic disorders, generalized lymphadenopathy, lobar consolidation, hepatosplenomegaly, and failure to thrive, especially marasmus, were important indicators of HIV infection.

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.

BACKGROUND: The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life. METHODS: From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis. FINDINGS: Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups. INTERPRETATION: Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.

PIP: A study was conducted to assess the safety and efficacy of short-course nevirapine compared with zidovudine given to women during labor and to neonates during the first week of life. 626 HIV-1 infected pregnant women attending the antenatal clinic from November 1997 to April 1999 at Mulago Hospital in Kampala, Uganda, were randomly given nevirapine or zidovudine. Infants were tested for HIV-1 infection at birth, at 6-8 weeks, and at 14-16 weeks. Findings revealed that the estimated risk of HIV-1 transmission in the zidovudine and nevirapine groups was 10.4% and 8.2%, respectively, at birth; 21.3% and 11.9%, by 6-8 weeks; and 25.1% and 13.1%, by 14-16 weeks. There was a 47% relative efficacy rate of the nevirapine regimen at 14-16 weeks compared to zidovudine. Based on the findings, nevirapine lowers the risk of HIV-1 transmission by nearly 50% during the first 14-16 weeks of life in breast-fed infants.