The value of repeated cytology at the time of first colposcopy: a retrospective analysis of 1,087 cases

Papanicolaou tests are often repeated just before the procedure for women who have been referred for colposcopy. The validity and clinical usefulness of this practice, however, is unclear. We retrospectively assessed the value of repeated cytology in a cohort of 1,087 consecutive patients who underwent repeated Papanicolaou testing at first colposcopy. The repeated cytology was considered clinically useful if the results could conceivably have influenced the physician's decision about more invasive diagnostic/therapeutic evaluation based on contemporary practice guidelines. Repeated cytology provided potentially clinically useful information in only a small proportion (3.6%) of the cases analyzed overall, including 41% (26/63) and 1.8% of the high- and low-grade squamous intraepithelial lesions referral cytology cases, respectively. Our data indicate that repeated cytology provides potentially clinically useful information in only a small percentage of overall cases but a substantial proportion of high-grade squamous intraepithelial lesion referral cytology cases, suggesting that high-risk referral cytology case subsets can be defined wherein the routine performance of repeated cytology would be most efficacious.     

A meta-analysis of the randomized controlled trials on elective neck dissection versus therapeutic neck dissection in oral cavity cancers with clinically node-negative neck

There is still no consensus on the optimal treatment of the neck in oral cavity cancer patients with clinical N0 neck. The aim of this study was to assess a possible benefit of elective neck dissection in oral cancers with clinical N0 neck. A comprehensive search and systematic review of electronic databases was carried out for randomized trials comparing elective neck dissection to therapeutic neck dissection (observation) in oral cancer patients with clinical N0 neck. A meta-analysis of the studies which met our defined selection criteria was performed using disease-specific death as the primary outcome, and the relative risk (RR) of disease-specific death was calculated for each of the identified studies. Both fixed-effects (Mantel-Haenszel method) and random-effects models were applied to obtain a combined RR estimate, although between-study heterogeneity was not found to be significant as indicated by an I(2) of 8.5% (p=0.350). Four studies with a total of 283 patients met our inclusion criteria. The results of the meta-analysis showed that elective neck dissection reduced the risk of disease-specific death (fixed-effects model RR=0.57, 95% CI 0.36-0.89, p=0.014; random-effects model RR=0.59, 95% CI 0.37-0.96, p=0.034) compared to observation. This reduction in disease-specific death rate supports the need to perform elective neck dissection in oral cancers with clinical N0 neck.     

Papanicolaou test interpretations of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" : an investigation of requisite duration and number of colposcopic procedures to a definitive diagnosis of high-grade dysplasia in routine practice

BACKGROUND: Management guidelines for women with Papanicolaou (Pap) test interpretations of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) reflect substantial risk, which ranges from 10% to 68%, of a cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in their follow-up histologic samples. The present study was initiated to determine the number of colposcopic procedures and the time frame that are typically required for a definitive diagnosis of a CIN2+ lesion after a Papanicolaou (Pap) test interpretation of ASC-H in routine practice. METHODS: Clinicopathologic data on consecutive ASC-H interpretations, 97% of which were on liquid-based preparations, were reviewed. The number of biopsies (which was used in this context as a surrogate indicator for the number of colposcopic procedures) as well as the average duration required for a follow-up histologic diagnosis of CIN2+ were determined. RESULTS: Of 500 ASC-H interpretations, 75 were excluded for a variety of reasons and 165 lacked follow-up in our records. The average age and follow-up duration for the remaining 260 patients was 35.6 years and 18.5 months, respectively. CIN2+ was diagnosed in 49 (40%) of the 122 patients with at least 1 histologic follow-up. Of these 49 patients, 72% (35 of 49) were diagnosed on the first follow-up cervical biopsy, 14% (7 of 49) and 8% (4 of 49) were diagnosed on the second and third follow-up biopsies, respectively; in only 6% (3 of 49) was a fourth follow-up biopsy required. Overall, an average of 1.53 biopsies (range, 1-4) was required to attain a definitive diagnosis of CIN2+, and 28% of patients required more than 1 follow-up biopsy. The average period between the index ASC-H interpretations and CIN2+ diagnoses was 5.5 months. The average time to CIN2+ diagnoses by the first follow-up biopsy was 3 months; for diagnoses made on subsequent biopsies, the average additional follow-up duration was 8 months. Of the eventual CIN2+ diagnoses, 84% were rendered within 12 months of their associated index ASC-H interpretations. CONCLUSIONS: 1) A substantial subset-28%-of patients with biopsy-proven CIN2+ after ASC-H interpretations required more than 1 colposcopy for a definitive diagnosis of a high-grade dysplastic lesion. 2) If a CIN2+ lesion is present, the vast majority can be diagnosed in a biopsy performed within 1 year of the ASC-H interpretation.     

Compulsory patent licensing and local drug manufacturing capacity in Africa

Africa has the highest disease burden in the world and continues to depend on pharmaceutical imports to meet public health needs. As Asian manufacturers of generic medicines begin to operate under a more protectionist intellectual property regime, their ability to manufacture medicines at prices that are affordable to poorer countries is becoming more circumscribed. The Doha Declaration on the TRIPS Agreement and Public Health gives member states of the World Trade Organization (WTO) the right to adopt legislation permitting the use of patented material without authorization by the patent holder, a provision known as “compulsory licensing”. For African countries to take full advantage of compulsory licensing they must develop substantial local manufacturing capacity. Because building manufacturing capacity in each African country is daunting and almost illusory, an African free trade area should be developed to serve as a platform not only for the free movement of goods made pursuant to compulsory licences, but also for an economic or financial collaboration towards the development of strong pharmaceutical manufacturing capacity in the continent. Most countries in Africa are in the United Nations list of least developed countries, and this allows them, under WTO law, to refuse to grant patents for pharmaceuticals until 2021. Thus, there is a compelling need for African countries to collaborate to build strong pharmaceutical manufacturing capacity in the continent now, while the current flexibilities in international intellectual property law offer considerable benefits.     

Foreign Body Impaction in the Esophagus: A Review of 10 Years Experience in a Teaching Hospital

This report reviews 271 cases of impacted foreign bodies in the esophagus seen at the Lagos University Teaching Hospital between January 1973 and January 1983. In 270 patients, esophagoscopy was employed to relieve the obstructions. One patient had a prolonged impaction requiring a surgical procedure. The diagnosis in two patients was made at autopsy.     

Induction of stable chimerism and transplantation tolerance to rat islet and heart allografts by ultraviolet-B modulation of bone marrow cells.

Ultraviolet-B irradiation (UV-B) (700 J/m2) of BM cells prior to transplantation into lethally gamma-irradiated (1050 rads) allogeneic rats prevents the development of GVHD and results in stable chimerism. This study was developed to determine if UV-B modulation of BMT is useful for preconditioning recipients for the induction of tolerance to donor islets and heart allografts. Lethally irradiated Lewis rats that received UV-B irradiated (700 J/m2) WF BMT (10(8) BM cells) demonstrated stable chimerism without any evidence of GVHD. The stable Lewis chimeras were made diabetic with streptozotocin (STZ) at 28-35 days after BMT and subdivided into 3 experimental groups that received 1000-1200 islets from WF, Lewis, or BN (third-party), respectively. The results showed that group I diabetic Lewis chimeras accepted permanently (greater than 300 days) BM donor WF islets and became normoglycemic. When 3 of 6 Lewis chimeras transplanted with WF islets were rechallenged with WF hearts 60 days after islet grafts, they accepted both islets and cardiac allografts permanently (greater than 240 days). Similarly, the remaining 3 animals accepted Lewis cardiac allografts permanently, thus indicating tolerance to both donor and recipient alloantigens. Group II diabetic chimeras accepted permanently (greater than 300 days) recipient (Lewis) islets. In contrast, group III chimeras rejected acutely (7-8 days) third-party (BN) islets. However, when these animals that rejected BN islets and again became diabetic were retransplanted with BM donor-type (WF) islets, they became permanently normoglycemic (greater than 200 days). This finding emphasizes the specificity of the induction of tolerance in this model and the apparent lack of organ-specific sensitization. To define the underlying mechanism of tolerance, in vivo adoptive transfer of 10(8) spleen cells to naive Lewis or WF recipients, obtained from tolerant Lewis chimeras carrying donor islets and heart allografts, showed no prolongation of cardiac allografts in the unmodified syngeneic hosts, thus questioning the role of suppressor mechanisms in the tolerant rats. Furthermore, cells from the tolerant chimeras that showed no mixed lymphocyte reaction (MLR) response to Lewis or; WF alloantigens failed to suppress anti-Lewis and anti-WF MLR-response in coculture MLR. These results suggest that tolerance to donor alloantigens in the UV-B BMT model is most likely due to selective elimination of anti-BM donor helper or effector cell precursors (clonal deletion) rather than induction of suppressor cell activity. This study demonstrates that this relatively simple and effective approach to modulation of T cells in BM treatment may be potentially useful in the induction of tolerance to donor organs.