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An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012;62:147-172. V C

To quantify repeat Pap testing and colposcopic biopsies among women in the National Breast and Cervical Cancer Early Detection Program between 2003 and 2006 (N=955,494).Rates of repeat Pap testing (two tests within 9 months) and colposcopic biopsies were estimated along with 95% confidence intervals (CIs). Odds ratios and 95% CIs for receipt of colposcopic biopsy compared with repeat Pap testing were estimated from multivariable logistic regression models. Finally, we estimated positive predictive values and 95% CIs of cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 3, carcinoma in situ, invasive cancer) for two strategies: 1) repeat Pap testing followed by colposcopic biopsy and 2) colposcopic biopsy alone.There were 39,583 and 53,880 women with repeat Pap testing and colposcopic biopsy, respectively, from 2003 to 2006. Overall, age-standardized rates of repeat Pap testing and colposcopic biopsies were 37.2 per 1,000 women and 39.3 per 1,000 women, respectively. Younger women, Hispanic women, and African-American women were more likely to receive colposcopic biopsies compared with repeat Pap tests. Positive predictive values of colposcopic biopsy were highest after abnormal Pap test results (27% after a result of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, 70% after a result of high-grade squamous intraepithelial lesion/squamous cell cancer).Colposcopic biopsies are common among young women after being screened for cervical cancer and, except among those with the most severe Pap test results, may not be efficient in detecting serious disease. These results conflict with current recommendations for less aggressive follow-up for most young women.II.

OBJECTIVE Annual cervical cancer screening in women with many prior normal Pap tests is common despite limited evidence on the cost-effectiveness of this strategy. We estimated the cost-effectiveness of screening women with 3 or more prior normal tests compared with screening those with no prior tests. METHODS We used a validated cost-effectiveness model in conjunction with data on the prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers for Disease Control and Prevention National Breast and Cervical Cancer Early Detection Program. Women were grouped according to age at the final Program Pap test (aged < 30, 30-44, 45-59, and 60-65 years) and by screening history (0, 1, 2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year and quality-adjusted life-year associated with annual, biennial, and triennial screening. RESULTS For women aged 30-44 years with no prior tests, incremental cost-effectiveness ratios ranged from 20,533 US dollars for screening triennially (compared with no further screening) to 331,837 US dollars for screening annually (compared with biennially) per life-year saved. Among same-aged women with 3 or more prior normal Program tests, incremental cost-effectiveness ratios for the same measures ranged from 60,029 US dollars to 709,067 US dollars per life-year saved. Inclusion of the most conservative utility estimates resulted in incremental cost-effectiveness ratios in excess of 100,000 US dollars per quality-adjusted life-year saved associated with annual screening of same-aged women with 3 or more prior normal tests compared with biennial screening. CONCLUSION As the number of prior normal Pap tests increases, the costs per life-year saved increase substantially. Resources should be prioritized for screening those never or rarely screened women. LEVEL OF EVIDENCE II-2.

OBJECTIVE To describe results of cervical cytology screening among low-income and uninsured women in the National Breast and Cervical Cancer Early Detection Program. METHODS We analyzed data from 750,591 women who received their first Papanicolaou (Pap) test in the program between July 1995 and March 2001. RESULTS Nearly 85% of the women were aged 40 years or older. Almost half were members of racial or ethnic minority groups. Overall, the percentage of abnormal Pap test results decreased with increasing age. The rates of cervical intraepithelial neoplasia (CIN) were highest in the younger age groups but the rate of invasive cancer increased with age. White women had the highest age-adjusted percentage of abnormal Pap test results and the highest rate of biopsy-confirmed CIN 2 or worse. CONCLUSIONS In this nationwide screening program, only 7% of all biopsy-confirmed high-grade cervical lesions (CIN 2 or worse) were invasive cancer. This underscores the success of Pap screening in identifying preinvasive disease and preventing cancer. LEVEL OF EVIDENCE II-3

Objective: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. Methods: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. Results: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle–Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. Conclusion: Observed results emphasize the duality of cervical neoplasia—CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening. (Obstet Gynecol 1998;92:745–52.)

Objective To determine whether previous cesarean delivery is an independent risk factor for ectopic pregnancy. Methods We analyzed data collected between October 1988 and August 1990 from a case-control study of ectopic pregnancy among parous, black, non-Hispanic women, 18–44 years old, at a major metropolitan hospital in Georgia. Cases were 138 women with confirmed ectopic pregnancy; controls were 842 women either seeking abortion or delivering an infant. Unconditional logistic regression was used to estimate the relative risk while controlling for the effects of potential confounders selected a priori. Results Adjusted for age, parity, marital status, history of pelvic inflammatory disease, infertility, douching, and smoking, the odds ratio was 0.6 (95% confidence interval 0.4–1.1), indicating no significant association. Conclusion: We found no evidence of an increased risk of ectopic pregnancy related to previous cesarean delivery.

Using the database of the National Breast and Cervical Cancer Early Detection Program of the Centers for Disease Control and Prevention (CDC) for the years 1991 to 2000, the authors investigated the risk of cervical cancer associated with longer screening intervals. The Markov model of the natural history of cervical cancer was used to estimate the numbers of cervical screenings and colposcopic examinations required to detect one case of cancer in any one screening interval. Cervical cytology was available for 938,576 women less than 65 years of age. Histologic results were from cervical biopsy, usually performed during a colposcopic examination. Fifty-four percent of the women were between 45 and 65 years of age. They identified themselves as white or nonwhite in equal numbers. Table 1 presents the results of cervical biopsy in the study group. The percentage of women diagnosed with grades 1, 2, and 3 cervical intraepithelial dysplasia (CIN) after 0, 1, or 2 negative cervical tests, respectively, was highest in women under 30 years of age. After 3 or more negative tests, women 30 to 44 years of age had the highest percentage of diagnoses of grades 1, 2, or 3 CIN. There was no invasive cervical cancer seen in women of any age group after 3 or more consecutive negative cervical smears. Less than 0.01% of women who had 1 or 2 consecutive negative tests were diagnosed with cervical cancer. Approximately 1 in every 1800 women who had not previously had a negative cervical smear in a CDC screening was found to have invasive cervical cancer. The risk of invasive cervical cancer decreased with advancing age and increasing numbers of consecutive negative cervical smear results. The Markov model predicted that women age 30 to 44 had a 5 in 100,000 risk of developing invasive disease after 3 consecutive negative screenings. The risk for women aged 45 to 59 years was 2 in 100,000, and for women 60 to 64 years of age, the risk was 1 in 100,000 after 3 negative smears. Compared with screening every 3 years after the last negative test, in 100,000 women, 1 additional case of invasive cervical cancer could be detected in women 30 to 44 years of age, given annual screening and an additional 69,665 cervical smears and 3861 colposcopic examinations. For women 45 to 59 years of age, with annual screening, an additional 209,324 cervical tests and 11,502 colposcopic examinations would be required to detect 1 additional case of invasive cervical cancer.

Four days after an elective caesarean section, a patient went blind within a few hours, associated with a sudden rise in blood pressure. The blindness, initially thought to be caused by a cerebral infarct, was ultimately diagnosed as a result of posterior reversible leuco-encephalopathy syndrome. This rare syndrome is reviewed.

In Australia in 2007, a woman with two previous normal vaginal deliveries underwent an emergency cesarean section at full dilatation of the cervix with a breech presentation. The woman died after a severe hemorrhage. The official Coroner's Report attributed the cause of death to postpartum hemorrhage, whereas the breech presentation was barely mentioned, suggesting that complications with breech cesarean deliveries are under-appreciated and under-reported.

Of patients with acute pancreatitis (AP), there remains a group who suffer life-threatening complications despite current modes of therapy. To identify factors which distinguish this group from the entire patient population, a retrospectiva analysis of 519 cases of AP occurring over a 5-year period was undertaken. Thirty-one per cent of these patients had a history of alcoholism and 47% had a history of biliary disease. The overall mortality was 12.9%. Of symptoms and signs recorded at the time of admission, hypotension, tachycardia, fever, abdominal mass, and abnormal examination of the lung fields correlated positively with increased mortality. Seven features of the initial laboratory examination correlated with increased mortality. Shock, massive colloid requirement, hypocalcemia, renal failure, and respiratory failure requiring endotracheal intubation were complications associated with the poorest prognosis. Among patients in this series with three or more of these clinical characteristics, maximal nonoperative treatment yielded a survival rate of 29%, compared to the 64% survival rate for a group of patients treated operatively with cholecystostomy, gastrostomy, feeding jejunostomy, and sump drainage of the lesser sac and retroperitoneum.

Mucoepidermoid carcinomas of minor salivary gland origin rarely arise in the nasal cavity. A patient with such a tumor in association with bilateral sphenoid sinus mucoceles is presented. This diagnosis was established preoperatively by CT and allowed an attempt at curative surgery to be made. The CT and pathological findings are discussed.

The effects on indirectly elicited muscle twitch amplitude associated with the calcium (slow) channel blocker, verapamil, with or without pancuronium were investigated using isolated bullfrog sciatic nerve-sartorius muscle preparations. Verapamil (2-8 mM) produced a dose-related depression of indirect muscle twitch height (P less than 0.05). Twitch response was depressed 11% below control by the lowest concentration employed and 86% by the highest concentration. Pancuronium (0.07 mM) depressed neuromuscular function 35% below control (P less than 0.05). The combination of 5 mM or 8 mM verapamil with 0.07 mM pancuronium caused significantly greater degrees of depression than either drug alone. Verapamil produced significant depression of twitch height in vitro in relatively high concentrations. The mechanism of action remains unknown. Verapamil possesses pharmacologic properties that may be unrelated to slow (calcium) channel inhibition. The reduction of muscle twitch height caused by verapamil alone (5 mM) could not be antagonized by neostigmine, calcium, or frequent washings.

Deliberate hypotension was produced during general anesthesia by the infusion of sodium nitroprusside in 13 patients undergoing total hip replacement. Hemodynamic data from these patients were compared with those obtained from 5 patients under normotensive anesthesia for the same procedure. During the hypotensive period, which averaged 1.5 hours, the cardiac index rose 20 percent compared with controls. No acidotic tendency was seen. Blood loss in the study group averaged 475 ml, compared with 1475 ml in controls. From these data, a dose-response curve was derived which may allow the accurate prediction of the minute dosage of sodium nitroprusside required to safely induce hypotension during anesthesia.

Three hundred patients were randomly selected and comprised two statistically balanced groups of 150 each. Group I received fresh autologous transfusions following extracorpeal circulation and homologous whole bank blood when further blood replacement was necessary. Group II served as controls, receiving whole bank blood following extracorporeal circulation and again when further blood replacement was necessary. Both groups were hemodiluted during bypass. The total amount of whole bank blood required during the hospital stay in group I was significantly less than in group II. There was no significant change in the preoperative and postoperative determinations of partial thromboplastin time, clotting time or prothrombin time in group I patients. These same time tests were increased in group II patients but were not clinically significant, attesting to the efficacy of a relatively brief period of extracorporeal circulation. Platelet counts and fibrinogen levels decreased during cardiopulmonary bypass in group I patients but increased immediately with reinfusion of the fresh autologous blood. An improved technic of hemospasia is described which reduces the demand for bank blood by roughly 50 percent.

Procaine suppresses the cough reflex, decreases laryngeal irritability, and has general anesthetic properties. For these reasons, 14 pediatric patients undergoing CO2 laser resection of laryngeal papillomas were studied in which an intravenous infusion of procaine (1 mg/kg/min) was added to N2O-O2 halothane/enflurane general anesthesia immediately following endotracheal intubation. These patients were compared to nine patients receiving the same anesthesia without procaine. The mean age of both groups was 11 years. There was no difference between the groups in duration of anesthesia or surgery. Emergence, however, averaged 15 minutes in study patients compared to 36 minutes in the control group (p less than 0.01). There was no difference in anesthetic concentrations required to maintain satisfactory operative conditions in the two groups. Muscle relaxants were required intraoperatively in seven control patients but in none of the study patients. The surgeon ranked the operative conditions excellent in all study patients but poor in seven of the nine control patients. Five of the latter required postoperative treatment of laryngeal complications, including reintubation in three. Only one of the study patients had postoperative stridor. No evidence of procaine toxicity was noted in the study patients with total doses ranging from 500--3600 mg. Intravenous procaine is useful in pediatric patients having endoscopic laryngeal operations.

Sodium nitroprusside (SNP) was used to produce deliberate hypotension in 30 selected patients, 9 to 78 years of age, for total hip replacement under halothane-N2O-O2 anesthesia. Hypotension was induced in the first 13 patients by infusing a 0.01% (100 mug/ml) solution of nitroprusside (NP) in 5% dextrose. Blood pressure was diminished to a level just producing a dry surgical field. Preliminary data demonstrated that the mean arterial blood pressure (MAP) achieving this condition was 65 torr (p less than 0.01) and that the minute dosage of NP (mug/min) required to consistently reduce MAP to 65 torr could not be predicted on the basis of body weight. However, the age/weight ratio (yr/kg) of each patient, plotted against the known minute dosage of NP given during anesthesia, produced a highly significant dose-response curve (p less than 0.001, r = -0.8226). The preliminary dose-response curve was examined in a double-blind study on an additional 17 patients. The curve derived from the prospective study did not differ from that of the preliminary study. In addition, the combined data from the retrospective and prospective studies (30 patients) gave a better statistical fit than did those from the preliminary study alone (p less than 0.001, r = -0.8939). The nomogram provides an additional margin of safety in the use of this potent, fast-acting drug. SNP has been found predictable and effective in reducing surgical blood loss in selected patients undergoing total hip replacement.

Because severe muscular weakness was noted in animals receiving verapamil in doses exceeding those used in humans, we studied the effects of verapamil on neuromuscular function and its correlation with myocardial conduction. The flexor carpi radialis and its nerves were surgically exposed in mechanically ventilated dogs during pentobarbital anesthesia. Indirect and direct electrical stimulation was applied and twitch height recorded following the intravenous administration of verapamil. Twenty animals received one of four dose schedules. The results showed a significant dose-related depression of twitch height to indirect stimulation. Twitch height to direct stimulation was reduced only with the highest dose. The onset of depression of indirect stimulation was temporally associated with onset of A-V conduction delay. However, recovery following indirect stimulation lagged behind recovery of the ECG by 30 min. Recovery times of twitch height following indirect stimulation ranged from 60-208 min and also were dose-related. The qualitative similarity of pancuronium and verapamil on indirect twitch height suggests a similar site of action, i.e., the neuromuscular junction. A presynaptic or postsynaptic effect of verapamil could not be discerned in this study. Verapamil may produce an unrecognized source of weakness in the anesthetized patient either alone or through interaction with anesthetic agents or adjuncts.