Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia.

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children. MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants' medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups. RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic ( p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination. CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine's effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine's effectiveness and protectability.

Postoperative complications of epidural analgesia at hysterectomy for gynecologic malignancies: an analysis of the National Surgical Quality Improvement Program.

OBJECTIVE: The aim of this study was to identify the rate of 30-day postoperative complications after the use of epidural in women undergoing hysterectomy for gynecologic malignancy. Secondary outcome was the impact of epidural on hospital length of stay. METHODS: A retrospective cohort study was conducted using the American College of Surgeons' National Surgical Quality Improvement Program database. This large dataset includes perioperative risk factors and 30-day post-operative outcomes from more than 680 hospitals. Women who underwent abdominal hysterectomy for a gynecologic malignancy from January 2014 to December 2017 were included. Adult patients (18 years or older) who underwent abdominal hysterectomy were identified using common procedure terminology and international classification of diseases codes. Only laparotomy cases were included, and minimally invasive cases (laparoscopy, transvaginal) were excluded due to the small prevalence of epidural cases in this cohort. All patients received general anesthesia. If patients were noted to have "epidural anesthesia" they were included in the epidural cohort and those receiving other adjuvant techniques (regional blocks or spinal anesthesia) were excluded. The primary outcome of interest was the 30-day occurrence of a pulmonary embolism, deep-vein thrombosis, pneumonia, and urinary tract infection. Those who received epidural analgesia were matched in a 1:1 ratio with a similar group of patients who did not receive epidural analgesia using a calculated propensity score to control for confounding factors. RESULTS: A total of 2035 (13.8%) patients undergoing abdominal hysterectomy for a gynecologic malignancy received epidural analgesia. 1:1 propensity-matched samples included 2035 patients in both epidural and no-epidural groups. Patient characteristics between groups were similar. Overall 30-day complication rates were higher in the epidural group (75.9% vs 62.0%, P<0.01). Specific complications that were higher in the epidural group included: blood transfusion (28.9% vs 22.8%); wound disruption (2.0% vs 1.1%); surgical site infection (10.1% vs 7.2%); and delay in return of bowel function (12.3% vs 9.3%) (all P<0.05). Hospital length of stay was significantly longer in the epidural group as compared with the no-epidural group (5.69 days vs 4.79 days, P<0.01) and readmissions were higher in the epidural group (10.5% vs 9.7%, P<0.01), but there was no difference in 30-day mortality between the groups (P=0.62). DISCUSSION: The rate of 30-day complications and length of stay among women undergoing an abdominal hysterectomy for gynecologic malignancy was higher for those who received epidural analgesia, but there was no difference in 30-day mortality. Although epidural analgesia can provide a number of benefits when used for postoperative pain control, the possible association with increased 30-day morbidity and length of stay needs to be considered.

Second primary anal and oropharyngeal cancers in cervical cancer survivors.

BACKGROUND: Human papilloma virus infection is responsible for approximately 31,500 new cancers in the United States annually. Almost all cervical cancers are linked to human papilloma virus infection. As early identification and treatment of cervical cancer improve, the incidence of cervical cancer has decreased and survival has improved. However, survivors continue to remain at risk for other human papilloma virus-related malignancies. The purpose of this study was to assess the risk of primary anal and oropharyngeal cancers among women with a history of squamous cell carcinoma of the cervix. STUDY DESIGN: A population-based cohort of 21,060 women diagnosed with cervical squamous cell carcinoma from 1973 through 2014 was identified from the Surveillance, Epidemiology, and End Results Program-9 data. Standardized incidence ratios for anal and oropharyngeal cancers were calculated to estimate the risk of a second primary human papilloma virus-related malignancy based on incidence in the general population. Results were further stratified by age (20-53, 54 years old or older) and latency period (2-11, 12-59, 60-119, 120 months or longer). The number needed to screen for oropharyngeal and anal cancers was estimated using study results and Centers for Disease Control and Prevention-reported incidence rates. RESULTS: Cervical squamous cell cancer survivors had a higher risk of being diagnosed with oropharyngeal cancer (standardized incidence ratio, 4.36, 95% confidence interval, 1.19-11.15) and anal cancer (standardized incidence ratio, 2.20, 95% confidence interval, 1.28-3.52). Patients diagnosed with cervical cancer between ages 20 and 53 years had an increased risk of anal cancer (standardized incidence ratio, 3.53, 95% confidence interval, 1.15-8.23). Age 54 years or older at cervical cancer diagnosis was associated with increased oropharyngeal cancer risk only (standardized incidence ratio, 5.04, 95% confidence interval, 1.37-12.91). Latency stratification was significant for increased OPC risk between 2-11 months and 12-59 months after diagnosis. At 120 months or longer, there was an increased risk of both oropharyngeal cancer (standardized incidence ratio, 7.97, 95% confidence interval, 2.17-20.42) and anal cancer (standardized incidence ratio, 2.60, 95% confidence interval, 1.34-4.54). The estimated number needed to screen for oropharyngeal cancer (number needed to screen for oropharyngeal cancer, 282) and anal cancer (number needed to screen for anal cancer, 1272) is significantly less than the number needed to screen for cervical cancer. CONCLUSION: Squamous cell cervical cancer survivors have a substantially increased risk of anal and oropharyngeal cancers. This increased risk is significant 10 or more years after the cervical cancer diagnosis. Health care providers and survivors should be aware of this increased risk. The development of effective and economical surveillance methods for anal and oropharyngeal cancers in cervical cancer survivors is urgently needed.

Pancreaticobiliary metastasis presenting as primary mucinous ovarian neoplasm: A systematic literature review.

True primary mucinous ovarian carcinomas are rarer than originally thought and their clinical behavior and treatment response are different than more common epithelial ovarian carcinomas. Secondary ovarian neoplasms often mimic the clinical and histological features of mucinous ovarian cancer making their diagnosis, and therefore treatment, more difficult. Misdiagnosis can have a significant impact on both treatment and prognosis. The majority of these secondary ovarian neoplasms arise from the gastrointestinal tract, with mucinous histology often of pancreaticobiliary origin. Our study objective was to review current evidence distinguishing pancreaticobiliary ovarian metastasis from primary mucinous ovarian carcinoma. We utilized a PubMed search using MeSH terms and selected articles were reviewed, synthesized and summarized. Thirty-nine articles were included in the review. The clinical, gross, histological and immunohistochemical features distinguishing primary mucinous ovarian carcinomas from pancreaticobiliary ovarian metastasis were identified. Compared to primary mucinous ovarian carcinoma, metastatic pancreaticobiliary tumors are more often bilateral, <10 cm, have irregular external surface and surface implants, display an infiltrative pattern of invasion and stain for MUC1 and CK17. Primary ovarian mucinous tumors rarely (<3%) have signet ring cells or involvement of the hilum. Metastatic mucinous tumors mimic their primary mucinous ovarian counterparts and their clinical and histopathological features overlap in many ways. However, these metastatic tumors have features that can help differentiate them from primary mucinous carcinoma. With a high index of suspicion and knowledge of the reviewed features, distinguishing these tumors will continue to become easier.

A preoperative risk score to predict red blood cell transfusion in patients undergoing hysterectomy for ovarian cancer.

BACKGROUND: Patients with ovarian cancer experience a high rate of anemia throughout their treatment course, with rates that range from 19-95%. Blood transfusions offer symptom relief but may be costly, are limited in supply, and have been associated with worse 30-day surgical morbidity and mortality rates. OBJECTIVE: The purpose of this study was to identify risk factors for blood transfusion with packed red blood cell and to develop a transfusion risk score to identify patients who undergo surgery for ovarian cancer and who are at lowest risk for a blood transfusion. Our aim was to help clinicians identify those patients who may not require a crossmatch to encourage resource use and cost-savings. STUDY DESIGN: This is a retrospective database cohort study of 3470 patients who underwent hysterectomy for ovarian cancer with the use the National Surgical Quality Improvement Program database from 2014-2016. The association between risk factors with respect to 30-day postoperative blood transfusion was modeled with the use of logistic regression. A risk score to predict blood transfusion was created. RESULTS: Eight hundred ninety-one (25.7%) patients received a blood transfusion. In multivariate analysis, blood transfusion was associated independently with age (odds ratio, 1.90, P<.01), African American race (odds ratio, 2.30; P<.01), ascites (odds ratio, 1.89; P=.02), preoperative hematocrit level <30% (odds ratio, 10.70; P<.01), preoperative platelet count >400×109/L (odds ratio, 1.75; P<.01), occurrence of disseminated cancer (odds ratio, 1.71; P<.01), open surgical approach (odds ratio, 7.88; P<.01), operative time >3 hours (odds ratio, 2.19; P<.01), and additional surgical procedures that included large bowel resection (odds ratio, 4.23; P<.01), bladder/ureter resection (odds ratio, 1.69; P=.02), and pelvic exenteration (P=.02). A preoperative risk score that used age, race, ascites, preoperative hematocrit level, platelets, presence of disseminated cancer, planned hysterectomy approach, and procedures accurately predicted blood transfusion with good discriminatory ability (C-statistic=0.80 [P<.001]; C-statistic=0.69 [P<.001] for derivation and validation datasets, respectively) and calibration (Hosmer-Lemeshow goodness-of-fit, P=.081; P=.56 for derivation and validation datasets, respectively). CONCLUSION: Patients who undergo hysterectomy for ovarian cancer experience a high incidence of blood transfusions in the perioperative period. Preoperative risk factors and planned surgical procedures can be used in our transfusion risk score to help predict anticipated blood requirements.

Abdominal wall reconstruction after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival and decrease recurrence of peritoneal metastasis in a select population of patients. Abdominal wall resection is often needed to achieve complete CRS and the extent of abdominal wall resection may necessitate abdominal wall reconstruction (AWR). We sought to investigate if postoperative morbidity and mortality was increased in patients who underwent AWR with CRS-HIPEC (AWR group) compared to CRS-HIPEC without AWR (non-AWR group) and to identify if patient, tumor, and operative risk factors were associated with poor outcomes following AWR. We postulate that AWR is a safe and viable treatment option in appropriately selected patients with peritoneal disease. METHODS: A retrospective chart review was conducted from 2012 to 2015. Demographics, comorbidities, intraoperative variables, and postoperative outcomes were analyzed and compared between the non-AWR group and the AWR group. RESULTS: A total of 30 patients underwent CRS-HIPEC at our institution; 19 recruited in non-AWR group and 11 in the AWR arm. Median follow-up was 19.1 mo for the non-AWR group and 15.6 mo for AWR. Overall survival and complications were not significantly different between groups. Six patients in the non-AWR group and three patients in AWR group died during the follow-up period (32% versus 27%, P = 0.75). Grade III/IV Clavien-Dindo complications were similar in AWR compared to non-AWR group (64% versus 50%, P = 0.46) however estimated blood loss (1000 mL versus 450 mL, P = 0.01) and operative time (663 min versus 510 min, P = 0.02) were significantly increased in the AWR group. CONCLUSIONS: The results of this study demonstrate that AWR is a safe and viable option and can improve wound closure and strength in select patient populations undergoing CRS-HIPEC. AWR is not associated with an increase in mortality or complication rate. Future studies will need larger sample sizes and randomization to identify patient and operative factors that increase morbidity with AWR and identify the ideal timing of AWR.

Theropod courtship: large scale physical evidence of display arenas and avian-like scrape ceremony behaviour by Cretaceous dinosaurs.

Relationships between non-avian theropod dinosaurs and extant and fossil birds are a major focus of current paleobiological research. Despite extensive phylogenetic and morphological support, behavioural evidence is mostly ambiguous and does not usually fossilize. Thus, inferences that dinosaurs, especially theropods displayed behaviour analogous to modern birds are intriguing but speculative. Here we present extensive and geographically widespread physical evidence of substrate scraping behavior by large theropods considered as compelling evidence of "display arenas" or leks, and consistent with "nest scrape display" behaviour among many extant ground-nesting birds. Large scrapes, up to 2 m in diameter, occur abundantly at several Cretaceous sites in Colorado. They constitute a previously unknown category of large dinosaurian trace fossil, inferred to fill gaps in our understanding of early phases in the breeding cycle of theropods. The trace makers were probably lekking species that were seasonally active at large display arena sites. Such scrapes indicate stereotypical avian behaviour hitherto unknown among Cretaceous theropods, and most likely associated with terrirorial activity in the breeding season. The scrapes most probably occur near nesting colonies, as yet unknown or no longer preserved in the immediate study areas. Thus, they provide clues to paleoenvironments where such nesting sites occurred.

Cervical conization for cervical intraepithelial neoplasia (CIN) 2 and 3 in HIV-positive women: a case-control study.

OBJECTIVE: The purposes of the study were to investigate the outcomes of cervical conization for cervical intraepithelial neoplasia (CIN) 2 and 3 in HIV-positive women and age-matched HIV-negative controls and to determine whether positive margin, positive endocervical curettage, CD4 count, or viral load was associated with the persistence of CIN 2,3 or residual CIN 2,3 on the specimen from repeat excision procedure or hysterectomy. MATERIALS AND METHODS: HIV-positive women and HIV-negative controls with CIN 2,3 on cervical conization were enrolled in the study. Patients who underwent repeat conization or hysterectomy were identified, and the specimens were evaluated for residual CIN 2,3. CD4 count and viral load within 8 weeks of procedure were analyzed. RESULTS: A total of 44 patients and 44 age-matched controls were identified. Persistent CIN 2,3 was diagnosed in 28 HIV-positive (63.6%) and 14 HIV-negative patients (31.8%; odds ratio [OR] = 4.7, 95% confidence interval [CI] = 1.9-11.5, p < .001). In HIV-positive women, a positive margin was associated with a higher persistence rate after cervical conization (OR = 5.3, 95% CI = 1.17-24.14, p = .03). In HIV-negative patients, positive endocervical curettage was associated with a higher persistence rate after conization (OR = 12, 95% CI = 2.24-64.23, p = .004). Of HIV-positive women, 75% had residual CIN 2,3 on the specimen from repeat procedure compared to 45.2% of controls (OR = 3.6, 95% CI = 1.3-10.6, p = .018). CD4 count or viral load was not associated with the rate of residual disease or persistence rate after cervical conization, but the lowest OR that the sample size allowed to assess with 90% power was 5.02. CONCLUSIONS: HIV-positive women have a higher rate of residual disease and higher persistence rate after conization for CIN 2,3 than age-matched HIV-negative controls.

Clear cell adenocarcinoma of the abdominal wall: a case report.

BACKGROUND: Primary clear cell adenocarcinoma of the abdominal wall is exceptionally rare and most likely arises within scar endometriosis. CASE: A 37-year-old woman with 3 prior cesarean sections developed an abdominal wall mass that was confirmed as clear cell adenocarcinoma. CONCLUSION: Clear cell adenocarcinoma is in the differential diagnosis of abdominal wall masses, particularly in cases of prior surgery. Fine needle aspiration may be helpful in establishing the diagnosis.

Vaginal blue nevus: report of a case and review of the literature.

OBJECTIVE: : Blue nevi are extremely rare in the vaginal canal and are suspicious for melanoma, especially when multiple lesions are present. We describe a woman with multiple blue nevi of the vagina. DESIGN: : We describe 1 case of multiple blue nevi of the vagina. RESULTS: : A 37-year-old woman, status after therapy for serous carcinoma of the ovary, presented with multiple blue to black macular lesions present throughout the vagina. Two of the lesions were examined by biopsy and demonstrated dendritic melanocytes. The patient has been closely followed, and the lesions remain unchanged. CONCLUSIONS: : Multiple vaginal blue nevi are an important differential diagnostic consideration for melanoma of the vagina. These lesions, however, are benign and require only clinical follow-up. Excision is unnecessary.

Paraneoplastic SIADH and Dermatomyositis in Cervical Cancer: A Case Report and Literature Review.

We present the first known case of a patient with cervical squamous cell carcinoma complicated by paraneoplastic syndromes of both dermatomyositis and inappropriate secretion of antidiuretic hormone (SIADH). The patient in this case presented with generalized body pain and vaginal bleeding. Her cervical cancer was diagnosed as stage IIB by physical exam, imaging, and cervical biopsy, her dermatomyositis was confirmed by muscle and skin biopsy, and her SIADH was diagnosed based on laboratory findings.

Predicting persistent/recurrent disease in the cervix after excisional biopsy.

OBJECTIVE: To evaluate the ability of various factors to predict persistent/recurrent disease after excisional biopsy of the transformation zone (cold knife conization or loop electrosurgical excision procedure) with special attention to the endocervical curettage (ECC). STUDY DESIGN: We reviewed the charts and histopathology findings of 152 women who underwent endocervical curettage at the time of conization (cold knife conization) or loop electrosurgical excision procedure (LEEP). Age, histopathologic findings on the cervical conization specimen, ectocervical margin, endocervical margin, and ECC specimens were assessed. These findings were analyzed for a relationship with the presence of cervical disease on subsequent follow-up (to include hysterectomy, repeat conization, colposcopically directed biopsies, endocervical curettage, and/or cytology). RESULTS: Positive endocervical margin (odds ratio [OR], 9.168; 95% confidence interval [95% CI], 3.939, 23.488), positive ectocervical margin (OR, 3.561; 95% CI, 1.626, 7.799), positive specimens (OR, 17.683; 95% CI, 5.308, 58.912), and severity of disease (OR, 2.730; 95% CI 1.507, 4.947) on the conization were all individually significantly associated with the presence of persistent/recurrent disease. Age of the patient at the time of cervical conization was not statistically associated with the ability to predict persistent/recurrent disease. In the multivariate analysis, the endocervical curettage (OR, 8.710; 95% CI, 2.302, 32.958) and the endocervical margin status (OR, 9.170; 95% CI, 2.887, 29.125) together were significant predictors of persistent/recurrent disease after adjusting for the other variable. However, when the degree of dysplasia and ectocervical margin status was included in the multivariate analysis, endocervical margin status (OR, 6.761; 95% CI, 2.657, 17.202) and severity of cervical disease (OR, 1.930; 95% CI, 1.038, 3.59) were the only statistically significant predictors of persistent/recurrent cervical neoplasia. CONCLUSION: In this retrospective analysis, positive endocervical or ectocervical margin, positive ECC specimens, and severity of cervical disease were all predictors of persistent/recurrent disease. However, on the multivariate stepwise logistic regression analysis, only endocervical margin status and severity of neoplasia significantly predicted the occurrence of persistent/recurrent disease. The results of the ECC, after adjustment for the degree of dysplasia and the endocervical margin status, do not add incremental value to the prediction of persistent/recurrent disease. At this time, ECC does not need to be routinely performed at the time of excisional biopsy of the cervical transformation zone.

Angiomyofibroblastoma of the retroperitoneum: a case report.

BACKGROUND: Angiomyofibroblastoma is a rare soft tissue neoplasm that presents most frequently in the genital region of young to middle-aged women. CASE: A 28-year-old woman presented with nausea, vomiting and pelvic pain. Computed tomography revealed a well-circumscribed, brightly enhancing pararectal mass in the retroperitoneum. A core needle biopsy suggested the diagnosis of angiofibromyoblastoma. Due to the highly vascular nature of the lesion, the patient underwent angiographically guided embolization in an effort to minimize surgical blood loss. This was followed by exploratory laparotomy and resection of the mass. CONCLUSION: This case illustrates an unusual presentation of angiomyofibroblastoma in the pelvic retroperitoneum and its management with preoperative selective embolization, which may have contributed to the minimal blood loss at the time of resection.

Fertility-sparing surgery for persistent gestational trophoblastic neoplasia in the myometrium: a case report.

BACKGROUND: Persistently low-level "real" serum human chorionic gonadotropin (hCG) after treatment for gestational trophoblastic neoplasia (GTN) in patients desirous of preserving fertility is a diagnostic and management challenge. Among the possible explanations is the presence of false positive ("phantom") hCG or of trophoblasts in a myometrial sanctuary. CASE: An 18-year-old woman had persistent low-level hCG values in her serum after treatment for nonmetastatic GTN. Her only child had died, and she wanted to preserve her fertility potential. Phantom hCG was excluded. Positron emission tomography (PET) showed increased uptake in an area of the uterus in which magnetic resonance imaging had shown an ill-defined, ovoid lesion. Removal of the lesion with preservation of the uterus followed by 2 courses of multiagent chemotherapy (methotrexate, dactinomycin and cyclophosphamide) resuited in clinical remission. CONCLUSION: PET can prove useful in detecting persistent disease in a myometrial sanctuary in patients with resistant, nonmetastatic GTN. Conservative surgical excision with uterine preservation is possible and can be of value in achieving remission.

Premalignant lesions in the contralateral ovary of women with unilateral ovarian carcinoma.

OBJECTIVES: A limited number of studies have looked at premalignant lesions of ovaries and the results are conflicting. Our goal is to identify, histologically and by immunohistochemistry, any features that may represent premalignant changes in the ovaries. METHODS: Our cases included 29 patients with unilateral ovarian cancer. These were compared to 19 controls that had unilateral benign ovarian pathology and to 39 controls with bilateral normal ovaries. Tissue sections from the contralateral normal ovary were examined. Analysis of histological features and immunohistochemical staining for the apoptosis inhibitor Bcl-2, the proliferation marker Ki-67 and the tumor suppressor gene p53 was performed. RESULTS: Epithelial stratification, nuclear atypia, and inclusion cysts were more often seen in the cases than in the two control groups. Epithelial stratification and nuclear atypia was statistically significantly more common among the cases than the normal controls. Inclusion cysts were present in more of the cases (P = 0.017) and in higher numbers than in the normal controls. Bcl-2 overexpression was statistically more commonly seen in the cases with contralateral ovarian cancer (39%) than in the normal controls (15%), while it was present in 28% of cases with contralateral benign pathology. CONCLUSIONS: Epithelial alterations and Bcl-2 overexpression was seen in all three groups studied. However, the epithelial alterations and Bcl-2 overexpression was more commonly seen in the contralateral ovary of women with unilateral ovarian cancer. This suggests an association between these changes and ovarian cancer. Although it is tempting to label the above changes premalignant, women with the above changes are at possibly higher risk of developing ovarian cancer rather than having acquired an oncogenic change that would inevitably lead to ovarian cancer.

Melphalan for the treatment of patients with recurrent epithelial ovarian cancer.

The purpose of this study was to determine the response to melphalan in patients with recurrent epithelial ovarian cancer after platinum-based therapy. This retrospective observational study analyzed 10 patients with recurrent epithelial ovarian carcinoma treated with melphalan between August 1995 and April 2001. All had received primary platinum-based therapy. Nine of the 10 patients had chemosensitive disease. All but one patient had received one or more second-line therapies prior to melphalan. The median time to recurrence after first-line therapy was 26 months (range, 3-68). Treatment with melphalan resulted in 2 (20%) complete responses and 1 (10%) partial response (response rate, 30%; 95% CI 8%, 65%). The median progression-free interval after initiation of melphalan therapy was 8 months (range, 3-23). The most common side effects were grade I thrombocytopenia (20% of courses) and grade II leukopenia (18% of courses). The use of melphalan as palliative chemotherapy in patients with recurrent ovarian cancer results in response rates similar to those reported with other more expensive agents. Melphalan at the doses reported here has a favorable toxicity profile.

Detection of female lower genital tract dysplasia using orally administered 5-aminolevulinic acid induced protoporphyrin IX: a preliminary study.

OBJECTIVE: Previous studies have suggested that 5-aminolevulinic acid (ALA) may be used topically on the cervix to allow optical detection of cervical dysplasia, based on the fluorescence of protoporphyrin IX (PpIX) synthesized in situ from ALA. However, the uniformity of distribution of topically applied PpIX and the sensitivity and specificity of detection are not optimal. The current study was undertaken to demonstrate the feasibility of administering ALA by mouth (po) with the hypothesis that systemic administration might provide a more reliable diagnostic tool. METHODS: Oral ALA was administered to 14 patients with abnormal Pap smears in a dose- and time-intensity design. Institutional review board approval was obtained. A starting dose of 10 mg/kg of po ALA was administered and colposcopy was performed in 3 patients at 1 h, 3 patients at 2 h, 6 patients at 3 h, and 2 patients at 4 h. The study was written with the intent to increase the dose in 10 mg/kg increments if fluorescence was not detected; however, fluorescence was detected at the first dose level. Liver function tests were checked pre and post ALA and follow-up telephone calls were made regarding possible side effects. Both white and blue light colposcopy examinations were performed by two blinded clinicians and biopsies of all abnormal areas were performed. RESULTS: All patients tolerated po ALA well, with no systemic side effects. At the 10 mg/kg dose there was no reported nausea or photosensitivity. Optimal fluorescence was achieved at the 3-h time point, with quenching noted at the 4-h time point. Excellent absorption was documented with fluorescence of the lip demonstrated with Wood's lamp. In some cases fluorescence correlated with dysplasia on biopsy. CONCLUSION: 5-ALA given via the po route and at the dose and time period studied is well tolerated and affords fluorescence of the cervix. Future study is needed to demonstrate the successful identification of dysplastic lesions, with the ultimate goal of treating dysplasia of the lower genital tract with 5-ALA and light therapy.