MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit.

MicroRNAs (miRNAs) have attracted attention because of their key regulatory functions in many biological events, including differentiation and tumorigenesis. Recent studies have reported the existence of a reciprocal regulatory loop between the family of let-7 miRNAs and an RNA-binding protein, Lin28, both of which have been documented for their important roles during cell differentiation. Hence, using bipotent K562 human leukemia cells and human CD34+ hematopoietic progenitor cells as research models, we demonstrate that let-7 and Lin28 have contrary roles in megakaryocytic (MK) differentiation with a dynamic balance; expression of miR-181 is capable of effectively repressing Lin28 expression, disrupting the Lin28-let-7 reciprocal regulatory loop, upregulating let-7, and eventually promoting MK differentiation. However, miR-181 lacks a significant effect on hemin-induced erythrocyte differentiation. These results demonstrate that miR-181 can function as a 'molecular switch' during hematopoietic lineage progression specific to MK differentiation, thus providing insight into future development of miRNA-oriented therapeutics.

Predictors of complications and hospital stay in gynecologic cancer surgery.

OBJECTIVE: To test the hypothesis that comorbid medical conditions can predict length of hospital stay and incidence of postoperative complications. METHODS: We reviewed the medical records of 187 women who had surgery for known or suspected gynecologic malignancies during 1996 and 1997, and 179 were included in the present study. Information on each woman's comorbid medical conditions, surgical history, surgicopathologic cancer diagnosis, American Society of Anesthesiologists' classification, surgical procedures, and postoperative complications was collected and analyzed. RESULTS: Women with two or more comorbid medical conditions had significantly longer mean hospital stays (8.62 days) than those with none or one comorbid medical condition (6.43 days) (P <.001). Women with two or more postoperative complications had significantly longer mean hospital stays (11.88 days) than those with none or one complication (6.02 days) (P <.001). Women with two or more postoperative complications also had significantly more comorbid medical conditions (mean 2.5) than those with none or one complication (mean 1.7) (P <.001). The American Society of Anesthesiologists class also was a significant predictor of postoperative complications and length of hospitalization. Age over 60 years also was associated with statistically significant increase in comorbid medical conditions and significantly longer hospitalizations. CONCLUSION: Our findings indicated that certain high-risk patients can be identified before hospital admission based on comorbid medical conditions. Certain risk indices, such as the American Society of Anesthesiologists classification score, also can predict postoperative complications and length of hospital stay. This information can be used to coordinate preoperative and postoperative hospital care and be a reference for certain future disease management systems.

Is colposcopy always necessary with atypical glandular cells of undetermined significance on Papanicolaou smears?

The objective of this study was to review a 5-year experience with atypical glandular cells of undetermined significance (AGUS) on Papanicolaou smear and to use the information to devise a triage method for patients presenting with this abnormality. Our Papanicolaou smear database was used to identify patients who were found to have AGUS results between January 1, 1994 and December 31, 1998. The medical records of these patients were reviewed for the results of follow-up studies, including repeat Papanicolaou smear, endocervical curettage, colposcopic directed biopsies, and endometrial biopsy. During the study period, 27,859 Papanicolaou smears were performed, with 306 (1.1%) being reported as AGUS; 18 patients had two AGUS smears. An additional 24 patients did not meet study criteria. The study group then consisted of 264 patients, of whom 244 (92.4%) reported for follow-up. There were 167 (63.3%) with atypical endocervical cells of undetermined significance (AECUS), 14 (5.3%) with atypical endometrial cells of undetermined significance, and 83 (31.4%) with AECUS plus a squamous cell abnormality. The overall prevalence of a high-grade squamous intraepithelial lesion (HSIL) was 11.8%. The prevalence of HSIL in the AECUS plus squamous cell abnormality group was 25.4%. None of the atypical endometrial cell group had HSIL. In the AECUS, favor dysplasia category, 29.4% had HSIL, whereas in the AECUS, favor reactive process or in unqualified, 2.3% had HSIL. Eighty-one patients underwent endometrial biopsy: three (3.7%) were found to have endometrial adenocarcinoma, and two (2.5%) had complex atypical endometrial hyperplasia. The prevalence of HSIL in patients with AECUS, favor reactive process or AECUS, unqualified Papanicolaou smears is low. Colposcopy is not necessary as an initial triage process for this category of patients. A significant percentage of patients with AECUS, favor dysplasia or AECUS with a squamous epithelial abnormality Papanicolaou smears have HSIL; this subset of patients should be investigated with colposcopy.

Thrombocytosis as a predictor of malignancy in women with a pelvic mass.

OBJECTIVE: To determine if thrombocytosis (platelets > 350,000/microL) is a predictor of malignancy in women with a pelvic mass. STUDY DESIGN: The charts of 323 patients who presented with a pelvic mass and subsequently underwent an exploratory laparotomy were reviewed for preoperative platelet count and final diagnosis. Thrombocytosis was defined as a platelet count > 350,000/microL. The data were analyzed utilizing the SPSS 6.1 software package (Chicago, Illinois); analysis of variance and chi 2 tests were used for data comparison. RESULTS: The difference in the platelet counts of patients with malignancy and benign tumors was statistically significant (P < .00001). Eighty-seven patients had cancer; of these, 42 (48.3%) had thrombocytosis. Only 31 (13.8%) patients with benign tumors had thrombocytosis. CONCLUSION: High preoperative platelet counts in women presenting with a pelvic mass may predict a final diagnosis of cancer.

Striae gravidarum as a predictor of vaginal lacerations at delivery.

BACKGROUND: Abdominal stretch marks found during pregnancy may be indicative of poor skin elasticity. One who does not have stretch marks may have better skin elasticity and may be less likely to tear perineal and vaginal tissue during vaginal delivery. This study was conducted to determine whether striae gravidarum could predict lacerations and their severity. METHODS: This prospective observational study included 168 women having vaginal delivery of infants who weighed more than 2,000 g. The absence or presence and degree of lacerations involving the perineum, vagina, labia, and periurethral regions were studied with a step-wise multivariate logistic regression analysis. RESULTS: Episiotomy was found to prevent spontaneous lacerations. Abdominal stretch marks were found to be statistically significant predictors of lacerations when controlling for episiotomy. CONCLUSIONS: Patients with striae gravidarum are at higher risk for lacerations at the time of vaginal delivery than patients who do not have abdominal stretch marks.

Abdominal sacral colpopexy resulting in a retained sponge. A case report.

BACKGROUND: During abdominal sacral colpopexy, a procedure used to correct vaginal vault prolapse, the vaginal cuff must be elevated intraabdominally to facilitate suturing. The use of a vaginal sponge stick to elevate the cuff can result in foreign body complications. CASE: A 70-year-old woman developed chronic pelvic pain and a vaginal discharge after undergoing abdominal sacral colpopexy. Radiographic films showed what appeared to be a retained surgical needle in the vaginal cuff. During an exploratory laparotomy to remove the foreign body, a fragment of the sponge used to elevate the vaginal cuff during abdominal sacral colpopexy was found to have been inadvertently incorporated into the apex of the vagina. CONCLUSION: An end-to-end anastomotic sizer should be used to elevate the vaginal cuff during abdominal sacral colpopexy to reduce the risk of foreign body complications.

Detection of sentinel lymph nodes with lymphazurin in cervical, uterine, and vulvar malignancies.

BACKGROUND: Identification of sentinel lymph nodes may allow prediction of metastatic disease in cancer patients. We did a prospective study to determine whether lymphazurin dye could identify sentinel lymph nodes in patients with cervical, uterine, and vulvar cancer. METHODS: In 33 patients having surgery for either uterine, cervical, or vulvar carcinoma, lymphazurin dye was injected into the respective organs before the tumor and node dissection began. Sentinel lymph nodes were identified and dissected in situ. RESULTS: The identification rate of sentinel lymph nodes was 0/8 (0%) for uterine cancer patients, 2/13 (15.4%) for cervical cancer patients, and 9/12 for vulvar cancer patients (75%). CONCLUSIONS: In a limited number of patients, lymphazurin day may be useful in identifying or assessing the sentinel nodes draining vulvar and cervical cancers. The role of this procedure in treatment planning for patients with gynecologic malignancies is yet to be determined.

Correlation between endometrial cells on Papanicolaou smear and endometrial carcinoma.

BACKGROUND: A retrospective study was done to assess the correlation between endometrial cells on routine cervical cytology and carcinoma of the endometrium. METHODS: In a 4-year period, endometrial cells of some type were identified on the Papanicolaou (Pap) smears of 61 women, of whom 52 had further diagnostic evaluation of the endometrium. Data were analyzed with a multivariate stepwise logistic regression. RESULTS: The results indicated an association of endometrial cells in Pap smears with carcinoma of the endometrium in seven patients (13.5%). In 45 patients (86.5%), the final diagnosis was benign. Factors that impacted the diagnosis of carcinoma were the findings of atypical or cancerous endometrial cells on Pap smear and abnormal vaginal bleeding. CONCLUSIONS: These data indicate the importance of further diagnostic evaluation with endometrial sampling in postmenopausal patients with endometrial cells seen in Pap smears, especially those with abnormal bleeding.

Body mass predicts the survival of patients with new International Federation of Gynecology and Obstetrics Stage IB1 and IB2 cervical carcinoma treated with radical hysterectomy.

BACKGROUND: The authors evaluated the impact of body mass on survival and morbidity of patients with new International Federation of Gynecology and Obstetrics (FIGO) Stage IB1 and IB2 cervical carcinoma managed with radical hysterectomy. METHODS: Two hundred twenty-nine patients with Stage IB1 or IB2 cervical carcinoma treated with radical hysterectomy were studied in a multivariate logistic regression analysis. The body mass index (BMI) and the ponderal index (PI) were used as measures of body mass and were analyzed as predictors of recurrence, survival, and complications in light of the new staging system. RESULTS: Twenty-seven of 229 patients died of recurrent disease. A low BMI or a high PI were predictive of poor survival. Tumor greatest dimension, lymph node involvement, BMI, and PI were all independent predictors of survival (P=0.0006). The only independent predictor of complications was para-aortic lymph node dissection (P=0.0026). CONCLUSIONS: Cervical carcinoma patients with a low body mass, as indicated by a low BMI or a high PI, were found to have poor survival after undergoing radical hysterectomy. Additional predictors of poor survival included lymph node metastases and increased tumor size. BMI and PI are more important predictors of survival than the new FIGO Stages IB1 and IB2. Body mass is not predictive of complications.

Retained surgical needle in the perineum. Report of a case with a novel method of search and rescue.

BACKGROUND: Retrieval of a broken or lost surgical needle can be a difficult task, often requiring extensive surgical exploration. CASE: A surgical needle was retained in the perineum. Needle-hookwire placement with biplane fluoroscopy allowed the precise localization and marking of the foreign body; surgical removal without extensive exploration was therefore possible. CONCLUSION: The use of needle-hookwire localization with biplane fluoroscopy should be considered for retrieval of foreign bodies in the perineum.

Turbo-gracilis myocutaneous flap for perineal reconstruction.

The turbo-gracilis flap, which has been described previously for the purpose of extending the unreliable gracilis skin island, and previously applied in forearm reanimation surgery, is now adapted for reconstruction in the perineal region. We present a case report of a patient with previous vulvar carcinoma treated with resection and radiation who presented with a very large defect of the perineal region. Reconstruction was carried out using a turbo-gracilis flap. The advantages of the flap are well demonstrated in the successful reconstruction, in that it provides an extensive amount of well-vascularized tissue due to an extended gracilis skin island which is vascularized by way of a vein graft from the proximal pedicle blood supply to a distal gracilis pedicle which, in turn, supplies the extended skin island. This allows an extensive amount of tissue to be harvested from a single donor site and ensures the viability of the skin island. A review of the advantages and disadvantages of various types of perineal reconstruction is also presented and contrasted with the turbo-gracilis method.

Surgical resection of endometriosis after prior hysterectomy.

Twenty-seven patients who underwent laparotomy after a prior hysterectomy for endometriosis were studied. The mean interval from index surgery to repeat surgery was 7.8 years. Abdominal/pelvic pain was the most common presenting complaint, followed by the objective finding of a pelvic mass. Six patients were taking estrogen replacement therapy. Physical findings suggested a pelvic mass or nodularity in 15 patients. Extensive pelvic adhesions with dense involvement of the ovaries was common. Surgery in 2 patients was complicated by an enterotomy, with 4 patients requiring a bowel resection and anastomosis. Postoperatively, 5 patients developed fever, 3 a postoperative ileus, 1 a wound breakdown, and 1 a small bowel obstruction. The mean hospital stay was 5 days. We conclude that in patients who have undergone a hysterectomy as treatment for endometriosis, subsequent surgery to remove the ovaries involved with recurrent endometriosis carries considerable morbidity. In light of readily available estrogen replacement therapy, conservation of the ovaries in patients who are undergoing a hysterectomy for endometriosis should be applied with caution.

Sacrospinous colpopexy: management of postoperative pudendal nerve entrapment.

BACKGROUND: Sacrospinous colpopexy requires the placement of a suture through the sacrospinous ligament, under which lies the pudendal nerve. Entrapment of this nerve may result in perineal or buttock pain. This report analyzes a case of pudendal nerve entrapment and studies the management of the resultant neuropathy. CASE: A 62-year-old patient experienced a chronic pudendal neuropathy with perineal and buttock pain following a sacrospinous colpopexy. Removal of the suture, 2 years after it was originally placed, resulted in immediate relief of her pain. She has been asymptomatic for 1 year following surgery. CONCLUSION: Pudendal nerve entrapment should be considered in the differential diagnosis of perineal or buttock pain after sacrospinous colpopexy. Relief of pain can be achieved even 2 years after initial surgery.

Massive pelvic hemorrhage during gynecologic cancer surgery: "pack and go back".

Over a 13-year period, intraabdominal packing has been used to control massive hemorrhage during surgery for gynecologic malignancy in six patients. Five patients had undergone total pelvic exenteration and one total abdominal hysterectomy with bilateral salpingo-oophorectomy for endometrial cancer. Massive hemorrhage was defined as infusion of more than 10 units of blood and replacement of more than one total blood volume. Tamponade was performed using continuous Kerlex rolls (Kendall Co., Boston, MA) in a bowel bag with directed pressure over the hemorrhaging site with abdominal closure. The packs were removed in 48 to 72 hr in the operating room, transabdominally in five patients and transvaginally in one. One postoperative death occurred within 8 hr of surgery. The packing was ultimately successful in the five remaining patients. In five of six patients, tumors were removed before the packing, whereas in one, the tumor was removed concurrently with the pack. In one patient, immediate repacking was required after pack removal, with ultimate hemostasis. Morbidity included "empty pelvis syndrome" in four patients, neuropathy in three (obturator in 1, sciatic in 2), and small bowel obstruction in one. In patients with severe intraoperative hemorrhage, intraabdominal packing has been successful as a mode of treatment.

Radical hysterectomy for stage IB1 vs IB2 carcinoma of the cervix: does the new staging system predict morbidity and survival?

Two hundred twenty-nine patients with Stage IB cervical cancer treated with radical hysterectomy were assigned to the new FIGO substages IB1 (n = 181) and IB2 (n = 48) based on clinical tumor diameter. Our purpose was to determine the impact of the new staging system for IB1 and IB2 cervical cancer on nodal status and survival. Additionally, we analyzed the morbidity of radical hysterectomy in light of the new staging system. The complications were similar between the two groups. Para-aortic lymphadenectomy was the only independent predictor of complications (P = 0.00026). Stage IB2 patients did have a significantly worse 5-year survival (72.8%) when compared with IB1 (90.0%) (P = 0.0265). Multivariate stepwise logistical regression analysis indicated that the new staging system did not have an independent impact on survival. Stage acts through nodal status in its impact on survival. Positive lymph nodes, tumor diameter, and Ponderal Index are all independent predictors of survival (P = 0.0001). Patients with Stage IB2 carcinoma of the cervix undergoing radical hysterectomy showed no significant increase in morbidity when compared with patients with Stage IB1 disease treated with the same procedure.

Intraoperative liver biopsy with the loop electrosurgical excision procedure in patients with gynecologic malignancies.

When patients with gynecologic malignancies undergo exploratory surgery, hepatic lesions suggestive of malignancy are occasionally encountered. In 18 patients undergoing laparotomy for gynecologic cancer, visible liver lesions suggestive of malignancy were biopsied with the loop electrosurgical excision procedure (LEEP). Hemostatic suture placement was required in 3 of these 18 patients, and in 15, hemostasis was achieved with electrocautery only. Three of the 18 biopsies (16.7%) were positive for malignancy. No intraoperative or postoperative complications were attributed to the liver biopsy. One patient required postoperative transfusion of 2 units packed red blood cells. A new technique is described using the LEEP to remove suspicious lesions during exploratory laparotomy in patients with gynecologic malignancies.

Radical hysterectomy for stage IB cervical cancer: recurrence interval as a predictor of survival.

Two hundred patients with stage IB carcinoma of the cervix were treated with radical hysterectomy. We evaluated the impact of recurrence interval on survival and determined its relationship to other prognostic factors. Thirty-one patients (15.5%) had recurrence, with a median follow-up of 2.8 years (range, 1 to 5 years). Multivariate analysis, using the Cox proportional hazard regression model, showed the impact of recurrence interval on survival and its relationship to other prognostic factors. Patients were 19 times more likely to die during follow-up if recurrence occurred shortly after the operation. However, the risk of death from recurrence decreased exponentially as recurrence interval increased, by a multiple of 0.93 m where m is recurrence interval in months. We conclude that in patients with stage IB carcinoma of the cervix treated initially with radical hysterectomy, the shorter the recurrence period after operation, the greater the likelihood the patient would die during 5-year follow-up. This information may help clinicians determine a patient's prognosis after confirmed recurrence.

Ability of visual tests to predict underlying cervical neoplasia. Colposcopy and speculoscopy.

OBJECTIVE: To describe the attributes of colposcopy and a low-power, magnified examination that utilizes chemiluminescent illumination (speculoscopy) in the visualization of cervical epithelium in a predefined, high-risk population and to compare how the two tests predict cervical histology. STUDY DESIGN: During this multicenter, prospective study, 395 women who were referred to our colposcopy clinic underwent a repeat cervical smear and speculoscopy followed immediately by colposcopy. Abnormal colposcopic lesions were biopsied and endocervical curettage performed when indicated. Histologic diagnoses were compared with cytology, speculoscopy and colposcopy results. RESULTS: Colposcopy was more sensitive than speculoscopy in the detection of cervical neoplasia (97% vs. 82%) (P < .001) and was superior in visualizing focal lesions and vascular patterns. An antecedent acetowhite abnormality detected during speculoscopy was highly predictive of subsequent abnormal colposcopy (97% positive predictive value). The "overall" rate of acetowhite lesions during speculoscopy was nearly half the rate during colposcopy (P < .001). CONCLUSION: Colposcopy is better suited than speculoscopy to the follow-up of patients with abnormal cervical cytology because it facilitates lesion grading and assists in directing biopsies. Speculoscopy is best utilized as a dichotomous screening test based on the presence or absence of at least one well-demarcated acetowhite lesion and may be more suitable than colposcopy as an adjunct to cervical cancer screening due to its lower overcall rate. The biophysical properties of blue-white chemiluminescent light as it relates to the diagnosis of cervical neoplasia are discussed.

Ileus following gynecologic surgery: management with water-soluble hyperosmolar radiocontrast material.

Postoperative ileus following gynecologic surgery can prolong hospitalization and may predispose patients to mechanical obstruction. Our objective was to study the safety and efficacy of a water-soluble, hyperosmolar, radiocontrast material in the management of postoperative ileus in patients having gynecologic surgery. Of 115 cases, 57 were studied prospectively and received water-soluble radio-opaque contrast material via a nasogastric tube if bowel function had not returned by the third day. Fifty-eight well-matched control cases were managed without this material and received a suppository on the third day. The contrast material was well tolerated. Return of bowel function, day of oral intake, subsequent postoperative recovery, and duration of hospital stay were similar in the two groups. Water-soluble, hyperosmolar, radio-opaque contrast material given on the third postoperative day was safe, but of no apparent clinical benefit in resolving ileus following gynecologic surgery.