Pathology and resection margins following mastectomy prior to immediate breast reconstruction.

Risk of local recurrence (LR) (and even distant disease-free survival) after mastectomy is associated with margin status. Furthermore, the vast majority of LR are located at the anterior (superficial) margin. Margins in mastectomy are considered anatomical borders and not true resection margins; such a conception may erroneously lead to underestimation of the risk of LR after mastectomy. If dissection is accurate along the fascia, only skin, subcutaneous tissue and minimal residual breast gland tissue (rBGT) are expected to remain in the patient. However, the subcutaneous fascia is an inconsistent anatomical structure that may be absent in almost half of patients. Studies and routine clinical practice suggest that resection may frequently, though often focally, be within the breast glandular tissue leaving various amounts of rBGT. Such areas may be nidus for subsequent de novo or recurrent premalignant or malignant disease. There is no consensus on handling of close/positive margins and intervention is extrapolated from studies on breast conserving surgery with subsequent radiotherapy. Handling of a close/positive margin is complicated by poor correlation between the ex vivo findings on the specimen and the attempt to relocate the area of concern in a patient with reconstructed breasts. In this clinical practice review, we strongly advocate for reporting of the lesion-to-margin distance in mastectomies to collect further evidence on the association between LR and margin status.

Distribution of Stromal Cell Subsets in Cultures from Distinct Ocular Surface Compartments.

PURPOSE: To reveal the phenotypic differences between human ocular surface stromal cells (hOSSCs) cultured from the corneal, limbal, and scleral compartments. METHODS: A comparative analysis of cultured hOSSCs derived from four unrelated donors was conducted by multichromatic flow cytometry for six distinct CD antigens, including the CD73, CD90, CD105, CD166, CD146, and CD34. RESULTS: The hOSSCs, as well as the reference cells, displayed phenotypical profiles that were similar in high expression of the hallmark mesenchymal stem cell markers CD73, CD90, and CD105, and also the cancer stem cell marker CD166. Notably, there was considerable variation regarding the expression of CD34, where the highest levels were found in the corneal and scleral compartments. The multi-differentiation potential marker CD146 was also expressed highly variably, ranging from 9% to 89%, but the limbal stromal and endometrial mesenchymal stem cells significantly surpassed their counterparts within the ocular and reference groups, respectively. The use of six markers enabled investigation of 64 possible variants, however, just four variants accounted for almost 90% of all hOSSCs, with the co-expression of CD73, CD90, CD105, and CD166 and a combination of CD146 and CD34. The limbal compartment appeared unique in that it displayed greatest immunophenotype diversity and harbored the highest proportion of the CD146+CD34- pericyte-like forms, but, interestingly, the pericyte-like cells were also found in the avascular cornea. CONCLUSION: Our findings confirm that the hOSSCs exhibit an immunophenotype consistent with that of MSCs, further highlight the phenotypical heterogeneity in stroma from distinct ocular surface compartments, and finally underscore the uniqueness of the limbal region.

Robotic Surgery Is Less Physically Demanding Than Laparoscopic Surgery: Paired Cross Sectional Study.

OBJECTIVE: To study musculoskeletal workload in experienced surgeons during laparoscopic surgery (LS) compared with robotic assisted laparoscopy (RALS). BACKGROUND: 70-90% of surgeons who regularly perform LS report musculoskeletal symptoms, mainly in neck and shoulders. Data regarding the potential ergonomic benefits of RALS in a clinical setting is very limited. METHODS: Twelve surgeons with advanced experience in both LS and RALS each performed 2 hysterectomies on the same day. LS was performed standing, RALS sitting, the latter allowing forearm and head support. Bipolar surface electromyogram (EMG) was recorded from several muscles and was expressed relative to EMG during maximum contractions (%EMGmax). Gaps per minute plus static (p0.1), mean (p0.5), and peak (p0.9) muscle activation were calculated. Perceived exertion was rated before and just after each surgery. RESULTS: Neck muscle activity (p0.1 4.7 vs. 3.0%EMGmax, p0.5 7.4 vs. 5.3%EMGmax, p0.9 11.6 vs. 8.2%EMGmax, all P < 0.05) and static shoulder muscle activity (p0.1 5.7 vs. 2.8%EMGmax, P < 0.05) were higher for LS than for RALS. Both a higher level of gaps during RALS and a lower rating of perceived exertion, also for the legs, after RALS supported these observations. However, low back muscle activity was higher for RALS. CONCLUSIONS: RALS is significantly less physically demanding than LS, and also feels less strenuous for the surgeons. However, for both types of surgeries, there still is room for improvement of working conditions. To further optimize these, we suggest a scheme to regularly observe and advise the surgeons.

Failed manual removal of the placenta after vaginal delivery.

PURPOSE: A retained placenta after vaginal delivery where manual removal of placenta fails is a clinical challenge. We present six cases that illustrate the heterogeneity of the condition and discuss the etiology and terminology as well as the clinical management. METHODS: Members of the European Working group on Abnormally Invasive Placenta (EW-AIP) were invited to report all recent cases of retained placenta that were not antenatally suspected to be abnormally adherent or invasive, but could not be removed manually despite several attempts. RESULTS: The six cases from Denmark, The Netherlands and the UK provide examples of various treatment strategies such as ultrasound-guided vaginal removal, removal of the placenta through a hysterotomy and just leaving the placenta in situ. The placentas were all retained, but it was only possible to diagnose abnormal invasion in the one case, which had a histopathological diagnosis of increta. Based on these cases we present a flow chart to aid clinical management for future cases. CONCLUSION: We need properly defined stringent terminology for the different types of retained placenta, as well as improved tools to predict and diagnose both abnormally invasive and abnormally adherent placenta. Clinicians need to be aware of the options available to them when confronted by the rare case of a retained placenta that cannot be removed manually in a hemodynamically stable patient.

Human papillomavirus infects placental trophoblast and Hofbauer cells, but appears not to play a causal role in miscarriage and preterm labor.

INTRODUCTION: Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. MATERIAL AND METHODS: In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. RESULTS: Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. CONCLUSION: Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded.

Structured Hysteroscopic Evaluation of Endometrium in Women With Postmenopausal Bleeding.

STUDY OBJECTIVE: To evaluate visual pattern parameters obtained with hysteroscopy for the prediction of endometrial cancer, to evaluate observer variation of these parameters, and to present a scoring system of the parameters for the prediction of malignancy compared with subjective evaluation. DESIGN: A prospective controlled study (Canadian Task Force classification II-1). SETTING: A university clinic. PATIENTS: One hundred forty-nine consecutive women with postmenopausal bleeding and an endometrium thickness ≥ 5 mm. Sixty-one (41%) had endometrial cancer. Forty-six of 149 women were referred based on suspected malignancy. INTERVENTIONS: Endometrial pattern characteristics for endometrial cancer were evaluated in hysteroscopic video clips. The reference standard was pathologic evaluation of resectoscopic samples or hysterectomy. Using multivariate logistic regression, image parameters were correlated with the presence of endometrial cancer. A scoring system of visual parameters for the prediction of malignancy was compared with subjective evaluation of malignancy. MEASUREMENTS AND MAIN RESULTS: A score for lesion surface, necrosis, and vessels had an area under the curve (AUC) of 0.89, 0.89, and 0.87, respectively. A hysteroscopic cancer (HYCA) scoring system based on unsmooth lesion surface, papillary projections, surface necrosis, "candy floss" necrosis, white hyperintense spots, irregular branching vessels, and irregular distribution of irregular vessels was able to predict cancer (AUC = 0.964) with higher accuracy than subjective evaluation (AUC = 0.859, p < .01). At a score value ≥ 3, sensitivity was 89% and specificity was 92% with moderate agreement between observers (kappa = 0.56 [0.42-0.71]). CONCLUSION: A systematic pattern evaluation of optimal parameters by a HYCA scoring system based on systematically defined terms may increase accuracy in the diagnosis of endometrial cancer and should be further elaborated and external validity tested in unselected women with postmenopausal bleeding.

Reproducibility of Endometrial Pathologic Findings Obtained on Hysteroscopy, Transvaginal Sonography, and Gel Infusion Sonography in Women With Postmenopausal Bleeding.

STUDY OBJECTIVE: To evaluate and compare interobserver variation in endometrial pattern recognition with hysteroscopy (HY) and transvaginal sonography (TVS) and gel infusion sonography (GIS) with regard to the diagnosis of endometrial pathology. DESIGN: Prospective study (Canadian Task Force II-1). SETTING: University clinic. PATIENTS: One hundred twenty-two consecutive women with postmenopausal bleeding and an endometrium thickness ≥ 5 mm. INTERVENTION: Two observers using HY and 2 others using TVS and GIS evaluated the endometrial pattern in recorded video clips. Interobserver agreement regarding findings obtained with TVS, GIS, and HY for a diagnosis of cancer, hyperplasia, polyps, and no endometrial pathology was expressed by κ coefficients and compared. MEASUREMENT AND MAIN RESULTS: Interobserver agreement (κ) was as follows: identification of normal endometrium: HY (.74), TVS (.68), and GIS (.48); diagnosis of cancer: HY (.56), TVS (.59), and GIS (.34); classification in all categories of endometrial pathology: HY (.70), TVS (.47), and GIS (.41) (p < .05 HY vs GIS). The presence of additional endometrial polyps decreased agreement on HY in patients with hyperplasia or cancer. Observer agreement was poor regarding the diagnosis of hyperplasia by all techniques. CONCLUSION: Observer agreement regarding both HY and TVS was reliable for the diagnosis of a normal endometrium but poor with HY, TVS, and especially GIS for a diagnosis of cancer. In patients with hyperplasia or cancer, agreement between observers was especially low in the presence of additional polyps when HY was used. These findings call attention to the need for systematic methods to improve reliability in endometrial pattern recognition.

Less extensive surgery compared to extensive surgery: survival seems similar in young women with adult ovarian granulosa cell tumor.

OBJECTIVE: To describe the outcome of adult granulosa cell tumor (AGCT) with respect to initial clinical findings, methods of surgery, and perioperative treatment. STUDY DESIGN: Retrospective follow-up study. SETTING: All hospitals in Jutland. SAMPLE: 163 women diagnosed with AGCT. METHODS: Follow-up by hospital data files, general practitioner, death certificate, and autopsy report. Revision of histopathology by a single pathologist. MAIN OUTCOME MEASURES: Survival and relapse by clinical data, stage, and type of surgery. RESULTS: The incidence of AGCT was 1.37 per year per 100,000 women (95% CI: 1.08, 1.68). The median follow-up time was 15 years and for the 79 surviving women 22 years. Stage I was found in 94% of cases. Relapse occurred in 24% of women in stage I and 100% of the other stages. Survival in stage I was 95%, 89% and 84% after 5, 10 and 20 years respectively. Increased survival of stage I in postmenopausal women was associated with surgery including hysterectomy and bilateral oophorectomy (p<0.001). In women younger than 40 years no difference in survival was found due to type of surgery. Endometrial carcinoma was found 138 times (95% CI: 48, 275) more prevalent than the expected rate. CONCLUSION: The survival of women was better in AGCT than in epithelial ovarian tumor. Age and type of surgery, besides stage, influenced survival. Total abdominal hysterectomy and bilateral salpingo-oophorectomy is the recommended treatment with advancing age. At younger age less extensive surgery was associated with similar survival compared to extensive surgery, but with advancing age conservative surgery increased the risk of relapse and death.