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Biomedical subjects

Michel Roy

Publications and source records attributed to Michel Roy.

At least 19 recordsLinked to original sources

Negative sentinel lymph node accurately predicts negative status of pelvic lymph nodes in uterine cervix carcinoma.

OBJECTIVE: The significance of negative sentinel lymph nodes (SLN) is important in the staging and treatment of melanoma and a few other cancers, but is controversial in uterine cervix carcinoma. Our study was aimed at correlating the SLN status in cervical carcinoma with non-sentinel lymph nodes (non-SLN), in a uniform and well controlled population. METHODS: This study includes 36 patients with stage I and IIA cervical carcinoma and bilaterally negative SLN on final pathology. SLN were identified using blue dye and radioisotopic techniques. Frozen section examination was performed for all SLN; the rest of the tissue was formalin fixed and paraffin embedded. The protocol used for SLN was also applied for non-SLN. For each block, six 4-micro m thick sections were cut at 40 micro m intervals and stained with H and E; an additional section taken between the 3rd and 4th levels was imunostained using AE1/AE3 cytokeratin. RESULTS: The mean age for the study population was 39 years (range 25-76); the number of SLN ranged from 2 to 6 (mean 2.7) and the non-SLN from 8 to 49 (mean 23) per case. No metastasis was found in any SLN and non-SLN by step sections and IHC. CONCLUSION: Our study demonstrates that bilaterally negative SLN on final pathology accurately predict the absence of metastases in non-SLN in cervical carcinoma. If confirmed by larger trials, these results may influence the clinical management of early cervical cancer.

Adult↗

Neoadjuvant chemotherapy followed by vaginal radical trachelectomy in bulky stage IB1 cervical cancer: case report.

BACKGROUND: We present 3 young women with bulky stage IB1 cervical cancer treated with neoadjuvant chemotherapy followed by laparoscopic pelvic node dissection and vaginal radical trachelectomy. CASES: In the last year, we have treated 3 young women with large cervical lesions who wished to preserve fertility with induction chemotherapy followed by fertility-sparing surgery. They all had lesions measuring 3 to 4 cm and felt to be too big to safely undergo a radical trachelectomy. Three cycles of platinum-based combination chemotherapy were given and were well tolerated. The 3 patients had a significant clinical response to chemotherapy. A complete pathological response was confirmed by the absence of residual invasive cancer in the three trachelectomy specimens. There has been no recurrence so far and no pregnancy yet. CONCLUSION: Neoadjuvant chemotherapy followed by a fertility-sparing surgery may become a valuable option for young women with bulky stage IB1 cervical cancer who wish to preserve their fertility potential.

Adult↗

Fertility-preserving options for cervical cancer.

Childbearing is one of the most important life goals for many women, and fertility preservation is a very important factor in the overall quality of life of cancer survivors. Cervical cancer frequently affects young women; because some women tend to delay childbearing, fertility preservation must be considered when treatment options are discussed. Over the past decade, the radical trachelectomy procedure has become a well established fertility-preserving option for young women with early-stage cancer; this procedure is associated with low morbidity, good oncologic outcome, and a high proportion of pregnancies that reach the third trimester and babies that are delivered at term. This article will review available literature on the vaginal radical trachelectomy procedure and data from other surgical approaches, such as the abdominal radical trachelectomy. In addition, the potential future application of neoadjuvant chemotherapy followed by fertility-preserving surgery in patients with locally advanced cervical cancer will be examined. Finally, ultraconservative surgical approaches (eg, conization alone with or without laparoscopic lymphadenectomy) in very early-stage disease will be discussed.

Abdomen↗

Laparoscopically assisted vaginal radical hysterectomy.

Young patients affected by an early-stage invasive cancer of the cervix are usually treated by surgery. Abdominal radical hysterectomy with pelvic lymphadenectomy is the most widely used technique. With the advent of more conservative surgical approaches, laparoscopy has gained acceptance in gynecologic oncology, opening the way for radical vaginal surgery for cervical cancer. Before this technique becomes widely accepted, it has to be demonstrated that the results, in terms of safety and efficacy, are comparable with the 'standard' abdominal approach. In this chapter we review the technique of laparoscopically assisted radical vaginal hysterectomy and evaluate results of published series.

Female↗

Epidermis promotes dermal fibrosis: role in the pathogenesis of hypertrophic scars.

Hypertrophic scarring is a pathological process characterized by fibroblastic hyperproliferation and by excessive deposition of extracellular matrix components. It has been hypothesized that abnormalities in epidermal-dermal crosstalk explain this pathology. To test this hypothesis, a tissue-engineered model of self-assembled reconstructed skin was used in this study to mimic interactions between dermal and epidermal cells in normal or pathological skin. These skin equivalents were constructed using three dermal cell types: normal wound (Wmyo) or hypertrophic wound (Hmyo) myofibroblasts and normal skin fibroblasts (Fb). Epidermis was reconstructed with normal skin keratinocytes (NK) or hypertrophic scar keratinocytes (HK). In the absence of keratinocytes, Hmyo formed a thicker dermis than Wmyo. When seeded with NK, the dermal thickness of Hmyo (121.2 +/- 31.4 microm vs 196.2 +/- 27.8 microm) and Fb (43.7 +/- 7.1 microm vs 83.6 +/- 16.3 microm) dermis was significantly (p < 0.05) reduced, while that of Wmyo (201.5 +/- 15.7 microm vs 160.7 +/- 21.1 microm) was increased. However, the presence of HK always induced significantly thicker dermis formation than observed with NK (Wmyo: 238.8 +/- 25.9 microm; Hmyo: 145.5 +/- 22.4 microm; Fb: 74.2 +/- 11.2 microm). These results correlated with collagen and MMP-1 secretion and with cell proliferation, which were increased when keratinocytes were added, except for the collagen secretion of Hmyo and Fb in the presence of NK. The level of dermal apoptosis was not different when epidermis was added to the dermis (<1% in each category). These observations strongly suggest that hypertrophic scar keratinocytes play a role in the development of pathological fibrosis by influencing the behaviour of dermal cells.

Apoptosis↗

Vaginal radical trachelectomy: a valuable fertility-preserving option in the management of early-stage cervical cancer. A series of 50 pregnancies and review of the literature.

OBJECTIVE: To report the obstetrical results following vaginal radical trachelectomy (VRT), a fertility-preserving surgery in the treatment of early-stage cervical cancer. METHODS: Retrospective review of our first 72 patients treated by a laparoscopic pelvic lymphadenectomy followed by a VRT from October 1991 to October 2003 with regards to their reproductive function. RESULTS: Patients' median age was 32 years old (21-42) and 53 (74%) were nulligravida. A total of 50 pregnancies occurred in 31 women. The majority (66%) had only one pregnancy, 19% had 2 pregnancies and 16% had 3 pregnancies or more. The rate of first trimester miscarriage was 16%, the rate of second trimester miscarriage was (4%) and 2 women (4%) elected to have pregnancy termination. A total of 36 pregnancies (72%) reached the third trimester. Of those, 3 (8%) ended prematurely at <32 weeks gestation, 5 (14%) delivered between 32 and 36 weeks and 28 (78%) delivered at term (>37 weeks). One newborn died of neonatal sepsis from E. coli infection and one died from cardiac malformation (trisomy-18). Seven patients (10%) had infertility problems: 3 from ovulatory causes of which 2 successfully conceived with IVF, one from endometriosis and low sperm count and 3 from probable cervical cause of which one conceived with IUI. One patient had a twin pregnancy following IVF and elected to have embryo reduction and subsequently delivered at 37 weeks. CONCLUSION: Based on our experience, the obstetrical results following VRT for early-stage cervical cancer are very encouraging. The majority of women can anticipate to conceive spontaneously and deliver near term.

Adult↗

Mucinous ovarian tumors of Mullerian-type: an analysis of 17 cases including borderline tumors and intraepithelial, microinvasive, and invasive carcinomas.

Mullerian-type mucinous tumors (MMTs) of the ovary are characterized by a papillary architecture similar to that of serous tumors and a content of endocervical-like mucinous epithelium. The latter may be admixed with other mullerian-type epithelia, including those of serous, endometrioid, and squamous types, and indifferent eosinophilic epithelial cells. We analyzed 17 MMTs, including 12 borderline tumors, 2 intraepithelial carcinomas, 2 microinvasive carcinomas, and 1 invasive carcinoma. Fourteen of 16 tumors (88%) with available staging were stage I; the remaining two cases (both borderline) were stage IIa and IIIc. Endometriosis was identified in eight cases (47%). Only two patients (12%) had bilateral tumors, a frequency of bilaterality lower than in previous studies. Five patients (31%) had conservative treatment consisting of a cystectomy or unilateral salpingo-oophorectomy. All patients had a favorable outcome, with no recurrences or disease-related deaths, regardless of the presence of high mitotic index, intraepithelial carcinoma, microinvasion, bilaterality, conservative treatment, or advanced stage. This indolent behavior of MMTs is similar to that previously reported, but additional cases of invasive carcinomas in this category are needed to better define their outcome.

Adenocarcinoma, Mucinous↗

Thrombotic microangiopathy with liver, gut, and bone infarction (catastrophic antiphospholipid syndrome) associated with HELLP syndrome.

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a thrombotic microangiopathy complicating pregnancy and shares many clinical and biological features with thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Thrombotic microangiopathy is also a pathological feature of catastrophic antiphospholipid syndrome (CAPS). An association between refractory HELLP syndrome and antiphospholipid syndrome (APS) has been reported in a few cases. We describe a 19-year-old woman with APS and multiorgan failure conforming to a diagnosis of CAPS who developed refractory HELLP syndrome.

Adolescent↗

Dexamethasone for the treatment of sore throat in children with suspected infectious mononucleosis: a randomized, double-blind, placebo-controlled, clinical trial.

OBJECTIVE: To evaluate the efficacy of a single oral dose of dexamethasone for pain relief in acute exudative pharyngitis associated with infectious mononucleosis. METHODS: We conducted a randomized, double-blind, placebo-controlled pediatric emergency department-based clinical trial. Patients aged between 8 and 18 years with a sore throat from clinically suspected infectious mononucleosis were eligible. Patients were randomized to receive either an oral dose of 0.3 mg/kg (maximum, 15 mg) of dexamethasone or a placebo. Patients completed a diary of symptoms and rated their pain on a visual analog scale from 0 to 100 mm at 0 hours, 12 hours, 24 hours, 48 hours, 72 hours, and on day 7. An improvement of 20 mm from baseline on the visual analog scale was evaluated as the primary end point. RESULTS: Twenty patients were recruited in each group; mean +/- SD age was 13.5 +/- 2.8 years. In comparison with the placebo group, a significantly greater proportion of patients given dexamethasone achieved pain relief within the first 12 hours (12/20 vs 5/19; P =.03). On further follow-up, the proportions achieving pain relief were similar between groups: 11 of 20 vs 6 of 20 at 24 hours (P =.10); 11 of 20 vs 11 of 20 at 48 hours (P>.99); 15 of 20 vs 15 of 19 at 72 hours (P =.93); and 18 of 19 vs 19 of 20 at day 7 (P>.99), with dexamethasone vs placebo, respectively. CONCLUSIONS: The short-lived relief of pain in acute exudative pharyngitis in children with suspected infectious mononucleosis may suggest that a single oral dose of dexamethasone may not be sufficient and that additional doses may be necessary for ensuring lasting relief.

Adolescent↗

Normal skin wound and hypertrophic scar myofibroblasts have differential responses to apoptotic inductors.

During wound healing, myofibroblasts play a central role in matrix formation and wound contraction. At the end of healing, there is evidence that myofibroblasts disappear via apoptotic pathways. Hypertrophic scars are a fibroproliferative disorder that leads to considerable morbidity. It has been postulated that a defect in myofibroblast apoptosis could be responsible for the pathological scar formation, but no evidence exists. We have isolated and cultured human normal wound (Wmyo) and hypertrophic scar (Hmyo) myofibroblasts and compared their basal apoptotic rates and their sensitivity to serum starvation and Fas antibody-induced apoptosis to that obtained for dermal fibroblasts (Fb). A higher rate of apoptosis as evidenced by morphological criteria and a propidium iodide assay was observed for Wmyo in comparison to Fb and Hmyo. These results came along with a low level of the anti-apoptotic proteins Bcl-2 and Bclx(L) in Wmyo, whereas there was an increase in the level of the pro-apoptotic molecule Bax when compared to the results obtained for Fb and Hmyo. Hmyo showed a higher level of Bcl-2 compared to Fb but no difference in the Bax or Bclx(L) level. After serum starvation, Wmyo revealed an increased apoptotic rate, whereas Hmyo and Fb did not show any difference. Anti-Fas treatment did not modify the levels of apoptosis but strongly increased the cell growth of Hmyo as compared to Wmyo. This is the first study presenting a broad vision of the apoptotic sensitivity of normal and pathological myofibroblasts. These results confirmed the hypothesis of defects in apoptosis and growth during pathological scar formation impeding myofibroblast disappearance at the end of healing.

Actins↗

Sensitivity of myofibroblasts to H2O2-mediated apoptosis and their antioxidant cell network.

During wound healing, the transition from granulation to scar tissue shows a decrease in myofibroblast cellularity. Previous results have correlated the disappearance of these cells with the induction of apoptotic cell death by some unknown stimuli. In contrast, hypertrophic scar appearance after wound healing is thought to be linked to a disorder of apoptotic function which induces myofibroblast persistence in granulation tissue. Oxidative stress being an important mediator of apoptosis, we have evaluated the apoptotic response of normal and pathological wound myofibroblasts (WMyo and HMyo respectively) in their interaction with two oxidative stress inducers: hydrogen peroxide, using a high concentration as a single dose, and sodium ascorbate which induced a continuous release of H2O2 at a low concentration. Our results showed that, according to the H2O2 treatment type, HMyo were more sensitive (after ascorbate treatment) or less sensitive (after H2O2 treatment) when compared to WMyo and Fb. We next assessed the presence of several molecules known to be involved in the antioxidant network protecting cells against H2O2 injury and found HMyo to have a higher level of activity of glutathione peroxidase and a lower level of activity of catalase than WMyo. These results can help explain the contradictory responses of myofibroblasts according to the oxidative stress treatment. This is the first study linking refractory oxidative stress mediated cell death to cellular phenotype in hypertrophic myofibroblasts, and indicates a pivotal role for the antioxidant enzyme system in this type of resistance.

Adult↗

Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature.

OBJECTIVE: To review the oncological results and complication rate of our first consecutive 72 completed cases of vaginal radical trachelectomies (VRT). METHODS: From October 1991 to October 2003, we have planned 82 VRT in patients with early-stage cervical cancer (stages IA, IB, and IIA). The VRT was preceded by a complete laparoscopic pelvic node dissection and laparoscopic parametrectomy. RESULTS: The planned procedure was successfully completed in 72 cases and was abandoned in 10 cases (12%) because of either positive nodes discovered at the time of surgery (4), positive endocervical margins (5) or extensive tubal adhesions (1). The median age of the remaining 72 patients was 31 and most (75%) were nulliparous. The majority of the lesions were stage IA2 (32%) or IB1 (60%) and 54% were grade 1. In terms of histology, 58% were squamous and 42% were adenocarcinomas. Vascular space invasion was present in 20% of cases, and 90% of the lesions measured </=2 cm. An average of 32 lymph nodes has been removed laparoscopically. The mean follow-up is 60 months (6-156). The intraoperative complication rate was low (6%) and the postoperative morbidity was also low mainly involving bladder hypotonia (16%) and vulvar edema (12%). There were no bladder or ureteral injuries. The average hospital stay was 3 days. Excluding one patient with a small cell neuroendocrine tumor who rapidly recurred and died, there were two recurrences (2.8%) and one death (1.4%). The actuarial recurrence-free survival is 95%. Tumor size >2 cm was statistically significantly associated with a higher risk of recurrence (P = 0.03). The recurrence-free survival of the nine patients who did not have the planned VRT because of more advanced disease was statistically significantly less (P = 0.003). CONCLUSION: VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size >2 cm appears to be associated with a higher risk of recurrence. The morbidity of the procedure is low and it allows fertility preservation.

Adult↗

Using imiquimod for genital warts in female patients.

Genital warts (GW) are the manifestation of infection with specific types of human papillomavirus (HPV), one of the most common sexually transmitted viral infections in the world. Genital warts can be either raised (exophytic) or flat. Exophytic genital warts are most commonly secondary to inoculation of the basal epithelium with nononcogenic HPV types 6 and 11, whereas flat warts are usually secondary to potentially oncogenic HPV types 16 and 31. Genital warts can occasionally cause irritation and discomfort, particularly during intercourse, although most cases are asymptomatic. It is the psychosocial effects of infection, such as a sense of shame, depression, and anxiety, that represent the more significant toll for most patients with GW. Current therapies for GW are mainly ablative and do not directly enhance the immune response to HPV. Therefore, recurrence is a problem for many patients. Imiquimod 5% cream is a patient-applied therapy that directly enhances the immune response to HPV and is safe and effective for the treatment of GW. A reduction in viral load is observed following treatment. Low recurrence rates compared to other treatment modalities may be due to the stimulation of the cell-mediated immune response by imiquimod.

Administration, Topical↗

Vaginal radical trachelectomy in the treatment of cervical cancer: the role of frozen section.

Vaginal radical trachelectomy (VRT) is a new, alternative surgical procedure to radical hysterectomy for early stage invasive cervical carcinoma in women who desire to preserve fertility. The specimen includes the cervix, parametria, and the vaginal cuff. This study was designed to determine the indications and the best method for evaluating the resection margins of VRT specimens intraoperatively by frozen-section examination. We reviewed 61 VRT specimens planned between October 1991 and January 2002 in our center. A complementary radical hysterectomy is recommended when the tumor extends to within <5 mm of the margin. Of 61 patients, 56 were eligible (5 excluded; 53 VRT and 3 VRT followed by hysterectomy). Of 56 cases, 17 had no macroscopic or microscopic residual tumor. Of 27 cases with a nonspecific macroscopic lesion, more than one-half had no residual microscopic tumor, and the others had minimally (<1 mm) invasive residual carcinoma. In the remaining two cases with a macroscopic tumor, a longitudinal rather than a transverse frozen section was preferred, because it allowed the evaluation of the distance between the tumor and the endocervical margin. We recommend a frozen section, using a longitudinal section, only in those VRT specimens with a grossly visible lesion.

Female↗

Sentinel node evaluation in gynecologic cancer.

The sentinel node evaluation has revolutionized the modern surgical management of cutaneous melanoma and breast cancer. In gynecologic oncology, sentinel node mapping has been mainly studied in vulvar and cervical cancer. In vulvar cancer, data from 12 studies including 353 cases indicate that the sentinel node detection rate is 92% and the negative-predictive value is 99%. Three groin recurrences have been documented so far (< 1%). The technique has more recently been studied in cervical cancer. Data from 12 studies including 323 cases indicate a lower sentinel node detection rate of 80% to 86% and a negative-predictive value of 99%. Three false-negative cases have been reported so far (< 1%). Review of the literature suggests that the combined approach with blue dye and lymphoscintigraphy is superior to the blue dye alone for sentinel node detection. It also suggests that the sentinel node mapping technique is feasible in vulvar and cervical cancer and that it may become a valuable alternative to the traditional groin and pelvic lymphadenectomy. However, results have not been duplicated in large multi-institutional trials, and the technique should still be performed in the context of clinical trials. Complications of the sentinel node mapping technique are rare and usually benign but physicians should be aware of the serious risk of anaphylactic reaction to the blue dye (1% to 2%). Before this technique becomes a standard approach in the management of gynecologic malignancies, more data will be needed to clarify some of the related controversies.

Female↗

Innovations in the treatment of invasive cervical cancer.

Invasive cervical cancer is characterized by basement membrane-invading lesions capable of metastasizing through the lymphatic and vascular systems. Treatment methods were reviewed by panelists at the Second International Conference on Cervical Cancer (Houston, TX, April 11-14, 2002), and new opportunities for translational research were discussed. Reviews encompassed hysterectomy with or without lymph node dissection or cervical conization in cases with microinvasion and radical trachelectomy with or without lymph node dissection as fertility-sparing surgery. Chemoradiation is used to treat advanced cervical malignancies, and the risks and benefits of radiotherapy are significant. Pelvic exenteration is used to treat certain types of recurrences. Use of the Miami pouch for continent urinary diversion was highlighted. Gynecologic oncologists expect novel in vivo imaging techniques currently being developed to help guide therapy choices within the next decade. The most significant research priorities are large group-randomized trials involving fertility-sparing procedures and the management of microinvasive carcinoma (MICA); better identification of candidates for chemoradiation; and the development of innovative approaches to exenteration. Improving diagnostic technologies, refining the criteria by which therapies are chosen, and preserving fertility remain challenges in selecting the most appropriate treatment for invasive cervical cancer. Research advances in both diagnosis and treatment are expected to improve therapy and outcomes.

Combined Modality Therapy↗

Long-term outcome of a randomized study comparing three techniques of conization: cold knife, laser, and LEEP.

OBJECTIVE: To evaluate the long-term recurrence rates and complication of different techniques of cervical ablation. METHODS: A randomized trial of three techniques of conization (cold knife, laser, and loop electrosurgical excisional procedure (LEEP)) for cervical intraepithelial neoplasia (CIN) in which 110 patients had been recruited. RESULTS: Eighty-six patients were followed-up for more than 3 years. Of these 28 had been treated with the cold knife, 29 with LEEP and 29 by laser. Five recurrences were observed, one in the cold knife group, two in the LEEP group and two in the laser group (P=NS). The only observed complication was cervical stenosis: zero cases in the laser group, one case in the LEEP group and four cases in the cold knife group (laser versus cold knife: P=0.03; LEEP versus cold knife: P=0.06). Fifty pregnancies were observed in 39 patients. First and second trimester outcomes of pregnancy were without complications. One patient treated with the LEEP presented with a premature rupture of membranes and premature labor at 36 weeks. A total of nine cesarean sections were performed with two cases for cervical dystocia. CONCLUSION: There is no major difference in obstetrical outcome between the three techniques.

Adult↗