Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Tertiary cytoreduction for recurrent endometrial cancer.

This paper reviews the surgical approach experiences in endometrial cancer recurrence and presents for the first time data on the surgical management of endometrial cancer patients at the time of their second recurrence. Surgery could represent a pivotal role in selected cases of recurrent endometrial cancer, offering long-term complete remissions and a survival advantage.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE: Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS: Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS: Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

Chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer: has this regimen still a role as neoadjuvant setting?

AIM: Neoadjuvant chemotherapy represents a promising alternative to concomitant chemo-radiation therapy in locally advanced cervical cancer patients. The aim of this study was the evaluation of pathologic response rates, toxicity and predictors of response in locally advanced cervical cancer patients treated with neoadjuvant cisplatin and paclitaxel followed by radical surgery. METHODS: Fourteen patients with stage IB2 to IIB cervical cancer received three cycles of cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 intravenously every three weeks followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Toxicity, pathologic response and predictors of response were evaluated. RESULTS: Chemotherapy related toxicities we-re as follows: alopecia 100%, asthenia 35.7%; nausea and vomiting 14.3%; paclitaxel hypersensitivity 7.1%, neutropenia 7.1%. Optimal, partial and no pathologic response was achieved in 21.4%, 64.3% and 14.2% of the patients, respectively. Based on lack of pathologic risk factors, 43% of the patients did not receive any adjuvant radiotherapy. Better response rates were obtained in patients with stage IIB, tumor diameter <5 cm, Hb >12 g/dL and SCC antigen <1.5 mg/dL. None of these variables reached statistical significance. CONCLUSION: Neoadjuvant chemotherapy with cisplatin and paclitaxel in locally advanced cervical cancer appeared to be well-tolerated. Even though the TIP regimen has been shown to be more effective than the TP regimen in randomized controlled prospective trial, the TP regimen remains a reasonable alternative in those patients in whom the TIP regimen is considered or shown to be too toxic.

Growth hormone-releasing hormone antagonists inhibit growth of human ovarian cancer.

Epithelial ovarian carcinoma is the leading cause of cancer-related deaths among women with gynecologic malignancies. Antagonists of the growth hormone-releasing hormone (GHRH) have been shown to inhibit growth of various cancers through endocrine, autocrine, and paracrine mechanisms. In this study, we have investigated the effects of GHRH antagonists (GHRHa) in ES-2 human clear cell ovarian cancer and in UCI-107 human serous ovarian cancer in vitro and in vivo. We evaluated the expression of mRNA for GHRH receptor, the binding to GHRH receptors, in specimens of ES-2 ovarian cancer. We evaluated also the in vitro effects of GHRHa on ES-2 cells and the in vivo effect of 2 different GHRHa on ES-2 and UCI-107 tumors. Nude mice bearing xenografts on ES-2 and UCI-107 ovarian cancer were treated with JMR-132 and MZ-J-7-118, respectively. Tumor growth was compared to control. ES-2 cells expressed mRNA for the functional splice variant SV1 of the GHRH receptor. JMR-132 inhibited cell proliferation in vitro by 42% and 18% at 10 and 1 µM concentration, respectively. Specific high affinity receptors for GHRH were detected in ES-2 cancer samples. In vivo daily subcutaneous injections of GHRHa significantly reduced tumor growth compared to a control group in both animal models. Our results indicate that GHRHa such as JMR-132 and MZ-J-7-118 can inhibit the growth of human ovarian cancer. The efficacy of GHRHa in ovarian cancer should be assessed in clinical trials.

The risk of premalignant and malignant pathology in endometrial polyps: should every polyp be resected?

AIM: There is no wide consensus in the literature on the clinical significance and management of symptomatic and asymptomatic polyps. Aims of the study are to evaluate frequency of premalignant and malignant histo-pathologic features in endometrial polyps resected hysteroscopically and identify clinical parameters able to predict final histopathologic diagnosis. METHODS: Clinical data and pathologic report of 90 consecutive operative hysteroscopies performed on women with endometrial polyps were collected. Frequency of premalignant and malignant histopathologic features on the polyps were calculated and relation to clinical risk factors analyzed. RESULTS: The frequency of premalignant and malignant histopathologic features in polyps was 6.7% and 2.2% respectively. Owing to the small sample size no statistical analysis to detect clinical risk factor for premalignant or malignant histopathologic features could be performed. CONCLUSION: Frequency of premalignant and malignant histopathologic features in symptomatic and asymptomatic patients is not negligible. Reported clinical risk factors for malignant degeneration of endometrial polypoid lesions are the same as those reported for endometrial cancer and are very common in patients with endometrial polyps. Every endometrial polyp should be resected.

The impact of obesity on surgery in gynecological oncology: a review.

Surgery represents a mainstay in the treatment of gynecological cancers. It is a common belief that operating on obese patients causes more peri- and postoperative complications than operating on nonobese patients. The surgical outcome in gynecological oncology can be evaluated by comparing intra- and postoperative complications, extent of lymphadenectomy, negativity of the specimens' margins, and percentage of optimal debulking between obese and nonobese patients affected by malignancies at the same stage. In this review, we analyze how obesity affects the feasibility of a correct oncologic procedure in case of cervical, endometrial, and ovarian cancer. We also describe the techniques that have been suggested in the literature to improve the surgical outcome on obese patients.

Uterine arteriovenous malformation: a case report diagnosed by sonohysterography.

PURPOSE OF INVESTIGATION: The aim of this report is to describe a case of uterine arteriovenous malformation that occurred in a 54-year-old postmenopausal woman referring recurrent postmenopausal bleeding, after two years of tamoxifen therapy. METHODS: Medical therapy with GnRh agonists was unsuccessful. Ultrasound and Doppler flow ultrasound scanning were normal and the following hysteroscopy was normal as well. RESULTS: Hysterosonography performed on the patient made us suspect the presence of an intracavitary vascular lesion which was confirmed histologically after hysterectomy. CONCLUSION: In our case hysterosonography allowed us--by creating optimal contrast between the uterine wall and the uterine cavity--to suspect and identify the lesion and to recognize the typical ultrasound findings of this pathology not visualized with standard transvaginal ultrasound.

Cytological analysis of the distension fluid used during diagnostic office hysteroscopies in patients with suspected endometrial pathology.

OBJECTIVE: Evaluation of the feasibility and usefulness of cytological analysis of the distension fluid used during diagnostic office hysteroscopy in patients with suspected endometrial pathology. METHODS: In 243 consecutive patients undergoing diagnostic hysteroscopy for suspected endometrial pathology a few milliliters of the distension medium used for uterine visualization were collected and sent for cytological analysis. Findings of these "endometrial washings" were compared to visual hysteroscopic impression, endometrial biopsy and uterine histology--when available. RESULTS: Endometrial washings were considered adequate in 227 patients (93.4%). In 12 cases (5.3%) atypical cells were detected: all of these presented either atypical complex hyperplasia or endometrial cancer at the final histological evaluation of the uterus. Four of the 16 (25%) patients diagnosed with endometrial cancer or atypical complex hyperplasia at the final histopathological analysis of the uterus had inadequate washings. No patient with cancer or atypical hyperplasia had negative cytology. CONCLUSIONS: Collection and analysis of the distension fluid is feasible and, when positive, has a remarkable value in the diagnosis of endometrial cancer and its precursors.

Modification of ultrasonographically measured endometrial thickness after discontinuation of adjuvant therapy with tamoxifen in postmenopausal breast cancer patients.

INTRODUCTION: The aim of this study was to evaluate endometrial changes after five years of tamoxifen treatment by measuring endometrial thickness with transvaginal ultrasonography. MATERIALS AND METHODS: Fifty-five asymptomatic postmenopausal women who had assumed tamoxifen, 20 mg daily, for five years were controlled six months after discontinuation of the therapy. Of these 42 were followed-up at 12 months. Statistical analysis was performed using the analysis of variance for repeated measures and the Anova test; p < 0.05 was considered statistically significant. RESULTS: We found a significant reduction in endometrial thickness at six months (p = 0.0046) and at 12 months (p = 0.0003) but not between six and 12 months (p = 0.06). CONCLUSION: A statistically significant reduction in endometrial thickness after discontinuation of tamoxifen therapy was found. This can probably be attributed to the cessation of the estrogenic side-effects of tamoxifen therapy.

Breast cancer metastatic to the vulva after local recurrence occurring on a rectus abdominis myocutaneous flap: a case report and review of the literature.

INTRODUCTION: Vulvar metastases are the third largest group of malignant tumors of the vulva. We report the tenth case of breast cancer vulvar metastases arising 11 years after the primary diagnosis of breast ductal carcinoma and the first occurring eight years after a local recurrence on a rectus abdominis myocutaneous flap. CASE REPORT: A 49-year-old woman presented with a voluminous lump of the left labium majus and enlargement of the ipsilateral inguinal lymph nodes. The mass was removed together with the ipsilateral inguinal lymph nodes. Microscopic evaluation of the removed lump revealed massive carcinomatous infiltration. No in situ lesions nor normal breast tissue were identified. CONCLUSIONS: Unusual breast cancer metastases sites should not be ruled out. Our case differs from the preceding cases because this patient underwent plastic surgery with reconstruction of the breast with a rectus abdominis myocutaneous flap one year after mastectomy and developed a local recurrence three years thereafter. It can be hypothesized that lymphatic spread through newly formed lymphatics occurred.

[The modified Shouldice inguinal hernioplasty. A clinical contribution]. / Ernioplastica inguinale secondo Shouldice modificata. Contributo clinico.

The Authors present their personal experience in the surgical treatment, using the Shouldice modified method, of 85 cases of patients suffering from inguinal hernia. The rarity of general and local complications and the relatively low percentage of relapse, if compared with other surgical methods, testify to the validity of this technique.

Lymphocyte subpopulations in pediatric age. Definition of reference values by flow cytometry.

In the present paper we have analyzed the age-related changes in the distribution and numbers per cubic millimeter of the circulating lymphocyte subpopulations. Lymphocyte subsets have been examined by monoclonal antibodies specific for surface antigens (namely CD2, CD3, CD4, CD8, CD16, CD20 and CD57) and flow cytometry in lysed peripheral blood of normal neonates (1-3 days old), 1-6 month, 7-12 month, 1-2 year old babies and 3-5 year, 6-10 year old children and young people up to 17 years of age. The results confirm the lymphocytosis at birth and at later stages of life and indicate that major changes in the distribution of lymphocyte subsets occur during the first two years of life; namely we have observed sharp increase of circulating B lymphocytes and prevalence of CD4+ T lymphocytes with high CD4/CD8 ratios in babies up to two years of age, compared to the values observed in normal adults. Very few CD8+ CD57+ lymphocytes were present at birth; cells bearing this phenotype appeared later in life. Lymphocytes expressing the CD16 antigen were already present in newborns. The authors discuss the functional meanings of the age-related changes observed in the distribution and in the numbers of circulating lymphocytes. The presented data represent valuable normal ranges of lymphocyte subsets to compare with values observed in sick babies or children.

[Neoplasms with unknown primary location]. / Neoplasie a sede primitiva ignota.

Neoplasms with unknown primary location (U.P.L.N.) represent an important chapter of oncological pathology which has not yet been completely defined regarding diagnostics, therapy and prognosis. U.P.L.N. recur in clinical practice in 0.5%-10% of cases and show equal sharing in both sexes: still mortality is high. This is in agreement with the biological behavior of U.P.L.N. which is that of a neoplastic illness, systemic from the onset and therefore immediately aggressive. Treatments commonly used only slightly alter the course of the disease. If the general state of the patients allows it, treatment must include every available therapeutical remedy (CHR, RDT, CHM) conveniently evaluated in every single case and preferably under the guidance of the apparent histotype and of the onset seat. The histotype of an U.P.L.N. sensibly affects the prognosis of the patient: there is an improvement in well differentiated and lodged forms and conversely, there is a sharp impairment with fast evolution in the less differentiated and variably metastasized forms. In our case-report, the U.P.L.N. rate has been 5.37% on 1786 cancer diagnoses from February 1980 until January 1988. In 65% of these cases, the histotype sustaining the pathology was represented by adenocarcinoma, in 21% by epidermoid carcinoma and in the remaining 14% by undifferentiated carcinoma. The clinical onset most frequently observed has involved the lymph nodes, followed by involvement of the serosa, bones, lungs and liver. Complex therapeutic treatments have not provided clear results, but the use of anthracyclines and cyclophosphamide seems promising. Finally, we suggest the use of immunomodulators (such as interferons, thymus hormone, lymphokines) in association with the classic chemotherapeutics.

[Clinical contribution to the knowledge of retroperitoneal tumors of the pelvic excavation]. / Contributo clinico alla conoscenza dei tumori retroperitoneali dello scavo pelvico.

Two cases of primitive retroperitoneal tumors of the pelvic excavation have been reported: a neurinosarcoma and a liposarcoma. Particular, this work emphasizes the rarity of the neurinosarcoma in that seat, the atypical clinical presentation, the complex diagnostic researches performed and the problems of the differential diagnosis. In the diagnosis of these neoplasms, the Authors emphasize, the main role performed by the "classic" radiology and its most recently acquired means as (ECO, TAC, EMR). These can give precise informations about the seat and the size of the neoplasms and especially, about it's relationship with the adjacent tissues. By using these new means, other examinations some what dangerous, can be avoided. The Authors conclude that from the therapeutical point of view, surgery is still the main weapon against these neoplasms, even if sometimes it is demolishing and does not sensibly improve the prognosis. Surgery can be associated with radiotherapy and/or chemotherapy.

[Aneurysm of the left gastric artery. Clinical contribution and review of the literature]. / Aneurismi dell'arteria gastrica sinistra. Contributo clinico e revisione della letteratura.

The extra-visceral aneurysms of the gastric arteries are very rare and their diagnosis occurs mostly in the presence of haemoperitoneum and shock due to their rupture. Through echography and selective arteriography a right diagnosis can be made before a rupture. The treatment is surgical with good results but treatment with embolisation through arteriography is preconized. Two cases treated in emergency are reported.

[Pretreatment evaluation of CA 72.4 in patients with carcinoma of the stomach (0-IV stage) versus CEA, TPA, CA 19-9, FER]. / Valutazione pretrattamento del CA 72.4 in pazienti con carcinoma gastrico (stadio 0-IV) vs CEA, TPA, CA 19-9 FER.

Before surgical treatments, sera of 54 pts suffering from gastric cancer, histologically typed and clinically staged (from stage 0 to 4), were assayed to evaluate CEA, TPA, CA 19-9 and Ferritin versus a new tumoral marker called TAG-72, in order to determine the biological behaviour and the relation to the clinical stage of this last one. Starting from their results, Authors say that the new marker TAG 72 has an increasing sensibility according to the clinical stage (4 th more than 1 st), and that the association of the TAG-72 plus CEA and/or TPA is rather significant in order to evaluate the evolution of the gastric cancer than other markers.