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Biomedical subjects

Roberto Tozzi

Publications and source records attributed to Roberto Tozzi.

11 recordsLinked to original sources

Integrated expression profiling of trophoblast cell-surface antigen 2 (TROP2), folate receptor alpha (FRα), and human epidermal growth factor receptor 2 (HER2) in endometrial Cancer across molecular classes, genomic alterations, and histologic subtypes.

OBJECTIVE: Antibody-drug conjugates (ADCs) are expanding treatment options in endometrial carcinoma, but the distribution of actionable surface targets across histologic, molecular, and genomic subgroups remains incompletely defined. METHODS: This single-institution retrospective tissue microarray (TMA) study included 312 endometrial carcinomas: 158 endometrioid and 154 serous tumors. Trophoblast cell-surface antigen 2 (TROP2) was quantified by histochemical score (H-score); human epidermal growth factor receptor 2 (HER2) was assessed using endometrial carcinoma-specific and gastric/DESTINY-PanTumor02 criteria; and folate receptor alpha (FRα) positivity was defined as ≥75% viable tumor cells with ≥2+ membranous staining. Molecular class was assigned using a hierarchical DNA polymerase epsilon (POLE)-mutant, microsatellite instability/mismatch repair-deficient (MSI/MMRd), p53-abnormal, and no specific molecular profile (NSMP) classifier. Tumor mutational burden (TMB) and recurrent genomic alterations were analyzed in relation to biomarker expression. RESULTS: TROP2 was broadly expressed, with median H-scores of 280 in endometrioid and 200 in serous carcinomas. HER2 gastric-score 2+/3+ expression and FRα positivity were enriched in serous versus endometrioid carcinoma (22.5% vs 8.9% and 20.1% vs 4.4%), restricted to FIGO grade 3 tumors, and concentrated in p53-abnormal disease. FRα positivity was absent in POLE-mutant and MSI/MMRd tumors. HER2 2+/3+ expression correlated with erb-b2 receptor tyrosine kinase 2 (ERBB2) alterations, whereas FRα-positive tumors were enriched for TP53 alterations and showed lower frequencies of ARID1A and PTEN alterations. Triple-negative TROP2/HER2/FRα tumors were uncommon (6/308, 1.9%). CONCLUSIONS: TROP2 is broadly expressed in endometrial carcinoma, whereas HER2 and FRα define a more restricted high-grade, serous/serous-like, p53-abnormal compartment, supporting biomarker-informed ADC development.

Humans↗

Does radical trachelectomy influence uterine blood supply?

OBJECTIVE: Radical trachelectomy in combination with pelvic and parametric lymphadenectomy is indicated in young patients with early cervical cancer and planned pregnancy. If pregnancy occurs, premature delivery is a known problem in these patients. We evaluated if uterine blood supply is decreased after radical trachelectomy as one of various possible causes of preterm birth. METHODS: Between October 2003 and April 2004, 14 consecutive patients with early cervical cancer underwent radical trachelectomy with pelvic and parametric lymphadenectomy. The uterine blood supply was measured as resistance index (RI) by Doppler sonography pre- and postoperatively. Doppler sonography of the uterine artery was also performed in 14 healthy students as a control cohort. RESULTS: Fourteen patients with histologically confirmed adenocarcinoma or squamous carcinoma of the cervix uteri stage Ia1 L1 to 1b1 underwent radical trachelectomy. Mean age of patients was 33.4 years (31-37). On average, 11.5 mm (5-23) of cervical length and 24.6 (14-35) tumor-free lymph nodes were removed. Decrease of RI of the uterine artery was 0.06 on the right side (0.76-0.70) and 0.07 (0.75-0.68) on the left side. The absolute RI values after radical trachelectomy were not different compared to the values in the control group (0.76 versus 0.70 right side, 0.74 versus 0.68 left side). CONCLUSION: Uterine perfusion after radical trachelectomy with pelvic and parametric lymphadenectomy remains unchanged.

Adenocarcinoma↗

Analysis of morbidity in patients with endometrial cancer: is there a commitment to offer laparoscopy?

OBJECTIVE: Benefits of laparoscopy over laparotomy in patients with endometrial cancer (EC) are well known. As many patients with EC carry co-morbid conditions, surgery is exposing them to increased risk of complications. A review of the patients with EC recruited so far in a clinical trial comparing laparoscopy to laparotomy was performed. The goal was to identify patients carrying specific risk factors for complications, who would most benefit of laparoscopy and be the ideal candidates for this surgical approach. PATIENTS AND METHODS: Between July 1995 and December 2002, 122 patients with uterine cancer entered the study. Sixty-three patients were allocated to the laparoscopy (LPS) arm (group A), while 59 were allocated to the laparotomy (LPT) arm (group B). Rate and type of intra-, early and late post-operative complications were prospectively recorded. Risk factors for complications are analyzed to define a group of patients truly benefiting from laparoscopy. RESULTS: Overall, 12 patients out of 122 (9.8%) have experienced intra-operative, 43 patients out of 122 (35.2%) early post-operative and 25 patients out of 122 (20.4%) late post-operative complications. Rate of intra-operative complications was 4.7% in group A (3 patients out of 63) vs. 15.2% in group B (9 patients out of 59), P = 0.082. Early post-operative complications rate was 23.8% in group A (15 out of 63) and 47.4% in group B (28 out of 59), P = 0.011. Rate of late post-operative complications was 7.9% (5 out of 63) in group A vs. 35.5% (21 out of 59), P = 0.001. Univariate analysis shows co-morbid medical conditions, weight >80 kg, Quetelet index >30 and age >65 years to be predictive of complications and, in fact, a subgroup of patients presenting with these characteristics (n = 57, 30 in group A and 27 in group B) has been recognized to accumulate 60% of the overall complications. In these patients, multivariate analysis identifies the surgical technique (LPS vs. LPT) to be the only significant risk factor for complications. CONCLUSION: At least one third of the patients with EC carry serious co-morbidities with an increased surgical risk for complications. For this subgroup of patients, a laparoscopic-vaginal approach significantly reduces the rate of complications and should be the standard of surgical treatment.

Adult↗

Laparoscopic treatment of early ovarian cancer.

PURPOSE OF REVIEW: Recently some studies have reinforced the arguments supporting the laparoscopic management of early ovarian cancer. These studies and reports questioning the use of laparoscopy in patients with early ovarian cancer will be reviewed. RECENT FINDINGS: Advances in laparoscopic techniques have enabled the surgeon to meet the staging criteria for early ovarian cancer as proposed by the International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although some reports highlight the risk of ovarian cancer mismanagement, the safety and reliability of laparoscopic surgical staging has been demonstrated with encouraging results. However, the numbers of patients included in these studies are still insufficient to draw conclusions. SUMMARY: Clinical evidence supports the use of laparoscopy in the treatment or completion of treatment in patients diagnosed with early ovarian cancer. If strict guidelines are respected, tumor rupture, dissemination and implant on the trocar insertion sites can be avoided and survival outcomes appear not to be jeopardized. Inadequate and hazardous laparoscopic management of early ovarian cancer is to be ascribed to the lack of guidelines and to surgeons without the competence to treat early ovarian cancer rather than to the surgical technique. The excellent outcomes could encourage studies with larger sample sizes to confirm the validity of laparoscopic treatment of patients with early ovarian cancer. Unfortunately, a clinical trial is unlikely to be undertaken due to the low incidence of this disease and the even lower number of events.

Female↗

Laparoscopic treatment of early ovarian cancer: surgical and survival outcomes.

OBJECTIVES: To investigate the feasibility and safety of laparoscopic surgery in patients with early ovarian cancer. PATIENTS AND METHODS: Between 05-1996 and 06-2003, 24 patients with ovarian cancer FIGO stage IA-B underwent either primary treatment or completion of staging by laparoscopy. Laparoscopic staging was performed according to the FIGO guidelines, which entails one-sided oophorectomy or bilateral salpingo-ophorectomy with laparoscopic-assisted vaginal hysterectomy, pelvic lymphadenectomy, infrarenal para-aortic lymphadenectomy, complete resection of the infundibulo-pelvic ligament, appendectomy and partial omentectomy. RESULTS: Eleven out of 24 patients (45.8%) underwent completion of staging after a mean of 12 days (range 4-21) after primary surgery, while 13 patients out of 24 (54.2%) underwent primary laparoscopic management of an adnexal mass, diagnosed as ovarian cancer by frozen section. Mean operative time was 166 min (range 118-206) for completion of staging and 182 min (range 141-246) for primary surgery. No major intraoperative complication occurred. One out of 24 patients (4.1%) developed chylos ascites postoperatively, which was managed conservatively. Five out of 24 patients (20.8%) received adjuvant chemotherapy after a median time of 7 days (mean 5-14) following surgery. No trocar metastasis occurred. Median follow-up is 46.4 months (range 2-72). Two out of 24 patients (8.3%) developed recurrence, which was treated with resurgery and chemotherapy. After a median follow-up of 46 months, disease-free survival is 91.6% and overall survival 100%. CONCLUSIONS: Laparoscopic management of early ovarian cancer is safe and effective and survival outcome seems acceptable.

Adult↗

Introduction of transperitoneal lymphadenectomy in a gynecologic oncology center: analysis of 650 laparoscopic pelvic and/or paraaortic transperitoneal lymphadenectomies.

OBJECTIVE: Lymphadenectomy is an integral part of staging and treatment of gynecologic malignancies. We evaluated the feasibility and oncologic value of laparoscopic transperitoneal pelvic and paraaortic lymphadenectomy in correlation to complication rate and body mass index. METHODS: Between August 1994 and September 2003, pelvic and/or paraaortic transperitoneal laparoscopic lymphadenectomy was performed in 650 patients at the Department of Gynecology of the Friedrich-Schiller University of Jena. Retrospective and prospective data collection and evaluation of videotapes were possible in 606 patients. Laparoscopic lymphadenectomy was part of the following surgical procedures: staging laparoscopy in patients with advanced cervical cancer (n = 133) or early ovarian cancer (n = 44), trachelectomy in patients with early cervical cancer (n = 42), laparoscopic-assisted radical vaginal hysterectomy in patients with cervical cancer (n = 221), laparoscopy before exenteration in patients with pelvic recurrence (n = 20), laparoscopic-assisted vaginal hysterectomy or laparoscopic-assisted radical vaginal hysterectomy in patients with endometrial cancer (n = 112), and operative procedures for other indications (n = 34). RESULTS: After a learning period of approximately 20 procedures, a constant number of pelvic lymph nodes (16.9-21.9) was removed over the years. Pelvic lymphadenectomy took 28 min, and parametric lymphadenectomy took 18 min for each side. The number of removed paraaortic lymph nodes increased continuously over the years from 5.5 to 18.5. Right-sided paraaortic, left-sided inframesenteric and left-sided infrarenal lymphadenectomy took an average of 36, 28, and 62 min, respectively. The number of removed lymph nodes was independent from the body mass index of the patient. Duration of pelvic lymphadenectomy was independent of body mass index, but right-sided paraaortic lymphadenectomy lasted significantly longer in obese women (35 vs. 41 min, P = 0,011). The overall complication rate was 8.7% with 2.9% intraoperative (vessel or bowel injury) and 5.8% postoperative complications. No major intraoperative complication was encountered during the last 5 years of the study. CONCLUSION: By transperitoneal laparoscopic lymphadenectomy, an adequate number of lymph nodes can be removed in an adequate time and independent from body mass index. The complication rate is low and can be minimized by standardization of the procedure.

Adolescent↗

Laparoscopic-assisted radical vaginal hysterectomy (LARVH): prospective evaluation of 200 patients with cervical cancer.

OBJECTIVE: The purpose of this study was to determine the survival of cervical cancer patients treated with laparoscopically assisted radical vaginal hysterectomy (LARVH). We quantify morbidity and correlate survival with known risk factors. METHODS: Between August 1994 and June 2002, 200 patients with cervical cancer (TNM stage 1a1, L1 n = 6, 1a2 n = 21, 1b1 n = 89, 1b2 n = 26, 2a n = 11, 2b n = 45, 3a n = 1, 4 n = 1; squamous cell carcinoma 76.5%, adenocarcinoma 23.5%) were treated with LARVH (type II n = 102, type III n = 98). RESULTS: Paraaortic lymphadenectomy was performed in 170 (85%) patients and pelvic lymphadenectomy was performed in all 200 patients. In 26 (13%) patients positive lymph nodes were found. Major intraoperative injuries occurred in 6% of patients. Postoperative complications occurred in 8% of patients. Incidence of complications decreased significantly when comparing the first half with the second half of patients. After a median follow-up time of 40 months, overall 5-year survival could be projected to 83%; 18.5% of patients experienced recurrence with 35% exclusively extrapelvic and 11% of patients died of recurrence. Independent prognostic factors for recurrence-free survival were tumor stage, lymph node status, and combined involvement of lymphovascular and angiovascular space. In the absence of these risk factors projected 5-year survival was 98%. CONCLUSION: Patients with tumor <4 cm, negative lymph nodes, and the absence of the combination of angio- and lymphovascular space involvement can be identified by laparoscopic staging and are ideal candidates for LARVH.

Adenocarcinoma↗

Laparoscopic paraaortic left-sided transperitoneal infrarenal lymphadenectomy in patients with gynecologic malignancies: technique and results.

OBJECTIVE: Left-sided paraaortic infrarenal lymphadenectomy is indicated in patients with gynecologic tumors of high metastasing potential. We evaluated whether left-sided paraaortic inframesenteric lymphadenectomy can be extended up to the left renal vein by laparoscopy. METHODS: Between January 2002 and August 2002, 46 consecutive patients with cervical (n = 26), or endometrial (n = 16), or early ovarian cancer (n = 4) underwent right-sided paraaortic lymphadenectomy up to the level of the right ovarian vein and left-sided inframesenteric paraaortic lymphadenectomy. Lymphadenectomy was extended up to the level of the left renal vein in 20 patients with high risk for lymph node metastasis: following elevation of the duodenum and the pancreas infrarenal lymph nodes in the area limited by the vena cava, left renal vein, left ovarian vein, inframesenteric artery, and aorta were laparoscopically removed under preservation of the inferior mesenteric artery. RESULTS: Patients with infrarenal lymphadenectomy (group 1) and without infrarenal lymphadenectomy (group 2) were comparable in body mass index: the age of patients in group 2 was higher (P = 0.023). Duration of lymphadenectomy was 31.3 min (11-57 min) longer in group 1. There was no intraoperative complication. Number of paraaortic lymph nodes was on average 19.6 (range 5-35) in group 1 compared to a mean of 9 lymph nodes (range 2-19) in group 2 (P = 0,0001). Postoperatively 2 patients (10%) in group 1 developed chylascos. CONCLUSIONS: Left-sided paraaortic infrarenal lymphadenectomy can be performed safely in adequate duration transperitoneally by laparoscopy. Compared to inframesenteric lymphadenectomy the number of removed lymph nodes can be doubled.

Adult↗

"Schauta sine utero": technique and results of laparoscopic-vaginal radical parametrectomy.

OBJECTIVES: Radical parametrectomy or radical cervical stump exstirpation is indicated in selected oncologic situations. We evaluated whether radical parametrectomy without or with cervical stump exstirpation can be performed by a combined laparoscopic-vaginal approach. METHODS: Between November 2001 and Dezember 2002 six patients with unexpected cervical cancer (n = 3) after simple hysterectomy, histologically confirmed vaginal recurrence of endometrial cancer (n = 1), or cervical stump recurrence of endometrial cancer after supracervical hysterectomy (n = 2) underwent radical parametrectomy. After cystoscopic placement of bilateral ureteral stents laparoscopic paraaortic and pelvic lymphadenectomy was performed. The vascular part of the cardinal ligament and the bladder pillar were transsected laparoscopically. According to a LARVH type III procedure vaginal vault or cervical stump with parametrial and paravaginal structures was removed transvaginally. RESULTS: In all patients R0 resection could be achieved (n = 4) or no residual tumor was detected (n = 2). There were no intraoperative complications. One patient developed acute kidney failure on postoperative day 1, with spontaneous recovery after 12 days. The median drop of hemoglobin on postoperative day 5 was 2.15 mmol/L (1.3-3.2) and no patient needed transfusion. Restitution of bladder function took 4.3 days on average. The mean operation time was 424 min (385-452). CONCLUSIONS: Radical parametrectomy can be performed by a combined laparoscopic-vaginal technique without complications. Together with laparoscopic paraaortic and pelvic lymphadenectomy, it is a valid alternative to open surgery in selected oncologic patients.

Adnexa Uteri↗

Explorative laparoscopy prior to exenterative surgery.

OBJECTIVE: The objective of this study was to identify the advantages and limits of laparoscopy for assessment of eligibility for exenterative procedures in patients with gynecologic malignancies. METHODS: Between April 1998 and April 2001, 41 consecutive patients with primary or recurrent gynecologic malignancy underwent explorative laparoscopy to detect eligibility for exenteration. RESULTS: Mean age of patients was 54 years (range, 31-80 years). Twenty out of 41 (48.7%) patients underwent exclusively explorative laparoscopy due to unresectable disease or intraabdominal spread of disease. Median operative time for this cohort of patients was 69.1 min (range, 10-278), median blood loss was 30 cc (range 10-60) and no complications occurred. Based on findings of explorative laparoscopy 21 out of 41 (51.2%) patients were eligible for exenteration. Evaluation of extension of disease was correctly done by laparoscopy and was not corrected at laparotomy. One patient out of 21 (4.76%) had extension of disease missed at both laparoscopy and laparotomy and discovered only at an advanced phase of exenteration. Histology of exenterative specimens confirmed laparoscopic evaluation in 20 out of 21 patients (95.25%). CONCLUSIONS: Laparoscopy proved effective for evaluation of patients who were candidates for exenteration and helped to avoid unnecessary laparotomy in half of the candidate patients.

Adult↗

Laparoscopy versus laparotomy in endometrial cancer: first analysis of survival of a randomized prospective study.

STUDY OBJECTIVE: Laparoscopy has been proved to be safe and reliable in staging of patients with endometrial cancer. It has definite advantages over laparotomy, but a comparable survival outcome is still to be verified in prospective randomized trials. DESIGN: Prospective, randomized clinical trial. SETTING: Department of Gynecology, Friedrich Schiller University, Jena, Germany. PATIENTS: One hundred twenty-two women with uterine cancer. INTERVENTIONS: Laparotomy and laparoscopy. MEASUREMENTS AND MAIN RESULTS: Sixty-three patients were allocated to the laparoscopy arm, and 59 were allocated to the laparotomy arm. Median follow-up for all patients was 44 months (range 5-96 months). Eight patients (12.6%) in the laparoscopy group had a recurrence versus five patients (8.5%) in the laparotomy group (p = .65). At median follow-up, disease-free survival (DFS) and overall survival (OS) in the laparoscopy group and laparotomy group were 87.4% versus 91.6% and 82.7% versus 86.5%, respectively. Cause-specific survival (CSS) was 90.5% in the laparoscopy group versus 94.9% in the laparotomy group. In patients with International Federation of Gynecology and Obstetrics stage I, DFS was 91.2% in the laparoscopy group versus 93.8% in the laparotomy group, OS was 86.5% versus 89.7%, and CSS was 93.4% versus 95.9%. CONCLUSION: Laparoscopic vaginal treatment of patients with endometrial cancer provides a survival outcome comparable with laparotomy. If these data are confirmed, laparoscopic procedures should be included in routine therapy for patients with endometrial cancer.

Adenocarcinoma↗