Systematic lymphadenectomy in ovarian cancer at second-look surgery: a randomised clinical trial.

BACKGROUND: The role of systematic aortic and pelvic lymphadenectomy (SAPL) at second-look surgery in early stage or optimally debulked advanced ovarian cancer is unclear and never addressed by randomised studies. METHODS: From January 1991 through May 2001, 308 patients with the International Federation of Gynaecology and Obstetrics stage IA-IV epithelial ovarian carcinoma were randomly assigned to undergo SAPL (n=158) or resection of bulky nodes only (n=150). Primary end point was overall survival (OS). RESULTS: The median operating time, blood loss, percentage of patients requiring blood transfusions and hospital stay were higher in the SAPL than in the control arm (P<0.001). The median number of resected nodes and the percentage of women with nodal metastases were higher in the SAPL arm as well (44% vs 8%, P<0.001 and 24.2% vs 13.3%, P:0.02). After a median follow-up of 111 months, 171 events (i.e., recurrences or deaths) were observed, and 124 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for progression and death were not statistically different (hazard ratio (HR) for progression=1.18, 95% confidence interval (CI)=0.87-1.59; P=0.29; 5-year progression-free survival (PFS)=40.9% and 53.8%; HR for death=1.04, 95% CI=0.733-1.49; P=0.81; 5-year OS=63.5% and 67.4%, in the SAPL and in the control arm, respectively). CONCLUSION: SAPL in second-look surgery for advanced ovarian cancer did not improve PFS and OS.

Multimodality approach in extra cervical locally advanced cervical cancer: chemoradiation, surgery and intra-operative radiation therapy. A phase II trial.

BACKGROUND: The goal of this study was to determine the rational of radical surgery with intra-operative high-dose radiotherapy after chemoradiation (RT-CT) in extra cervical locally advanced cervical cancer (LACC) patients. METHODS: Between 2000 and 2007, 42 LACC (stage IIA bulky-IVA) patients were treated at the Gynecologic Oncology Unit of the C.R.O. of Aviano in a Phase II Clinical Trial. Radiotherapy was administered to the whole pelvic region (50.4 Gy in 28 fractions) in combination with cisplatin (60 mg/mq) plus 5FU (750 mg/mq for 4 days) on first and fifth week of RT. Radical surgery with Intra-Operative Radiation Therapy (IORT) was performed 6-8 weeks after the end of RT-CT treatment. RESULTS: After RT-CT, 35/42 patients (83%) underwent radical surgery and IORT treatment. At pathologic examination 8/35 (23%) patients showed complete response, while the rest (27/35) had residual disease either microscopic (17/27) or gross (10/27). The 5-year disease free survival (DFS) and the 5-year overall survival (OS) were 46% and 49% respectively. There were significant better DFS and OS when residual tumor was absent or limited to the cervix, respectively 78% versus 16% and 81% versus 20% (p < 0.001). All recurrences occurred within 24 months from treatment. CONCLUSIONS: RT-CT followed by surgery and IORT in LACC patients seems to be active in a subgroup of patients with pathological complete response to treatment or partial response with residual tumor limited to the cervix.

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

[Current surgical management in ovarian cancer recurrences]. / Attuale management chirurgico delle recidive di carcinoma ovarico.

Ovarian cancer is a tumor with a high trend of recurrence and this occurrence consistently increases the difficulty of the patient cure and reduces the efficacy of current treatments. The role of surgery in persistent or recurrent ovarian cancer is controversial and the type of surgery can be different according to the different stages and invasion of tumor; it can be a debulking surgery followed by chemotherapy (to eradicate the most part of ovarian cancer, leaving a minimal tumoral residue), an interval surgery (for advanced ovarian cancer stage in previously operated patients, followed by 2 or 3 inductive chemotherapy cycles and subsequently a cytoreductive redo surgery) and a cytoreductive secondary surgery, after optimal primary surgical treatment and minimal tumoral recurrence. In some cases it is possible either to perform a debulking surgery during a primary (after the conclusion of primary treatment) or a salvage or palliative surgery (to improve, after an acceptable time period, clinical symptoms in patients with progressive cancer or resistant to treatments). The aims of surgical therapy, to be performed in a patient with ovarian cancer relapse, are to reduce, as much as possible, the tumour size, to increase the quality of life and to increase the survival time; in this review different surgical techniques to be carried out in each case, selected for disease staging, for tumour cells kinetic and for surgical goals, are discussed.

Lack of association of CYP1 B1*3 polymorphism and ovarian cancer in a Caucasian population.

CYP1B1 is the enzyme with the highest efficiency of conversion of estradiol to 4-hydroxyestradiol in humans. This metabolite has a well-known carcinogenic effect interacting with genomic DNA and has been hypothesized to be partly responsible for the role played by estrogens in ovarian cancer development. A polymorphism has been described for this enzyme causing a Leu to Val substitution in position 432 (CYP1B1*3). The Val432 allele has a higher efficiency of conversion of estradiol to 4-hydroxyestradiol and has been reported to increase the risk of ovarian cancer. A previous study reported a higher, significant prevalence of CYP1B1*3 polymorphism in ovarian cancer patients of mixed ethnicity. The aim of this study was to investigate the role of CYP1B1*3 polymorphism as a risk factor for ovarian cancer in a Caucasian population. The polymorphism frequency was determined in 223 cases of ovarian cancer and compared with that of 280 healthy female blood donors. Genetic analysis was performed on genomic DNA from PBMC and RFLP methods were used for mutation detection. No significant difference between cases and controls was found. These results do not support a favoring role of CYP1B1*3 in ovarian cancer development in our population.

Percutaneous endoscopic gastrostomy (PEG) in palliative treatment of non-operable intestinal obstruction due to gynecologic cancer: a review.

Percutaneous endoscopic gastrostomy (PEG) is a relatively simple method in achieving non-surgical gastric decompression in patients with upper gastrointestinal tract obstruction from metastatic pelvic and abdominal tumors.

Feasibility and pain control in outpatient hysteroscopy in postmenopausal women: a randomized trial.

BACKGROUND: Three methods of diagnostic hysteroscopy have been tested for both women's compliance and feasibility of procedures in postmenopause. METHODS: Three hundred and sixty-two postmenopausal women were enrolled in a three-arm study: 5 mm diagnostic sheath (Group 1, 119 women), 5 mm sheath with paracervical block (Group 2, 121 women), and 3.5 mm sheath (Group 3, 121 women). CO2 was the distention medium. Both feasibility of hysteroscopy (procedures failed due to stenosis or incomplete distention of cavity) and discomfort of women have been recorded. Pain perception has been measured on a visual numerical rating scale. Statistical analysis was performed by t-test for unpaired samples and chi-square test. RESULTS: Paracervical block was per se painful in 18.2% and bleeding from injection site occurred in 38.8%. Hysteroscopy failure due to stenosis occurred in 9%, 10% and 0.4% of the three groups respectively (p<0.01). Intolerable pain was reported by 17% of women in Group 1, 6% in Group 2 (p<0.05) and in none of Group 3 (p<0.01). Pain score improved from Group 1 to Group 3 (p<0.01). Hysteroscopy was incomplete because of gas leakage in 1.7% of both Group 1 and 2 and in 13.2% of Group 3 (p<0.01). CONCLUSIONS: Pain perception in postmenopausal women was reduced when paracervical block was used, but discomfort was even less with the narrow sheath hysteroscope. The narrow sheath will expose to a high percentage of inconclusive procedures but it can be overcome by changing to the large sheath hysteroscope without affecting patient pain perception.

Different patterns of postoperative bleeding following cytoreductive surgery for gynecological cancer.

PURPOSE OF INVESTIGATION: To study the possible causes of postoperative bleeding following maximal cytoreductive surgery for gynecological cancers. METHOD: We have retrospectively reviewed all our cases of postoperative bleeding following major abdominal and pelvic cytoreductive surgery within a 48-hour period. In the postoperative period, replacement therapy was ineffective in achieving hemodynamic stability. During re-operation, the entire abdominal cavity was evaluated for bleeding sites that were adequately ligated or electrocoagulated. RESULTS: Of 942 women undergoing major cytoreductive surgery 22 women (2.3%) were re-operated for postoperative bleeding after a mean of 14.2 hours. Bleeding was either localized from a vessel in 9 women (40.9%) or diffuse (capillary oozing) in 13 women (59.1). Operative deaths have been as high as 36.8%. CONCLUSION: Postoperative bleeding following cytoreductive surgery can be from a single group of vessels or a capillary oozing from the edges or denuded areas of excised peritoneum.

Primary cytoreductive surgery with rectosigmoid colon resection for patients with advanced epithelial ovarian carcinoma.

BACKGROUND: The impact of radical bowel resection with multiple organ resection on the survival if patients with advanced ovarian carcinoma has not been well defined. The authors investigated whether primary cytoreductive surgery including rectosigmoid colon resection would affect the recurrence free interval and survival of these patients. METHODS: Between April 1990 and April 1997, 66 previously untreated Stage IIIC-IV ovarian carcinoma patients with macroscopic involvement of the rectosigmoid colon were enrolled. All patients underwent cytoreductive surgery with rectosigmoid colon resection to remove residual tumor less than 2 cm in greatest dimension and received 6 cycles of cisplatin-based postoperative chemotherapy. RESULTS: The median follow-up was 26 months (range, 7-104 months). In multivariate analysis, residual disease and depth of tumor infiltration of the bowel wall were independently associated with overall survival and recurrence free interval. Disease stage was independently associated only with overall survival. Residual tumor was the most strongly predictive factor for recurrence or death. The 2-year estimated survival rates according to the amount of residual tumor were 100% for 24 patients with no macroscopic residual disease and 77.3% for 28 patients with residual disease less than 1 cm. None of the 14 patients with residual disease larger than 1 cm were alive 2-years after operation. Overall, 48 patients (72.7%) developed disease recurrence: 43 (65.1%) in the abdomen, 19 (29.8%) in the liver, and 3 (4.5%) in the pelvis. CONCLUSIONS: The current findings suggest that cytoreductive surgery with rectosigmoid colon resection should be considered for ovarian carcinoma patients with bulky pelvic disease to help ensure that they are left with no residual disease after debulking surgery.

Treatment of vaginal intraepithelial neoplasia (VAIN) with the carbon dioxide laser.

The increasing incidence of VAIN especially in young women, the frequent relapses, and renewed interest in maintaining sexual function have prompted gynecologists to a conservative management of the disease. Over the last decades, surgery, 5-fluorouracil, chemosurgery, electrocautery and cryotherapy were used. Carbon dioxide laser ablation therapy of VAIN has been reported from various authors with different results. From June 1991 through December 1998, 39 patients affected by VAIN were treated with laser surgery (35 vaporizations and 4 excisions). To achieve complete elimination of all lesions, seven patients had two vaporizations and one patient three. One patient was submitted to six combined repeated treatments. Five patients were not evaluable and three presented persistence of VAIN. One patient died because of AIDS. The remaining 30 patients, treated with laser surgery, were lesion free: 7 patients were negative at 12-24 months, 10 at 24-36 months and 13 at 37-90 months. No important complications occurred. Sexual function was not compromised. Carbon dioxide laser is a safe and efficacious tool in the treatment of pre-neoplastic lesions of the vagina.

[Percutaneous endoscopic gastrostomy (PEG) in upper gastrointestinal tract occlusion in gynecologic oncology]. / La gastrostomia percutanea endoscopica (PEG) nelle occlusioni dell'alto tratto intestinale in ginecologia oncologica.

BACKGROUND AND AIMS: Intestinal obstruction is a frequent cause of death in patients suffering from gynecological cancer, who have undergone multiple treatment in the form of surgery and/or chemotherapy and/or radiotherapy. The usual form of rescue treatment consists in the use of a nasogastric tube to administer support and analgesic treatment. Surgical gastrostomy is not a viable proposition in these extremely weak patients with large masses compressing and displacing the stomach. Percutaneous endoscopic gastrostomy (PEG), a technique first introduced for nutritional purposes, can be beneficially used to achieve decompression in these patients. METHODS: PEG was performed in a total of 67 patients who had already undergone multiple treatment for abdominal-pelvic neoplasia with upper gastrointestinal obstruction, who could no longer be operated and who had a life expectancy of less than sixty days. In three cases positioning was not possible owing to the lack of transillumination of the gastric and abdominal wall. 54/64 patients had previously undergone at least two operations. RESULTS: Esophagogastric lesions were found in 29% of patients, some of which were attributed to the nasogastric tube. Symptomatic wellbeing was obtained in 76.5% a few days after PEG. PEG remained in situ from 4 to 472 days. Slight peristomal infection was observed in 9% of cases. In seven cases it was necessary to add octreotide owing to the reappearance of symptoms. CONCLUSIONS: PEG is relatively easy to use and allows obstructive symptoms to be resolved in the majority of patients. Special medical skills are not required and the patient may be easily managed at home together with support therapy and pain management. Once PEG has been performed, it is possible to take fluids and semi-liquid foods, offering the patient a chance to taste flavours which have often been forgotten. PEG enables neoadjuvant chemotherapy to be performed in patients with previously untreated intestinal obstruction.

Maximal cytoreductive surgery as a reasonable therapeutic alternative for recurrent endometrial carcinoma.

OBJECTIVE: The objective was to determine if maximal cytoreductive surgery could carry any benefit in pelvic and abdominal recurrent endometrial carcinoma. METHODS: Twenty women at their first large pelvic or abdominal recurrence from endometrial carcinoma were treated with maximal cytoreductive surgery. Women were classified as R1 (residual tumor) or R0 (no residual tumor) by tumor left at the end of surgery. Adjuvant postoperative therapy was undertaken upon clinical judgement. Progression-free, overall, and cancer-related survivals were analyzed with the product-limit method and compared with the log-rank test. The Cox regression model was used to study the variables involved in progression-free and overall survival. RESULTS: Complete macroscopic resection of tumor was feasible in 13 women (65%). R0 group women had a significant both progression-free (median reached at 9.1 months) and overall survival (median reached at 11.8 months) compared to R1 group women. There were 2 (10%) perioperative deaths. Eight women died of cancer, 5 in the R1 group and 3 in the R0 group. There were four intercurrent deaths in women still free from the disease. Local control of neoplasia was achieved in 84.6% of R0 women and their survival was affected mostly by distant recurrences or intercurrent deaths. Residual tumor at the end of surgery was the only significant variable to affect both progression-free and overall survival. CONCLUSION: Intensive surgery is a valid treatment option in women with large pelvic or abdominal recurrence from endometrial carcinoma. Tumor can be completely resected and local control of the disease can be achieved in most of the patients, although survival could be affected by distant recurrence and intercurrent deaths.

Risk factors for endometrial cancer according to familial susceptibility.

Endometrial cancer (EC) shares some environmental or genetic risk factors with colorectal cancer (CRC). It represents a risk factor for CRC. Furthermore, EC is the most frequent extracolonic neoplasm in HNPCC (hereditary nonpolyposis colorectal cancer) and, in this syndrome, it has the same inheritance pattern as CRC. Neoplastic family history and clinical features were evaluated in women with EC in a health care district (Pordenone Province) in Northeastern Italy from 1990 to 1995, to examine the proportion of patients with hereditary cancer and the relation with clinical characteristics of EC. We interviewed 215 patients with EC (average age 61 years, range 35-88) in relation with some risk factors (age, weight, diabetes, menstrual and reproductive pattern, synchronous and metachronous neoplasms) and we obtained their family pedigree. Twenty-nine patients (13.5%) had a CRC family history, 66 (30.7%) showed an aspecific cancer aggregation in their families and more than half (120, 55.8%) had a negative cancer family history. Family pedigrees were consistent with a dominant inherited cancer pattern in 8 patients (3.7%) belonging to the CRC-related family history group. A different pattern of family history distribution emerged in relation with age (< 55 vs. > or = 55, p < 0.001) and body mass index (BMI) (< 26 vs. > or = 26, p = 0.002). Patients with a CRC pedigree were more numerous in the younger group, in the group with lower BMI and in pre-menopausal women.

Squamous intraepithelial cervical lesions in human immunodeficiency virus-seropositive women.

OBJECTIVE: To evaluate the relationship between human immunodeficiency virus (HIV) infection, CD4 serum level, cervical squamous intraepithelial lesions (SILs) and risk factors for human papillomavirus (HPV)-related dysplasia in HIV-positive women. STUDY DESIGN: All 51 eligible patients who were seen at the Colposcopic Outpatient Service, Aviano Cancer Center, Aviano, Italy, from July 1, 1993, to June 30, 1994, were studied for risk factors for HPV and HIV infection and had cervical cytologic smears, colposcopy with cervical biopsy and a serum CD4 count. RESULTS: Thirty of 51 patients (59%) had cytohistologically confirmed SIL. The prevalence of SIL was higher in HIV Centers for Disease Control stage IV disease than stages II and III (22/29 vs. 8/22 P < .05). There was no significant difference in the CD4 count between women with or without SIL (321 +/- 310 vs. 401 +/- 295/mm3 [mean +/- SD]). No relationship was found between CD4 count and severity of SIL (low grade SIL, 210 +/- 203/mm3; high grade SIL, 580 +/- 357/mm3). CONCLUSION: In our series there was no relationship between CD4 count and cervical SIL, suggesting that the expression of HPV-related dysplasia is a complex process in which risk factors for genital SIL play an important role, while the role of HIV must be defined again.

Palliative treatment of upper intestinal obstruction by gynecological malignancy: the usefulness of percutaneous endoscopic gastrostomy.

The usefulness of percutaneous endoscopic gastrostomy (PEG) for decompression in patients with unresolving intestinal obstruction by gynecological malignancy is examined. Between April 1993 and August 1995, 34 consecutive patients with small-bowel obstruction by gynecological cancer, heavily pretreated with surgery and chemotherapy, were admitted to our prospective study. PEG was performed in 32/34 patients (94.1%). Failure in the placing of the tube occurred in 2 patients (5.9%). Twenty-seven patients (84.4%) experienced symptomatic relief after a few days from PEG and tolerated soft and liquid foods. All of these patients were discharged from the hospital and underwent parenteral nutrition at home. The median postoperative hospital stay was 7 days (range 3-45). No major complications due to PEG placement itself occurred in our patients. Only 4 patients (12.5%) had postprocedure nausea and vomiting that was unresponsive to the conventional therapy. The use of Octreotide (0.6 mg/24 hr) obtained relief from symptoms until death. The gastrostomy remained in place for a median of 74 days (range 5-210). Relief from symptoms after PEG placement and total parenteral nutrition permitted continuation of palliative chemotherapy in 8 patients (25%). We suggest percutaneous endoscopic drainage gastrostomy technique as the procedure of choice for long-term drainage of unresolving small bowel obstruction in patient with metastatic abdominal gynecologic malignancy.

Percutaneous endoscopic gastrostomy as a decompressive technique in bowel obstruction due to abdominal carcinomatosis.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is a simple method of achieving nonsurgical gastric decompression in patients suffering from metastatic abdominal tumors and upper gastrointestinal tract obstruction. The aim of this prospective study was both to evaluate the efficacy of PEG for intestinal decompression in patients with disseminated abdominal cancer and to compare two catheters with different diameters. PATIENTS AND METHODS: Over a one-year period, 22 consecutive female patients (mean age 53.7, range 29-73) were referred to us and a PEG was successfully placed in 21. In four patients with unsatisfactory endoscopic trans-illumination of the anterior abdominal wall, an ultrasound unit was used to identify an adequate site for PEG placement. RESULTS: All patients experienced substantial symptomatic relief after a few days: vomiting and nausea completely resolved, and abdominal pain persisted in one patient only. No gastrostomy-related additional morbidity was noticed. We randomly inserted a 15-French or a 20-French tube: no statistically significant difference was noticed between the two in the symptomatic relief provided. CONCLUSIONS: Our data support the hypothesis that PEG is an effective, safe, and well-tolerated method of achieving gastric decompression in cancer patients; ultrasound guidance was an interesting option in positioning a tube in difficult situations; a standard nutritional tube, namely 15 or 20 French in diameter, may be large enough to obtain excellent clinical results.

Systematic pelvic and para-aortic lymphadenectomy during cytoreductive surgery in advanced ovarian cancer: potential benefit on survival.

A case-control study was carried out to evaluate the potential benefit on survival of systematic pelvic and para-aortic lymphadenectomy (SL) during primary or secondary cytoreductive surgery on patients with Stage IIIC-IV of epithelial ovarian cancer. A total of 105 optimally cytoreduced (macroscopic disease < 2 cm on peritoneal surfaces) patients were divided into two groups: Group A, consisting of 60 patients (30 previously untreated and 30 pretreated at other institutions), underwent SL; Group B, consisting of 45 patients (23 previously untreated and 22 pretreated at other institutions), did not undergo SL. Consideration was given toward the inclusion of previously untreated and pretreated patients in two different groups for survival analysis. Each group had statistically equivalent stage, histology, grading, age, performance status, largest diameter metastasis (> 10 cm), type of surgery, and variety of cytoreductive operations performed. Group A patients had a longer median operation time than Group B patients (P = 0.01). SL could be carried out with an acceptable morbidity and no mortality. All 105 patients received postoperative chemotherapy including Carboplatin. Comparison on survival revealed that SL significantly improved the survival of previously untreated patients (P < 0.001). Cox's proportional analysis shows that SL was the most significant covariate, followed by stage of disease. The survival was not significantly different in Group A and Group B pretreated patients. Only stage of disease (III vs IV) significantly influenced the survival (P < 0.01). The results of the present study show that aggressive surgical cytoreduction with SL may be advisable only in previously untreated patients optimally cytoreduced. We also suggest the need for a randomized, prospective study to clarify the clinical role of SL.

Squamous cell carcinoma in ovarian endometriosis. A case report.

A primitive squamous cell carcinoma of the ovary arose in ovarian endometriosis. The patient underwent a radical hysterectomy and radiotherapy. The other few similar reported cases had a poor prognosis. In our case the patient died 11 months after surgery.