Secondary Cytoreduction in Platinum-Resistant Recurrent Ovarian Cancer: A Single-Institution Experience.

BACKGROUND: The purpose of this study was to observe the role of secondary cytoreductive surgery in platinum-resistant recurrent ovarian cancer (OC) patients. METHODS: We collected data of patients affected by recurrent OC treated between 1995 and 2013. Inclusion criteria were: invasive epithelial OC histologically documented, cytoreductive surgery and platinum-based chemotherapy at first-line treatment with evidence of complete response to treatment, disease-free interval <6 months, and no concomitant neoplasia. Patients considered susceptible of cytoreductive surgery (group A) were compared with a historical series of patients with similar characteristics but not eligible for surgery (group B). RESULTS: Of 122 platinum-resistant patients, 18 met the inclusion criteria for the study and were enrolled. They were compared with a historical series of 18 patients not surgically treated with analogous clinical and pathological features. The most frequent sites of relapse included pelvic and aortic lymph nodes (39 %), peritoneum (33 %), bowel (28 %), and pelvis (22 %). A low rate of intraoperative and postoperative complications was reported. No deaths were recorded. Overall survival was significantly longer in cytoreductive group when compared with the control group (P = 0.035). Median overall survival was 44 months. Estimated 5-year overall survival rates were 57 versus 23.5 % for groups A and B, respectively. CONCLUSIONS: Surgery could represent a useful adjunct to chemotherapy in the management of platinum-resistant recurrent OC patients, carefully selected, in highly selected centers. Larger prospective trials are needed to further confirm our experience.

The endogenous oxytocin after manipulative osteopathic treatment in full-term pregnant women.

OBJECTIVE: The aim of this study is to assess whether the touch of osteopathic manipulative treatment (OMT) can affect the endogenous production of oxytocin in full-term pregnant women and the assessment of well-being following the treatment. PATIENTS AND METHODS: In this study have been enrolled 57 pregnant women at full-term pregnancy (37th-41st week) for evaluation of the concentration of salivary oxytocin 2 minutes before and 2 minutes after a single session of OMT by an osteopath lasting for 30 minutes. Pre-OMT and post-OMT saliva samples were collected with the use of Salivette® salivary swabs. 7 salivary swabs were excluded from the analysis. 50 samples were analyzed with an appropriate ELISA kit. RESULTS: The mean OT salivary concentration pre-OMT was 89.98±16.39, and post-OMT was 100.60±19.13 tends to increase with p=0.0000051. In multivariate analysis, two subgroups show interesting data in the mean difference in OT salivary concentration post-OMT: women with painful contractions (p=0.06) and women under 35 years (p=0.09). CONCLUSIONS: The results of this study demonstrate that the effectiveness of OMT-increasing endogenous oxytocin is statistically significant in full-term pregnant women. The sensation of well-being found in most women indicates that there has been a predominantly central rather than peripheral oxytocin release after OMT.

The role of peritoneal lavage in benign gynecologic laparoscopic surgery.

OBJECTIVE: Laparoscopic surgery offers many advantages compared to invasive surgery but one of the main problems is postoperative pain, partially resulting from the peritoneal inflammatory process mediated by inflammatory cytokines. The rationale of this study is that intraperitoneal washing could remove inflammatory mediators that are the cause of postoperative pain and could help in the removal of CO2 from the abdominal cavity. This article aims to analyze the effects of peritoneal lavage in the reduction of postoperative shoulder pain. PATIENTS AND METHODS: 277 patients enrolled to undergo laparoscopic gynecologic surgery were included in the study. Women are randomized into two groups, according to the use or non-use of peritoneal lavage with saline solution at the end of laparoscopic gynecological major procedures. RESULTS: Data show that the peritoneal lavage can significantly reduce postoperative pain in the first 36 hours after surgery, as well as patients' requests for analgesics: during the first 3 postoperative days, requests for paracetamol were lower in the YW (Yes Washing) group than the NW (No Washing) group (77 vs. 101; p<0.05); similar results are obtained considering ketorolac administration (62 vs. 71; p<0.05). CONCLUSIONS: Peritoneal lavage after gynecological laparoscopic procedures may be effective in the reduction of postoperative pain and use of analgesics.

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.

[Prevention of postoperative abdominal adhesions in gynecological surgery. Consensus paper of an Italian gynecologists' task force on adhesions]. / Aderenze addominali postoperatorie e loro prevenzione in chirurgia ginecologica. Documento di consenso si una "task force" di ginecologi italiani sulle aderenze.

Adhesions are the most frequent complication of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with considerable morbidity and expense, and an important mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in most patients. There is rising evidence, however, that surgeons can take important steps to reduce the impact of adhesions. A task force of Italian gynecologists with a specialist interest in adhesions having reviewed the current evidence on adhesions and considered the opportunities to reduce adhesions in Italy, have approved a collective consensus position. This consensus paper provides a comprehensive overview of adhesions and their consequences and practical proposals for actions that gynecological surgeons in Italy should take. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. They should be adopted particularly in high risk surgery and in patients with adhesiogenic conditions. Patients also need to be better informed of the risks of adhesions.

[The role of laparoscopy in ovarian carcinoma]. / Il ruolo della laparoscopia nel carcinoma ovarico.

The role of minimally invasive surgery in the management of gynecologic cancers is continuously expanding. Although few trials have focused on the safety of laparoscopy in oncology, laparoscopy is now widely used for most gynecological malignancies. Laparoscopy is widely used to manage benign ovarian masses, but its role in managing ovarian cancer still needs to be defined. The role of laparoscopy in ovarian cancer surgery may be divided into three following categories: 1) laparoscopic staging of apparent early ovarian cancer; 2) laparoscopic assessment of disease extent and potential for resectability; 3) laparoscopic reassessment, or second-look operation, or rule out recurrence. Laparoscopic approach has shown several advantages like a reduction in operating time, blood loss, hospital stay, and total hospital charges. The limitations of laparoscopic practice include inadequate port-site metastasis, tumour dissemination due to cyst rupture and incomplete staging. In addition, there were limitations in performing extensive laparoscopic sampling of areas of tumor persistence including retroperitoneal lymph nodes. In literature there are no randomized studies assessing the use of laparoscopy in the management of ovarian cancer. Moreover, most of the studies in literature comparing laparoscopy and laparotomy are carried out by surgeons specialized in one of two approaches, so that the results can not be compared.

[Prevention of postoperative adhesions]. / Aderenze postchirurgiche: attuali strategie preventive.

Postoperative adhesions represent a common consequence in patients who underwent abdominal or pelvic surgery. Such adhesions can be asymptomatic, but they can cause complications such as chronic abdomino-pelvic pain, secondary infertility, an increase in bowel obstruction risk and more complexity for future surgery, including longer surgery times and an increase in morbidity. Normally, adhesions appear after offences against the peritoneum, causing flogosys, and develop both in new sites, previously not involved, and in sites already interested in adhesiolysis. Previous laparotomy is an important risk factor, as after laparatomy a minimum of 93% of patients present adhesions during a following surgery. Furthermore, the rate of recurrence after adhesiolysis is 85%. Among several strategies employed, valid prevention methods are: using minimally invasive surgery techniques, reducing the incision area, containing tissue dehydration during surgery and an accurate hemostasis. Also, for preventing and reducing adhesions, the usage of NSAIDs, fibrinolytics and anticoagulants, as well as the application of substances acting as a physical barrier, have been proposed. Recently, crystalloid solutions have been introduced, using the hydro-flotation principle for intraperitoneal organs. This research aims to analyze causes and epidemiology for postoperative adhesions, with particular regard to gynecological operations and to describe and compare the means available to prevent them.

[Use of bulking agents in urinary incontinece]. / L'utilizzo dei bulking agents nel trattamento dell'incontinenza urinaria.

Urinary incontinence consist in voluntary urine leakage. Female affected in the world are about 200 thousand. Urinary incontinence affect severely women quality of life. There are different kinds of urinary incontinence that can be treated in different ways. We can use pelvic floor rehabilitation, drug therapy, invasive and non-invasive surgical treatment. Different treatments are used for different incontinence types. Periurethral injection is the most common procedure between non-invasive surgery. The most recent bulking agents occasionally determine severe adverse reaction or complication. Frequently we can have just pain during injection and a temporary urine retention. During the latest years we used a lot of bulking agents: bovine collagen, autologous fat, carbon particles, macroplastique, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, dextranomer. Urethral injection have success in 40-90%. We can assert that macroplastique is the most efficacy and safe on the basis of literature data and of our experience data. This surgical procedure, in fact, has good percentage of success in accurately selected patients. In our experience Macroplastique can also be used in oncological patients, in elderly women, in patients with important comorbidity and with high surgical risk with good objective and subjective results.

Hemorrhagic cystitis in pregnancy: Case report and review of the literature.

Hemorrhagic cystitis is generally a benign self-limited disorder, however there are some severe cases which are associated to a significant blood loss. The etiology may be either bacterial, viral or chemical in origin; though the cause is not identified in most of the cases. Immunocompromised patients or patients who have undergone chemotherapy or radiation constitute the highest risk group. There are only a few articles about hemorrhagic cystitis in pregnancy, frequently associated with preterm labor. We describe, for the first time in literature, one patient with a clinical status of hematuria in two consequent pregnancies, without any identified cause and a medical history negative for recurrent or hemorrhagic cystitis and we report an overview of literature concerning this topic.

[Up-date on cytoreductive surgery in the management of advanced ovarian cancer]. / Aggiornamenti in tema di citoriduzione nel trattamento del carcinoma ovarico avanzato.

Epithelial ovarian cancer represents the most aggressive neoplasm of women genital apparatus with a total 5-year survival rate ranging from 17% to 35% if the disease is in the metastatic phase. Its aggressiveness derives from the fact that it is an asymptomatic disease until it spreads in abdominal cavity. Therefore, in 70% of the cases, the diagnosis is done when tumor is already in advanced phase (Stage FIGO IIB-IV). Data from international literature suggest that standard treatment for advanced ovarian cancer is optimal cytoreductive surgery with adjuvant chemotherapy platinum-based. However, in the last decades, many authors have described the enthusiastic results of neoadjuvant chemotherapy and interval debulking surgery. Griffiths, first, underlined the importance of residual mass after cytoreductive surgery as a prognostic factor. Currently, cytoreduction is defined optimal when residual mass is microscopical or absent. Nevertheless, surgery for ovarian cancer turns out to be a particularly aggressive surgery that needs an operator's remarkable technical ability and a cultural Background: Many studies demonstrated that the frequency of feasibility of optimal cytoreductive surgery also varies within the gynecologic oncology specialized centers. During the last few years, new technologies (such as Cavitron Ultrasonic Surgical Aspirator, CUSA, and argon's coagulator) and new surgical techniques have been introduced. Ovarian cancer turns out to be a particularly chemosensitive tumor. Its responsiveness has been the object of numerous studies and protocols in literature, such as European Organisation of Research and Treatment of Cancer (EORTC) and Gynecologic Oncology Group (GOG) trials.

Total rectosigmoidectomy versus partial rectal resection in primary debulking surgery for advanced ovarian cancer.

PURPOSE: To compare in a sample of Italian patients intraoperative, perioperative complications, Quality of Life (QoL), recurrence rate and overall survival of advanced ovarian cancer (AOC) patients according to the type of surgery performed on sigma-rectum, total rectosigmoid resection (TRR) versus partial rectosigmoid resection (PRR). METHODS: From May 2004 to May 2010, consecutive patients affected by epithelial AOC (FIGO Stage III-IV) were assessed for this prospective case-control study, According to the type of colorectal surgery performed to approach rectosigmoid involvement, patients were allocated into Group A (TRR) and Group B (PRR). PRR was performed when the complete removal of disease led to a laceration <30-40% of intestinal wall circumference. RESULTS: 82 and 72 patients were included in Group A and Group B respectively. Surgical outcomes were statistically similar except hospital stay which was significantly lower in the PRR group. There was not a statistically significant difference as regarding intra-operative, perioperative and postoperative complications, even if a higher rate of major complications were recorded in TRR. An improvement in QoL's scores has been recorded in PRR's group. There was not a statistically difference concerning the optimal debulking rate (92% and 96% respectively) and 5-year Overall Survival (48% and 52% respectively). CONCLUSIONS: PRR seems to be feasible in over 40% of patients with advanced ovarian cancer and recto-sigmoid colon involvement. It is related to higher QoL and can be easily performed, without jeopardizing surgical radicality, in those cases in which conservative surgery at intestinal tract does not compromise residual tumor.

Hereditary and sporadic ovarian cancer: genetic testing and clinical implications (review).

The two most common forms of hereditary ovarian cancer are: the breast ovarian cancer syndrome, and ovarian cancer associated with HNPCC (hereditary nonpolyposis colorectal cancer) syndrome. Studies have shown that these diseases may be associated with mutations in a number of tumor suppressor genes, mainly BRCA1 and BRCA2. Malfunction of the protein products of these genes have also been found to be involved in sporadic ovarian cancer, which makes up the majority of ovarian cancer cases. HNPCC-ovarian cancer associated families reveal frequent mutations in at least four genes (hMSH2, hMLH1, hPMS1, and hPMS2) involved in the repair of mismatched DNA. With ovarian cancer being such an important health issue, the push is on to design reliable screening tests to detect defective inherited or somatic alleles in individual carriers. So far, most progress has been demonstrated in those patients with family histories of the disease who are at increased risk. The ramifications of such research may impact a variety of scientific, clinical, legal, ethical, and psychosocial issues. In addition to current treatment modalities, positive results of these tests may indicate the need for increased clinical surveillance, prophylactic treatment, and genetic counseling of patients on an individual basis. It remains to be seen whether the technology can be made reliable enough to not only benefit high-risk individuals but also the general population.

Comparison of cytotoxicity and cell kinetic perturbations of 5 platinum compounds in gynecologic cancer cell-lines.

New platinum derivatives were synthesized to overcome problems of cisplatin resistance and nephrotoxicity. Five platinum derivatives were evaluated by using the ATP chemosensitivity assay and flow cytometry in a panel of 10 human gynecologic cancer cell lines: AE7, ECC1, HEC1A, HEC1B, AN3, BG1, CAOV3, SKOV3, SKUT1B and ME180. Five platinum derivatives and their referenced concentrations (X) were: Cisplatin (DDP) 2.5 mug/ml (8.3 muM), Carboplatin (CARBO) 28 mug/ml (75.5 muM), Tetraplatin (TETRA) 2 mug/ml (4.4 muM), 254S at 5 mug/ml (16.5 muM) and NK121 at 5 mug/ml (11.4 muM). Drug exposure was performed at 0, 0.1, 0.2, 0.5, 1, 2 and 5 X for 90 minutes. The ATP chemosensitivity assay was performed on day 7 as previously described. Cell samples were taken at 0, 24, 48, 72, 96 and 168 h timepoints for flow cytometry. Mean IC50s were: DDP 29.1+/-17.4 muM, 254S 18.2+/-6.6 muM, NK121 13.7+/-5.7 muM, CARBO 120.8+/-37.8 muM, and TETRA 30.8+/-20.7 muM. Both 254S and NK121 offered significant improvement of potency over DDP (p=0.02, 0.05 respectively). Similarly, Fell cycle kinetic studies revealed that both 254S and NK121 induced significantly more S and G2 blocks than DDP (p<0.02). Thus, from the chemo-sensitivity and cell kinetic standpoints, both NK121 and 254S appeared more potent and deserve further investigation.

Use of lonidamine to potentiate the effect of cisplatin and carboplatin on platinum resistant human ovarian cancer cells.

Lonidamine (LND), an indazole-3-carboxylic-acid derivative, is a new, relatively non-toxic, chemotherapeutic agent. LND, which interferes with energy metabolism, has been shown to potentiate the antineoplastic effects of chemotherapeutic agents and radiation. In this study, we evaluated the effect of LND in combination with cisplatin (DDP) or carboplatin (CARBO) on platinum resistant ovarian cancer cells. The ovarian cancer cell line BG-1 was selected as platinum resistant cell line, defined as cell line with survival fraction >50% at 0.5 peak plasma concentration (PPC). Cells were treated during the proliferative phase of cell growth with DDP and CARBO using doses between 0.1 and 1x (x = PPC). PPC of DDP = 2.5 mu g/ml, PPC of CARBO = 28 mu g/ml. Cells were also treated with LND at doses varying between 10 and 100 mu g/ml (PPC 20-50 mu g/ml). Drugs were used as single agents and in combination. Experiments were performed by treating the cells with DDP or CARBO for 90 min and with LND continuous exposure or 90 min only. The ATP cell viability assay was used to assess the antiproliferative effect of the drugs tested. Experiments were repeated at least 3 times. The synergistic interaction formula for anticancer agents and the t-test were used for the analysis of the results. LND was shown to be effective when used in continuous exposure only (IC50 = 0.58). The IC50 of DDP was 1.1 and the IC50 of CARBO was 0.64. Significant dose related antiproliferative effect of LND alone, as well as DDP and CARBO cytotoxicity potentiation was observed (p<0.05). LND was shown to have synergistic effect when combined with platinum compounds to treat ovarian cancer cells at doses of 20 and 30 mu g/ml. These doses are achievable in patients. LND, a relatively new antineoplastic agent with good clinical tolerance, has been shown to synergistically potentiate the antiproliferative effect of platinum compounds on platinum resistant ovarian cancer cells. LND is an agent of potential use for the treatment of ovarian cancer patients in combination with DDP or CARBO.

Comparison of bimanual examination with ultrasound examination before hysterectomy for uterine leiomyoma.

OBJECTIVE: To correlate the preoperative bimanual examination with ultrasound examination with regard to estimating the size of enlarged nongravid leiomyomatous uteri. METHODS: We performed a retrospective review of 161 patients who underwent hysterectomy for uterine leiomyoma between January 1994 and December 1994 and between July 1995 and April 1996. Uterine size was estimated clinically by bimanual examination. Ultrasound reports were reviewed. Uterine weights and dimensions in pathology reports were compared with findings on bimanual examination and ultrasonography. Body mass index (BMI) was calculated and patients were divided into two groups, one with BMIs of more than 30 and another with BMIs of less than or equal to 30. RESULTS: Ultrasound examination was ordered in 111 patients (68.9%) preoperatively. There was a strong correlation between the bimanual examination findings and the ultrasound dimensions. The equation for this relationship is ultrasound length (cm)=3.68 + 0.68 x number of weeks (r=.78, P < .001). Ultrasound length also was related strongly to size given in the pathologic reports; the equation for this relationship is ultrasound length (cm)=2.94 + 0.75 x pathology length (cm) (r=.73, P < .001). The correlation between bimanual examination and ultrasound findings was similar in obese and in nonobese patients, when uterine size could be estimated. CONCLUSION: There is a strong correlation between bimanual and ultrasound examinations with regard to determining the size of leiomyomatous uteri. Routine ultrasound is not indicated when an experienced examiner can assess uterine size. Ultrasonography may be appropriate when physical assessment is difficult, as in the case of obesity.

Gestational trophoblastic disease in a fifty-one year old woman.

Molar pregnancy has always been of interest to physicians because of the diagnostic and management challenges it presents. Its occurrence in patients older than 50 years of age is rare and misdiagnosis is common. A 51 year old black female presented to the gynecology emergency room with vaginal bleeding for twenty days. She was diagnosed with a molar pregnancy by a pelvic ultra-sound. Prior to presenting to the emergency room she had a negative work-up for hyperthyroidism, including a biopsy of a benign thyroid nodule and was also started on Inderal for new onset hypertension. She underwent a primary hysterectomy and subsequently required five courses of actinomycin D for plateauing of the BhCG. The different forms of presentation of gestational trophoblastic disease should be kept in mind so that the diagnosis can be made promptly and appropriate treatment started early, especially in patients with advanced age.

Effect of interferons on hormone-receptor levels of endometrial cancer-cells.

Endometrial cancer is a hormone sensitive tumor. Hormone receptor positive tumors respond better to progestins than hormone receptor negative tumors. Interferon has been shown to increase the hormone receptor level of melanocytes, breast and endometrial cancer. We have previously shown that interferons enhance the progesterone receptor level of AE-7 endometrial cancer cell line, which has a considerably high baseline level of progesterone receptors (201+/-19.7 fmole/mg of proteins). In this study the effect of interferons of two other endometrial cancer cell lines (HEC-1A and HEC-1B), with a low baseline level of estrogen and progesterone receptor levels (25+/-7-32+/-8 fmole/mg of proteins), was studied. Interferons have shown to possess similar cytostatic activity in the endometrial cancer cells studied, regardless of their hormone receptor status. However, hormone receptor levels in cells with low baseline hormone receptor levels were not significantly affected by the four interferons studied.

Use of interferon and medroxyprogesterone acetate for the treatment of endometrial cancer.

Endometrial cancer is a hormone sensitive tumor. Response rate to progestational therapy is related to steroid receptor expression of the tumor. Interferons have been shown to enhance hormonal receptors. In this study the effect of four different interferons and medroxyprogesterone acetate (MPA), on three human endometrial cancer cell lines (AE-7, HEC-1A and HEC-1B), was studied. The ATP cell viability assay was used to measure the antiproliferative activity of the agents used. Synergistic effect was noted only when interferons and MPA were used in combination for the treatment of AE-7, which is the only cell line with a high baseline level of progesterone receptors. These observations indicate that the use of interferons and MPA may have a role for the treatment of endometrial cancer patients with progesterone receptor positive cells.

Advanced mucinous adenocarcinoma in pregnancy.

The incidence of masses in pregnancy is estimated to occur in 1/81 to 1/2,500 pregnancies. The development of colorectal carcinoma during pregnancy is a more rare event, with less than 30 cases above the peritoneal reflection reported in the last 70 years. The differential diagnosis of mucinous adenocarcinoma of ovarian vs. gastrointestinal origin is often difficult. We report a pregnant patient affected by advanced colorectal cancer, who presented with an asymptomatic unilateral adnexal mass on ultrasound. A 28-year old woman was referred to our hospital after a routine ultrasound examination at 26 weeks gestation showing a right adnexal mass. At elective exploratory laparotomy, the patient was found to have metastatic mucinous adenocarcinoma. Diagnostic and treatment choices of such a cancer in a pregnant patient were explored. The final diagnosis of colorectal cancer was made only at the time of a subsequent emergency laparotomy. The goal of an obstetrician/gynecologist and other care givers of pregnant patients, is to achieve a healthy mother and child. Unfortunately, physicians may unwillingly sacrifice the health of the mother by denying or delaying her procedures or treatments simply because she is pregnant. It is especially important in the case of adnexal masses and their related pathology, due to the difficulty in detection and management of such cases during pregnancy, that doctors actively assume the responsibility of assuring that pregnant patients receive the proper care they need.