Ports and complications for intraperitoneal chemotherapy delivery.

Intraperitoneal access ports are essential to the delivery of chemotherapy agents into the peritoneal cavity of women with ovarian cancer, but their malfunction and adverse effects are frequently responsible for the failure to complete planned therapy. Complications, such as obstruction of the catheter, infection, leakage, rotation, retraction, and pain, together with bowel and vaginal perforation, cause delays in treatment, patient suffering and the expenditure of medical resources. A wide variety of ports have been used, including vascular access devices and intraperitoneal access devices. This paper reviews the development and use of ports for intraperitoneal chemotherapy, their complications and reported methods of prevention.

Differential expression of T-cell CD3-zeta chains in patients with cervical dysplasia before and after treatment.

This study addresses whether CD3-zeta suppression associated with cervical intraepithelial neoplasia (CIN) I, II, and III is mediated by a circulating factor and if this suppression is reversed following treatment. Serum was isolated from patients with CIN before and after curative therapy. Jurkat T cells were incubated with patient-derived sera for 4 days, and CD3-zeta expression was analyzed by western immunoblot. Sera from control female volunteers did not suppress CD3-zeta expression of Jurkat cells, while sera from women with CIN I, II, and III suppressed 58.9%, 75.3%, and 80.5%, respectively. Suppression observed in women with CIN I was significantly different from that observed with CIN II and III. Posttreatment zeta suppression was noted to be reversed in women with CIN II and III although the decreased suppression in CIN III patients was not statistically significant. Our study demonstrates that in vivo suppression of zeta chains in patients with CIN can be the result of a circulating factor. In vitro zeta expression increased in patients with CIN II and III after treatment, although the increase was only statistically significant in patients with CIN II.

Retinoids for preventing the progression of cervical intra-epithelial neoplasia.

BACKGROUND: Invasive cervical carcinoma is preceded by a precancerous phase, cervical intra-epithelial neoplasia (CIN), which can be detected on cervical smears and confirmed by colposcopy and biopsy. Moderate and severe intra-epithelial neoplasia (CIN2 and CIN3) are treated mainly with surgery to prevent progression to invasive carcinoma. Medical methods of preventing the progression or inducing regression of CIN are needed. Retinoids are potent modulators of epithelial cell growth and differentiation and may have potential for the treatment of CIN. OBJECTIVES: To ascertain whether retinoids can cause regression or prevent progression of CIN. SEARCH STRATEGY: Cochrane Gynaecological Cancer Review Group's Specialised Register and Non-Trials Database, Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2,2007),MEDLINE and EMBASE (June 2007). SELECTION CRITERIA: Randomized controlled trials (RCTs) and non-RCTs of retinoids for treating CIN in women. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from the trials. Adverse effects information was also collected from the trials. MAIN RESULTS: Five RCTs comparing the efficacy of four different retinoids were identified. Two studies examined the effect on CIN2 and CIN3 of retinoids N-(4-hydroxyphenyl)retinamide (fenretinide) (Follen 2001) and 9-cis-retinoic acid (aliretinoin) (Alvarez 2003) given orally and two examined the effect of all-trans-retinoic acid given topically to the cervix (Meyskens 1994; Ruffin 2004). The fifth study investigated the use of 13-cis-retinoic acid (isotretinoin) given orally in HIV positive patients with CIN1 and condyloma (Robinson 2002).Four studies reported no significant effect of retinoids on the progression to higher grades of CIN, whilst the fifth did not report data on progression. In all studies retinoids had no significant effect on regression of CIN3. Two studies reported that retinoids were associated with regression of CIN2. One reported a greater complete regression of CIN2 over placebo, which was of borderline statistical significance, odds ratio(OR) = 0.5 (95% confidence interval (CI) 0.25 to 1.02). The other study reported a non-significant dose-related trend towards increased rates of complete and partial regression compared with placebo. One study reported a significantly worse outcome in women receiving retinoid, OR for regression = 6.00 (95% CI 1.00 to 35.91). In general, the retinoid medications were well tolerated. AUTHORS' CONCLUSIONS: The retinoids studied are not effective at causing regression of CIN3 but may have some effect on CIN2. The data on CIN1 is inadequate. Retinoids are not effective at preventing progression of CIN of any grade. At the doses given and duration of treatment studied, the retinoids were reasonably well-tolerated.

Retraction of an intraperitoneal chemotherapy port: a case report and literature review.

Delivery of chemotherapy directly into the peritoneal cavity is becoming part of the standard frontline management of patients with optimally cytoreduced ovarian carcinoma. Traditionally, the peritoneal access devices used for this have had relatively high complication rates including infection, blockage, leakage, and difficulties with port access. In order to reduce the risk of infection, we have been using a Bard 9.6F silastic infusaport that does not have a Dacron cuff to secure it into the tissues of the anterior abdominal wall. It has the added advantage of being more easily removed at the end of treatment. We report a case of spontaneous retraction of such a port out of the peritoneal cavity into the subcutaneous tissues. This complication associated with a silastic cuffless port is presented to raise awareness of this possible complication and suggest ways of preventing it.

Cytoreduction and intraperitoneal heated chemotherapy for the treatment of endometrial carcinoma recurrent within the peritoneal cavity.

Our experience with hyperthermic intraperitoneal chemotherapy (IPHC) in conjunction with surgical resection for endometrial cancer recurrent within the abdominal cavity was reviewed. Eligible patients underwent exploratory laparotomy with the aim of resecting disease to < or =5 mm maximum dimension followed immediately by intraperitoneal perfusion of cisplatin (100 mg/m(2)) heated to 41-43 degrees C (105.8-109.4 degrees F) for 1.5 h. Data for analysis was extracted from retrospective chart review. Five patients underwent surgery and IPHC between September 2002 and January 2005 for abdomino-pelvic recurrence. Original stage and histology were 1A papillary serous (1), 1C endometrioid with clear cell features (1), and 1B endometrioid (3). Mean age was 61 (41-75) years, mean prior laparotomies were 1.4 (1-2), and mean chemotherapy agent exposure was 1.6 (0-4). Mean time from initial treatment to surgery and IPHC was 47 (29-66) months. Mean length of surgery was 9.8 (7-11) h after which three patients had no residual disease and two had < or =5 mm disease. The mean duration of hospital stay was 12.6 (6-20) days. Postoperative surgical complications included wound infection with septicemia in one patient. Mean maximum postoperative serum creatinine was 1.02 (0.6-1.70) mg/dL. There was no ototoxicity or neuropathy and no perioperative mortality. No patients have been lost to follow-up. Two are living disease free at 28 and 32 m and two are living with disease at 12 and 36 m. One patient died at 3 m without evidence of cancer. Two patients who had no residual macroscopic disease at the end of surgery are alive at 32 and 36 m. The combination of IPHC with surgery for recurrent endometrial carcinoma is relatively well tolerated. The unexpectedly long survival seen in this cohort supports a phase II trial of IPHC with cisplatin for recurrent endometrial cancer.

Enhancing adherence following abnormal Pap smears among low-income minority women: a preventive telephone counseling strategy.

BACKGROUND: Although the incidence of precancerous conditions of the cervix has recently been increasing, prompt initial and long-term follow-up care can effectively reduce unnecessary morbidity and mortality. For example, the 4-year survival rates among those individuals at greatest risk for cervical cancer (i.e., minority women of low socioeconomic status) approach 95% with early detection. Women who present with advanced disease have a much poorer outlook (0%-39% survival). Yet, high-risk individuals are least likely to adhere to recommended diagnostic regimens. PURPOSE: We tested the effectiveness of a brief telephone counseling intervention directed to low-income, inner-city women after they had received an abnormal Pap smear result. The women were counseled on the importance of having an initial and 6-month repeat follow-up diagnostic procedure (i.e., colposcopic examination of the cervix). METHODS: A randomized trial design was used to compare the effects on these women of telephone counseling with (n = 192) or without (n = 203) a booster counseling telephone call prior to the appointment for a repeat colposcopy 6 months later, with a telephone appointment confirmation/reminder call (n = 216) and with standard care (i.e., no telephone contact) (n = 217). The telephone counseling protocol probed for and addressed three psychologic barriers to adherence (i.e., attendance at appointment for colposcopy examination): 1) encoding/expectancy (e.g., did the patient understand her risk of developing cervical cancer?); 2) affective/emotional (e.g., was the woman worried about the condition and its consequences?); and 3) self-regulatory/practical (e.g., was the woman likely to forget medical appointments?). Logistic regression was used to analyze the effects of the intervention group and the type of psychologic barriers elicited on colposcopy adherence. RESULTS: The results of logistic regression analysis (using those who received an appointment confirmation/reminder telephone call as the comparison group) revealed that telephone counseling produced significantly higher adherence rates to the initial colposcopy visit compared with telephone confirmation (300 [76%] of 395 women versus 147 [68%] of 216; odds ratio [OR] = 1.50; 95% confidence interval [CI] = 1.04-2.17). Additionally, standard care resulted in significantly lower adherence rates than did telephone confirmation (109 [50%] of 217 women versus 147 [68%] of 216; OR = 0.47; 95% CI = 0.32-0.73). Regarding attendance at the 6-month repeat colposcopy appointments, the 80 patients who had received telephone counseling prior to the initial visit (and were recommended for follow-up colposcopy) were significantly more likely to adhere than were the 47 patients who had received telephone confirmation (49 [61%] of 80 women versus 17 [36.2%] of 47; OR = 2.70; 95% CI = 1.15-6.51). The 6-month adherence rates for patients in the telephone confirmation group and the standard care group (n = 30) were low and did not differ significantly (17 [36.2%] of 47 women versus nine [30.0%] of 30; OR = 1.08; 95% CI = 0.40-2.89). Forgetting medical appointments (OR = 0.31; 95% CI = 0.19-0.51) and having scheduling conflicts (OR = 0.45; 95% CI = 0.28-0.72) were also associated with lower rates of adherence. CONCLUSION: The use of telephone counseling appears to be an effective strategy for enhancing initial and long-term adherence to a follow-up cervical diagnostic procedure in a traditionally underserved population. Patients who respond to a positive Pap test result with a particular profile of psychologic barriers may require more intensive and targeted counseling interventions.

Serological survey of chlamydial antibody in post-natal sera.

Questionnaires (3426; 72.8%) and blood samples (3890; 82.6%) were analysed from 4704 women post-natally. The answers to the questionnaire confirmed that those patients living in areas with the highest percentage employed in agriculture were most likely to be in direct or indirect contact with sheep or sheep products. When the 788 (20.3%) of the sera with group specific antibody were examined for type-specific antibody, 291 (7.5%) reacted with Chlamydia trachomatis, 153 (3.9%) with Chlamydia pneumoniae, but only one (0.03%) with Chlamydia psittaci. Thus, it would appear that C. psittaci was not an important pathogen in this survey, despite the largest proportion of blood samples being submitted from those most likely to be employed in agriculture. However, in the course of this survey the three patients who had previously suffered chlamydia-associated abortion had successful pregnancies and submitted blood specimens. Serological studies on the serial bloods from these patients showed that, despite developing antibody to the C. psittaci pool and the ovine abortion strain of C. psittaci following abortion, this antibody waned. At the time of the subsequent successful pregnancy, serological results would not have detected a previous C. psittaci infection, but one due to C. pneumoniae. Thus, the results of a survey such as this must be interpreted with caution.

LLETZ is an acceptable alternative to diagnostic cold-knife conization.

Large loop excision of the transformation zone (LLETZ) provides a pathologic specimen similar to a cold-knife cone (CKC) biopsy of the cervix. One hundred twenty women with indications for a cone biopsy were evaluated with LLETZ to determine if this procedure is an acceptable alternative to traditional cold-knife conization of the cervix. All patients had LLETZ performed in the clinic under local anesthesia. An average of 2.1 slices was required to remove the transformation zone. Coagulation artifact interfered with histologic diagnosis in only 1.8% of specimens. The number of slices taken during the LLETZ procedure significantly correlated with the amount of heat artifact in the pathology specimen (P = 0.02) and interfered with the ability of the pathologist to determine complete excision of dysplasia (P = 0.03). LLETZ is an acceptable alternative to diagnostic CKC and can offer a substantial cost savings. To facilitate histopathologic interpretation, every effort should be made to minimize the number of slices and to maintain orientation of the LLETZ specimen. Endocervical curettage performed after LLETZ can identify a group of patients who are at high risk for CIN recurrence.

Prospective randomized trial of LLETZ versus laser ablation in patients with cervical intraepithelial neoplasia.

Three hundred seventy-five patients with CIN on referral Pap and with a distinct cervical lesion on colposcopy were prospectively randomized to treatment with LLETZ or to standard colposcopic evaluation with directed cervical biopsies, endocervical curettage, and laser ablation of the transformation zone for biopsy proven CIN. Of the 195 patients that randomized to treatment with LLETZ, 32.5% had no evidence of dysplasia, 26.5% had CIN 1, 17.3% had CIN 2, 22.7% had CIN 3, and 0.5% had microinvasive carcinoma on final histologic evaluation. Of the 180 patients randomized to laser ablation, initial cervical biopsies demonstrated no evidence of dysplasia in 52.8% of patients, CIN 1 in 22.0%, CIN 2 in 18.3%, and CIN 3 in 5.7%. Only 114 (63.3%) of the women in the laser group required therapy. Complications were comparable for each treatment arm. Only 6.7% of patients randomized to LLETZ and 4.4% with laser ablation had persistent CIN on follow-up Pap. LLETZ appears to be effective, well tolerated, and less expensive, but the cost savings advantage of LLETZ over laser ablation may not apply to patients with CIN 1 on referral Pap smear since many do not require treatment.

The rhomboid transposition flap for repair of the perineal defect after radical vulvar surgery.

A detailed account is given of experience at a single institution with the rhomboid transposition flap used to repair the perineal defect after surgery for carcinoma of the vulva. In 13 of 15 assessable cases, the flaps healed completely or had insignificant separation of a segment of the flap. In 2 cases, more major breakdown occurred in association with infection, but in both cases, satisfactory healing occurred without further surgery. In 14 cases, passage of a speculum and inspection of the vagina was possible at follow-up and only 1 patient experienced introital stenosis.

A matched study of surgically treated stage IB adenosquamous carcinoma and adenocarcinoma of the uterine cervix.

Thirty-eight patients with surgically treated stage IB adenosquamous carcinoma of the uterine cervix (AS) have been matched with patients with other histologic subtypes of adenocarcinoma (A) for stage, lesion size, node status, grade of adenocarcinoma and age at diagnosis. An additional six patients with AS were unable to be matched. Overall 5-year survival and disease-free survival for the matched AS and A were not significantly different, 83 vs. 90%, and 78 vs. 81% nor were the number of recurrences, 8/38 AS vs. 6/38 A, but the mean time to recurrence was significantly shorter in the AS group: 11 vs. 32 months (P = 0.003). A subgroup of AS with a high risk of a poor outcome can be identified based on either lesion size >/= 4 cm, depth of invasion >/= 10 mm or plevic lymph node metastasis. These patients may be suitable candidates for adjuvant therapy before or after surgical treatment.

A unique c-myc-targeted triplex-forming oligonucleotide inhibits the growth of ovarian and cervical carcinomas in vitro.

A 27-base pair triplex forming oligonucleotide (G27-oligonucleotide) targeted to the "puf" regulatory protein-binding domain of the human c-myc oncogene has been conjugated with the DNA-binding molecule acridine (G27-conjugate) in order to obtain a drug with high binding affinity as well as high sequence specificity. Both the triplex-forming oligonucleotide and its acridine conjugate are shown to form triple-stranded DNA at the site of the target sequence by DNase 1 footprinting. When the cervical carcinoma cell line HeLa was exposed to 4 microM concentrations of the G27-oligonucleotide the viable cell count fell to 89, 56, and 49% of control at 25, 50, and 72 hr. After exposure to 1 microM G27-conjugate the viable cell count fell to 87, 50, and 33% of control. Nonspecific reductions in cell number were found for the control oligonucleotides to 79 and 82% of control. When SKOV-3 cells were exposed to the same concentrations of oligonucleotides, viable cell count in relation to control fell to 43, 50, and 67% with the G27-oligonucleotide and 57, 52, and 53% with the G27-conjugate at 24, 48, and 72 hr. The control oligonucleotides again caused a small nonspecific drop in the viable cell number.

A matched comparison of single and triple incision techniques for the surgical treatment of carcinoma of the vulva.

Thirty-two patients with invasive squamous cell carcinoma of the vulva (SCC) undergoing radical vulvectomy or radical local excision with bilateral superficial groin node dissection using a triple incision technique (TI) were matched for new FIGO stage, lymph node status, size of lesion, and site of lesion with patients with SCC undergoing traditional radical vulvectomy with en bloc bilateral groin (but not pelvic) node dissection using a single incision (SI) technique. Average operative time (134 min: 191 min), blood loss (424 ml: 733 ml), and hospital stay (9.7 days: 17.2 days) were significantly less in the TI group. After SI 6/32 (19%) patients and after TI 1/32 (3%) patients experienced complete breakdown of the groin wounds. There was no significant difference in overall survival (P = 0.56) or disease-free survival (P = 0.53) between the two groups. There was no significant difference in survival between the two groups by lesion size or by FIGO (1989) stage. Disease recurred in six patients after SI compared with seven after TI (P = 0.75). There were no skin bridge recurrences in the TI group. Two patients in each group had isolated vulvar recurrences and all four were successfully treated by local excision. These data indicate that outcome following TI surgery is essentially equal to that of SI in early-stage disease but major morbidity is much reduced.

Carcinoma of the cervix in women up to 35 years of age.

50 women aged up to 35 years were diagnosed as having carcinoma of the cervix in Brighton, England between 1980 and 1985. The overall 5-year actuarial survival was 65% and 73% for stage IB. The 5-year survival for those aged 29 years or less was significantly worse than for those aged between 30 and 35 years, 39% versus 80%. There was a higher incidence of advanced stage and high-grade tumours in the younger women. It is suggested that the natural history of the tumour in women under 30 years is shorter than that in older women, and this is likely to be associated with high-grade, rapidly advancing carcinomas of poor prognosis.

Intraplacental choriocarcinoma: a case report.

A recent paper has again drawn attention to the occurrence of intraplacental choriocarcinoma. We present a similar case in which a small intraplacental choriocarcinoma was identified after delivery of a full-term stillborn fetus. Interpretation of this lesion was influenced by the presence of normal villi and its full significance appreciated only after diagnosis of choriocarcinoma in the mother. This case presents histological proof that choriocarcinoma may arise from an otherwise normal placenta.

Synchronous colonic adenocarcinoma and extragenital malignant mixed mesodermal tumour.

A synchronous occurrence of large bowel adenocarcinoma and extragenital malignant mixed mesodermal tumour (MMMT) is reported. This case represents the sixth extragenital MMMT reported in the literature.

Asymptomatic bladder neck incompetence in nulliparous females.

This study investigated 29 nulliparous women using the technique of transvaginal ultrasound to assess whether their bladder necks were open or closed at rest. The patients comprised 2 groups: 4 reported occasional episodes of stress incontinence, all of whom had closed bladder necks; the remaining 25 patients were totally asymptomatic. Overall a 21% incidence of an open bladder neck was recorded. It is likely that the true incidence of open bladder necks in young nulliparous women is higher than this, since none of these patients had troublesome stress incontinence. Since women with open bladder necks are more likely to develop stress incontinence if the integrity of the distal sphincter mechanism is compromised by neural damage, antenatal recognition of this problem should provide a contraindication to traumatic vaginal delivery and may in the future reduce the incidence of symptomatic stress incontinence in the population.

Sheep-acquired severe Chlamydia psittaci infection in pregnancy.

There have been five confirmed cases of severe Chlamydia psittaci infection during pregnancy, three having been treated in Edinburgh, Scotland. The most recent case is presented and previous experience is reviewed. The illness usually causes thrombocytopenia with disseminated intravascular coagulation, renal failure and hepatic dysfunction during the late second and early third trimester. The outcome for the fetus is usually fatal and the infection only resolves after delivery or abortion. The main hope is for education to prevent infection occurring in susceptible populations.