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Intraperitoneal P-32 is not an effective consolidation therapy after a negative second-look laparotomy for epithelial carcinoma of the ovary.

Thirty-four patients with epithelial carcinoma of the ovary were entered into a trial of adjuvant intraperitoneal P-32 following induction chemotherapy and a negative second-look laparotomy. The breakdown by initial Stage was Stage IC, 5; Stage II, 3; Stage III optimal, 22; and Stage III suboptimal, 4. Previous treatment consisted of 4-12 cycles (median 6) of cisplatin or carboplatin-based combination chemotherapy. Fifteen millicuries of P-32 were instilled via a Tenckhoff catheter placed at the time of second-look laparotomy. Because of a 22% incidence of bowel injury in the first 23 patients, the P-32 dose was reduced to 12 mCi in the last 11 patients. To date, there have been no bowel injuries at the lower dose. Eighteen of the 34 (53%) patients have relapsed with a median time to relapse of 20 months and a median follow-up for all patients of 31 months. There has been no difference in the relapse rate between a dose of 12 and 15 mCi. Intraperitoneal P-32 does not appear to reduce the relapse rate following a negative second-look laparotomy. The incidence of bowel injury is dose dependent and is higher than that seen in patients treated as an adjuvant following initial surgery without subsequent chemotherapy or second-look laparotomy.

Adult↗

Second-look operation in ovarian carcinoma: postchemotherapy.

One hundred and three patients with advanced ovarian cancer underwent a second-look operation following chemotherapy. Patients should have ten or more courses of chemotherapy before second-look operation. Those patients with no evidence of disease at second laparotomy should discontinue their chemotherapy. Patients who continued chemotherapy after the second-look operation did better than those who were treated with radiation after surgery. Only patients with clinical remission benefit from the second-look procedure. Advantages of second-look operations following chemotherapy are discussed.

Dose-Response Relationship, Drug↗

[Relationship between serum CA125 level and second-look findings in ovarian cancers].

Serum CA125 levels were monitored in 30 patients with epithelial ovarian cancer prior to second-look laparotomy. All patients had undergone cytoreductive surgery and multiple courses of chemotherapy and with no clinical and radiologic evidence of tumor. All ten patients who had had negative second-look finding gave normal serum CA125 levels (less than or equal to 35 u/ml). Of the 20 patients who were positive in second-look, 11 had normal CA125 levels, with a false negative rate of 55% including 67% (4/6) patients with microscopic evidence of tumor and 50% (7/14) patients with gross residual tumor. All 9 patients with elevated serum CA125 levels were positive in their second-look. 73% (8/11) patients with residual tumor having greatest diameter less than or equal to 2 cm had normal CA125 with a median value of 13 u/ml. 33% (3/9) patients with tumors having the greatest diameter greater than 2 cm had normal CA125 and the CA125 median value was 114 u/ml. These results show that the size of the residual tumor found in second-look was related to the serum CA125 level. As CA125 level within normal limits gave more false negatives, the necessity of second-look can not be judged by serum CA125 assay though elevated CA125 levels do predict the presence of tumor.

Adenocarcinoma, Mucinous↗

Ploidy analysis of epithelial ovarian cancers using image cytometry.

We used a computerized image analysis system to determine the DNA content of 103 epithelial ovarian cancers using touch imprints of frozen tumor samples. Similar to prior studies of ploidy using flow cytometry, we found that most ovarian cancers (78%) were aneuploid while a minority (22%) were diploid. There was no relationship between ploidy and stage, histologic grade, or the ability to perform optimal cytoreductive surgery. Also, like prior studies using flow cytometry, negative second-look laparotomy and survival were somewhat more common in advanced-stage patients with diploid cancers than in those with aneuploid cancers. We conclude that ploidy of ovarian cancers can be determined using a computerized image analysis system to quantitate feulgen staining of cells in touch imprints. Ploidy is unlikely to play a role in treatment planning for patients with advanced-stage disease. Larger studies of patients with early-stage disease are needed, however, to determine whether ploidy is a more accurate means of predicting which patients are most likely to benefit from adjuvant therapy.

Aneuploidy↗

The role of secondary cytoreductive surgery in epithelial ovarian malignancies.

The benefit of aggressive primary cytoreductive surgery in the management of patients with advanced epithelial ovarian cancer has been confirmed. The value of secondary cytoreductive surgery, however, is less clear. This approach is being studied in four categories of patients: (1) those clinically free of disease after a planned regimen of first-line chemotherapy who are found to have macroscopic tumor at second-look laparotomy; (2) patients found to have bulky, unresectable tumor at initial surgery and who undergo interval cytoreduction as part of a planned chemosurgical treatment approach; (3) those with recurrent disease after a prolonged disease-free interval; and (4) patients who progress on first-line therapy. This article reviews the technical success rates, complications, and survival in patients undergoing these secondary cytoreductive procedures.

Combined Modality Therapy↗

The role of second look laparotomy and tumor markers in the follow-up of endodermal sinus tumor of the ovary. A case report and review of the literature.

Endodermal sinus tumor (EST) of the ovary is extremely rare and little information exists about therapy and the role of second-look laparotomy in the management of this entity. A case of EST of the ovary in a 21 year old woman is reported. She received conservative surgery and six courses of combination therapy consisting of Vincristine, Actinomycin D and Cyclophosphamide before second-look laparotomy. Due to progression of the disease second-line polychemotherapy with Vinblastine, Bleomycin and Cisplatin was administered. This new regimen reduced the alpha-fetoprotein to normal levels although the patient was not free of disease on second-look laparotomy. Precise guidelines for the management of this disease, especially in advanced stages, are still lacking.

Adult↗

Reversible elevation of plasma CEA associated with iatrogenic unilateral hydronephrosis in a patient operated for colorectal cancer.

A patient is reported with progressively rising plasma levels of CEA in association with iatrogenic, unilateral hydronephrosis, subsequent to surgery for colorectal cancer. The CEA level returned to normal with spontaneous recovery of the hydronephrosis. The knowledge of this association should serve as an additional guideline when a "second-look" operation is being considered in colorectal cancer patients (who have been previously rendered free of disease by pelvic surgery) when plasma CEA begins to rise progressively.

Carcinoembryonic Antigen↗

Colorectal cancer. Principles of postoperative follow-up.

Monitoring patients after primary large bowel surgery for malignancy is predicated on the concept that early detection of recurrence may provide salvage treatment for cure. Knowledge of the pathologic site and stage provides important information as to the probability of recurrence and the patterns of failure that are likely to occur. Available methods to detect recurrence include clinical, roentgenographic, and serum tests that are done more frequently during the first 2 years after surgery. Monitoring plasma carcinoembryonic antigen levels can lead to identification of asymptomatic recurrences, but there is controversy about the curability of recurrences outside the liver. Newer techniques (such as computed tomographic portography, intraoperative ultrasonography, and radioimmunoguided surgery) provide greater diagnostic accuracy and lead to more appropriate procedures during "second-look" operations. For example, hepatic resection in properly selected patients offers up to a 30% chance of cure and should be pursued aggressively. A search for metachronous cancers by endoscopy also should be done. Knowledge of the potential and patterns of failure can provide a useful guide during the postoperative follow-up care of the patient with large bowel cancer.

Colorectal Neoplasms↗

Surgery for ovarian cancer.

Surgery is a critical component of the multimodality approach to ovarian cancer. Surgery confirms the diagnosis and establishes the stage of disease, especially important when the tumor appears to be limited to the ovaries. In advanced disease, surgical cytoreduction improves response to chemotherapy and survival. Second-look laparotomy provides a means for assessing response to therapy, predicting prognosis, and determining the need for further therapy. Surgery can also provide palliation of intestinal obstruction.

Female↗

The CHAD and HAD regimens in advanced ovarian cancer: combination chemotherapy including cyclophosphamide, hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II).

Combination chemotherapy consisting of hexamethylmelamine, adriamycin, and cis-dichlorodiammineplatinum(II) was given to 27 patients with advanced epithelial ovarian cancer whose disease had progressed while receiving therapy including alkylating agents. Eighteen patients (67%) had objective partial or complete remissions for a projected median duration of 7 months. Based on this high level of activity in this poor-risk group, the three drugs were combined with cyclophosphamide in a four-drug regimen (CHAD) for initial therapy suitable for outpatient administration. Nineteen of 21 evaluable patients (90.4%) receiving CHAD responded. Complete clinical remissions were noted in ten patients (47.6%) and were confirmed at "second-look" laparotomy in two of these. An additional five patients without evaluable disease after initial surgery are free from relapse at 4--15 months. Toxicity was only moderately severe; 28% of the patients had wbc counts less than 2000/microliters at some point. Nephrotoxicity from cis-dichlorodiammineplatinum(II) was almost completely prevented by a 2-hour outpatient regimen of hydration and diuresis. A prospective randomized trial is planned comparing CHAD to melphalan in previously untreated women with advanced ovarian cancer.

Adult↗

The controversial 'second-look' laparotomy.

To determine optimal indications for and clinical assessment of the significance of relaparotomy, the data of 304 women with malignant ovarian tumours (of epithelial origin, predominantly, 72%) who had undergone a 'second-look' operation were analysed. 'Second-look' relaparotomies were performed 10-22 months after the initial operation, on the following clinical indications: 1) clinical remission after initial combined treatment (surgery + chemotherapy) in cases where malignant cells are found at systematically performed cytological examinations of ??? or lavage from peritoneal surfaces of the Douglas cul-de-sac plus high levels of CA 125 in blood serum (8 patients with stages I and II, FIGO classification); 2) remission after adequate combined treatment and following 6-10 cycles of polychemotherapy, in order to decide whether to abandon or continue with treatment (13 patients with stages III and IV); 3) clinical remission following initial operation which was voluminously non-radical (117 patients); 4) suspicion of tumour recurrence after adequate combined treatment (114 patients); 5) no suspicion of cancer recurrence, though with ventral hernia or other pathology requiring relaparotomy (22 patients). Complications arising at the 'second-look' operation or during the postoperative period were observed in 29 of the 304 patients (9.5%), giving a postoperative mortality of 0.9%. According to experience, the positive significance of 'second-look' operations to optimize treatment of patients with malignant ovarian tumours is obvious.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment strategy for nodular renal blastema and nephroblastomatosis associated with Wilms' tumor.

Nodular renal blastema and nephroblastomatosis were present in 8 of 118 patients (6.8%) with Wilms' tumor. Five of these 8 patients (63%) had bilateral Wilms' tumors. Two had hemihypertrophy. Preoperative renal angiograms were accurate in detecting these metanephric anomalies. The surgical approach consisted of removal of the most diseased kidney and biopsy for diffuse tumors and wedge resections for localized tumors for the remaining kidney. Postoperatively, radiation was administered when tumor extended outside the kidney. Chemotherapy consisted of vincristine and dactinomycin for 18 mo and adriamycin for 6 mo. This method of management resulted in tumor-free survival of these 8 patients for 1--44 mo (median 24 mo). Nodular renal blastema and nephroblastomatosis may possibly develop into Wilms' tumor. All of these three conditions respond to surgery, chemotherapy, and radiation. When a Wilms' tumor is encountered, it is better to explore and possibly biopsy the opposite kidney. There is a place for second-look laparotomy in this spectrum of congenital anomalies.

Child↗

Pre- and postoperative uses of CEA.

CEA plasma levels obtained prior to definitive surgery in patients with colorectal cancer in our hands have predictive ability. An elevated CEA greater than 2.5 ng/ml recorded by our laboratory means an increased risk of subsequent local recurrence or of later metastatic disease. The question as to whether or not this is additive as a prognostic variable when tested against careful histopathological staging remains. As a monitor, CEA will detect recurrence. Again, the problem as to how accurate this is remains. If we use two consecutive elevations of plasma CEA greater than 2.5 ng/ml as a criteria, we encounter about 15% false positives which must be weighed against finding disease significantly earlier in about one-third of the patients followed. Our data for second-look procedures indicate clearly that when used in patients with an elevated CEA laparotomy may be useful and further studies showed the presence of disease in 11 of 14 patients with an elevation following surgery for two consecutive tests were greater than 2.5 ng/ml. Two were operable. The significance of these findings is described.

Carcinoembryonic Antigen↗

Tumors of low malignant potential.

In the past two decades increasing interest has been directed toward defining tumors of low malignant potential with regard to diagnosis, treatment, and biologic behavior. Three factors that appear to be of prognostic significance include stage, cellular DNA content, and residual disease. Patients with tumors of low malignant potential should undergo surgical staging and optimal cytoreductive surgery when technically feasible. Although adjuvant chemotherapy does not appear to be efficacious in patients with tumors of low malignant potential as a whole, there may be a small subset of patients with poor prognostic factors that would benefit from chemotherapy. Second-look laparotomy is not indicated in the management of this disease except in the research setting.

Antineoplastic Combined Chemotherapy Protocols↗

Laparoscopic myomectomy.

Fifty-six patients presenting with infertility (17); bleeding, pain, and pressure symptoms (32); and pelvic mass (seven) associated with leiomyomas were managed with laparoscopic myomectomy. Twenty-four second-look procedures were performed to evaluate healing and adhesion formation. Operative time ranged between 45-443 minutes (mean 157), estimated blood loss varied from 10-400 mL (mean 75), and the mean length of hospital stay was 1 day. Traditional morcellation was used initially but was abandoned because of long operating time; vaginal or abdominal removal (depending on size) proved more satisfactory. Three patients developed subcutaneous emphysema and one had febrile morbidity due to upper respiratory tract infection. There were no other complications. In 24 second-look procedures, adhesions were present in 16 subjects (66%). Twelve of 17 in the infertility group conceived (71%); all 39 patients with other complaints experienced satisfactory relief. There were no reoperations. When myomectomy is indicated, the laparoscopic approach appears to offer an alternative to abdominal surgery in selected patients.

Adult↗

The concomitant determination of different serum tumor markers in epithelial ovarian cancer: relevance for monitoring the response to chemotherapy and follow-up of patients.

The levels of CA125, CA19.9, CA15.3 CA72.4, and TATI were serially measured during and after chemotherapy in 43 patients with epithelial ovarian cancer having elevated concentrations of one or more of the antigens before initial surgery. The value of 35 U/ml was chosen as cutoff level of CA125 for the monitoring of disease. Changes in the serum levels of CA125, CA19.9, CA15.3, CA72.4, and TATI correlated with the clinical course of disease in 87.4% of 215, 76.3% of 80, 71.3% of 122, 76.0% of 167, and 48.5% of 101 instances, respectively. After the sixth course of monthly primary chemotherapy, elevated antigen levels were strong predictors of persistent disease, while normal antigen values were associated with both positive and negative second-look findings. It is worth noting that antigen levels above the cut-off limits before the third course, but still in the normal range after the sixth course, seemed to be predictive of positive second-look findings. Among patients with elevated antigen levels at diagnosis, clinical detection of neoplastic progression after treatment was stopped was preceded by an elevation of serum CA125 in 93.3% of 15 patients, of serum CA19.9 in 80.0% of 5 patients, of serum CA15.3 in 66.7% of 9 patients, of serum CA72.4 in 81.8% of 11 patients, and of serum TATI in 40% of 10 patients. In patients with positive CA125 assay at diagnosis, the concomitant evaluation of the other antigens did not seem to be of additional benefit for monitoring epithelial ovarian cancer. However, the measurement of the other tumor markers could represent an interesting biochemical tool for the management of patients with negative CA125 assay. In particular the evaluation of serum CA19.9 or CA72.4 could be very useful in the monitoring of patients with mucinous ovarian cancer, which often fails to express CA125 antigen.

Antigens, Tumor-Associated, Carbohydrate↗

Value of CA 125 as a marker of ovarian cancer.

Elevated CA 125 level was noted in 0.2-5.9% healthy women, 2.2-27.8% patients with benign ovarian cysts, and approximately 80% patients with nonmucinous ovarian cancer. In the early stages of cancer, CA 125 level was lower than in the disseminated process (with tendency to higher levels in cases of accompanying exudates to body cavities). The level was found to correlate with the mass of tumor, extent of surgery and response to chemotherapy. Maintenance or increase in CA 125 level after three months of chemotherapy was found to indicate ineffectiveness of the treatment, suggesting a more aggressive therapeutic strategy. The estimation of CA 125 half life after the first two courses of chemotherapy was noted to be a good prognostic factor (9.2 to 10.73 days in patients with total remission, and 22.6 to 44.87 days in patients with progression). The monitoring of ovarian cancer courses using CA 125 level estimations in the serum facilitated decisions at to the timing of the second-look operation; elevated level of the marker was found to indicate that the latter was superfluous. Elevated CA 125 level proceeded clinical diagnosis of relapse by 3 to 6 months, but only in the patients who at earlier stages of the treatment also showed abnormal levels of the marker. The monitoring of patients with complete remission who showed normal CA 125 level throughout the treatment was found useless.

Antigens, Tumor-Associated, Carbohydrate↗

Chemotherapy in advanced ovarian cancer.

Most patients with epithelial cancer of the ovary are not cured by surgery, since their cancer has spread beyond the ovaries. The majority of these patients are not suitable for postoperative irradiation therapy, since the residual tumors are too large to be effectively treated with irradiation or they have metastasized to areas that cannot be effectively irradiated. Approximately 50% of the patients with advanced ovarian cancer who are treated postoperatively with melphalan will benefit from this chemotherapy. Approximately 40% of the patients who do not respond to chemotherapy with melphalan will benefit from treatment with a combination of actinomycin D, 5-fluorouracil, and cyclophosphamide. A second-look operation after 12 or more cycles of chemotherapy is often helpful in planning future treatment of patients, and it may be curative in a few patients if all the remaining tumor can be excised.

Altretamine↗