Extraperitoneal metastases after intraperitoneal chemotherapy of ovarian cancer patients with a negative second-look laparotomy

The site of the first detectable recurrence was recorded in 17 consecutive stage II–IV ovarian carcinoma patients who, after a negative second-look laparotomy, received intraperitoneal chemotherapy with cisplatin and thiosulfate kidney protection. Although the progression-free interval and survival were favorable, 11 patients eventually had a recurrence and in six (54.5%) of these it was extraperitoneal. Brain metastases were detected in three patients. The appearance of extraperitoneal metastases is not always ominous.     

Second-look laparotomy in ovarian cancer: evaluation of pathologic variables

From 1977 through 1982, 135 patients with ovarian cancer, having a mean age of 53.7 years and no clinical evidence of disease after approximately 1 year of treatment, underwent a "second-look" laparotomy. Of the 135 patients, 58 (43%) had histologic confirmation of disease at the second-look procedure. Persistent disease was positively correlated with the original stage and negatively correlated with the extent of the original reductive surgery. The original histologic grade or cellular subtype did not significantly influence the findings at reexploration. Patient survival, as judged by percentage of patients alive 3 years after the second-look laparotomy, was dependent on the following surgical/pathologic parameters: tumor size at reexploration, peritoneal cytologic features, residual tumor after reexploration, and histologic grade.     

Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings

Objective: To determine long-term survival and predictors of recurrence in patients with platinum-treated ovarian cancer who were followed for 10 years after second-look laparotomy with negative findings.Methods: Records were reviewed of 91 consecutive patients with negative findings on second-look laparotomy after platinum-based chemotherapy between January 1978 and January 1987. Statistical analysis used Kaplan-Meier survival curves, Cox proportional hazards, and multiple logistic regression.Results: Mean age of patients was 57 (range 30–79) years. Distribution by stage and grade was as follows: stage I, ten; II, 18; III, 57; IV, six; grade 1, 18; 2, 28; 3, 45. Forty-seven of 91 women had optimal initial cytoreduction. Recurrence-free survival rates for all subjects were 75% at 2 years, 55% at 5 years, and 52% at 10 years. For women with stage I disease, the recurrence-free survival rate was 90% at 2, 5, and 10 years. For women with stage II disease, recurrence-free survival rates were 78, 72, and 66% at 2, 5, and 10 years, respectively. Patients with stage III or IV disease had recurrence-free survival rates of 72, 44, and 40% at 2, 5, and 10 years, respectively. Risk of recurrent disease was related to tumor stage (relative risk [RR] 2.02; 95% confidence interval [CI] 1.2, 3.3; P = .005), grade (RR 2.00; 95% CI 1.3, 3.2; P = .004), and presence of a residual tumor of more than 2 cm at the end of initial surgery (RR 3.19; 95% CI 1.2, 8.5; P = .02).Conclusion: Ovarian cancer patients face an appreciable risk of recurrence in the first 5 years after second-look laparotomy with negative findings after platinum-based chemotherapy, but those who remain disease free at 5 years have excellent long-term survival rates. Tumor stage, grade, and presence of a residual tumor of more than 2 cm after initial surgery are significant predictors of recurrence.     

Serum CA-125 as a guideline for the timing of a second-look operation and second-line treatment in ovarian cancer

Summary In the assessment of response to treatment of ovarian cancer patients, clinical examination is unreliable in detecting small tumor masses. The second-look laparotomy is therefore an accepted procedure. The optimal timing of second-look laparotomy, however, is uncertain. We therefore examined the usefulness of serial serum CA-125 estimations in the timing of second-look laparotomies in 33 patients suffering from ovarian cancer. Increasing CA-125 concentrations were always followed by relapses or progressive disease, whereas decreasing serum concentrations indicated response to treatment. In future we propose to perform second-look laparotomies when CA-125 levels have declined to a steady plateau and to star a secondary treatment when CA-125 levels start to rise again.     

卵巢恶性肿瘤二次剖腹探查术中行腹膜后淋巴结清除术的研究

目的　探讨卵巢恶性肿瘤腹膜后淋巴结清除术的最佳时机和临床价值。方法　回顾性分析了 5 0例二次剖腹探查术 (SLL)中行腹膜后淋巴结清除术的卵巢恶性肿瘤患者的临床资料。结果　患者中位数年龄 49岁 ,其 3年和 5年生存率分别为 72 %和 62 %。SLL阳性率为 40 % ( 2 0 / 5 0 ) ,其中临床分期 [国际妇产科联盟 (FIGO)标准 ]Ⅰ期SLL阳性率为 0 % ( 0 / 15 ) ,Ⅱ期和Ⅲ期分别为 40 %( 4/ 10 )、62 % ( 15 / 2 4) ,Ⅳ期为 1例中 1例。SLL阳性率与临床分期的期别呈正相关 ,其中Ⅰ～Ⅱ期( 16% ,4/ 2 5 )和Ⅲ～Ⅳ期 ( 64 % ,16/ 2 5 )患者SLL阳性率比较 ,差异有极显著性 (P <0 0 1)。腹膜后淋巴结转移率为 3 2 % ( 16/ 5 0 ) ,其中Ⅰ、Ⅱ、Ⅲ期分别为 0 % ( 0 / 15 )、2 0 % ( 2 / 10 )、5 4% ( 13 / 2 4) ,Ⅳ期为 1例中1例。SLL阳性患者中 ,4例 ( 8% )仅盆腹腔内有转移灶 ,淋巴结无转移 ;6例 ( 12 % )仅显微镜下淋巴结转移 ,而无盆腹腔转移灶。SLL中 ,行二次肿瘤细胞减灭术共 2 0例 ,其中术后 13例残留灶直径≤ 0 5cm ,7例残留灶直径 >0 5cm。中位数随访时间 44个月 ( 2 4～ 10 4个月 ) ,至随访截止日SLL阴性者 ( 3 0例 )均无肿瘤复发。结论　腹膜后淋巴结清除术在SLL术中进行比较合理 ,而且对降低SLL阴性患     

Brain metastasis of ovarian cancer after negative second-look laparotomy

We present a case of ovarian carcinoma that had brain metastasis seven months after having a negative second-look laparotomy and 13 months after the onset of diagnosis. Despite intense multidisciplinary treatment with surgery, chemotherapy and radiotherapy, the patient died seven months after second-look laparotomy.     

A review of second-look laparotomy for ovarian cancer

One hundred twenty-seven patients underwent second-look laparotomies from July 1969 to June 1982. To be included in this report they must have met the following criteria: a documented ovarian neoplasm; previous surgery; adequate chemotherapy for cessation if no disease was found; and no X-ray, chemical, or clinical evidence of disease including an exam under anesthesia. Forty-one percent had residual disease at second-look laparotomy. The original stage and the percentage of tumor debulked at initial surgery were inversely related to the likelihood of finding residual disease. Age, histologic type and grade, and type of chemotherapy did not show a significant relationship with the likelihood of disease persisting. Recurrent tumor was subsequently detected in 16% of patients who had been found to be free of disease at second-look laparotomy. Of thirty stage III and IV patients treated with combinations containing cis-platinum, 10 (33%) had recurrences. This rate of recurrence was significantly greater than the 17.6% recurrence rate in 17 patients with Stage III and IV disease whose chemotherapy consisted of single alkylating agents or with combinations without cis-platinum. Twenty patients underwent a third-look laparotomy after completion of additional chemotherapy. Nine were found to have no residual disease. Two of the nine (22%) subsequently had recurrence of disease. Three of the eleven patients with persistent disease at the time of a third-look laparotomy underwent a fourth-look laparotomy. All were found free of disease and none have recurred. Six (55%) of those with persistent disease at the third-look laparotomy have died despite continued therapy. The ability to successfully treat some patients with persistent disease continues to be a justification for the use of a second-look laparotomy. However, the high rate of recurrence after cessation of treatment following the finding of no residual disease raises the question of whether it is appropriate to discontinue all therapy at this time.     

Survival of patients with ovarian epithelial carcinomas after second-look laparotomy

Survival of ovarian carcinoma patients undergoing second-look laparotomy after primary surgery and adjunctive chemotherapy was evaluated by retrospective chart review. From August 1976 to August 1987, 102 patients with stage I-IV disease underwent second-look laparotomy. Optimal tumor debulking and early (stage I or II) disease were positively correlated with a negative second-look laparotomy. Of the 49 patients with a "negative" second look, 15 demonstrated recurrent tumor from 12.5 to 52.5 months after laparotomy. Of the 15 recurrences, 6 were documented more than 3 years following second look. Half of the 28 patients with stage III disease and a "negative" second look have demonstrated recurrent tumor. Fifty-three patients (52%) were found to have residual disease at second-look laparotomy. Initial chemotherapy (melphalan or multiple agent) and the adequacy of primary debulking surgery (optimal vs suboptimal) were not significant factors contributing to patient survival after a positive second look. However, the size of residual disease at second-look laparotomy was a significant factor in subsequent patient survival (P less than or equal to 0.01). Fifteen patients were free of gross disease at laparotomy, but had residual tumor on microscopic examination of the specimens submitted. These patients had a 2-year actuarial survival of 78%. Forty-seven percent have survived 5 or more years after second look. Nineteen patients with tumor implants 2 cm or smaller had 2- and 5-year actuarial survivals of 61 and 31%, respectively. Nineteen patients with tumor nodules larger than 2 cm in diameter had a 2-year actuarial survival of 6%. Only 1 of 19 patients with nodules greater than 2 cm could be effectively redebulked.     

Long-term survival of 106 stage III ovarian cancer patients with minimal residual disease after second-look laparotomy and consolidation radiotherapy

OBJECTIVE: Attempts to increase survival in stage III ovarian cancer patients with minimal residual disease at second-look laparotomy have included consolidation radiotherapy. We present long-term survival of 106 consecutive patients treated between 1983 and 1993 in 4 French institutions for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease <1 cm and consolidation radiotherapy. METHODS: Median age was 52 years. Residual disease after first look surgery was <1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4-12). Residual disease <1 cm at second-look laparotomy was observed in 79% of the patients, with 33% of patients in complete histologic remission. Residual disease <1 cm was obtained in all patients after tumor excision during second-look surgery. Radiation was performed using a linear accelerator with a whole abdomen dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an additional 12 Gy lombo-aortic boost for 33 patients. RESULTS: Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term toxicities included radiation enteritis in 21 patients with 9 patients requiring surgery for bowel obstruction. Four deaths were related to enteritis complications. Overall survival at 5 and 10 years was respectively 53% and 36%. CONCLUSION: This sequential treatment with final consolidation abdominopelvic radiotherapy is an effective treatment for a selected group of stage III ovarian cancer patients with a high intestinal toxicity incidence.     

Evaluation of treatment and survival after positive second-look laparotomy

During the 9-year interval 1977 through 1985, of 250 patients undergoing second-look laparotomy, 116 (46%) were found to have clinically occult ovarian carcinoma. Salvage therapy consisted of external irradiation in 37, intraperitoneal 32P in 12, chemotherapy in 63, and no therapy in 3 or other therapy in 1. Eligible follow-up time ranged from 1 to 9 years. The Kaplan-Meier projected median time-to-progression and survival were 15 and 22.5 months, respectively, with 4-year progression-free and overall survival rates being 21 and 27%, respectively. Survival was independent of the original stage of disease but was significantly influenced by histologic grade and microscopic (55%) versus macroscopic (19%) residual tumor after the laparotomy. Projected 4-year salvage rates in patients with microscopic or residual disease less than or equal to 5 mm was 72, 39, and 19% for intraperitoneal 32P, external irradiation (33/37, whole abdominopelvic), and chemotherapy, respectively. However, multivariable analysis demonstrated that histologic grade and isotope therapy retained independent influence on survival, but no therapeutic advantage for external irradiation over chemotherapy was demonstrable. Furthermore, use of regimens that were identical to, partially altered from, or different from the first-trial agents did not affect chemotherapy salvage rates.     

What should be the cut-off level of serum CA125 to evaluate the disease status before second-look laparotomy in epithelial ovarian carcinoma?

To assess the predictive value of serum CA125 level prior to second-look laparotomy in epithelial ovarian carcinoma, 45 patients who were clinically or radiologically tumor-free prior to a second-look laparotomy were studied. Serum CA125 levels were measured 10 days prior to the operation, and were compared with the surgico-pathological results. Twenty-eight (62%) patients were found to have tumor at surgery. The serum CA125 levels were  35 U ml⁻¹ (42%) patients. Tumors were found in 14 (74%) of these 19 patients. Although a serum CA125 level  35 U ml⁻¹ was a strong predictor of the presence of an intraperitoneal tumor, a level <35 U ml⁻¹ was not predictive of a tumor-free state. When the cut-off level was accepted as 20 U ml⁻¹, 28 patients (62%) were found to have elevated CA125 level. The sensitivity, the specificity, the positive and negative predictive value and the false negative ratio were calculated as 79%, 65%, 79%, 65% and 21% respectively. The threshold value for a raised CA125 level was considered and a lower level of 20 U ml⁻¹ was suggested as a cut-off level prior to second-look laparotomy in evaluating patients with known epithelial ovarian cancer.     

Role of an early second-look laparotomy in ovarian cancer

Of a group of 68 patients treated with standard polychemotherapy (CAP-5), 52 were evaluated by an early second-look laparotomy, preferably after three cycles of treatment. Of 21 patients with initial tumor residuals smaller than 2 cm, only 5 had residual tumor, and of 31 patients with tumor larger than 2 cm, 27 had residuals, which could be surgically debulked in 9 patients. Surgical evaluation led to termination of treatment in 6 patients with stable disease and to intensification of treatment in 5 younger patients with microscopic or bulky residuals. Thus, the second-look influenced therapeutic decisions and treatment policy in a total of 20 patients. The procedure went without severe complications for the duration of anesthesia; there was no difference between biopsy and debulking, but a larger amount of blood was lost during debulking surgery. Second-look laparotomy is well tolerated but should be performed only in selected cases, depending on the therapeutic options available.     

The impact of diabetes on survival in women with ovarian cancer

Objective

Diabetes is increasingly common among cancer patients and plausible biologic mechanisms exist by which diabetes may influence cancer prognosis. We aimed to investigate the impact of diabetes on ovarian cancer outcomes.

Methods

We assessed the outcomes of 570 non-diabetic and 72 diabetic patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer over a ten-year period. All inpatient and outpatient records were reviewed. The primary end points were overall and disease-free survival.

Results

Of the 642 cases, 11.2% had type II diabetes. Diabetics were more likely to be older, had a higher BMI (33.4 vs. 27.8), and had more comorbid conditions. Diabetics were less likely to have been surgically staged as compared to non-diabetics (p = 0.04) although stage, grade, and likelihood of optimal cytoreduction were similar between groups. Over a period of 10 years, with an average of 44 months of follow-up, the median overall survival for diabetics was 1503 days. The median overall survival for non-diabetics was 2464 days (log rank test, p = 0.02). In a Cox proportional hazards multivariable model, diabetes remained a significant predictor of overall survival (HR = 2.04, p < 0.01).

Conclusions

Diabetics with ovarian cancer demonstrate strikingly poorer survival. The underlying reason for this is yet unknown and deserves further attention. Differences in care, competing risks of death, and changes within the tumor biology are plausible mechanisms for the observed difference in survival.     

Recurrence after negative second-look laparotomy for ovarian cancer: analysis of risk factors

To determine the long-term rate of recurrence and define risk factors for recurrence, we have analyzed clinical information on 83 patients followed up for a minimum of 4 years (median, 69 months) after negative second-look laparotomy. Overall, 21 of 83 patients (25.3%) had a recurrence. Median interval to recurrence was 14 months. Stage, grade, and type of chemotherapy were significantly related to risk of recurrence. In patients with stage I disease only one of 27 (3.7%) had a recurrence. Patients with stage I disease were not included in further analysis of risk factors. In stages II, III, and IV, 20 of 56 patients (35.7%) had a recurrence. Recurrence rates by grade (excluding stage I) are as follows: grade 1, three of 21 (14.3%); grade 2, six of 17 (35.5%), and grade 3, 11 of 17 (64.7%). Platinum-treated patients in stages II, III, and IV had a 50% (12/24) recurrence rate compared with 25% in nonplatinum-treated patients (8/32) (p = 0.05). Differences in disease-free survival between platinum- and nonplatinum-treated patients were significant at the p = 0.02 level. When treated with platinum-based regimens, more patients will achieve complete clinical remission and subsequently negative second-look laparotomy. However, the recurrence rate in these patients is considerably higher than that in patients treated for longer durations with nonplatinum regimens.     

Synchronous ovarian metastases at the time of laparotomy for colon cancer

OBJECTIVE: The aim of the study was to identify clinical features, define prognostic factors and optimize treatment in patients with colorectal cancer with synchronous ovarian metastases at the time of initial diagnosis. METHODS: A retrospective analysis of patients treated by the gynecologic oncology service at Barnes Jewish Hospital between 1990 and 2001 was performed. Twenty-eight patients with colorectal carcinomas with synchronous ovarian metastases at the time of diagnosis were identified. Clinical and pathological characteristics were evaluated, and survival was analyzed by the method of Kaplan and Meier. RESULTS: Abdominal pain was the most common symptom at presentation. Only 14% of the patients presented with gastrointestinal bleeding. Fifty-four percent of patients who underwent barium enema had intrinsic colonic lesions, while 40% of patients who had endoscopies performed had their colonic tumors identified. Preoperatively colon cancer was considered in the differential diagnosis of 71% of the patients. At exploration, the ovarian metastases were significantly larger than the primary colon tumors. Overall, 68% of patients had intraperitoneal nodal metastasis and 86% had transmural extension of their tumors. The only pathological variable associated with survival was tumor grade. The median disease-free survival was 10.3 months while the median overall survival was 18.4 months. CONCLUSION: Most patients with colon cancer with synchronous ovarian metastases present with vague symptoms. At exploration, locally advanced tumors and other distant metastases such as in the liver are common. Surgical management should include extirpation of the primary tumor and any bulky ovarian metastases. Cytoreduction may be considered in highly selected patients.     

Second-look laparotomy after modified posterior exenteration: patterns of persistence and recurrence in patients with stage III and stage IV ovarian cancer

OBJECTIVE: The purpose of this study was to determine patterns of persistence and recurrence in patients with advanced ovarian cancer (stage IIIC and stage IV) after modified posterior exenteration. STUDY DESIGN: Retrospective chart review was used to determine patterns of persistence and recurrence of disease in patients undergoing modified posterior exenteration. From January 1, 1987, to September 15, 1998, 151 of 212 (71.2%) patients undergoing modified posterior exenteration in addition to other cytoreductive surgical procedures for stage IIIC and stage IV ovarian cancer underwent second-look laparotomy. The average age of the patients was 60.3 years (range, 20.3-86.3). A total of 207 of the 212 (97.6%) had grade 2 or 3 disease. Papillary serous carcinoma (113/212; 53.3%) and adenocarcinoma (75/212; 35.4%) were the most frequent cell types encountered. After initial cytoreductive surgery, minimal disease (<5 mm) was present in 206 of the 212 (96.2%) patients with 153 of 212 (72.2%) having no visible residual disease. There were 4 (1.9%) postoperative deaths. In 13 patients (6.1%) progressive disease was noted. Second-look laparotomy was not undertaken in 61 of the 212 (28%) patients. Fluid for cytologic testing was obtained from all four intra-abdominal quadrants, and biopsies of previously noted sites of disease were performed, in addition to random biopsies of diaphragmatic peritoneum, colonic gutters, and pelvic peritoneum. If present, the retroperitoneal lymph nodes were resected; biopsy specimens of these sites were obtained if there was no evidence of intraperitoneal disease. RESULTS: Findings at second-look laparotomy were negative for cancer in 85 of 151 (56.3%) and positive for cancer in 66 of 151 (43.7%). Only 8 of 151 (5.3%) patients had persistent disease in the pelvis. In the remainder (58/151; 38.4%) disease was found either in the upper abdomen or in the bowel mesentery. Recurrence was documented in the upper abdomen only (71/212; 33.5%), upper abdomen and pelvis (18/212; 8.5%), multiple sites excluding the pelvis (22/212; 10.4%), pelvis only (2/212; 0. 9%), chest alone (5/212; 2.4%), head alone (4/212; 1.9%), or groin alone (2/212; 0.9%). Median survival in the overall group was 51.1 months, with estimated 5- and 10-year survival rates of 44.2% and 32. 9%, respectively. CONCLUSIONS: Modified posterior exenteration is an effective surgical means of eliminating pelvic disease in patients with advanced ovarian cancer. Results of second-look laparotomy confirmed that only 8 of 151 (5.3%) had persistent disease in the pelvis.     

宫颈癌根治术中行卵巢移位的临床效果分析

目的探讨宫颈癌根治术中行卵巢移位术术后卵巢的功能状况。方法1999年1月至2003年12月江门市新会区人民医院等2家医院收治43例年龄26~40岁宫颈癌ⅠB~ⅡA期患者,其中22例在宫颈癌根治术中行卵巢移位术为观察组,21例行传统的宫颈癌根治术为对照组。术后应用血FSH、LH、E2及Kuppermann评分进行卵巢功能测定,随访1~4年。结果观察组术后4年内卵巢功能基本正常,对照组术后1个月卵巢功能丧失。两组记录生存质量的改良Kuppermann评分比较差异有非常显著性意义(P<0·01),而复发率和存活率比较差异无显著性意义(P>0·05)。结论宫颈癌患者在宫颈癌根治术时行卵巢移位术,可保留卵巢功能。