Microinvasive carcinoma of the uterine cervix: A long-term followup study of eighty cases

One hundred and eleven patients with microinvasive carcinoma of the uterine cervix were studied over a 21-year period. Thirty-five cases of carcinoma in situ with questionable stromal invasion were excluded. Cases with pathologic examination of less than a cervical cone or the entire cervix were not accepted. The sole pathologic criterion for inclusion was unequivocal invasion to a depth of no more than 5.0 mm. Ninety-one patients were followed for 5 years or until death, and 80 patients for 10 years or until death. One patient was lost to follow-up at 5.5 years. The two deaths officially attributed to cervix cancer prior to 10 years were signed out by nonphysician assistant coroners. Available clinical evidence indicates that at least one of these patients, and probably both, did not die of cervix cancer. From these data, simple hysterectomy would seem to be the maximal treatment indicated. Since the prognosis of microinvasive carcinoma is similar to that of carcinoma in situ, it is suggested that such cases not be included when considering the end results of Stage I cervix cancer.     

Experience and results of application of remote afterloading system (RALS) optimization program for intracavitary treatment of squamous cell carcinoma of the uterine cervix

An optimization program for a remote after-loading system (RALS) for intracavitary treatment of cancer of the uterine cervix was established in 1982 by Tabushi and his co-workers. This system has been used in our hospital since 1986, using MODULEX. Seventy-three cases of untreated squamous cell carcinoma of the uterine cervix have been treated under RALS, 29 under conventional RALS and 44 under the RALS optimization program. The cumulative 5-year survival rates were obtained for the groups treated under each system by the Kaplan-Meier method. The 5-year survival rate of stage II cases treated under the RALS optimization program was 68.2%, and that of stage III cases 58.5%. On the other hand, that of stage II cases treated under conventional RALS was 56.3%, and that of stage III cases 44.9%. There was no significant difference between these two groups. Local control rates for stage II and III cases were higher than 5 year-survival rates. Among complications, the frequency of grade 2 radiation colitis was 15.9% with the RALS optimization program cases, and that of grade 2 radiation cystitis was 4.5%. We consider the RALS optimization program to be a clinically useful method for the intracavitary treatment of squamous cell carcinoma of the uterine cervix.     

Stage IA1 cervical adenocarcinoma: definition and treatment

OBJECTIVE: To propose a definition for stage IA1 cervical adenocarcinoma, based on the International Federation of Gynecology and Obstetrics (FIGO) staging system, and to determine if patients meeting criteria might be candidates for conservative surgery. METHODS: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed. RESULTS: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up was 76 (30-172) months and median (range) patient age was 38 (24-75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences. CONCLUSION: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA1 cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment.     

Angiogenesis in squamous cell carcinoma in situ and microinvasive carcinoma of the uterine cervix

OBJECTIVE: To evaluate angiogenesis in squamous cell carcinoma in situ (CIS) and microinvasive squamous cell carcinoma of the uterine cervix and to investigate the relations among angiogenesis, stromal inflammation, and depth of invasion. METHODS: Three groups of women were studied: 22 controls who had undergone hysterectomy for benign conditions; 18 with squamous cell CIS of the cervix who underwent cone biopsy, hysterectomy, or both; and 14 with microinvasive squamous cell carcinoma who underwent conization of the cervix and subsequent surgical management according to depth of invasion. All specimens were stained immunohistochemically for factor VIII-related antigen. Areas below the basement membrane with the highest angiogenic density were selected. The degree of stromal inflammatory reaction was assessed. Statistical analyses included Kruskal-Wallis, analyses of variance and covariance, Scheffe and Bonferroni-Dunn post hoc procedures, and Pearson correlation analysis. P < .05 was considered statistically significant. RESULTS: Microvessel counts per high-power field (x 400) of microinvasive squamous cell carcinoma of the cervix differed significantly from those of controls and squamous cell CIS (median 34.5 per high-power field, range 9-76 versus median 17, range 7-47, and median 19, range 8-39, respectively; P < .005). Microvessel counts per high-power field in squamous cell CIS did not differ significantly from those of controls (P = .91). Among patients with microinvasive squamous cell carcinoma of the cervix, no significant correlation was found between microvessel counts per high-power field and the depth of invasion (r = 0.19, P = .51). Stromal inflammatory reaction (graded 0-3) differed significantly among controls, squamous cell CIS, and microinvasive carcinoma (mean 0.40, 0.83, and 1.64, respectively; P < .005). CONCLUSIONS: Microinvasive squamous cell carcinoma of the uterine cervix is angiogenic, but depth of invasion is not associated with increased angiogenicity. Squamous cell CIS is not angiogenic.     

The importance of the results of pretreatment pelvic lymphographies in the prognosis of carcinomas of the uterine cervix. A critical evaluation of the proposal to classify these tumors according to the TNM system (author's transl)

Between 1966 and 1969, 494 patients with carcinoma of the uterine cervix stages I a to IV were admitted in our hospital for primary treatment. In 420 of these patients with carcinoma of the cervix stage I b to IV, complete results of bilateral pretreatment pelvic lymphography are available. The correlation between the results of the lymphographies, the choice of the operative treatment and the cure rates in these 420 cases are reported. All the correlations between the results of the pretreatment lymphography and the prognosis are described. A positive lymphography was in our series of high prognostic value. A plea is therefore made to include the results of the pretreatment lymphography into the classification of carcinoma of the cervix. Classification of the carcinoma of the cervix into the TNM categories is desirable. Our series is reported in these TNM categories. The advantages of such classification are described. The morbid entity of carcinoma of the cervix becomes more transparent to the observer and the choice of operative therapy becomes easier. The prognosis is more clearly established. The proposals of the TNM committee of the UICC for the classification of carcinoma of the cervix according to the TNM categories and the staging according to these categories are discussed critically.     

The long-term course of carcinoma in situ of the uterine cervix

The malignant potential of carcinoma in situ (CIS) of the uterine cervix has been the subject of great controversy. Despite refinements and additions to knowledge in this area, few reports on the long-term course of the disease have appeared in the past decade. Recent developments in diagnostic and therapeutic techniques coupled with changes in the patient population with this disease have prompted renewed interest in conservative management. Results of long-term observation of a group of patients followed initially without ablative therapy are reported. The data indicate that CIS of the uterine cervix is not the inevitably progressive disease that it has been considered to be. Unequivocal invasive cancer develops in only a small percentage of cases and can be controlled, if not cured, by current therapeutic modalities. The intraepithelial lesion, however, tends to persist despite conization, and eventually requires ablative therapy in most cases. Conservative procedures should be regarded as temporizing, at least until their long-term benefits can be recorded.     

Efficacy of radical hysterectomy as treatment for patients with small cell carcinoma of the cervix

BACKGROUND: This study was performed to identify pathologic and clinical features that best predict disease free survival of patients with early stage small cell carcinoma of the cervix treated by radical hysterectomy. METHODS: Three hundreds and seventy patients with cervical carcinoma were analyzed retrospectively to define those variable that best predict disease free survival (DFS). Variables included age, weight, race, marital status, economic status, tumor size, depth of invasion (DI), lymph-vascular space involvement (LVSI), cell type, tumor grade, lymph node metastasis (LNM), and total number of lymph nodes removed. Patients with lymph node metastasis, parametrial involvement, and positive or close surgical margins were offered postoperative radiation. RESULTS: Twelve patients were found to have small cell carcinoma (3.2%). One patient had microinvasive carcinoma of the cervix (MIC) as defined by the Society of Gynecologic Oncologists with a depth of invasion of 3 mm or less and no lymph-vascular space invasion, and has been reported previously. A detailed analysis of the other patients with nonsmall cell carcinoma is presented separately. Five patients achieved a DFS of at least 5 years, whereas 7 patients died with disease. Excluding the patient with MIC, the 5-year DFS rate was 36.4%. CONCLUSIONS: Relative to other cell types, small cell carcinomas of the cervix is an aggressive neoplasm with a higher rate of LVSI and LNM despite smaller DI and tumor size. These data suggest that multimodality therapy, combining radical surgery and radiation with cytotoxic chemotherapy, may provide these patients with the best chance for cure.     

Stage I carcinoma of the uterine cervix in patients under 40 years of age

A retrospective analysis was made 94 patients, 39 years of age or younger, who were treated for Stage I carcinoma of the uterine cervix from 1942 through 1972 at the Los Angeles Tumor Institute and the Southern California Cancer Center. Comparisons were made between the frequency of Stage I and other stages of carcinoma of the uterine cervix, as well as the frequency of Stage I carcinoma in young and older individuals. Survival rates for the younger group were compared to those for the same stage of disease for all ages of patients. There is discussion of the treatment modalities used in light of recommendations for future plans of therapy for these young patients. Tumor recurrences are discussed, with special reference to 43 patients who survived over 10 years. Eight of these patients were found to show new or recurrent tumors after this period of time. The importance of careful, long-term follow-up and early secondary treatment for recurrent lesions is emphasized, since subsequent radical surgery may salvage a number of these individuals.     

Unindicated preoperative testing: ASA physical status and financial implications

Adenoid basal carcinoma of the uterine cervix is rare and its cell origin is still obscure. We report a case of adenoid basal carcinoma of the uterine cervix discovered incidentally in a 69-year-old woman who had been hysterectomized due to endometrial adenocarcinoma of the uterine corpus. Histologically, small round-to-oval cancer cell nests with peripheral cell palisading were seen budding from the basal cell layer of the uterine cervix showing carcinoma in situ. Immunohistochemically, the basaloid cells of the adenoid basal carcinoma were positive for keratins 14, 17 and 19 and resembled reserve cells of the cervical epithelium. The results of this study clearly demonstrated that adenoid basal carcinoma shows a phenotype similar to reserve cells of the uterine cervix. A review of the literature indicated that this tumor has a favorable prognosis and should be clearly separated from adenoid cystic carcinoma, which has a much poorer outcome.     

An evaluation of procedures used in staging carcinoma of the cervix

A review of 227 cases of invasive carcinoma of the cervix was undertaken to determine the efficacy of procedures using in the staging of this disease. All patients had a pretreatment chest radiography and intravenous pyelogram. 96.5% had pretreatment cystoscopy, 98.6% had pretreatment proctoscopy, and 92% had a pretreatment barium enema. These patients were retrospectively staged on the findings of physical examination only. Each additional procedure was then evaluated by comparison with the initial staging. Cystoscopy and chest film findings each would have changed the clinical stage in fewer than 1% of cases, barium enema in 1.4%, and proctoscopy in 2.2%. No patient had a positive barium enema without a positive proctoscopy, while two patients had positive proctoscopies with negative barium enemas. The overall yield of positive findings by pretreatment intravenous pyelography was 7.3%. Lymphangiography, although inconsistently done, yielded positive findings in all stages. Chest radiographs, intravenous pyelography, proctoscopy, and lymphangiography are recommended as part of the pretreatment workup of patients with carcinoma of the cervix. Routine barium enema is no longer recommended, and cystoscopy is only recommended in patients with clinical stage IIB disease or greater.     

Radiation therapy results for patients undergoing inappropriate surgery in the presence of invasive cervical carcinoma

Total vaginal or abdominal hysterectomy was considered an inadequate treatment method for invasive uterine cervix cancer. Usually the procedure was inadvertently performed on patients who were thought preoperatively to have benign or premalignant conditions. Between 1985 and 1993, 64 patients undergoing hysterectomy in the presence of invasive cervical cancer were treated with external radiation therapy and/or intracavitary radiotherapy. Preoperative diagnoses were carcinoma in situ (36), severe dysplasia (2), and early invasive cancer (14), and others were benign disease. Overall 5-year survival and relapse-free survival rates were 75.8 and 77.5%, respectively. For patients in retrospective stage IA, IB, and IIB (gross residual after surgery), overall 5-year survival rates were 90.9, 88.8, and 27.9%, respectively. Thirteen patients developed treatment failure; most of them (10/13) were patients with gross residual disease. Patients with early invasive cervical cancer (stage IA) had no treatment-related failure. Prognostic factors affecting survival by univariate analysis were retrospective stage (P = 0.0000) and preoperative diagnosis (P = 0.0021). Tumor histology was marginally significant factor (P = 0.0938). By multivariate analysis, only retrospective stage was significant prognostic factor (P = 0.0001). Adjuvant radiotherapy appears to be an effective treatment method for patients with presumed stage IA and IB after inadvertent hysterectomy. Survival for patients with gross disease remaining after inappropriate hysterectomy is poor. So, early cancer detection and proper management with precise pretreatment staging is necessary to avoid inadherent hysterectomy, especially in cases of gross residual disease.     

Epidermo?d carcinoma of uterine cervix with bone metastases in lower limbs (author's transl)

Bone lesions are infrequent in the evolution of epidermo?d carcinoma of the uterine cervix. Direct bone invasion from the primary tumor, extension from lymph node metastases and distant metastases can be seen. The frequency of these lesions is about 3 to 4%. Hematogen bone metastases are very uncommon. They are often located in the lower limb. We report a case of a patient with a cervical carcinoma who developed isolated bone metastases in all the bones of a lower limb.     

How to manage locally advanced primary and recurrent cancer of the uterine cervix: The surgeon's view

Locally advanced cancer of the uterine cervix covers a broad disease spectrum comprising primary tumours of >4 cm in size or FIGO stage >IIA and all local tumour relapses except the rare cases of small recurrences in a retained cervix. Treatment designs have to consider the probability of pelvic and periaortic lymph node metastases and – albeit less frequent in primary disease – distant metastases.Established treatment standards aiming to achieve pelvic and eventually periaortic tumour control are chemoradiation for locally advanced primary disease as well as post-surgical pelvic recurrences, and pelvic exenteration for post-radiation central relapses. A subset of patients with pelvic side wall relapses can now be successfully treated by laterally extended endopelvic resection as well. Based on the current results it is not evident whether neoadjuvant chemotherapy, radical hysterectomy and eventually adjuvant radiation are comparable or superior treatment alternatives for locally advanced intermediate stage cases. Likewise, the benefit of (laparoscopic) surgical staging including the exstirpation of bulky pelvic and periaortic lymph nodes has not been convincingly demonstrated to date. Both surgical treatment concepts need further well-designed prospective randomized trials for their evaluation. From the surgeon's perspective total mesometrial resection, therapeutic lymph node dissection, laterally extended endopelvic resection and new developments in restoration/substitution of pelvic functions have the potential to improve the therapeutic index for defined cohorts of patients suffering from locally advanced cancer of the uterine cervix.     

Familial Wilms'' tumor associated with a WT1 zinc finger mutation

Cardiac metastasis from gynecological malignancies is rare. Only six cases of carcinoma of the uterine cervix have been reported where the diagnosis of malignant pericardial effusion was made antemortem. The treatment of neoplastic pericardial effusion is controversial; both surgical and nonsurgical treatments are advocated. We present a patient with pericardial effusion secondary to carcinoma of the cervix and recommend subxiphoid pericardial fenestration for reliable long-term control of malignant effusion.     

Primary surgery for stage IB-IIA cervical cancer, including short-term and long-term morbidity and treatment in pregnancy

Radical hysterectomy and pelvic lymphadenectomy are indicated for the treatment of cervical carcinoma that is localized clinically to the cervix and upper vagina. Intraoperative complications have been reported in 1.1%-7.4% of patients. Long-term complications include bladder dysfunction (2% at 3 years), urinary fistula (vesical, 0.8%; ureteral, 1.2%), stress urinary incontinence (29%), ureteral stricture (1%), rectal dysfunction (80%), severe constipation (5.3%), lymphocysts (20% by ultrasonography; 2% clinically), and lymphedema (10%). The operative mortality is 0.7%. The 5-year survival rate for patients with stage IB disease is 85.7% and for stage IIA is 69.6%. The recurrence rate is 27.2%. Recurrences are distributed equally between the pelvis and extrapelvic sites. Radical hysterectomy is the treatment of choice for pregnant patients with early cervical cancer. It affords termination or delivery of the pregnancy at the same time that the treatment is provided. For patients with stage I disease treated with radical hysterectomy, the survival rate is 92.1%.     

Abdominal radical trachelectomy: a new surgical technique for the conservative management of cervical carcinoma

Traditionally radical hysterectomy has formed the mainstay of treatment for early stage cervical carcinoma. More recently radical trachelectomy and laparoscopic lymphadenectomy have been introduced to allow preservation of fertility. We present a new approach to fertility-sparing surgery, namely abdominal radical trachelectomy. The technique is similar to a standard radical hysterectomy and lymphadenectomy. In our technique the ovarian vessels are not ligated and, following lymphadenectomy and skeletonisation of the uterine arteries, the cervix, parametrium and vaginal cuff are excised. The residuum of the cervix is then sutured to the vagina and the uterine ateries re-anastomosed.     

Method for determining optimal intracavitary radiotherapy conditions for carcinoma of the uterine cervix with tumor infiltration of the vaginal wall

Stage III carcinoma of the uterine cervix is occasionally accompanied by tumor infiltration of the vaginal wall. Currently, the vaginal wall has to be irradiated in the same manner as the uterine cervix. The authors have developed a system for determining the optimal irradiation conditions for treating the two regions, uterine cervix and vaginal wall, at the same time. A comparison of two methods is shown in simulation, and then a clinical case is reported. The first method consists of two treatment plans, one for the uterine cervix without tumor infiltration of the vaginal wall, and the other for the vaginal wall without carcinoma of the uterine cervix. The second, newly developed method considers the two regions together. Irradiation times of ovoid sources obtained with the second method are 15-25% less than those of the first method. Isodose curves obtained with the two methods are very different, and thus the uterine cervix and vaginal wall must be considered together in order to determine irradiation conditions.     

Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases

Electrosurgical loop conization of the cervix is a new procedure that is being rapidly accepted for treatment of cervical intraepithelial neoplasia (CIN). Concerns include fragmentation of the specimen that is frequently mandated by the size of the transformation zone and difficulty in using the largest electrosurgical loops. Two cases are presented that demonstrate the inability to accurately assign depth of invasion in cervical cancer when the focus of invasion is transfected. As a result, the patient and physician were forced to decide on whether a radical hysterectomy and pelvic lymphadenectomy were needed based on incomplete information. It is recommended that electrosurgical loop conization be confined to patients where invasive carcinoma is not expected. The use of this new technique for patients with suspected invasive carcinoma needs further evaluation.     

Stromal invasion by carcinoma of the cervix: assessment with dynamic MR imaging

OBJECTIVE: The purpose of this study was to evaluate dynamic MR imaging in assessing the depth of stromal invasion by carcinoma of the cervix and to compare dynamic MR imaging with T2-weighted and contrast-enhanced T1-weighted MR imaging. SUBJECTS AND METHODS: Forty-one patients with carcinoma that was clinically considered to be confined to the cervix were examined with T2-weighted, dynamic, and contrast-enhanced T1-weighted MR imaging before surgery. We evaluated enhancement patterns of the cervix and tumor and assessed the degree of stromal invasion with MR imaging. The degree of stromal invasion was divided into two groups: superficial disease (no stromal invasion or invasion of < or = 3 mm) and deep invasion (> 3 mm of stromal invasion). Then we compared these MR findings with histologic results for the depth of stromal invasion. RESULTS: With dynamic MR imaging, cervical carcinoma with deep invasion was seen as a focal enhanced area in the early dynamic phase. The cervical epithelium and stroma enhanced less vividly. In distinguishing deep invasion from superficial disease, we found the accuracy of T2-weighted MR images, dynamic MR images, and contrast-enhanced T1-weighted MR images to be 76%, 98%, and 63%, respectively. In particular, the detectability of 3.1-5.0 mm of stromal invasion with dynamic MR images was significantly higher than that with the other techniques: with T2-weighted MR images, we saw 3.1-5.0 mm of stromal invasion in 23% of patients; with dynamic MR images, in 92%; and with contrast-enhanced T1-weighted MR images, in none. Superficial disease was not revealed with any of the three MR techniques. CONCLUSION: We believe that dynamic MR imaging is superior to T2-weighted MR imaging and contrast-enhanced T1-weighted MR imaging when assessing the depth of invasion of cervical carcinoma.     

A seven year review of invasive carcinoma of the cervix treated at the Johns Hopkins Hospital

172 cases of invasive carcinoma of the cervix treated at the Johns Hopkins Hospital are reviewed. Failure rates are examined by stage, demonstrating a high percentage of local recurrences in patients with late stage disease treated by a traditional regime of radiotherapy. Reasons for these failures are explored and a proposal for a more individualized approach to therapy is made.