A survey of tumor markers in patients with squamous cell carcinoma of the uterine cervix

The circulating levels of carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and chorionic gonadotrophin (B-hCG) were correlated with the extent of disease in 47 patients with squamous cell carcinoma of the uterine cervix. Pretherapy serum CEA levels were elevated (> 10 ng/ml) in 12 of 47 (26%) of the patients. The greatest incidence and the highest CEA elevations were observed in the sera of patients with Stage III disease. No elevations of serum AFP were observed in any of the patients, and B-hCG was elevated in only 4 of the 47 cases. In 2 of the 4 cases, elevations of the serum B-hCG were associated with pregnancy and in the remaining 2 cases the serum CEA value was also elevated. Contrary to a study reported by other investigators, our data indicate the the tumor marker profile consisting of CEA, AFP, and B-hCG does not increase the incidence of abnormal findings when compared to the CEA test used alone. Also, our CEA data are consistent with other reports which demonstrate that CEA may be a useful tumor marker in 23% of the patients with Stage I and II disease, 57% of the patients with Stage III disease, and 33% of patients with Stage IV disease. The serum CEA test does not appear to be useful for the early detection of noninvasive (in situ) disease.     

Selective radiation therapy in stage IB uterine cervical carcinoma following radical pelvic surgery

Thirty-five patients with squamous cell cancer of the cervix, Stage IB, treated by radical hysterectomy and bilateral pelvic lymph node dissection are analyzed for histopathologic factors including (1) depth of cervical stromal invasion, (2) degree of differentiation of the tumor, (3) vascular tumor invasion, and (4) lymph node involvement. The influence of these factors on the outcome is studied. A correlation is found in that the advanced depth of cervical stromal invasion appears to increase the risk of nodal involvement and also the subsequent recurrence in patients with negative nodes. The Grade 2 and Grade 3 disease is more often present in patients with outer one-third cervical stromal invasion, while the vascular tumorous invasion was only found in patients with middle and mostly with outer one-third cervical stromal invasion. A subgroup of patients is described, who are at high risk for recurrent disease following surgery and who may benefit from adjuvant radiation therapy.     

Peritoneal cytology in patients with uterine cervical carcinoma.

We studied the relationship between cytological diagnosis of peritoneal washing and pathohistological findings in 97 cases of stage Ib and 103 cases of stage IIa or b cervical carcinoma. No positive cytology was found in 24 cases classified as pT1 by pTNM classification. Positive cytology was found in 8 out of 40 cases with retroperitoneal lymph node metastasis, 2 out of 5 cases with uterine corpus infiltration, and 3 out of 4 cases with ovarian metastasis. Negative cytology was often found even in cases with metastasis to several retroperitoneal lymph nodes, while positive cytology was also found in cases without metastasis. The mechanism of cervical carcinoma metastasizing to retroperitoneal lymph nodes may not be the same as that of spreading into the abdominal cavity. Many cases with positive peritoneal cytology tended to recur with peritoneal carcinoma as compared to those with negative cytology. The above findings indicate that chemotherapy, including intraperitoneal administration, is necessary in addition to radiation therapy for patients with cervical carcinoma with positive peritoneal washings.     

A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical carcinoma

CA125 (reference value [RV] = 35 U/mL), CA50 (RV = 20 U/mL), CA72.4 (RV = 3.8 U/mL) and SCC (RV = 3.6 ng/mL) levels were retrospectively assayed in blood samples collected at diagnosis from 42 patients with endometrial carcinoma, 45 patients with cervical carcinoma and 68 patients with benign uterine pathology as controls. Among the patients with endometrial carcinoma. CA50 was the antigen with the highest sensitivity (SE) (34.4%) followed by CA125 (26.2%), CA72.4 (21.9%) and SCC (16.7%). The incidence of elevated serum CA125 and CA72.4 levels was significantly greater in advanced stages than in early ones (66.7% vs 19.4%, p = 0.032 for CA125; 66.7% vs 11.5%, p = 0.012 for CA72.4), while CA50 positivity was not significantly correlated with the extent of disease (50% in advanced stages vs 30.8% in early ones, p = 0.38). Among the patients with cervical carcinoma, CA125 and CA50 respectively showed a SE of 33.3% and of 42.9% for adenocarcinoma, while SCC had a SE of 33.3% and of 42.9% for squamous cell adenocarcinoma; in particular among the patients with squamous cell carcinoma, the incidence of elevated SCC levels was correlated with the extent of tumor (57.1% in advanced stages vs 12.5% in early ones, p = 0.013). In conclusion, CA50 and CA125 were the most sensitive tumor markers in both endometrial carcinoma and cervical adenocarcinoma, while SCC was the most reliable antigen for squamous cell carcinoma of the cervix. Because of the affinity of SCC, CA50 and CA125 for different histological types of cervical carcinoma, the combined evaluation of SCC with CA50 or CA125 showed an increased SE with respect to each marker alone.     

A multiparametric approach to tumor markers detectable in serum in patients with carcinoma of the ovary or uterine cervix

A comparison of several serum tumor markers (lactate dehydrogenase (LDH), sialyltransferase (ST), carcinoembryonic antigen (CEA), β₂ microglobulin (β₂M), γ-chain fetal hemoglobulin (HbF), immune complexes (ImCp), and spermine (Spm)) was made in patients with carcinoma of the ovary or cervix uteri and healthy control subjects. The greatest positive results were obtained with the markers LDH (40%) and β₂M (46%) for patients with carcinoma of the cervix and ovary, respectively. However, based on false positive results, the most suitable single marker for patients with carcinoma of the cervix was Spm (30%). When a multiparametric approach was taken, a combination of four of the seven markers resulted in an increase in the positive results, that is, the cancer patients were positive for one of the four markers. This was 76% for patients with carcinoma of the cervix using the markers LDH, ST, Spm, and β₂M and 79% for patients with carcinoma of the ovary using the markers ST, CEA, HbF, and β₂M. All markers in both groups of cancer patients were elevated above control levels with the exception of ST which was decreased in patients with carcinoma of the ovary. ST, CEA, and HbF were found to be associated by multilinear regression analysis in the ovarian cancer group. As the ST approached normal levels CEA and HbF became elevated. Similarly there was a linear relationship between β₂M and ImCp demonstrating positively at similar times.     

Tumor cell kinetics in uterine cervical carcinoma following irradiation

15 cases of squamous cell carcinoma of uterine cervix which received radiotherapy were investigated in order to elucidate tumor cell kinetics following irradiation. The DNA content of Pararosanillin-Feulgen stained tumor cells were measured by fluorescence cytophotometry which provided great precision in the field of microspectrophotometry. Besides the cell preparation, tumor cells were precisely identified under blue light excitation (405nm). It is of great value to obtain a reliable DNA histogram of tumor cells with this method. In both groups of radioresistant cases (n = 3) and radiosensitive cases (n = 12), the same trend in cell kinetics was noted until 1400 rad, such as G2-block, endoreduplication, and a decrease in the 2c cell (G0 + G1) population. Most of the residual cells at 3000 rad of radioresistant cases showed little irradiation-induced morphological change. These cells were proved to be 2C cells in this study. This indicates that these radioresistant cells were non-cycling cells (G0). The mean value for the 2C cell population before irradiation was 65% in radioresistant cases and 46% in radiosensitive cases, respectively. The former contained a larger proportion of 2C cells than the latter. Clinically, the 2C cell population before irradiation may be used as a useful parameter to forecast radiosensitivity.     

Modification of radiation therapy following operative evaluation of patients with cervical carcinoma

Twelve of thirty-nine patients with cervical cancer who underwent bilateral pelvic and periaortic lymphadenectomy through an extraperitoneal approach had lymph node metastases. Four patients had metastases to pelvic lymph nodes only and eight had metastases to common iliac or periaortic lymph nodes in addition to other pelvic lymph nodes. The operative findings permitted the modification of radiation therapy on the basis of known extent of tumor. All patients with common iliac or periaortic lymph node metastases had ports of external therapy extended to the level of the diaphragm and had more emphasis placed on external radiation therapy and less on intracavitary therapy. The sequence of operation through an extraperitoneal approach followed by conventional or extended radiation therapy was tolerated with minimal morbidity and no mortality.     

Second lower genital tract squamous cell carcinoma following cervical cancer. A clinical study of 46 patients

BACKGROUND: Patients after treatment for cervical cancer have increased risk of developing second squamous cell malignancy of the lower genital tract. MATERIAL AND METHODS: A retrospective study of 46 patients with second lower genital tract epidermoid cancers following previous treatment for invasive cervical carcinoma. RESULTS: Patient age at diagnosis of cervical cancer was 27 to 68 years (median 44 years) and at diagnosis of the second malignancy - 43 to 72 years (median 63 years). There were four cases (9%) of synchronous cancers. Time span between metachronous malignancies ranged from 66 to 406 months (median 206 months). In 32 cases (70%) second lesion was located in the vagina and in 14 (30%) - in the vulva. Out of 35 previously irradiated patients, in 24 (69%) second tumor was located within the high dose volume and in 11 (31%) - outside it. Treatment of second cancer consisted of surgery in 12 patients (26%), radiotherapy in 23 (50%), combined surgery and radiotherapy--in five (11%), chemotherapy in four (9%) and surgery plus chemotherapy - in one case. Median survival was 52 months and five-year survival from the diagnosis of second malignancy - 47.5%. No prognostic factors for survival were identified. CONCLUSION: Treatment outcome in patients with second lower genital tract carcinoma is unsatisfactory due to poor feasibility of another definite treatment after previous radical surgery and/or radiotherapy.     

Clinicopathological study of recurrent uterine cervical squamous-cell carcinoma

OBJECTIVE: To improve prognoses of patients with recurrent uterine cervical squamous-cell carcinoma. PATIENTS AND METHODS: We clinicopathologically analyzed 464 patients with uterine cervical squamous-cell carcinoma (126 positive, 338 negative pelvic lymph-node metastasis) who were treated at the Saitama Cancer Center from January 1, 1976 to December 31, 1991. RESULTS: The recurrence rates of negative pelvic lymph-node metastasis patients were 14. 2% (39/274) in pT1b and 32.8% (21/64) in pT2b. But for positive lymph-node metastasis patients the rates were 39.0% (23/59) in pT1b and 58.2% (39/67) in pT2b. The interval to recurrence was shorter in positive pelvic lymph-node patients than in negative patients. The 5-year survival rates after relapse of negative lymph-node patients with intrapelvic, extrapelvic, and both-sites recurrence were 53, 12, and 40%, respectively. But among distant recurrent sites, lung metastasis in negative lymph-node patients and lymphatic tract metastasis brought relatively fair prognoses. CONCLUSIONS: Regular long-term checks are necessary and active retreatments are recommended for patients with local recurrences, lung metastasis, or lymphatic vessel metastatic lesions.     

卵巢上皮性癌血清肿瘤标志物谱变化的临床意义

目的 探讨卵巢上皮性癌(卵巢癌)患者化疗后肿瘤标志物谱的变化及其潜在的临床意义.方法 选择1999年1月至2007年7月期间经肿瘤细胞减灭术及规范化疗的卵巢癌患者102例,对其术前、术后、每次化疗前、随访期间和复发前后的血清肿瘤标志物CA125、CA19-9和CP2的水平进行检测、分析,其中48例患者的肿瘤标志物记录完整而纳入分析,复发患者为28例,初治化疗患者20例(均为耐药病例).根据肿瘤标志物谱变化与否,分别将复发和初治化疗患者分为肿瘤标志物谱变化组与未变化组.平均随访时间为25个月.结果 (1)肿瘤标志物谱的主要变化表现为标志物的数最变化和(或)标志物的种类改变.28例复发患者中肿瘤标志物谱发生变化者占46%(13/28),20例初治化疗患者中标志物谱发生变化者占45%(9/20).(2)肿瘤标志物谱变化的复发患者中,病理类型以浆液性癌所占比例最高,为77%(10/13),而初治化疗患者中,以黏液性癌所占比例最高,为4/9.(3)复发患者肿瘤标志物谱变化组的无疾病进展期和中位总生存时间分别为22.2、60.0个月,较未变化组(分别为17.4、46.0个月)明显延长(P均<0.05);初治化疗患者肿瘤标志物谱变化组的中位总生存时间较未变化组(分别为15.9、25.0个月)明显缩短(P<0.05).结论 卵巢癌化疗期间和复发后肿瘤标志物谱可发生变化,化疗及随访期间应对肿瘤标志物进行联合检测.     

A prospective study of nerve-sparing radical hysterectomy for uterine cervical carcinoma in Taiwan

ObjectiveSurgical therapy for cervical carcinoma carries a significant risk of functional impairment to the bladder. This study evaluates the feasibility and complications of nerve-sparing radical hysterectomy (NRH) in Taiwan.MethodsBetween March 2010 and March 2011, consecutive patients diagnosed with early stage cervical cancer (FIGO stage Ia2 to Ib1) and tumor size < 3 cm were recruited prospectively to undergo NRH or conventional radical hysterectomy (RH). Patients with histories of urinary stress incontinence or bladder dysfunction disease were excluded. A modified Tokyo nerve-sparing radical hysterectomy was performed.ResultsA total of 30 patients were enrolled. Among these, 18 patients underwent NRH with successful bilaterally nerve-sparing procedures in 15 cases (83%), unilaterally nerve-sparing procedures in 2 cases (11%), and a failure in 1 case (6%). The indwelling catheter was removed on postoperative day 6. The mean ± SD duration from operation to spontaneous voiding was 6.8 ± 1.5 days for women who underwent NRH; the corresponding duration for women who underwent RH or failed NRH was 20.6 ± 3 days. None of the patients who underwent NRH required intermittent catheterization. All 12 patients who underwent RH needed self-catheterization after discharge. There was a significant reduction in the incidence of postoperative self-catheterization (p < 0.01) and bladder dysfunction (p < 0.006). Average satisfaction score analyzed by the Likert-scale questionnaire was 4.5 for the NRH group and 1.9 for RH group (p < 0.0001).ConclusionsWe concluded that the new technique of NRH can reduce postoperative bladder dysfunctions.     

Sigmoid perforation following radiation therapy in patients with cervical cancer.

OBJECTIVE: We describe the clinical presentation, evaluation, management, and outcome of patients experiencing sigmoid perforation following radiation therapy for cervical cancer. METHODS: A database consisting of over 5000 patients with stage IB-IIIB cervix cancer treated between 1963 and 1992 revealed 35 patients with sigmoid perforation. Twenty-seven were diagnosed and managed at one institution, and they form the study group. RESULTS: The median age at the time of perforation was 50 years, and the median follow-up care was 78 months (range 6-396). The median time from completion of radiotherapy to perforation was 13 months (range 3-98). The mean interval from the first documented complaint to the index admission was 90 days. Nine (33%) of 27 patients were treated with high-dose radiation therapy. The most common complaint was abdominal pain in 25 (93%) patients, nausea occurred in 12 (44%) patients, weight loss in 12 (44%) patients, and vomiting in 10 (37%) patients. The pain was described as mild in 16 (73%) of 22 patients. Only 5 (18.5%) of 27 patients had physical signs of acute peritonitis, 8 (30%) of 27 patients had some form of tenderness, and 11 (41%) of 27 had a benign exam. A total of 20 (74%) patients had an abdominal radiograph, and 12 (44%) patients had a contrast enema for evaluation. Evidence of perforation was present in 5 (25%) of 20 plain abdominal radiographs and 1 (8%) of 12 contrast enemas. Following admission, 17 (63%) patients were observed initially with subsequent surgery after symptoms either failed to resolve or worsened. The median duration under observation was 4 days (range 1-23). Surgery was performed immediately in 8 patients (30%), and 2 (7%) were observed without operation. In these 2 patients, perforation was diagnosed postmortem. Seventeen (68%) of 25 patients had a localized abscess. Three of the patients who underwent immediate exploration and 7 who had surgery after a period of observation died postoperatively (10/25, 40%). Five (55%) of 9 patients in the group who received high-dose radiation therapy died because of sigmoid perforation. When the time frame of presentation was evaluated, we noted that 10 (50%) of 20 patients died between 1960 and 1979 and 1 (14%) of 7 died between 1980 and 1992. CONCLUSIONS: Sigmoid perforation following pelvic radiation for cervical cancer does not usually present with the typical signs of a ruptured viscus. A high degree of suspicion remains a priority in the care of radiated patients who present with abdominal pain given the atypical presentation of perforation in this group.     

The use of para-aortic radiation therapy based on lymphangiogram interpretation in uterine cervical carcinoma

From January, 1965, to June, 1979, 79 nonrandomized patients with carcinoma of the uterine cervix had a bipedal lymphangiogram (LAG) prior to radiotherapy at the Stanford University Medical Center. In 32 patients the LAGs were interpreted as normal. Of the remaining 47 patients, 28 had LAGs interpreted as positive for metastatic involvement of pelvic nodes alone, 11 as positive for pelvic and para-aortic (PA) metastasis, and 8 as positive in PA nodes alone. Five-year survival and freedom from relapse (FFR) were found to be similar for patients with LAGs interpreted as normal or positive in pelvic nodes only (all stages combined). The addition of elective PA irradiation in those patients with positive pelvic nodes alone (median 5000 rad/5 weeks) did not enhance either survival or FFR in this group. The 19 patients with positive PA nodes had significantly worse survival and FFR when compared with the other groups. Survival was not enhanced by the addition of therapeutic PA irradiation (median 5000 rad/5 weeks) and the 7 patients in this group so treated appeared to have a reduced FFR when compared to the 12 untreated patients. Irrespective of the location of nodal abnormality on LAG and regardless of stage, the majority of relapses ( ) occurred either centrally or at the pelvic sidewalls. It is concluded that the LAG is a good predictor of subsequent relapse and survival, but that the addition of either elective or therapeutic PA radiotherapy based on LAG interpretation does not affect survival of FFR and should, therefore, be considered for investigational or palliative use only.     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

宫颈癌术后复发60例临床分析

目的　通过对子宫颈癌术后复发原因的分析,旨在提高宫颈癌病人手术成功率。方法　对 1990年 1月至 2000年 12月四川省肿瘤医院术后复发的子宫颈癌 60例进行回顾性分析,了解子宫颈癌术后复发部位、复发时间及术后复发与肿瘤病理和临床治疗方法的关系。结果　60例术后复发患者中,盆腔复发和远处转移分别占 80.0%、8.3%,同时有盆腔复发和远处转移占 11.7%。最常见的复发部位是盆腔 (阴道及宫旁 ),淋巴结转移者与脉管瘤栓、切缘阳性、宫旁或盆腔脏器受侵者的盆腔复发率分别为 72.8%、100.0%,远处转移率分别为54.6%、7.1%。结论　子宫颈癌术后以盆腔复发最为常见,有盆腔淋巴结脉管内转移者易出现远处转移。要提高手术成功率必须做到术前诊断与分期准确、严格掌握手术适应证、进行规范的手术操作以及必要的术前综合治疗。     

Adjunctive hysterectomy following radiation therapy for bulky carcinoma of the uterine cervix: prognostic implications of tumor persistence

Twenty-five patients underwent adjunctive extrafascial hysterectomy 14-60 days following completion of external and intracavitary irradiation for bulky carcinoma of the uterine cervix. Review of the operative histopathology and correlation with subsequent patient outcomes suggests that morphologically persistent cancer is prognostically ominous and that cancer near the surgical margin is viable in the majority of instances.     

Correlation of tumor size with other prognostic factors in uterine serous carcinoma: A large multi-institutional study

ObjectiveUterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~ 40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor.MethodsClinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan–Meier method; multivariate analysis was performed via cox-regression.ResultsThe patients' mean age was 67.2 years (range 40–91). Survival ranged from 0 to 184 months (mean 42.8). We used a tumor size cut-off of 1 cm and noted significant associations with myometrial invasion (p < 0.0001), angiolymphatic invasion (p < 0.0001), peritoneal washings (p = 0.03), stage (p = 0.015) and positive lymph nodes (p = 0.05). Furthermore, recurrence was associated with larger tumors (p = 0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors < 1 cm in both univariate and multivariate analysis.ConclusionsTreatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1 cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.     

Development of endometrial cancer following radiation therapy for cervical carcinoma

The clinical and histologic findings in five cases of endometrial cancer, which developed following radiation therapy for squamous cell carcinoma of the cervix, are described. The mean age at endometrial cancer diagnosis was 69 years and average latency period from initial therapy to development of endometrial carcinoma was 13.4 years. For endometrial cancer, one patient had Stage Ib, one patient had Stage IIIa, two patients had Stage IIIc, and one patient did not undergo laparotomy. The histological types were carcinosarcoma in two patients, endometrioid adenocarcinoma, grade 3 in one patient, and clear cell carcinoma in one patient. All patients died of disease within 33 months of diagnosis. Endometrial cancers that develop after radiation treatment have a preponderance of high-risk histological subtypes, and consequently have a poor prognosis. Long-term follow-up should be mandatory for patients surviving radiation therapy for cervical cancer in order to detect and effectively treat second malignancies.