IB IIB Research Articles

Human papillomavirus type and tobacco use as predictors of survival in early stage cervical carcinoma

Objective. Molecular and environmental co-factors are known risk factors for cervical cancer. The aim of this study was to define the prognostic significance of HPV 18 and its phylogenetically related viruses and smoking on survival in patients with early stage cervical cancer. Methods. HPV typing was performed on stage IB–IIB cervical tumors. Subjects positive for HPV 18 or 45 were compared to the remainder of the cohort and to women with tumors containing HPV 16, 31, or 52. Tobacco use was ascertained by patient questionnaire. Results. Tumors of 255 women were evaluated. The presence of HPV 18 or 45 was associated with decreased survival. In a multivariable Cox proportional hazards analysis comparing patients with HPV 18 or 45 containing tumors to the rest of the cohort, the hazard ratio for death from cervical cancer was 2.08 (95% CI, 1.07–4.04). The hazard ratio for death from cervical cancer was 2.41 (95% CI, 1.17–4.96) when the HPV 18 and 45 group was compared to women with HPV 16 or its related viruses, 31 and 52. Smoking was associated with a decreased survival for women with HPV 18 or 45, even after adjusting for other known prognostic factors ( P = 0.031). Conclusions. In addition to pathologic indicators, molecular and environmental co-factors are important determinates of outcome in early stage cervical cancer. The presence of HPV 18 or 45 is associated with a decreased survival. The adverse effect of HPV 18 and 45 on survival is compounded by tobacco use.

Nonsurgical Treatment of Closed Mallet Finger Fractures

Surgical repair of closed mallet finger fractures has been favored for displaced injuries involving more than one third of the articular surface and for injuries with palmar subluxation of the distal phalanx. This study analyzed the results of nonsurgical treatment for closed and displaced mallet finger fractures with greater than one-third articular surface damage, comparing cases with and without concomitant terminal joint subluxation. Twenty-two closed mallet finger fractures in 21 patients who were treated nonsurgically and involving more than one third of the articular surface were reviewed retrospectively. The patients were treated by continuous extension splinting of the distal interphalangeal joint for a mean of 5.5 weeks. The average patient age at the time of injury was 35.2 years, with a mean delay to treatment of 21 days. Nine cases showed a reduced distal interphalangeal joint at presentation (type IB) and 13 cases showed palmar subluxation of the distal phalanx (type IIB). Complications from splinting were limited to 2 cases of transient skin irritation. All patients returned for new finger radiographs and completed a survey to assess pain, function, and satisfaction at an average of 24.5 months after injury. Patients expressed negligible pain, minimal difficulties with activities of daily living and work, relatively high satisfaction with finger function and treatment outcome, but only marginal satisfaction with finger appearance. The differences between type IB and type IIB cases were not significant. The resultant terminal joint extensor lag improved in both groups. Moderate and large joint prominences, swan-neck deformities, and moderate arthritis were seen more commonly in type IIB cases but the differences between groups were not significant. This study supports the rationale for nonsurgical treatment of closed and displaced mallet finger fractures with greater than one-third articular surface involvement. Pain likely will be negligible and patient satisfaction with finger function and treatment outcome is projected to be relatively high at 2-year follow-up evaluation. A dorsal joint prominence, terminal joint extensor lag, swan-neck deformity, and degenerative joint changes, however, may develop, particularly in cases with palmar subluxation of the distal phalanx.

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: A pilot clinical study

Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.

Comparative study of chemoradiation and neoadjuvant chemotherapy effects before radical hysterectomy in stage IB–IIB bulky cervical cancer and with tumor diameter greater than 4 cm

Tumor size seems to be a determinant in the prognosis of early cervical cancer. Patients with tumor greater than 4 cm (bulky) in diameter have worse outcome. The purpose of this study was to compare the efficacy of preoperative combined chemoradiation and neoadjuvant chemotherapy (NAIC) programs followed by radical hysterectomy in stage IB–IIB bulky cervical cancer. From September 1999 to April 2002, 60 patients with stage IB–IIB bulky cervical cancer were treated with preoperative external-beam radiotherapy to 45 Gy plus weekly cisplatin 50 mg/m2or preoperative NAIC by cisplatin 50 mg/m2and vincristin 1 mg/m2every 7–10 days, for three courses. Surgery was performed 4–6 weeks after the completion of the preoperative treatment. There were no significant difference between age, stage, tumor size, and histopathologic type in two groups (P> 0.05). Toxicity associated with two treatment methods was usually mild. In chemoradiation group, two patients developed vesicovaginal fistula, and four patients developed long-term hydronephrosis that needed urethral stenting. Before surgery, complete and partial clinical response had no significant difference between two groups (P> 0.05). After surgery, lymph node and parametrial involvement had no significant difference between two groups (P> 0.05). In NAIC group, more patients had significantly residual tumor (P= 0.012), but residual tumor size had no significant difference between two groups (P> 0.05). Pathologic complete response was significantly higher in chemoradiation group (P= 0.004). According to the result of this study, it seems that NAIC and chemoradiation had similar effects in survival prognostic factors.

Acute inflammatory response after inguinal and incisional hernia repair with implantation of polypropylene mesh of different size

The purpose of this study was to assess the modifications of interleukin (IL)-6, C-reactive protein (CRP), leukocytes and fibrinogen after implantation of polypropylene mesh. Thirty-six patients were included in this study and divided into two groups. To the first group were allocated patients affected by inguinal hernia and undergoing conventional repair (subgroup Ia) or hernioplasty with 40-cm(2) polypropylene mesh (subgroup Ib). To the second group were allocated patients affected by incisional hernia and undergoing conventional repair (subgroup IIa) or incisional hernia repair with 400-cm(2) polypropylene mesh (subgroup IIb). Peripheral venous blood samples were collected 24 h before surgery and then 6, 24, 48 and 168 h postoperatively. We present evidence that serum levels of IL-6, CRP, leukocytes and fibrinogen were significantly increased postoperatively in all subgroups compared with their baseline values. In particular, the production of inflammatory mediators was higher in subgroups Ib vs Ia and IIb vs IIa. Comparing the entities of the inflammatory responses among various groups we found that it was clear that they were similar in subgroups Ib and IIa, and that the highest were in subgroup IIb and the lowest in subgroup Ia. The data show that conventional inguinal and incisional hernia repair induces an inflammatory response, which is smaller than that observed if both operations are carried out with polypropylene meshes. Furthermore, the results suggest that a larger mesh is associated with a higher production of inflammation mediators.

New approaches to pathogenic gene function discovery with human squamous cell cervical carcinoma by gene ontology

Purpose. This study utilized mRNA differential display and the Gene Ontology (GO) analysis to characterize the multiple interactions of a number of genes with gene expression profile involved in squamous cell cervical carcinoma. Methods. mRNA differential displays were used to identify potential transcripts that were differentially expressed between cervix cancers of 13 patients (invasive cancer stages Ib–IIb) and universal reference RNAs comprised of 17 different normal cervixes. Aberrant bands were excised and used to make cDNA, which was sequenced. DNA sequences were compared to other nucleic acids in the NCBR database for homology. Transcript expression was verified in select samples using RT-PCR and North blotting. The specific functions were correlated with gene expression patterns via gene ontology. Results. Fifty-eight genes were up- or down-regulated above 2-fold and organized into reciprocally dependent sub-function sets depending on the cervical cancer pathway. The GO analysis showed that squamous cell cervical carcinogenesis underwent complete up-regulation of cell cycle, transport, epidermal differentiation, protein biosynthesis, and RNA metabolism. Also, genes belonging to protein metabolism and catabolism activity were significantly up-regulated. In contrast, significant down-regulation was shown in muscle development, cell adhesion, and damaged DNA binding activity. Conclusion. The GO analysis can overcome the complexity of the gene expression profile of the squamous cell cervical carcinoma-associated pathway and identify several cancer-specific cellular processes as well as genes of unknown function. Also, GO analysis can serve as a powerful basis for a molecular classification of carcinogenesis.

Post-hysterectomy radiotherapy in FIGO stage IB–IIB uterine cervical carcinoma

Objective This study is a retrospective analysis of stage IB–IIB cervical carcinoma patients who had received postoperative radiotherapy (PORT). Methods Eight hundred patients with stage IB–IIB cervical carcinomas who received PORT after radical hysterectomy and bilateral pelvic lymph node dissection (PLND) between February 1979 and March 2000 were analyzed. Results The median follow-up duration was 100 months. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 88% and 81%, respectively. One hundred forty-six patients (18%) failed, and 103 of these had distant metastases. Multivariate analysis revealed that pelvic lymph node (LN) metastasis significantly compromised OS, DFS, pelvic failure-free survival (PFFS), and distant failure-free survival (DFFS) ( P < 0.05). Patients with age <50 years, deep stromal invasion (DSI), and lymphovascular space invasion (LVSI) were significantly associated with a higher risk of distant metastasis after PORT. The incidences of late rectal, urinary, and small bowel complications of grade 3 or higher were 1.6%, 1.4%, and 1.0%, respectively. Conclusions PORT achieved good OS and DFS in the patients with risk factors after radical hysterectomy for stage IB–IIB cervical carcinomas. Distant metastasis was the major pattern of treatment failure after PORT. Effective systemic chemotherapy might be a breakthrough in improving the outcome of PORT in patients with cervical carcinomas.

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion

Objective. To evaluate patterns of failure in cervical cancer patients with histopathologic parametrial invasion treated with postoperative pelvic radiation therapy. Methods. Records of 117 stages IB–IIB cervical cancer patients with parametrial invasion treated with postoperative radiation therapy from 1985 to 2002 were retrospectively reviewed. Patients were divided into two groups based on status of pelvic lymph nodes. Patterns of recurrence and prognosis by status of pelvic lymph nods were statistically analyzed. Results. Status of pelvic lymph nodes had significant impact on both recurrence and survival. Extrapelvic recurrence was observed in 23 of 66 node-positive patients compared with 6 of 51 node-negative patients ( P = 0.005). Of 66 patients with a positive pelvic lymph node, 18 developed visceral metastases, whereas only three visceral metastases were noted in the 51 node-negative patients ( P = 0.003). Five-year overall survival in node-positive and -negative patients was 52% and 89%, respectively ( P = 0.0005). Corresponding rates for recurrence-free survival were 44% and 83%, respectively ( P = 0.0002). The correlation between nodal metastasis and prognosis was enhanced when node-positive patients were stratified into two groups based on number of positive nodes ( n = 1 and n ≥ 2). Five-year recurrence-free survival rates for patients with negative, one positive, and two or more positive nodes were 83%, 61%, and 31%, respectively ( P = 0.0001). Conclusions. Extrapelvic recurrence was uncommon in node-negative patients with parametrial invasion. These findings do not support use of systemic therapy for cervical cancer patients with parametrial invasion if pelvic lymph node metastasis is negative.

Laterally extended parametrectomy (LEP), the technique for radical pelvic side wall dissection: Feasibility, technique and results

A new surgical method was introduced for the treatment of Ib lymph node positive and IIb cervical cancer patients. The lateral resection plane corresponds to the true pelvic side wall, the plane represented by the internal obturator muscle, the linea arcuata, and the piriformis muscle with the convergent branches of the sacral plexus. The LEP procedure overcomes the limitations of the standard class III-IV radical hysterectomy, which leaves in situ the gluteal superior, inferior and pudendal nodes, thus improving local control and survival.

Prognostic Factors in Surgically Treated Stage Ib–IIb Cervical Carcinomas with Special Emphasis on the Importance of Tumor Volume

Objective. The aim of the study was to analyze the importance of tumor volume as a prognostic factor for overall survival (OS) in surgically treated stage Ib–IIb cervical carcinoma.Methods. One hundred thirteen of one hundred sixty-five patients with histopathological stage Ib–IIb cervical carcinoma (44 Ib1, 24 Ib2, 10 IIa, 35 IIb) treated by radical abdominal hysterectomy between 1989 and 1999, for whom tumor volume could be assessed, were included in this study. Of the 113 patients, 90 (79.6%) received postoperative radiotherapy. Measurement of tumor volume was performed on giant histological sections using a semiautomatic image analyzer. The prognostic significance of tumor volume was analyzed and compared with that of various clinicopathological parameters using uni- and multivariate statistics.Results. The 5-year disease-free survival was 71.4%. Increasing tumor volume was associated with more frequent lymph node metastases and a significant decrease in OS (P = 0.0112). The Median tumor volume was smaller in stage IIa tumors than in stage Ib2 tumors, and histopathological stage did not correlate linearly with lymph node metastases as well as OS. Stage Ib2 tumors were associated with worse overall survival than stage IIa tumors. In univariate analysis, lymph node metastases, histopathological stage, lymph vascular space involvement, tumor volume, parametrial spread, and tumor involvement of resection margins were significant parameters for OS. In multivariate statistical analysis, only lymph node metastases and histopathological staging remained independent prognostic factors for OS.Conclusions. Tumor volume does not seem to confer additional prognostic information if histopathological stage and lymph node status are known. However, it may provide important prognostic information if lymph node status is not known or histopathological stage cannot be assessed.

Ten-Year Survival of Patients with Locally Advanced, Stage IB–IIB Cervical Cancer after Neoadjuvant Chemotherapy and Radical Hysterectomy

Objective(s). The aim of this study was to evaluate the effects of neoadjuvant chemotherapy and radical hysterectomy on long-term survival in stage IB–IIB locally advanced cervical cancer by conducting a 10-year follow-up.Methods. Between August 1983 and May 1990, 80 locally advanced, stage IB–IIB cervical cancer patients with tumor diameter greater than or equal to 4 cm were treated with neoadjuvant VBP chemotherapy (cisplatin, vinblastine, and bleomycin) followed by radical hysterectomy with pelvic lymphadenectomy. After this therapeutic modality, patients were followed for more than 10 years. Ten-year survival rates and factors affecting recurrence after this therapy were evaluated.Results. Of 80 patients, 75 (93.7%) showed a reduction in tumor size after neoadjuvant chemotherapy. At pathologic examination, stage reduction was noted in 53 (66.2%) patients and 20 patients (25%) showed no residual or microinvasive cervical tumor. Pelvic lymph node metastases were found in 17 patients (21.3%). During the 10-year follow up, 2 patients were lost and 16 patients recurred. Overall 5-year and 10-year disease-free actual survival rates were 82.0 (64/78) and 79.4% (62/78), respectively. Clinical stage, initial tumor size, clinical response, and residual tumor size were not risk factors for recurrence after this therapy. However, pelvic lymph node metastasis was a significant risk factor for recurrence.Conclusion(s). Neoadjuvant VBP chemotherapy followed by radical hysterectomy in locally advanced, stage IB–IIB cervical cancer patients seemed to improve the long-term survival rate for these patients compared to that of conventional therapy. However, randomized controlled trials are needed to confirm this result.

Glutamate 83 is important for stabilization of domain-domain conformation of Thermus aquaticus glycerol kinase.

The gene glpK, encoding glycerol kinase (GlpK) of Thermus aquaticus, has recently been identified. The protein encoded by glpK was found to have an unusually high identity of 81% with the sequence of GlpK from Bacillus subtilis. Three residues (Arg-82, Glu-83, and Asp-244) of T. aquaticus GlpK are conserved in all the known GlpK sequences, including those from various bacteria, yeast and human. The roles that these three residues play in the catalytic mechanism were investigated by using site-directed mutagenesis to produce three mutants: Arg-82-Ala, Glu-83-Ala, and Asp-244-Ala. Replacement of Asp-244 by Ala resulted in a complete loss of activity, thus suggesting that Asp-244 is important for catalysis. Taking k(cat)/K(m) as a simple measure of catalytic efficiency, the mutants Arg-82-Ala and Glu-83-Ala were judged to cause 190- and 37,000-fold decrease, respectively, when compared to the wild-type GlpK. Thus, these three residues play a critical role in the catalytic mechanism. However, only mutant Glu-83-Ala was cleaved by alpha-chymotrypsin, and proteolysis studies showed that the mutant Glu-83-Ala involves a change in the exposure of Tyr-331 at the alpha-chymotrypsin site. This indicates a large domain conformational change, since the residues corresponding to Glu-83 and Tyr-331 in the Escherichia coli GlpK sequence are located in domain IB and domain IIB, respectively. The apparent conformational change caused by replacement of Glu-83 leads us to propose that Glu-83 is an important residue for stabilization of domain conformation.

Fast growing cervical carcinomas: A retrospective analysis of 20 IB–IIB FIGO

Introduction: Fast growing cervix carcinomas have a pejorative outcome: they may occur quickly after cervical smears qualified as normal – within an interval from 12 to 18 months in women less than 50 years old, and involveing the endocervix. This retrospective analysis is aimed at assessing 5-year outcomes. Materials and methods: Twenty cases of fast-growing cancer of the uterine cervix classified according to the FIGO clinical staging system as IB ( n=14), IIA (3), and IIB (3), have been reviewed and compared to a cohort of 160 cases not having this feature. As regard to fast-growing carcinoma, the median age was 41 years (range 25–50), and the median follow-up 22 months (8–213) as compared to 54 years (27–79) and 80 months (5–199) for the reference cohort. The comparison of the two cohorts shows only a difference of breakdown which concerns the histological pelvic lymph nodes status ( P<0.05), more often positive in fast-growing forms. The treatment policy was equally distributed between a radio-surgical approach, cesium 137 intracavitary irradiation followed by radical hysterectomy and lymphadenectomy, or a definitive irradiation with pelvic external irradiation followed by cesium 137 intracavitary irradiation. Results: Thirteen deaths are reported in the fast-growing series instead of 54 in the other series. The 5-year overall survival is, respectively, 34 (13–55) vs. 74% (68–82) ( P<0.001), the loco-regional-free survival 58 (33–84) vs. 85% (79–81) ( P<0.001), the 5-year metastasis-free survival 61 (38–84) vs. 84% (78–90) ( P=0.004). Conclusion: These poor results emphasize the need to intensify loco-regional therapy with a concurrent cisplatin-based chemotherapy within the framework of a multidisciplinary approach.

Type of Human Papillomavirus and Expression of p53 in Elderly Women with Cervical Cancer

To clarify the age-related genetic events in cervical cancer in elderly (≧65 years) women, 66 tissue specimens obtained from patients with stage Ib–IIb cervical carcinoma among two groups of women, 64 years of age or younger and 65 years of age and older, were analyzed for human papillomavirus (HPV) typing via polymerase chain reaction, the expression of p53 via immunohistochemical study, and clinical behavior. The prevalence of HPV DNA was higher in the younger group than in the older group (84.0 vs. 50.0%) as was the detection rate of HPV 16 (44.0 vs. 6.3%). In contrast, HPV 18, 33, 52, 58, and X were frequently detected in older patients. The positive rate of p53 overexpression in the older group was similar to that in the younger group (46.7 vs. 48.8%). There was no significant difference in the incidence of lymph node metastasis, histology, and the distribution of clinical stage between the two groups. Thus, in elderly Japanese women with stage Ib–IIb, the association of HPV of types other than HPV 16 is suggested to influence the progression of cervical cancer.

Clear Cell Carcinoma of the Uterine Cervix: Pathology and Prognosis in Surgically Treated Stage IB–IIB Disease in Women Not Exposed in Utero to Diethylstilbestrol

Objective. The purpose of this research was to compare the clinical behavior, pathology findings, and prognosis of surgically treated FIGO stage IB–IIB clear cell carcinomas of the cervix with those of squamous cell carcinomas and non-clear cell adenocarcinomas.Methods. Fifteen patients with clear cell adenocarcinomas of the cervix (8 FIGO stage IB, 7 FIGO stage IIB) were reviewed. The control group consisted of 444 squamous cell carcinomas and 59 non-clear cell adenocarcinomas. None of the patients had a history of in utero exposure to diethylstilbestrol. All patients underwent radical abdominal hysterectomy with systematic pelvic lymphadenectomy. All specimens were processed as serial giant frontal sections. The mean follow-up in the clear cell group was 83 (13–182) months. Statistical analysis was done with contingency tables, χ2 tests, and Fisher's exact test.Results. Twelve of the fifteen clear cell carcinomas (80%) were endophytic and tended toward deep cervical infiltration. Clear cell carcinomas extended to the uterine corpus significantly more often than squamous cell and non-clear cell adenocarcarcinomas (P < 0.001). The rates of parametrial involvement and pelvic lymph node involvement were 40 and 47%, respectively. Four patients (27%), all with positive pelvic nodes, developed recurrences an average of 14 (4–48) months after initial therapy. The extrapelvic sites of relapse were the lung, liver, and bone. Clear cell carcinomas had a worse 5-year survival rate (67%) than squamous cell carcinomas (80%) and non-clear cell adenocarcinomas (77%) but this was not statistically significant (P = 0.6). No significant differences were seen for age, growth pattern, parametrial and vaginal involvement, parametrial and pelvic lymph node metastases, frequency of recurrent disease, and time to first recurrence.Conclusion. The clinicopathologic findings and prognosis of surgically treated patients with stage IB–IIB clear cell carcinomas without exposure to diethylstilbestrol in utero are similar to those of patients with squamous cell carcinomas and non-clear cell adenocarcinomas.

Quantum Chemical Analysis and Experimental Study of the Cycloaddition Reaction between Aminoacetylenes and 6-Nitroindolizines. NMR and ab Initio Evidence for the [4+2] Adduct Formation

7-Methyl-6-nitro-2-phenylindolizine (Ia) reacts with 1-(diethylamino)-2-methylacetylene (IIa) giving 1:1 cycloadduct IIIa and not the expected product of dipolar [8+2] cycloaddition cyclazine IVa. According to NMR data the structure of IIIa consists of 1,2-oxazine fragment corresponding to the [4+2] cycloaddition of the acetylene to the sequence C(5)−C(6)−N−O of nitroindolizine. The mechanism of model reactions between nitroindolizine Ib and aminoacetylenes IIb,c is studied by an ab initio and AM1 method. Results of calculations indicate that the initially formed zwitterionic intermediates may undergo further ring closure either to cycl[3.2.2]azines IVb,c or 1,2-oxazine cycloadducts IIIb,c. Although the structures IV are lower in energy than III, the activation barrier for the formation of III is smaller than the barrier leading to IV.

Chemotherapy versus Radiotherapy versus Observation for High-Risk Cervical Carcinoma after Radical Hysterectomy: A Randomized, Prospective, Multicenter Trial

Background.Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence. However, it has not been clearly demonstrated that adjuvant radiation, adjuvant chemotherapy, or both improve the outcome. To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy, the Austrian Gynecologic Oncology Group conducted a prospective, randomized, multicenter clinical trial between 1989 and 1995.Material and Methods.Seventy-six patients with stage IB–IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and/or vascular invasion randomly received adjuvant chemotherapy (400 mg/m2carboplatin, and 30 mg bleomycin), standardized external pelvic radiation therapy, or no further treatment.Results.After a median follow-up of 4.1 years (range, 2–7) there were no statistically significant differences (P= 0.9530) in disease-free survival among the three treatment arms.Conclusion.The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy. The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy.

Vascular endothelial growth factor is implicated in early invasion in cervical cancer

The association between the expression of vascular endothelial growth factor (VEGF) and clinicopathological factors has scarcely been examined in cervical cancer. This study examines the level of VEGF messenger RNA (mRNA) expression in invasive cervical cancer and its association with clinicopathological features including microvessel density. The level of VEGF mRNA was assessed by semiquantitative reverse transcription–polymerase chain reaction (RT-PCR) using β-actin as an internal control in 66 patients with stages Ia–IVb invasive cervical cancer. In 42 patients who underwent surgery, the microvessel count was also assessed by immunostaining for factor VIII-related antigen in the most neovascularised area of the specimen. The highest level of VEGF mRNA expression was observed in early invasive cervical cancers. Except for stage IVb, the stage of the disease inversely correlated with the level of VEGF mRNA ( P<0.05). There was no significant difference in the level of VEGF mRNA with respect to histological cell types. 38 patients with stages Ib–IIb cervical cancer underwent radical hysterectomy and pelvic lymphadenectomy. There was no significant difference in the level of VEGF mRNA with respect to lymph node metastasis, depth of stromal invasion, tumour size, parametrial involvement or vaginal involvement among these patients. A significant relationship was found between the microvessel density and the level of VEGF mRNA ( P<0.01). These findings provide evidence that the expression of VEGF is involved in the promotion of angiogenesis in cervical cancer and plays an important role in early invasion.

Medium-dose-rate brachytherapy of cancer of the cervix: preliminary results of a prospectively designed schedule based on the linear-quadratic model

Purpose: To compare results and complications of our previous low-dose-rate (LDR) brachytherapy schedule for early-stage cancer of the cervix, with a prospectively designed medium-dose-rate (MDR) schedule, based on the linear-quadratic model (LQ).Methods and Materials: A combination of brachytherapy, external beam pelvic and parametrial irradiation was used in 102 consecutive Stage Ib–IIb LDR treated patients (1986–1990) and 42 equally staged MDR treated patients (1994–1996). The planned MDR schedule consisted of three insertions on three treatment days with six 8-Gy brachytherapy fractions to Point A, two on each treatment day with an interfraction interval of 6 hours, plus 18 Gy external whole pelvic dose, and followed by additional parametrial irradiation. The calculated biologically effective dose (BED) for tumor was 90 Gy10and for rectum below 125 Gy3.Results: In practice the MDR brachytherapy schedule achieved a tumor BED of 86 Gy10 and a rectal BED of 101 Gy3. The latter was better than originally planned due to a reduction from 85% to 77% in the percentage of the mean dose to the rectum in relation to Point A. The mean overall treatment time was 10 days shorter for MDR in comparison with LDR. The 3-year actuarial central control for LDR and MDR was 97% and 98% (p = NS), respectively. The Grades 2 and 3 late complications (scale 0 to 3) were 1% and 2.4%, respectively for LDR (3-year) and MDR (2-year).Conclusions: LQ is a reliable tool for designing new schedules with altered fractionation and dose rates. The MDR schedule has proven to be an equivalent treatment schedule compared with LDR, with an additional advantage of having a shorter overall treatment time. The mean rectal BED Gy3 was lower than expected.

CD44 exon v6 correlates with cellular differentiation but not with progression and metastasis of cervical cancer

The purpose of this study was to investigate whether CD44v6 expression correlates with progression or metastasis of cervical cancer. The presence of mRNA for CD44v6 was examined, the association with clinicopathological features was assessed in 80 patients with cervical cancer by reverse transcriptase–polymerase chain reaction (RT–PCR) and subsequent Southern blot hybridisation with an oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 53 of 80 cervical cancers expressed an isoform containing exon v6 in combination with other variant exons. In addition, longer size transcripts of more than 1350 bp (long form) were identified in 22 of the 53 CD44v6 positive patients. The expression of CD44v6 and CD44v6 long form in squamous cell carcinomas was significantly higher than that in non-squamous cell carcinomas ( P<0.001). The expression of CD44v6 long form in histological grade 1 and 2 was significantly higher than that in grade 3 ( P<0.05). 47 patients in stage Ib–IIb cervical cancers were treated by radical hysterectomy and pelvic lymphadenectomy. We did not find any association between the expression of the long form or the short form of CD44v6 and any pathological features, except for histological cell type. These findings suggest that the regulation of CD44v6 seems to be different between different histological cell types and different tumour grades, and the expression of CD44v6 might not be implicated in the progression and metastasis of cervical cancer.