Penis conserving treatment for T1 and T2 penile carcinoma: clinical implications of a local recurrence.

PURPOSE: We evaluated our experience with primary tumor treatment for T1 and T2 penile squamous cell carcinoma and discussed the clinical implications of a local recurrence. MATERIALS AND METHODS: The primary tumor treatment and clinical course of 257 patients with T1 or T2 penile carcinoma were evaluated. Primary tumor treatment consisted of penis preservation in 157 and (partial) amputation in 100 patients. Median followup was 106 months (range 16 to 541). RESULTS: The 5-year local recurrence-free estimate after penis preservation was similar for T1 and T2 tumors (log rank test p = 0.1) and overall 63% (CI: 54%-72%) compared to 88% (CI: 81%-95%) for partial amputation (log rank test p = 0.0003). In case of a local recurrence after penis preserving treatment, local control could be achieved in 94% (51 of 54) of cases. Of patients with T1 tumors treated with penis preservation, regional recurrence developed in 33% (7 of 21) of patients with local recurrence compared to only 6% (3 of 47) of patients without local recurrences (Fisher's exact test p = 0.005). Of the patients with T2 tumors treated with penis preservation, regional recurrence developed in 27% (9 of 33) of patients with local recurrence compared to 27% (12 of 45) of patients without local recurrence (chi-square test p = 0.96). Of 10 patients with a local recurrence after partial amputation of the penis, 9 died of disease. CONCLUSIONS: The incidence of local recurrence increases with penis preservation but can be treated accurately in most cases. Local recurrences can signify lymphatic regional spread. A local recurrence after penile amputation carries a poor prognosis.

Patients with penile carcinoma benefit from immediate resection of clinically occult lymph node metastases.

PURPOSE: In this retrospective study we compared the clinical outcome of early vs delayed excision of lymph node metastases in patients with penile squamous cell carcinoma. MATERIALS AND METHODS: A total of 40 patients with a T2-3 penile carcinoma with lymph node metastases were included in this study. All patients initially presented with bilateral impalpable lymph nodes. In 20 patients (50%) metastases were removed when they became clinically apparent during meticulous followup (median interval 6 months, range 1 to 24). There were 20 patients (50%) who underwent resection of inguinal metastases detected on dynamic sentinel node biopsy before they became palpable. The histopathological characteristics of the tumors and lymph nodes were reevaluated. RESULTS: The 2 populations were similar in terms of patient age, T-stage, pathological tumor grade, vascular invasion and infiltration depth. Disease specific 3-year survival of patients with positive lymph nodes detected during surveillance was 35% and in those who underwent early resection, 84% (log rank p = 0.0017). In multivariate analysis early resection of occult inguinal metastases detected on dynamic sentinel node biopsy was an independent prognostic factor for disease specific survival (p = 0.006). CONCLUSIONS: Early resection of lymph node metastases in patients with penile carcinoma improves survival.

Sarcomatoid squamous cell carcinoma of the penis: a clinical and pathological study of 5 cases.

PURPOSE: We analyzed clinical, morphological and immunohistochemical features in 5 cases of sarcomatoid or spindle cell squamous cell carcinoma of the penis. MATERIALS AND METHODS: The clinical and pathological files of all patients with penile carcinoma treated at our hospital between 1956 and 2002 were reviewed. Cases diagnosed as sarcomatoid squamous cell cancer were selected. RESULTS: Five of 341 patients (1.4%) had sarcomatoid penile carcinoma. Tumor stage was T2N0 in 2 patients, T2N2 in 2 and T4N3 in 1. In all patients partial or total penectomy was eventually performed. Three patients underwent bilateral inguinal lymphadenectomy. Four of 5 patients had distant metastatic disease and died within 1 year after diagnosis. One patient had exclusive hematogenous spread without lymph node involvement. Foci of distant metastatic tumor sites were the lung, skin, bone, pericardium and pleura. In 4 patients the diagnosis was based on the expression of keratin filaments in a predominantly spindle cell penile tumor or by the identification of carcinomatous and sarcomatoid areas on hematoxylin and eosin stained slides of the primary tumor. In 1 case a squamous component in a lymph node metastasis rendered the keratin negative spindle cell primary tumor sarcomatoid squamous cell carcinoma. CONCLUSIONS: Sarcomatoid squamous cell carcinoma of the penis is a subtype of squamous cell carcinoma with a poor prognosis often associated with wide hematogeneous spread. It is a rare malignancy that is often difficult to diagnose, requiring additional immunohistochemical stains.

Management of clinically node negative penile carcinoma: improved survival after the introduction of dynamic sentinel node biopsy.

PURPOSE: We evaluated the clinical outcome of clinically node negative penile carcinoma managed by surveillance or further diagnosed by dynamic sentinel node biopsy with subsequent resection of lymph node metastases. MATERIALS AND METHODS: From 1956 to 1994, 85 patients with primary T2-3N0M0 penile squamous cell carcinoma were treated with initial surveillance of the regional lymph nodes. From 1994 until 2001, 68 patients underwent dynamic sentinel node biopsy. RESULTS: The 2 populations were similar in terms of patient age, clinical T stage, tumor grade, vascular invasion and infiltration depth. Disease specific 3-year survival in the surveillance and sentinel node groups was 79% and 91%, respectively (log rank test p = 0.04). CONCLUSIONS: Early detection of lymph node metastases by dynamic sentinel node biopsy and subsequent resection in clinically node negative T2-3 penile carcinoma improves survival compared with a policy of surveillance.

A comparison of physical examination and imaging in determining the extent of primary penile carcinoma.

OBJECTIVE: To determine the accuracy of physical examination and imaging in assessing the extent of the primary tumour in squamous cell carcinoma of the penis. PATIENTS AND METHODS: A physical examination, ultrasonography and magnetic resonance imaging (MRI) were used before surgery in 33 patients with penile carcinoma. The tumour size, infiltration of the penile structures and infiltration depth were assessed. The results were compared with the histopathological examination of the resected specimen. RESULTS: Tumour size was determined with the highest precision by the physical examination (residual sd of 8.1 mm); ultrasonography and MRI were less precise (residual sd 8.9 mm and 9.3 mm). In assessing infiltration depth, ultrasonography and MRI had comparable precision (residual sd 3.7 mm and 3.8 mm). The positive predictive value of corpus cavernosum infiltration was 6/6 for physical examination, 4/6 for ultrasonography and 6/8 for MRI; the sensitivity was 6/7, 4/7 and 6/6, respectively. CONCLUSION: Physical examination is a reliable method for estimating penile tumour size and predicts corpus cavernosum infiltration with a high positive predictive value. Tumours for which the infiltration of the corpora cannot be determined properly by physical palpation only should be examined by imaging.

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53.

BACKGROUND AND PURPOSE: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. PATIENTS AND METHODS: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. RESULTS: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years;P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). CONCLUSION: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen.

BACKGROUND: Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. METHODS: We did a nationwide case-control study on the risk and prognosis of endometrial cancer after tamoxifen use for breast cancer. Information on tamoxifen use and other risk factors for endometrial cancer was obtained from 309 women with endometrial cancer after breast cancer (cases), and 860 matched controls with breast cancer but without endometrial cancer. For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53. FINDINGS: Tamoxifen had been used by 108 (36.1%) of 299 cases and 245 (28.5%) controls (relative risk 1.5 [95% CI 1.1-2.0]). Risk of endometrial cancer increased with longer duration of tamoxifen use (p < 0.001), with relative risks of 2.0 (1.2-3.2) for 2-5 years and 6.9 (2.4-19.4) for at least 5 years compared with non-users. Endometrial cancers of stage III and IV occurred more frequently in long-term tamoxifen users (> or = 2 years) than in non-users (17.4% vs 5.4%, p=0.006). Long-term users were more likely than non-users to have had malignant mixed mesodermal tumours or sarcomas of the endometrium (15.4% vs 2.9%, p < or = 0.02), p53-positive tumours (31.4% vs 18.2%, p=0.05), and negative oestrogen-receptor concentrations (60.8% vs 26.2%, p < or = 0.001). 3-year endometrial-cancer-specific survival was significantly worse for long-term tamoxifen users than for non-users (76% for > or = 5 years, 85% for 2-5 years vs 94% for non-users, p=0.02). INTERPRETATION: Long-term tamoxifen users have a worse prognosis of endometrial cancers, which seems to be due to less favourable histology and higher stage. However, the benefit of tamoxifen on breast-cancer survival far outweighs the increased mortality from endometrial cancer. Nevertheless, we seriously question widespread use of tamoxifen as a preventive agent against breast cancer in healthy women.

Expression of CD3-zeta on T-cells in primary cervical carcinoma and in metastasis-positive and -negative pelvic lymph nodes.

Lymphocytic infiltrate is often present in cervical cancer lesions, possibly reflecting an ongoing, but ineffective, immune response to the tumour. Recently, evidence has accumulated for systemically impaired T-cell functions in cancer patients, associated with decreased expression of signal-transducing zeta (zeta) chain dimer molecules on circulating T-cells and NK-cells. Here, we report on the intralesional down-regulation of zeta chain expression on T-cells in cervical carcinoma. Paraffin-embedded or snap-frozen sections from 24 different cervical cancer specimens were studied. Paraffin-embedded tumour-positive (n = 7) and tumour-negative (n = 15) pelvic lymph nodes were also included in the study. Immunostaining was performed on consecutive sections with antibodies specific for CD3-epsilon or the CD3-associated zeta chain dimer. Antigen retrieval by sodium citrate/microwave treatment was essential for zeta staining of paraffin sections. The amount of zeta positive cells was quantitated and related to the number of CD3-epsilon+ cells in corresponding tumour areas. Of the 24 cervical cancer specimens studied, zeta chain dimer expression was reduced in seven cases and strongly reduced in the other 17 samples. In tonsil control sections, CD3-epsilon and CD3-zeta were always co-expressed in almost equal numbers. Also, both tumour-negative and -positive lymph nodes showed zeta chain expression which equalled that of CD3-epsilon expression. These data indicate that a decreased expression of signal-transducing zeta molecules on tumour-infiltrating T-cells is frequent in cervical cancer. The apparently unimpaired zeta chain expression within draining lymph nodes suggests that local tumour-derived factors at the primary site are instrumental in zeta chain down-regulation.

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. METHODS: 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. RESULTS: Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. CONCLUSIONS: The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice.

Prognostic significance of serum fragments of cytokeratin 19 measured by Cyfra 21-1 in cervical cancer.

Pretreatment sera of 78 patients with squamous cell cervical cancer were tested for the presence of cytokeratin 19 (CK 19) fragments to determine the relationship among this parameter, tumor stage, various histopathologic characteristics, and prognosis. For the quantitative determination of CK 19 fragments in serum, the enzyme assay Cyfra 21-1 was used. This assay, based on the simultaneous sandwich principle, utilizes two different monoclonal antibodies. The test was considered positive when levels of Cyfra 21-1 were > or = 1.2 micrograms/liter. Cyfra 21-1 was positive in the majority of patients and in all patients with advanced disease (FIGO III or IVa). A highly significant relationship was found between pretreatment Cyfra 21-1 level and FIGO stage (P < 0.0001). Mean Cyfra 21-1 concentration was elevated in the case of macroinvasive disease (FIGO Ib, IIa, IIb, III, IVa). A distinct relationship was found between tumor size (P < 0.001; r = 0.73) and Cyfra 21-1 level. In the univariate Cox analysis Cyfra 21-1 level was significantly related to both disease-free interval (P < 0.0001) and survival (P < 0.0001) of patients. Patients with an increased Cyfra 21-1 level had a significantly worse prognosis. However, in the stepwise Cox regression analysis, these variables had no additional value over known prognostic factors such as FIGO stage and tumor size. It is concluded that Cyfra 21-1 may be of significance as an additional marker in the management of patients with cervical cancer, but further investigation is needed.

Expression of cytokeratin 10, 13, and involucrin as prognostic factors in low stage squamous cell carcinoma of the uterine cervix.

BACKGROUND: The identification of pretreatment markers with predictive significance for the presence of lymph node metastases and treatment outcome in low stage cancer of the uterine cervix is clinically important. Because the presence of differentiation-related markers varies in this type of cancer, the authors investigated whether loss of these markers is related to a poor clinical course. METHODS: An indirect immunoperoxidase technique was applied to formalin fixed, paraffin embedded tissue sections of 80 patients with International Federation of Gynecology and Obstetrics Stage IB and IIA primary squamous cell cervical carcinomas for detection of expression of cytokeratin 10 and 13, and involucrin. Comparisons were made of the expression of each of these markers among 40 patients with regional node metastases and 40 age-matched patients with no lymph node metastases. Differences in the frequency of expression of these markers also were analyzed in relation to histopathologic characteristics, recurrence, and survival. RESULTS: Expression of cytokeratin 10, 13, and involucrin was found in 24, 64, and 53%, respectively, of all patients studied. The authors found no differences between patients with positive regional lymph nodes and those with negative lymph nodes. Expression of cytokeratin 13 and involucrin was associated with tumor grade (P = 0.01). No relationship was found between expression of the markers used and recurrence or survival in the entire group. Within the lymph node-positive group, however, the survival rate of patients with tumors with cytokeratin 13 expression was significantly higher than that of patients with tumors lacking cytokeratin 13 expression (P = 0.02). CONCLUSION: Expression of cytokeratin 10, 13, or involucrin in the primary tumor is of no predictive value with respect to the presence of regional lymph node metastases in low stage squamous cell cervical cancer. However, cytokeratin 13 expression appears to be of prognostic significance in patients with positive regional lymph nodes.

Prognostic significance of serum antibodies to human papillomavirus-16 E4 and E7 peptides in cervical cancer.

BACKGROUND: The objective of this study was to investigate the prognostic significance of serum antibodies to human papillomavirus (HPV)-16 peptides in patients with squamous cell cervical cancer. METHODS: Pretreatment sera from 78 patients and 198 control women were tested by an enzyme-linked immunosorbent assay technique for reactivity with HPV-16 E4 (E401p) and E7 (E701p) synthetic peptides. The presence and serum level of these antibodies were correlated with tumor stage, histologic features, and prognostic parameters. RESULTS: The median follow-up was 65 months (range, 6-97 months). Antibodies to E401p peptide were found in 5 of the 198 (3%) control subjects, 4 of the 43 (9%) patients with low tumor stage (International Federation of Gynecology and Obstetrics [FIGO] Ia, Ib, IIa), and 7 of the 35 (20%) patients with advanced tumor stage (FIGO IIb, III, IVa). Antibodies to E701p were found in 25 (13%), 11 (26%), and 11 (31%) women, respectively. The differences between patients and control subjects were significant (P < 0.002). Seropositivity against these peptides showed no correlation with tumor stage. Antibody levels to both peptides were significantly higher in patients compared with control subjects (P < 0.05). Furthermore, antibody levels to E401p were higher in patients with advanced tumor stage versus patients with low tumor stage (P = 0.0097). Such a relation was not found for anti-E701p antibodies. In the univariate analysis, a high level of anti-E701p antibodies was associated with a shorter disease free interval (P = 0.012) and poor survival (P = 0.049). However, this variable possessed no prognostic value after adjusting for FIGO stage and tumor size. CONCLUSIONS: The authors' findings indicate that the prognostic significance of serum antibodies to the HPV-16 E4 and E7 peptides used in this study of patients with cervical cancer is limited.

Squamous cell carcinoma of the vagina in a male pseudohermaphrodite with 5alpha-reductase deficiency.

A 50-year-old Spanish male pseudohermaphrodite (karyotype 46, XY) is described, who had a squamous cell carcinoma of the vagina, FIGO stage IV B. He was reared as a girl and changed gender at puberty. The phenotype was typical for 5alpha-reductase deficiency, as were the laboratory findings. A radical vulvectomy and dissection of the groins revealed inadequate resection near the urethra. Postoperative external irradiation was given. Human papillomavirus 16 DNA sequences were found in the tumor and in a groin metastasis. He died 3.5 years postoperation because of a tumor of the lung, probably a metastasis, without signs of local recurrence. Some 60 male pseudohermaphrodites due to 5alpha-reductase deficiency have been described. Many of them had to cope with the traumatic experience of a change of gender at puberty, because early gonadectomy was seldom done. The sex-life and family-life of our patient were unsatisfactory. We recommend early gonadectomy to prevent virilization at puberty. Psychologic care, genetic counseling and corrective surgery of the genitalia are necessary. Although there are predisposing factors, testicular malignancies have not been reported. This is the first report of squamous cell carcinoma of the vagina in a male pseudohermaphrodite with 5alpha-reductase deficiency and human papillomavirus 16 DNA sequences.

Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours.

In previous studies we have shown down-regulation of class I major histocompatibility complex (MHC) expression in a significant proportion of primary cervical carcinomas, which was found to be strongly correlated with loss of expression of the transporter associated with antigen presentation (TAP). By contrast, class II MHC expression was frequently up-regulated on neoplastic keratinocytes in these malignancies. In order to investigate whether these changes are associated with biological behaviour of the tumours, 20 cervical carcinomas were analyzed for MHC (HLA-A, HLA-B/C, HLA-DR) and TAP-1 expression in the primary tumours and in lymph node metastases by immunohistochemistry. The results showed a significant increase in the prevalence of HLA-A and HLA-B/C down-regulation in metastasised neoplastic cells as compared with the primary tumour (P = 0.01). In all cases this was accompanied by loss of TAP-1 expression. Up-regulated HLA-DR expression was found exclusively in primary tumours and was absent in the corresponding metastases (P = 0.002). These data are consistent with the hypothesis that loss of TAP-1 and the consequent down-regulation of class I MHC expression provides a selective advantage for neoplastic cervical cells during metastasis. Furthermore, the lack of class II MHC expression in metastasised cells either reflects a different local lymphokine production or indicates that these cells may have escaped CD4+ cytotoxic T-lymphocyte (CTL)-mediated killing.

Ultrasound in squamous cell carcinoma of the penis; a useful addition to clinical staging? A comparison of ultrasound with histopathology.

OBJECTIVE: As part of the staging procedure in squamous cell carcinoma of the penis, we assessed the role of ultrasound examination, in particular its role in assessing the extent and the invasion into the corpora. METHODS: From 1988 until 1992, all patients referred for primary treatment underwent ultrasound assessment with a 7.5 MHz linear array small parts transducer as part of the clinical workup. All ultrasound images were reviewed by one radiologist, without knowledge of the clinical outcome and were compared with the results obtained at histopathologic examination. RESULTS: In 16 patients the primary tumor and in 1 patient a recurrent cancer after primary therapy were examined. All tumors were identified as hypoechoic lesions. Ultrasound examination in the region of the glans was not able to differentiate between invasion of the subepithelial tissue and invasion into the corpus spongiosum, but absence or presence of invasion into the tunica albuginea of the corpus cavernosum was clearly demonstrated. Accurate measurement by ultrasound of maximum tumor thickness was seen in seven of sixteen examinations. CONCLUSIONS: While ultrasound examination is inexpensive and easily done, it is not accurate enough for staging small penile cancers located at the glans penis. However, for larger tumors ultrasound can be a useful addition to physical examination by delineating reliably the anatomic relations of the tumor to structures such as the tunica albuginea, corpus cavernosum, and urethra.

Resectable retroperitoneal soft tissue sarcomas. The effect of extent of resection and postoperative radiation therapy on local tumor control.

BACKGROUND: Soft tissue malignancies of the retroperitoneum are rare. Surgery is commonly considered the first choice of treatment. There is still no consensus concerning the precise value of the extent of surgery and the value of additional treatment modalities. METHODS: From 1973 to 1990, 34 patients were initially treated by surgery for retroperitoneal soft tissue sarcomas at the Netherlands Cancer Institute. In a retrospective study, the prognostic effect of extent of primary surgery and postoperative radiation therapy was examined. RESULTS: Liposarcomas (47%) and leiomyosarcomas (29%) were the histologic types most commonly found. Grade of malignancy was defined as medium to high (II/III) in 44% and as low (I) in 38%. Complete (extended or marginal) resection of the tumor was achieved in 29 patients. After complete resection, the 5-year survival rate and the local recurrence rate were 35% and 63%, respectively. Extended surgery (performed in eight patients) showed a local recurrence rate of 50%. Thirteen patients received high-dose postoperative radiation therapy, which was found to have a significant favorable effect on the recurrence-free interval (P < 0.01). CONCLUSIONS: We conclude that complete (extended) resection followed by high-dose postoperative radiation therapy improves the prognostic outcome of patients with retroperitoneal soft tissue sarcomas.

HPV DNA presence and HPV genotypes as prognostic factors in low-stage squamous cell cervical cancer.

Sixty-four patients with FIGO stages IB and IIA squamous cell carcinoma of the uterine cervix were studied to assess the prognostic potential of the presence of HPV DNA and HPV genotypes in the tumor, as detected by a general primer-mediated polymerase chain reaction followed by a type-specific PCR on paraffin-embedded tissue sections of the primary tumor. The prevalence of various HPV types in 32 patients with positive lymph nodes was compared to the prevalence found in 32 age-matched controls with negative lymph nodes. In both patient groups HPV DNA was found in all cases. The prevalence rates of HPV types 16, 18, and X in the positive and negative lymph node group were 78% versus 72%, 13% versus 9%, and 3% versus 16%, respectively. These differences were not statistically significant. HPV genotypes 6, 11, and 31 were not found. Differences in recurrence rate and 5-year survival rate between the patient groups with different tumor-containing HPV genotypes were not statistically significant. Nor was there any statistically significant relationship between HPV type and other well-known prognosticators. In conclusion, in our study a 100% HPV DNA prevalence was found in squamous cell cervical carcinomas. Neither the presence of HPV DNA nor the HPV genotype appeared to be related to either the presence of lymph node metastases at the time of initial treatment or to 5-year survival.

Possible role for cytotoxic lymphocytes in the pathogenesis of acute interstitial nephritis after recombinant interleukin-2 treatment for renal cell cancer.

A patient with renal cell cancer developed acute renal failure due to biopsy-proven acute tubulo-interstitial nephritis (AIN) in the 6th week of continuous infusion of 9 x 10(6) IU m-2 day-1 recombinant interleukin-2 (rIL-2). We investigated whether the AIN was the result of a cellular cytotoxic reaction induced by the rIL-2 treatment. The cytolytic activity of cryopreserved peripheral blood lymphocytes (PBL), isolated before and at the end of the rIL-2 treatment (at the time of AIN), was studied after 5 days of culture with or without rIL-2 or anti-CD28 and immobilized anti-CD3 antibodies. The PBL isolated before and at the end of the rIL-2 treatment showed cytolytic activity towards a number of allogeneic targets. However, only the PBL isolated at the end of the rIL-2 treatment showed, when stimulated with rIL-2 in vitro, significant cytolytic activity against an autologous renal cell line cultured from the AIN biopsy specimen and against an allogeneic renal cell cancer cell line. These PBL displayed no enhanced killing capacity towards autologous PBL and the melanoma cell line M14. These observations suggest that the AIN may be the result of a cytotoxic lymphocyte-mediated reaction induced by the rIL-2 treatment.

Intestinal obstruction due to diffuse peritoneal fibrosis at 2 years after the successful treatment of malignant peritoneal mesothelioma with intraperitoneal mitoxantrone.

A 44-year-old man who had achieved a complete remission of malignant peritoneal mesothelioma after the intraperitoneal administration of 25 mg/m2 mitoxantrone presented with clinical and radiological signs of intestinal obstruction suggestive of recurrent disease at about 2 years following the initial treatment. However, laparotomy revealed extensive adhesive fibrosis but no sign of malignant mesothelioma. The peritoneal complications of intraperitoneal cytostatic treatment are discussed.

Intraperitoneal chemotherapy for malignant peritoneal mesothelioma.

4 patients with malignant peritoneal mesothelioma have been treated with intraperitoneal chemotherapy in the Netherlands Cancer Institute in the recent years. 1 patient achieved a complete remission for 36+ months and another patient had a partial remission that lasted for 10 months. Intraperitoneal chemotherapy alone or in combination with other treatment modalities may yield a response rate of 58% with 24% complete remissions in 70 patients reviewed in the literature. Although these data should be considered with caution because of the heterogenicity of the patient group treated, cisplatin-based intraperitoneal chemotherapy seems to be the best available treatment for malignant peritoneal mesothelioma at present.