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Graft-versus-host disease (GvHD) causes severe mucositis, impairs feeding and favors infection. The objective of this study was to identify the impact of GvHD in the oral cavity. We reviewed all consecutive patients who developed oral GvHD after HSCT. The study period was over 14 years. 53 patients were identified. M/F = 1.4; median age was 48.6 years; the median follow-up was for up to 3 years and 6 months. Conditioning regimens included several drugs (e.g., busulfan, cyclophosphamide and fludarabine). In 11 cases, radiotherapy (RT) was also used. Patients treated with RT were more likely to have tooth decay requiring fillings (p = 0.029), to need canal root interventions (p = 0.005) and to have tartar requiring oral hygiene interventions (p = 0.011). Patients with a lymphoma diagnosis were more likely to develop perioral scleroderma and chronic oral GvHD (cGvHD) (p = 0.045). Oral acute GvHD (aGvHD) was seen in 26 patients (49.1%). 21 (39.6%) patients developed cGvHD. GvHD of the tongue was seen in 21 (40%) patients. Oral mucositis was seen in only 5 patients (9.4%). Conditioning regimens with RT are more likely to induce oral aGvHD. The tongue is often affected by GvHD.

Purpose The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT. Patients and Methods From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis. Results Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm. Conclusion In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.

Background Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal. Objectives To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up. Study design In a multicentre retrospective follow-up study of a consecutive series (1997–2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan–Meier method. Results For patients testing HPV-positive at the first follow-up visit ( n = 44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients ( n = 47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2–80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43–0.77) after 26 months. The median time to detection was 5 months. Conclusions If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease.

Graft versus host disease (GvHD) is a clinically important complication after allogeneic hematopoietic stem cell transplantation (HSCT). Its diagnosis relies on clinical and histopathological findings. In order to evaluate and improve inter-institutional diagnostic agreement on histological diagnosis and grading of acute gastrointestinal GvHD, we conducted a round robin test, which included 33 biopsies from 23 patients after HSCT. Five pathologists from different institutions independently evaluated the original sections from the biopsies submitted for diagnosis. Based on their results, consensus qualitative criteria for the assessment of typical histological features of GvHD (e.g., apoptosis, crypt destruction, mucosa denudation) were proposed, including detailed descriptions as well as histological images. In a second round robin test with involvement of the same pathologists, the reproducibility of both diagnosis and grading had improved. Remaining differences were mostly related to differential diagnostic considerations, including viral infection or toxic side effects of medication, which should be resolved by integrating histopathological findings with proper clinical information.

To evaluate the ability of MRI in predicting histological grade of endometrial cancer (EC).IRB-approved retrospective study; requirement for informed consent was waived. 90 patients with histologically proven EC who underwent preoperative MRI and surgery at our Institution between Sept2011 and Nov2016 were included. Myometrial invasion (/50%) was assessed. Neoplasm and uterus volumes were estimated according to the ellipsoid formula; neoplasm/uterus volume ratio (N/U) was calculated. ADC maps were generated and histogram analysis was performed using commercially available software. MRI parameters were compared with the definitive histological grade (G1 = 28 patients, G2 = 29, G3 = 33) using ANOVA and Tukey-Kramer tests.Deep myometrial invasion was significantly more frequent in G2-G3 lesions than in G1 ones (p 0,005). N/U ratio was significantly higher for high-grade neoplasms (mean 0,08 for G1, 0,16 for G2 and 0,21 in G3; P = 0,002 for G1 vs. G2-G3); a cut off value of 0,13 enabled to distinguish G1 from G2-G3 lesions with 50% sensibility and 89% specificity. ADC values didn't show any statistically significant correlation with tumour grade.N/U ratio0.13 and deep myometrial invasion are significantly correlated with high grade EC, whereas ADC values are not useful for predicting EC grade.

This study aimed to compare the interobserver Cohen κ on HE staining and on HE plus p16(INK4a) staining of all cervical biopsy specimens in a population-based screening program.All the colposcopy-guided biopsies generated by the routine screening of 23,258 women aged 25 to 64 years were stained with HE and HE plus p16. Biopsy specimens were reviewed by six external experts.The four diagnoses were available in 441 cases. The interobserver κ values were 0.52 (95% confidence interval [CI], 0.45-0.58) and 0.48 (95% CI, 0.42-0.56) with HE and HE + p16, respectively, when using a five-group classification (normal, CIN 1, CIN 2, CIN 3, and cancer); adopting a two-group classification (≤CIN 1 and ≥CIN 2), the values were 0.75 (95% CI, 0.66-0.82) and 0.70 (95% CI, 0.61-0.79), respectively.The use of p16 on all cervical biopsy specimens in a screening program showed virtually no effect on reproducibility of the histologic diagnosis.

BACKGROUND: In the New Technologies for Cervical Cancer Screening (NTCC) randomized controlled trial, no significant increase in the sensitivity of liquid-based cytology (LBC) was observed compared with conventional cytology. Both were interpreted by cytologists who had limited previous LBC experience. The objective of the current study was to assess whether different results could be expected with experienced LBC interpreters. METHODS: A stratified, random sample of 818 LBC slides from the NTCC study was obtained. These slides were reviewed blindly and independently by 3 international experts who did not participate in the NTCC. The sensitivity and specificity of external experts were estimated for cervical intraepithelial neoplasia grade 2 or greater (CIN2+) and for CIN3+ histology, and the differences were compared with the sensitivity and specificity of the original cytologic interpretation using cutoffs of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL). RESULTS: With the endpoint of CIN2+ histology, the difference in sensitivity between external experts and the original interpretation was −5.3 (95% confidence interval [CI], −16.0 to 5.4) with ASCUS as the cutoff and 3.8 (95% CI, −8.2 to 15.8) with LSIL as the cutoff. External experts had slightly lower specificity using ASCUS as the cutoff (−3.4; 95% CI, −3.9 to −2.9) and LSIL as the cutoff (−0.7; 95% CI, −1.0 to −0.4). CONCLUSIONS: The accuracy of the external experts' interpretation was similar to that of the original interpretation. Therefore, the current results indicated that LBC is not expected to increase sensitivity even if it is used by interpreters who have extensive experience with this technique. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.

Objectives To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guerin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells. Methods A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series. Results Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity (P = 0.512) and specificity (P = 0.558) for the uCyt+ test in the two groups of patients. Conclusions The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.

To compare the diagnostic performance of T2-weighted images (T2-WI)+contrast-enhanced T1-weighted images (CE T1-WI) with the one of T2-WI+diffusion-weighted images (DWI) in the assessment of myometrial and cervical stromal infiltration by endometrial carcinoma (EC).Institutional review board approved our retrospective study; requirement for informed consent was waived. 56 patients with histologically proven EC who underwent preoperative MRI and surgery at our Institution over a 34 months period were included. Two radiologists independently evaluated T2-WI+CE T1-WI and T2-WI+DWI of each patient. Confidence in imaging evaluation (0-3), depth of myometrial invasion (/≥50%) and presence of cervical stromal infiltration (Yes/No) were assessed. MRI findings were compared with pathological ones.Confidence in imaging evaluation was higher for T2-WI+CE T1-WI (2.83/3) than for T2-WI+DWI (2.62/3). T2-WI+DWI showed a better diagnostic performance than T2-WI+CE T1-WI in recognizing deep myometrial infiltration by EC (accuracy, sensitivity and specificity of 0.89, 0.89 and 0.89 vs. 0.86, 0.84, 0.86; p0.05) whereas both imaging sequences combinations showed the same diagnostic performance in recognizing cervical stromal infiltration (accuracy, sensitivity and specificity of 0.95, 0.98 and 0.80, p0.05).T2-WI+DWI can reliably replace the "classical" combination T2-WI+CE T1-WI for local staging of endometrial carcinoma.

Objectives: Allogeneic bone marrow transplantation (BMT) is a procedure mostly used for high-risk hematologic malignances. In women, follow-up protocols after BMT include gynecologic checkups with Papanicolaou (Pap) smears. Methods: We evaluated 117 Pap smears in 54 women who underwent allogeneic BMT and correlated the smear morphology with the BMT-related medical treatment. Results: Abnormal Pap smears after BMT were found in 13 (24.1%) women. Four (7.4%) women had at least one smear with atypical squamous cells of unknown significance, six (11.1%) had a low-grade squamous intraepithelial lesion, and three (5.6%) had atypical squamous cells/high-grade lesion cannot be excluded (ASC-H). The three patients with ASC-H showed high-grade atypia mimicking cancer but had a negative follow-up. Nine women, including the three with ASC-H, had undergone a conditioning therapy for BMT that included busulfan. No association between other drugs and therapy-related atypia was found. Conclusions: Pap smears after BMT show a high incidence of dysplastic lesions. Moreover, conditioning including busulfan is often associated with therapy-related cytologic atypia, which may lead to unnecessary colposcopies and biopsies. Knowledge of the patient’s history and a careful evaluation of the smears are mandatory in these cases.

P16-INK4A overexpression has been proposed as a prognostic marker to manage the follow up of women with positive cytology and/or HPV test but without high-grade cervical intraepithelial neoplasia (CIN2+). This study measures the relative risk (RR) of CIN2+ of p16 positive versus negative in these women. All the women referred to colposcopy from October 2008 to September 2010 with negative or CIN1 colposcopy-guided biopsy were included in the study; women surgically treated or having a CIN2-3 were excluded. All baseline biopsies were dyed with hematoxylin and eosin and p16. Women were followed up according to screening protocols, with cytology or colposcopy at 6 or 12 months. CIN2/3 RRs and 95% confidence intervals (95%CI) were computed. Of 442 eligible women, 369 (83.5%) had at least one follow-up episode. At baseline, 113 (30.6%) were CIN1, 248 (67.2%) negative, and 8 (2.2%) inadequate histology; 293 (79.4%) were p16-negative, 64 (17.3%) p16 positive and 12 (3.2%) not valid. During follow up, we found ten CIN2 and three CIN3; of these, six were p16 positive (sensitivity 46%, 95% CI 19-75). The absolute risk among p16 positives was 9.4/100 compared to 1.7/100 of the p16 negatives (RR 5.5; 95% CI 1.7-17.4). The risk was also higher for CIN1 than for histologically negative women (RR 4.4; 95% CI 1.3-14.3). The RR for p16 in CIN1 did not change (RR 5.2; 95% CI 0.6-47.5). P16 overexpression is a good candidate for modulating follow-up intensity after a negative colposcopy but is limited by its low prospective sensitivity.

Anti-p53-autoantibodies (a-p53-aabs) may suppress the development of distant metastases, but not lymph node metastases. This could explain the significantly prolonged survival of patients with UICC stage III tumors who have a-p53-aabs compared to those without a-p53-aabs.Mutation within the tumor suppressor gene p53 leads to increased intracellular p53 protein levels and an increased antibody formation against this molecule. Altered p53 has been proposed to be associated with poor prognosis, and the present study investigated whether the detection of a humoral response to p53 gives evidence for a prognostic or diagnostic parameter in pancreatic disorders.We screened 145 patients with pancreatic cancer and 95 patients with chronic pancreatitis for the development of a-p53-aab via ELISA and Western-blotting. p53 expression was examined by immunohistochemistry.We found that 41% of the tissues of patients suffering from pancreatic carcinoma overexpressed p53, and 15.9% of the patients suffering from pancreatic cancer developed a-p53-aab. In pancreatic cancer, we could exhibit a significant correlation between grading, p53-overexpression, survival, and antibody response against p53. A-p53-aabs were significantly more frequent in patients with stage III tumors (tumors with lymph node metastases, but not distant metastases, p0.02).

The benefits of cytology-based cervical cancer screening programs in reducing morbidity and mortality are well recognized. Especially, overtreatment of human papillomavirus (HPV) high-risk positive early dysplastic lesions may have a negative impact on reproductive outcomes for fertile women. To optimize the clinical management an objective standard is needed to distinguish precancer that requires treatment, from spontaneously resolving HPV infections. In the current study, we examined the prognostic relevance of HPV-L1 capsid protein analysis with Cytoactiv in an international prospective multicenter study including 908 HPV high-risk positive early dysplastic lesions (LSIL/HSIL) during a follow-up period of 54 months. The clinical end points of the study were histologically confirmed CIN3+ as progression, CIN1/2 for stable disease and repeated negative Pap smears as spontaneous clinical remission. The difference of the clinical outcome of HPV-L1-negative and HPV-L1-positive cases was statistically highly significant (P-value

Objective The present study assessed the clinical outcome of patients conservatively treated for cervical adenocarcinoma in situ (AIS) and their predictive factors using univariate and multivariate population averaged (PA) generalized estimating equation (GEE) model in a longitudinal setting. Methods A series of 166 consecutive women (mean age 39.8 yrs; range 23–63 yrs) underwent conservative treatment of AIS as the primary treatment and were followed-up (mean 40.9 mo) using colposcopy, PAP-smear, biopsy and HPV-testing with Hybrid Capture 2. Results Hysterectomy was performed as part of the primary management in 47 patients, who were excluded from the follow-up (FU) analysis. Out of 119 women closely followed-up, additional therapeutic procedures were performed in 69. At study conclusion, 7 patients (5.9%) showed persistent disease, while 8 (6.7%) had progressed to invasive adenocarcinoma (AC). Positive HR-HPV test was the only independent predictor of disease recurrence (adjusted OR = 2.72; 95%CI 1.08–6.87), and together with free cone margins (OR = 0.20; 95%CI 0.04–0.92), HR-HPV positivity was also the single most powerful predictor of disease progression to AC, with OR = 3.74; 95%CI 1.84–7.61 (p = 0.0001) in multivariate PA-GEE. Conclusions These results suggest that testing HR-HPV positive at any time point during FU is the most significant independent predictor of progressive disease, while showing free margins in cone has a significant protective effect against progression to AC. Furthermore, because 4.3% women with persistent, recurrent or progressive disease experienced a late (5th and 6th FU) diagnosis of HG-CGIN or microinvasive AC, a close surveillance should be scheduled for at least three years in conservatively treated AIS patients.

Reduced-intensity conditioning regimens have reshaped the clinical presentation of graft-versus-host disease after hematopoietic stem cell transplants. However, histopathologic features of graft-versus-host disease following reduced-intensity conditioning regimens have not been fully characterized. In a series of 112 biopsies (skin, n = 60; gastrointestinal [GI] tract, n = 44; liver, n = 8), we described the morphologic profile of graft-versus-host disease following reduced-intensity conditioning and investigated whether histopathologic changes of graft-versus-host disease following reduced-intensity conditioning have a diagnostic and/or prognostic value. Forty-four patients (49.5%) experienced acute graft-versus-host disease, 2(2.2%) late-onset acute graft-versus-host disease (grade I, n = 13; grade II-IV, n = 33), 24(27.0%) chronic graft-versus-host disease (de novo n = 12, progressive n = 12) and 19 (21.3%) overlap syndrome. In the skin, we observed: (i) phase-nonspecific changes, such as acute graft-versus-host disease features in chronic graft-versus-host disease patients (n = 4/24; 16.6%), (ii) subtle alterations such as superficial fibrosis in widened dermal papillae (n = 8), in acute graft-versus-host disease/late-onset graft-versus-host disease (n = 6/46; 13.0%) or chronic graft-versus-host disease (n = 2/24, 8.3%) patients, and (iii) features of chronic and acute graft-versus-host disease coexisting in the same specimen in overlap syndrome (n = 3/19; 15.7%). In the GI tract, we did not demonstrate peculiar features differing from those commonly observed in the myeloablative setting. By univariate analysis, a reduced overall survival was associated with graft-versus-host disease type (chronic graft-versus-host disease P = .006, acute graft-versus-host disease P = .03), older age (P = .04), and histopathologic diagnosis of "consistent with" + definite graft-versus-host disease (P = .02). Histopathologic diagnosis retained an independent prognostic value by multivariate analysis (P = .01). The present study indicates that pathologists should be aware of the peculiar morphologic changes of cutaneous graft-versus-host disease following reduced-intensity conditioning and further recommends histopathology in the diagnostic workup of graft-versus-host disease in patients undergoing reduced-intensity conditioning regimen. (C) 2011 Elsevier Inc. All rights reserved.

As only a minority of low-grade dysplastic lesions of the cervix uteri will eventually progress to carcinoma, predicting the behavior of these lesions could be of high value in clinical practice. The aim of the study was to evaluate p16 ink4a and L1 as immunohistochemical markers of the biologic potentiality of low-grade dysplasia of the uterine cervix. The study included 38 conization specimens with coexisting cervical intraepithelial neoplasia grade 1 (CIN1) and 3 (CIN3) (group A) and 28 punch biopsies from women with CIN1 and proven spontaneous regression in the follow-up (group B). In group A, all CIN3 were p16 ink4a positive (p16+) and L1 negative (L1-). The CIN1 of this group were p16+L1- and p16+L1+ in 68.42% and 31.57%, respectively. No other expression pattern was found in this group. In group B, the p16+L1-, p16+L1+, p16-L1+, and p16-L1- patterns were found in 3.57%, 25%, 14.29%, and 57.14%, respectively. Overall, 96.29% p16+L1- CIN1 were found in group A, whereas all the p16-L1+ and p16-L1- CIN1 were found in group B. A significant difference between staining pattern distributions of group A and B was observed (P0.0001). The results of the study show that p16 ink4a and L1 immunohistochemistry can be helpful for estimating the biologic potentiality of low-grade squamous cervical lesions. Particularly in cases in which the grade of the lesion is morphologically difficult to assess, the p16/L1 expression pattern could be useful for planning the clinical management of these women.

An increasing proportion of cervical carcinomas are adenocarcinomas, and many studies have shown that both adenocarcinoma and adenocarcinoma in situ (AIS) are frequently missed by conventional cytologic study. This study examined clinical outcomes in 42 consecutive women who had conservative treatment of AIS by cervical conization and were prospectively followed up for 40 months on average by colposcopy, Pap smear, biopsy, and human papillomavirus (HPV) testing (with hybrid capture II). Six follow-up assessments were planned at 6-month intervals. All but one of the women had been referred for colposcopy because of an abnormal Pap smear. Only 43% of the 42 women had atypical glandular cells in their referral Pap smears. Colposcopy was negative in 17% of cases and unsatisfactory in another 55%. Twenty-four patients, 57% of those studied, had pure AIS, while 18 had AIS combined with a squamous-cell lesion. Four of the latter patients had invasive squamous-cell carcinoma. Persistent or recurrent disease was documented in 17 women, 40% of those enrolled in the study. The incidence was 19% in patients with free margins and 65% when involved margins were seen on initial conization. Four patients were diagnosed during follow-up as having stage IA1 adenocarcinoma. All 42 women were free of disease at the end of follow-up. Results of HPV testing were a significant predictor of the clearance or persistence of disease (odds ratio, 12.6; 95% confidence interval, 1.18-133.89). In contrast, at no time did the Pap smear have significant predictive power. The combination of a Pap smear and HPV testing was 90% sensitive and 50% specific, with positive and negative predictive values of 53% and 89%, respectively, at initial follow-up. At the second follow-up visit, the combination was 100% sensitive and 53% specific, and had positive and negative predictive values of 40% and 100%, respectively. All AIS lesions had disappeared by the time of the fourth follow-up assessment. A combination of cytology and HPV testing is clearly superior to cytology alone when monitoring women who have been conservatively treated for cervical AIS.

BACKGROUND The purpose of the current study was to compare the efficacy of liquid-based cytology and conventional smears in the cytologic follow-up of cases with “atypical squamous cells, cannot exclude a high-grade lesion” (ASC-H) or “atypical glandular cells” (AGC). METHODS Cytologic follow-up was performed on 214 cases with ASC-H/AGC diagnosis an conventional smears using either ThinPrep (n = 100) or conventional Papanicoloau (Pap) tests (n = 114). Results were then compared with further histologic and/or cytologic follow-up. RESULTS Repetition on conventional smears enabled a definite diagnosis (within normal limits [WNL], squamous intraepithelial lesion [SIL] or carcinoma) in 58 cases (50.9%). ASC/AGC was confirmed in 50 cases (43.9%), and 6 of the smears (5.3%) were inadequate. WNL, SIL, or carcinoma was diagnosed in 82 (82.0%) cases by following the patients with ThinPrep cytology, whereas ASC or AGC was confirmed in 18 cases (18.0%). No inadequate specimens were found. A diagnosis of SIL or greater (SIL +) was confirmed histologically in 11 of 11 (100.0%) conventional smears and in 31 of 34 (91.2%) ThinPrep specimens. Of the 87 WNL specimens, 9 (8 conventional smears and 1 ThinPrep specimen) developed a histologically confirmed SIL during further follow-up. Specimen adequacy was significantly better in the ThinPrep specimens compared with conventional smears. CONCLUSIONS Because of better specimen adequacy, ThinPrep cervical cytology appears to significantly reduce the occurrence of ASC/AGC compared with conventional Pap smears. Cancer (Cancer Cytopathol) 2003;99:342–5. © 2003 American Cancer Society.

The aim of this study was to evaluate whether human papilloma virus (HPV) testing at LLETZ for CIN can be useful to identify patients with high risk of recurrent disease.In 62 women treated with LLETZ for CIN the status of the resection margins was recorded and related to the HPV status as assessed with Hybrid Capture II immediately after surgery. A control typing was repeated 3-9 months later. In all cases, a ThinPrep thinlayer cytology was further performed.In 19 of the 62 surgical specimens (30.6%) the resection margin was positive for dysplasia or dysplastic epithelium was close (0.5 mm) to the margin (RM+), while in 43 cases (69.4%) the margins were negative (RM-). At surgery, 21 out of 62 cases (33.9%) were HPV+ (47.4% RM+, 27.9% RM-) and 13 turned HPV- at the control typing. From the 41 out of 62 (66.1%) initially HPV-cases, 12 turned into HPV+. Cytological follow-up was abnormal (ASC+) in 65% HPV+ cases, whereas all HPV- were WNL.Post-operative HPV testing with HC-II is well-suited to detecting women with residual HPV infection, even in cases with negative surgical margins. Furthermore, HPV testing at surgery could replace endocervical curettage and help in distinguishing true residual disease from reinfections.

Objectives To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma. Methods Included in this prospective study were 235 patients (mean age 71.5 years, range 32 to 86). Of these, 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer (UC). All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep (thin layer). All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy. Results A total of 102 patients had histologically proven UC. In the group of patients with signs and symptoms suspicious of UC, the sensitivity of cytology increased from 5% for G1 to 84.6% for G3 tumors; for uCyt+, it was 85% for G1, 100% for G2, and 92.3% for G3 tumors. Combining cytology and uCyt+, the sensitivity was 85% for G1 and 100% for G2 and G3. In the group of follow-up patients, the sensitivity of cytology increased from 4.3% for G1 to 94.4% for G3 tumors; for uCyt+, it was 78.2% for G1, 70% for G2, and 94.4% for G3 tumors. Combining both tests, the sensitivity was 78.2% for G1, 90% for G2, and 100% for G3. Conclusions The uCyt+ is a valid test in the detection of UC of all grades and stages. It improves the sensitivity of cytology in low-grade tumors. The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance.

p16 is a tumor suppressor gene that plays a central role in the regulation of the cell cycle. In squamous cervical cancers, overexpression of p16 is induced by HPV and associated with the carcinogenesis of cervical epithelia. The aim of this study was to determine whether immunostaining of p16 is useful in detecting adenocarcinomas of the cervix uteri in histologic and cytologic routine specimens. A total of 45 surgical specimens, including 18 cases of invasive carcinoma, 8 cases of adenocarcinoma in situ, 4 cases of endocervical glandular atypia (cervical glandular intraepithelial neoplasia), and 15 reactive lesions of the endocervical glands were immunostained using a specific anti-human p16 monoclonal antibody (clone E6H4, mtm laboratories AG, Heidelberg, Germany). Furthermore, immunocytochemical analysis was performed on 10 preoperative ThinPrep cytologic samples with abnormal glandular cells and compared with the human papillomavirus status as assessed with the Hybrid Capture II test. p16 was detected immunohistochemically in all 26 cases of adenocarcinoma of the cervix uteri, including 18 invasive and 8 in situ carcinomas. Only a focal expression was evidenced in the four specimens with endocervical glandular atypia, and no reaction was found in reactive lesions. Also, the immunocytochemical analysis on the 10 ThinPrep specimens evidenced a strong expression of p16 in neoplastic endocervical cells. In all cases this was associated with a high-risk HPV-positive typing. p16 is a useful marker for the detection of the adenocarcinoma of the cervix uteri and its precursors. The immunocytochemical detection on ThinPrep specimens may contribute to an early detection of endocervical lesions.

We report on a 19-week-old fetus with a 46,XX karyotype, normal female external genitalia, complete gonadal agenesis, large encephalocele, spina bifida, and omphalocele. We postulate a new syndrome. Hitherto no consistent malformation patterns have been observed in agonadism patients. True agonadism, including even the unusual finding of an XX gonosomal status, is obviously not as rare as suggested.

As the goals of palliative cancer treatments have not always been clearly specified, this paper describes how frequently the goals of palliative cancer treatment can be specified according to a given definition and how frequently those specified goals can be achieved. The clinical problems of 171 cancer patients were discussed in the Interdisciplinary Oncologic Conference (IOC) of the Cancer Centre University of Ulm (CCUU) and recommendations concerning further diagnostic treatments and/or therapy were provided. These recommendations had been documented and analysed retrospectively. The goals were classified as either cure or palliation or further investigation. If the goal was palliation, it was investigated whether or not the goal was specified as either alleviation of existing problems or prevention of impending problems. The achievement of the specified goals was assessed. Palliation was the goal of treatment in 119 (71%) of the 168 evaluable recommendations. In 83 of the 119 cases (70%), immediate treatment was recommended. The goal was specified in 57 (69%) of the 83 recommendations and could be realized in 24 of 57 specified cases (42%). Patients in this group survived longer (p0.01) than patients in whom the goals could not be achieved. Impending problems could be prevented more often (p = 0.001) in 14 out of 18 cases, while existing problems could be alleviated in only 10 out of 34 cases. It is concluded that specification of the goals of palliation is necessary because it is impossible to decide if a goal of treatment could be achieved or not unless the goal of treatment has been defined (as existing/impending problem). The prevention of impending problems could be investigated in prospectively controlled clinical trials.