A novel method to visualise the three-dimensional organisation of the human cerebral cortical vasculature.

Current tissue-clearing protocols for imaging in three dimensions (3D) are typically applied to optimally fixed, small-volume rodent brain tissue - which is not representative of the tissue found in diagnostic neuropathology laboratories. We present a method to visualise the cerebral cortical vasculature in 3D in human post-mortem brain tissue which had been preserved in formalin for many years. Tissue blocks of cerebral cortex from two control cases, two Alzheimer's brains and two cases from Alzheimer's patients immunised against Aß42 were stained with fluorescent Lycopersicon esculentum agglutinin (Tomato lectin), dehydrated and cleared using an adapted three-dimensional imaging of solvent cleared organs (3DISCO) protocol to visualise the vascular endothelium. Tissue was imaged using light sheet and confocal microscopy and reconstructed in 3D using amira software. The method permits visualisation of the arrangement of the parallel penetrating cortical vasculature in the human brain. The presence of four vascular features including anastomosis, U-shaped vessels, spiralling and loops were revealed. In summary, we present a low cost and simple method to visualise the human cerebral vasculature in 3D compatible with prolonged fixation times (years), allowing study of vascular involvement in a range of normative and pathological states.

New targets for the immunotherapy of colon cancer-does reactive disease hold the answer?

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women, posing a serious demographic and economic burden worldwide. In the United Kingdom, CRC affects 1 in every 20 people and it is often detected once well established and after it has spread beyond the bowel (Stage IIA-C and Stage IIIA-C). A diagnosis at such advanced stages is associated with poor treatment response and survival. However, studies have identified two sub-groups of post-treatment CRC patients--those with good outcome (reactive disease) and those with poor outcome (non-reactive disease). We aim to review the state-of-the-art for CRC with respect to the expression of cancer-testis antigens (CTAs) and their identification, evaluation and correlation with disease progression, treatment response and survival. We will also discuss the relationship between CTA expression and regulatory T-cell (Treg) activity to tumorigenesis and tumor immune evasion in CRC and how this could account for the clinical presentation of CRC. Understanding the molecular basis of reactive CRC may help us identify more potent novel immunotherapeutic targets to aid the effective treatment of this disease. In this review, based on our presentation at the 2012 International Society for the Cell and Gene Therapy of Cancer annual meeting, we will summarize some of the most current advances in CTA and CRC research and their influence on the development of novel immunotherapeutic approaches for this common and at times difficult to treat disease.

Health care cost and utilization project analysis of comorbid illness and complications for patients undergoing hysterectomy for endometrial carcinoma.

OBJECTIVE: The objective was to study the association of race, comorbid illness, and lymph node dissection (LND) with complications in patients undergoing hysterectomy for endometrial carcinoma. METHODS: The Health Care Cost Utilization Project analysis studied women undergoing hysterectomy for endometrial carcinoma in 1996. Chi-square and Student t tests were used to determine differences in means or proportions. Linear, stepwise, and three-stage regression analyses were used to build predictive models for charges and lengths of stay (LOS). RESULTS: The mean age of the 5730 patients was 64.5 (standard deviation, 12.37); 72% of the patients were white, 5% were African American, and 23% were classified as "other." Ninety percent underwent total abdominal hysterectomy, 5% total vaginal hysterectomy (TVH), 4% radical abdominal hysterectomy, and 1% TVH/laparoscopy. Thirty-eight percent also underwent LND. Lymph node dissection was performed more frequently at teaching hospitals (P = 0.0000) and was associated with more complications. Comorbid illness (i.e., diabetes, heart disease) was documented in 51% of admissions, and > or = 1 comorbidity was documented in 21.5%. African Americans were more likely to have one or more comorbid illnesses, underwent more LNDs (P = 0.02), suffered more complications (P = 0.0001), and were more likely to die in the hospital compared with whites or others (P = 0.000). Although LND, complications, and longer LOS were more likely to occur in teaching hospitals (P = 0.0005), total charges and inpatient death were not higher in teaching hospitals. CONCLUSIONS: The higher frequency of comorbid illness, complications, LND, and inpatient death in African Americans reflects severity of medical illness and cancer in these patients. Teaching hospital admission was associated with more complications and longer LOS, but not a higher death rate.

Orbital cellulitis due to occult orbital lymphangioma.

A 12-year-old female patient with atypical orbital and periorbital cellulitis was found to have an occult lymphangioma of the orbit. Recognition of this entity provided an explanation for the atypical features of the case and guided appropriate medical management.

Repeat cervical cytology at the time of colposcopy. Is there an added benefit?

OBJECTIVE: To determine if repeating the Pap smear (PS) at colposcopy offers added benefit in the detection of cervical squamous intraepithelial lesions (SILs). STUDY DESIGN: Eight hundred fifty-two women were subjects of this study. Patients with cervical SIL were defined as women with SIL on the repeat PS, or SIL on the colposcopic cervical biopsy (bx) or a negative repeat PS and bx but confirmed SIL on both the previous and follow-up PS or bx. The sensitivities of repeat PS and bx in detecting SIL were calculated. The chi 2 test was used to assess statistical significance. The total cost of repeating the PS was calculated by multiplying the total number of patients (852) by the estimated cost of a single PS ($25). RESULTS: The sensitivities of repeat PS, bx and PS/bx combined were .89, .69 and .92 for low grade SIL (LSIL) and .74, .77 and .98 for high grade SIL (HSIL), respectively (P < .0001). Sixteen percent of the HSIL and 28% of the LSIL cases were diagnosed on repeat PS only (negative bx). If repeat PS was omitted, $21,300 would have been saved.

Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice.

PURPOSE: Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)-derived oxidants such as peroxynitrite and tested this hypothesis in a mouse model of ROP. METHODS: Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor N:(G)-nitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. RESULTS: Oxygen-induced retinal vaso-obliteration was significantly reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso-obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. CONCLUSIONS: These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP.

Human papillomavirus absence predicts normal cervical histopathologic findings with abnormal papanicolaou smears: a study of a university-based inner city population.

INTRODUCTION: We studied the role of human papillomavirus (HPV) typing in predicting cervical dysplasia in women with abnormal Papanicolaou (Pap) test results. STUDY DESIGN/METHODS: A university colposcopy clinic-based consecutive sample of 179 women completed a questionnaire and underwent colposcopy, HPV typing (Hybrid Capture System HPV DNA Assay II; Digene Diagnostics, Gaithersburg, MD, USA), and biopsy (if indicated). RESULTS: No severe dysplasia was observed in women with low-risk HPV or in women with negative HPV test results who had a low-grade abnormality on the Pap test. High-risk (HR) HPV was present in every case of severe dysplasia on biopsy. The cumulative odds risk for cervical dysplasia was 1.11 in HIV(+) women with low-grade squamous intraepithelial lesion on the Pap test who were older than 21 years of age and HPV-HR(+). CONCLUSIONS: In the population studied, HPV typing is a valuable adjunct to a low-grade abnormality on the Pap test in predicting the absence of cervical dysplasia on biopsy. Larger prospective population-based studies are needed to study the role of HPV as a negative predictor of disease in cervical dysplasia.

Cervical cancer outcomes analysis: impact of age, race, and comorbid illness on hospitalizations for invasive carcinoma of the cervix.

OBJECTIVE: The aim of this study was to evaluate the association of age, race, and comorbid illness with procedures and complications in hospitalized patients with invasive carcinoma of the cervix in a statewide population-based database over a 3-year period. METHODS: Hospitalizations were classified into homogeneous subgroups based on a diagnosis of invasive cervical cancer. Cancer-related complications and comorbid diseases were evaluated. chi(2) and t tests determined differences in means or proportions. Linear regression techniques were applied to build models for hospitalization charges and lengths of stay (LOS). RESULTS: There were 1009 admissions. The mean age was 49.5, with a median age of 46 (21-100, SD 15.4). Of the total, 606/1009 (60%) were white, 354/1009 (35%) were African-American (AA), and 5% were "other" races. AAs were more likely to have Medicaid or be uninsured (44% vs 23%, P = 0. 001) and were more likely to be admitted for an emergency (unadjusted odds ratio (OR) = 1.6; 1.2-2.2), to have a comorbid illness (P = 0.001), to be admitted for a cancer-related complication (P = 0.036), to be admitted for a transfusion (P = 0. 01), and to be admitted for radiation therapy rather than surgery (P = 0.001). The following were associated with LOS and higher hospital costs: emergency admissions for complications of cancer, comorbid illness, and older age. CONCLUSIONS: Racial differences exist in patterns of admission, type of therapy, and severity of illness; however, there were no differences in charges or LOS for similar procedures. The large percentage of African-Americans uninsured or insured by government-supported programs indicates the potential impact of public policy on the care of these patients. Socioeconomic status rather than phenotypic appearance may be a more important determinant of outcome.

Pharmacokinetic and pharmacodynamic study of the combination of docetaxel and topotecan in patients with solid tumors.

PURPOSE: The sequence in which chemotherapeutic agents are administered can alter their pharmacokinetics, therapeutic effect, and toxicity. We evaluated the pharmacokinetics and pharmacodynamics of docetaxel and topotecan when coadministered on two different sequences of administration. PATIENTS AND METHODS: On cycle 1, docetaxel was administered as a 1-hour infusion at 60 mg/m(2) without filgrastim and at 60, 70, and 80 mg/m(2) with filgrastim on day 1, and topotecan was administered at 0.75 mg/m(2) as a 0.5-hour infusion on days 1 to 4. On cycle 2, topotecan was administered on days 1 to 4, and docetaxel was administered on day 4. Cycles were repeated every 21 days. Blood samples for high-performance liquid chromatography measurement of docetaxel (CL(DOC)) and topotecan (CL(TPT)) total clearance were obtained on day 1 of cycle 1 and day 4 of cycle 2. CL(DOC) and CL(TPT) were calculated using compartmental methods. RESULTS: Mean +/- SD CL(DOC) in cycles 1 and 2 were 75.9 +/- 79.6 L/h/m(2) and 29.2 +/- 17.3 L/h/m(2), respectively (P: <.046). Mean +/- SD CL(TPT) in cycles 1 and 2 were 8.5 +/- 4.4 L/h/m(2) and 9.3 +/- 3.4 L/h/m(2), respectively (P: >. 05). Mean +/- SD neutrophil nadir in cycles 1 and 2 were 4,857 +/- 6, 738/microL and 2,808 +/- 4,518/microL, respectively (P: =.02). CONCLUSION: Administration of topotecan on days 1 to 4 and docetaxel on day 4 resulted in an approximately 50% decrease in docetaxel clearance and was associated with increased neutropenia.

Augmented Hummelsheim procedure for paralytic strabismus.

PURPOSE: To report a modification of the Hummelsheim procedure for use in the management of paralytic strabismus. METHODS: Eight patients with paralytic strabismus secondary to third nerve palsy (n=1), sixth nerve palsy (n=3), combined cranial nerve palsy (n=1), or extraocular muscle damage (n=3) were treated using a modification of the Hummelsheim transposition procedure. The procedure involves half-tendon transpositions of the adjacent rectus muscles to the insertion of the paralyzed muscle, coupled with resection of the transposed halves. Further augmentation was achieved by surgical or pharmacologic weakening of the ipsilateral (n=6) or contralateral (n=1) antagonist. One patient underwent the procedure bilaterally. All patients underwent at least 6 weeks of follow-up. RESULTS: The mean preoperative primary position deviation in the seven unilateral cases was 54 prism diopters (delta) (range: 25-85 delta). Preoperative forced ductions were positive in four cases. Resections varied from 4-8 mm. Ipsilateral antagonist recession varied from 0-14 mm. The mean change was 52 delta (range: 25-85 delta). Five cases were aligned within 15 delta of orthotropia at 6 weeks. No cases of anterior segment ischemia or induced vertical deviation were noted. CONCLUSION: The modified Hummelsheim procedure appears capable of correcting large angles of strabismus associated with muscle palsy of various etiologies. It is safe, amenable to adjustable sutures, and relatively tissue- and vessel-sparing. Additional study is required to understand more fully the procedure's component effects and its interaction with ocular rotation.

Vascular endothelial growth factor activates STAT proteins in aortic endothelial cells.

Vascular endothelial growth factor (VEGF) intracellular signaling in endothelial cells is initiated by the activation of distinct tyrosine kinase receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1/KDR). Because the tyrosine kinase-dependent transcription factors known as STAT (signal transducers and activators of transcription) proteins are important modulators of cell growth responses induced by other growth factor receptors, we have determined the effects VEGF of on STAT activation in BAEC (bovine aortic endothelial cells). Here, we show that VEGF induces tyrosine phosphorylation and nuclear translocation of STAT1 and STAT6. VEGF also stimulates STAT3 tyrosine phosphorylation, but nuclear translocation does not occur. We found that placenta growth factor, which selectively activates VEGFR1, has no effect on the STATs. However, upon VEGF stimulation, STAT1 associates with the VEGFR2 in a tyrosine kinase-dependent manner, indicating that VEGF-induced STAT1 activation is mediated primarily by VEGFR2. Thus, our study shows for the first time that VEGF activates the STAT pathway through VEGFR2. Because the growth-promoting activity of VEGF depends upon VEGFR2 activation, these findings suggest a role for the STATs in the regulation of gene expression associated with the angiogenic effects of VEGF.

Cervical cancer--the impact of clinical presentation, health and race on survival.

This study evaluated the association of race, comorbid illness, insurance status, and other prognostic factors on treatment and survival of patients with invasive carcinoma of the cervix, using as its methodology a retrospective study of patients with invasive carcinoma of the cervix treated from 1991 to 1998 at the University of Maryland. Of 161 such patients, 153 met the study criteria. Of these 153 women, 83 (54%) were African Americans and 70 (46%) were white. The mean (+/- SE) age of African American women was 52 +/- 1.8 years and that of white women was 50 +/- 1.8 years. African American women were more likely to present with stages II-IV disease (P = 0.01) and, as a consequence, underwent radiation therapy rather than surgery (P = 0.04). The survival of African American women with stage I-II disease was significantly lower than for white women. In the final regression model, stage III-IV disease (hazard ratio 3.2, 95% (CI 1.7, 6.1) African American race, (hazard ratio 1.9; 95% CI 1.0, 3.3) and comorbid illnesses (hazard ratio 2.3; 95% CI 1.3-4.0) were associated with poor survival. Adverse outcomes of African American women with cervical cancer persist after adjustment for stage of disease and other factors and are particularly apparent in stage I-II disease. The role of comorbid illness is deserving of further study.

Discordant retinoblastoma in monozygotic twins.

PURPOSE: We report cases of discordant retinoblastoma in twins confirmed to be monozygotic by DNA analysis. METHODS: Twin A demonstrated severe, bilateral, multifocal retinoblastoma, which was recalcitrant to external beam irradiation and chemoreduction. Twin B has not demonstrated retinoblastoma. DNA analysis was performed with polymorphic microsatellite markers to confirm monozygosity. Single-stranded conformation polymorphism and Southern blot analysis of the retinoblastoma gene were performed. RESULTS: Molecular genetic analyses confirmed monozygosity but failed to disclose a retinoblastoma gene mutation in either twin. CONCLUSIONS: The extreme phenotypic discordance may best be explained by an unidentified, postzygotic retinoblastoma gene mutation in early embryonic development of the affected twin.

Current trends in the management of carcinoma of the cervix, vulva, and vagina.

In this review, current basic and clinical literature that describes innovative strategies for staging diagnosis and management of cancers of the cervix, vulva, and vagina are reviewed. The reviewed literature includes investigations of viral oncogenesis, the role of angiogenesis in tumor development, pretreatment staging, and the emerging role of chemotherapy in the treatment of locally advanced disease.

The effect of blood transfusion protocol on retinopathy of prematurity: A prospective, randomized study.

OBJECTIVE: Controversy exists regarding the potential influence of anemia and blood transfusions on the rate of retinopathy of prematurity (ROP) in premature infants. A prospective, randomized, masked trial was performed to determine the influence of red blood cell transfusion protocol on ROP incidence and severity in a population of high-risk infants. METHODS: A total of 50 infants with birth weights <1251 g were divided randomly into two groups beginning on day of life 29. Group 1 (n = 24) received red cell transfusions during the 6-week study period, only if certain symptom-based guidelines were met. Group 2 (n = 26) received red cell transfusions to maintain the hematocrit level above 40% for the entire 6 weeks. Infants were monitored for ROP, growth, and associated morbidity. Serial measurements of serum glucose, lactate, ferritin, total iron-binding capacity, and iron were performed. RESULTS: ROP occurred in 83% of infants in group 1, and 73% of infants in group 2. There were no statistically significant differences in ROP severity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or any of the laboratory values except hemoglobin (10.8 vs 13.2 g/dL) and hematocrit (33.9% vs 41.8%) between the groups. Combining data from both groups, there was no association between hemoglobin or hematocrit ratios and ROP incidence or severity. CONCLUSIONS: A transfusion policy aimed at limiting the amount of blood given to premature infants (symptom-based) during the neonatal period does not impart a significantly different risk for ROP or other associated conditions, than does a policy in which transfusions are given more liberally for replacement purposes.

Cluster of diplopia cases after periocular anesthesia without hyaluronidase.

PURPOSE: To describe a cluster of cases of iatrogenic diplopia after cataract surgery that occurred in 1998, when hyaluronidase was unavailable for use in periocular anesthetic regimens. SETTING: The clinical practices of the authors. METHODS: This study comprised a retrospective chart review. RESULTS: Twenty-five cases of transient or permanent diplopia were reported. Of these, 13 eyes had retrobulbar and 10 had peribulbar injections; in 2 cases the injection technique was unknown. The inferior rectus was affected in 19 eyes; of these, 1 had a temporary palsy and 18 had permanent restriction. Temporary paresis developed in the lateral rectus in 5 cases and the superior rectus in 2. Eleven cases were submitted by 4 anterior segment surgeons, who collectively had a zero incidence of iatrogenic postoperative diplopia in the preceding 4 to 11 years of practice (approximately 6900 cases). CONCLUSION: Hyaluronidase may be more important than previously suspected in preventing anesthetic-related damage to the extraocular muscles. The inferior rectus muscle is particularly vulnerable, presumably because of the injection technique.

The negative psychosocial impact of strabismus in adults.

INTRODUCTION: The goal in the treatment of strabismus is to realign the visual axes to eliminate diplopia, produce or restore binocular vision, expand the binocular visual field, and/or provide a normal appearance. The treatment of strabismus in adults who do not experience diplopia or who do not have binocular potential has sometimes been regarded as "cosmetic." Many adults with strabismus have stated that it has had a negative effect on their lives. This study was designed to ascertain whether there is a negative social bias against adult patients with strabismus that could affect interpersonal relationships and limit employment opportunities. METHODS: An orthotropic person was photographed in primary, right, and left gaze. These photographs were then digitally altered to produce an esotropia and exotropia of similar magnitude. Subjects were then asked to evaluate a single photograph with reference to personality characteristics that are important for social interaction and employment capability. RESULTS: Overall, the strabismic faces were judged significantly more negatively, across 11 descriptive characteristics, than the nonstrabismic face. The effect of esotropia was worse than exotropia. CONCLUSION: Strabismus creates a significant negative social prejudice. These biases can have a detrimental impact on socialization and employability. Treatment of strabismus may positively alter perceived characteristics of individuals and improve their ability to socialize normally and obtain employment. Therefore, the treatment of strabismus should not be considered cosmetic even when there is no hope of improving binocular vision.

Treatment of posttraumatic ocular dysmotility using autogenous buccal fat grafts in a porcine model.

Diplopia occurring after orbital trauma is a complex and difficult clinical problem. Numerous potential mechanisms exist by which it may occur. Restrictive ocular dysmotility caused by intraorbital scarring is a major component in diplopia's pathogenesis. The current large animal study was conducted to develop an experimental model of restrictive ocular dysmotility that would quantitatively characterize the biomechanical properties of the globe rotations. Using this model, a novel method of restoring the low-friction milieu within the orbit by interposing a buccal fat graft was tested. In the initial stage, the baseline force duction was measured in 20 pig eyes using a highly sensitive, digital tensiometer. Traumatic violation of Tenon's fascia with electrocautery into the extraconal fat and the periorbita was followed by direct suturing of the extraocular muscle to the nearest orbital periosteum. After 6 weeks, the measurements (again in the field of the traumatized muscle) were repeated, and the eyes were divided into two treatment groups (n = 10 eyes per group). The left eye received the standard lysis of adhesion, whereas the right eye received lysis and buccal fat interposition grafting. The third and final force measurements were performed 6 weeks after treatment. The results showed a baseline linear load-displacement curve of 0 to 8 mm, with the globe rotating 400 microm for every 1000 mg of tensile load. Surgical trauma increased the slope as defined by load/displacement but, surprisingly, the relationship remained linear in the entire range from 2 to 8 mm. This linear relationship was seen in all stages: baseline, after trauma to Tenon's fascia, after surgical lysis alone, and after lysis with buccal fat interposition. The difference was in the slope, or stiffness. Lysis alone partially reduced the slope, but it was still higher than baseline. Lysis and buccal fat grafting returned the slope to near baseline. This, however, did not reach the level of statistical significance. It seems that a focal intervention along the course of an extraocular muscle altered the composite behavior of orbital resistance to globe rotation. Although buccal fat grafting did not significantly improve motility, it did not worsen it.

Artifact in cervical LLETZ specimens: correlation with follow-up.

The effect of cautery artifact on the ability to accurately diagnose dysplasia and predict abnormal follow-up in large loop excision specimens of the transformation zone (LLETZ) has not been adequately addressed in the pathology literature. One hundred consecutive conization specimens with cytologic and/or histologic follow-up were studied. Indications for the procedure were high-grade squamous intraepithelial lesion (on Pap smear and/or biopsy) in 64 cases, low-grade squamous intraepithelial lesion in 28, atypical squamous cells of unknown significance (ASCUS) in 3, atypical glandular cells of unknown significance in 2, adenocarcinoma in situ, squamous carcinoma in situ, and invasive squamous carcinoma in 1 each. Twenty-four specimens were cold-knife conizations (CKCs) and 76 LLETZs. All LLETZs had at least 1+ artifact, and in 46 cases (61%) it interfered with at least one aspect of evaluation. In 21 cases (28%), 1+ artifact interfered only with margin assessment. In 25 cases (33%), there was 2+ or 3+ artifact precluding not only margin assessment, but also diagnosis and grading of dysplasia. Of the 43 LLETZs received in more than one piece, 33 (77%) had interfering artifact, and in 21 (49%) it was 2+ or 3+, at least focally interfering with diagnosis and grading. In contrast, of 33 LLETZs received in a single piece, only 13 (39%) had interfering artifact, which was 2+ or 3+ in 4 (12%), (p < 0.05). Positive follow-up (including ASCUS, favor dysplasia, and ASCUS, not otherwise specified) was found in 6 of 7 CKCs with positive margins (86%), 10 of 16 LLETZs with positive margins (63%), and 4 of 7 LLETZs with unassessable margins (57%). In cases with negative cone margins, positive follow-up was found in 2 of 17 CKCs (12%), and 18 of 53 LLETZs (34%), p < 0.05; a higher frequency of interfering artifact (p < 0.05) was seen in these cases. LLETZ margin status and postprocedure endocervical curettage (ECC) specimens were not good predictors of residual disease, unlike margin status in CKC. Post-CKC ECC was a better predictor of subsequent abnormal follow-up than post-LLETZ ECC (p < 0.05). The presence of interfering artifact was only rarely mentioned in the original pathology report. In conclusion, the status of margins is a better predictor of abnormal follow-up in CKC than in LLETZ specimens. Fragmentation of the specimen is an additional factor, compounding the inevitable artifact. Postprocedure ECC is not a useful indicator of residual dysplasia. The pathologist should not hesitate to comment on specimen adequacy in surgical pathology reports.