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Purpose To describe 10 patients with Morbihan syndrome, a rare condition characterized by the slow appearance of erythema and solid edema on the upper portion of the face, and review the literature. Methods Retrospective case series and review. Results The majority of patients were male (80%), and the mean age at presentation was 67 years (range, 48-88 years); 60% had asymmetrical disease (affecting mainly the right side). All subjects underwent a lid biopsy to support the diagnosis of Morbihan syndrome, which showed features of inflammation and vascular dysfunction, highly suggestive of a rosacea histological picture complicated by chronic lymphoedema. A range of medical and surgical treatment were used with variable success. The most effective ones included oral isotretinoin, intralesional triamcinolone injections, and debulking surgery. Conclusions Morbihan syndrome is a rare and chronic condition. It can be difficult to treat and may require a range of interventions.

This case report deals with two patients with lacrimal sac swellings. Case 1 presented with bilateral sac swelling and Case 2 with a unilateral presentation. Dacrocystorhinostomy (DCR) followed by biopsies of both sacs in Case 1 revealed inflammatory polyps of the sac mucosa, identical in appearance to typical nasal allergic inflammatory polyps. The biopsies were accompanied by typical allergic mucin, featuring tiered mucin layers between which were numerous eosinophils, accompanied by Charcot-Leyden crystals. The histology of the dacryocystectomy specimen for Case 2 showed identical histopathological changes with the additional feature of prominent numbers of Immunoglobulin G (IgG)4-positive plasma cells in the stroma of the lacrimal sac inflammatory polyps. These features extend the sites affected by allergic inflammatory polyps and allergic mucin and possible pathogenesis is discussed.

Background/objectives To evaluate the outcomes of orbital evisceration with primary implant placement in acutely infected/inflamed eyes, using implant exposure/extrusion as a surrogate of success. To contextualise this with previously published literature. Subjects/methods A retrospective case series of all patients with acutely infected/inflamed eyes undergoing urgent orbital evisceration with primary implants, at a British tertiary centre between January 2006 and August 2018. A systematic literature review of orbital eviscerations with primary implant placement in acute endophthalmitis/infection and recent trauma. Results Twenty-six eyes were eviscerated in the context of acute infection/inflammation. Twenty-four eyes had primary orbital implants. Indications for evisceration included endophthalmitis (18/26, 69%), microbial keratitis with corneal perforation (4/26, 15%), non-infectious corneal perforation (3/26, 12%), and recent trauma (1/26, 4.8%). The implants used were acrylic (15/24, 63%), MEDPOR (5/24, 21%), and silicone (4/24, 17%). The follow-up period was 15 months to 14 years. Implant exposure occurred in two (8.3%), managed with implant exchange and scleral reformation in one, and implant removal with dermis fat grafting in the other. One patient (4.2%) had conjunctival wound dehiscence with spontaneous healing. Six (25%) required further surgery for minor complications as follows: conjunctival prolapse, upper lid ptosis with slight sulcus loss, lower lid entropion with shortened fornix, and lower lid ectropion. The systematic literature review showed that the mean rate of orbital implant exposure/extrusion in this subset of patients was 7.8% (95% CI: 2.7%, 12.9%, SD 8.0%), range 0-27%. Conclusions In acutely infected/inflamed eyes, the implant exposure/extrusion rate following orbital evisceration with primary implant placement is acceptable.

AimsThe aim is to study staged periocular basal cell carcinoma (BCC) excision in a tertiary oculoplastic referral centre in Sheffield, UK. In particular, we examined patients with close or positive margins and no tumour seen on re-excision to identify demographics and tumour characteristics in this population.MethodsA retrospective review of medical records of 437 cases of staged periocular BCC excisions over a 10-year period (2007–2017) was carried out. Patients had surgical excision with 3 mm clinically clear margins. Staged excision was performed for all cases included in this study. Standard reconstruction techniques were employed. Histopathology was analysed for tumour type, subtype and stage.ResultsOver the 10-year period, of the 437 periocular BCCs, 156 had close or involved margins. Residual tumour was found in 29 (18.6%), whereas in 122 eyelids of 120 patients (78.2%) no residual tumour was identified on histological examination. Micronodular (54.1%) and nodular (23.7%) growth patterns of BCC, as well as lower eyelid location (72.1%), were the most prevalent in this population. Two patients (1.6%) had recurrence of BCC over a mean follow-up of 57 months (range 1–125 months).ConclusionsA significant proportion of BCCs transected on initial excision show no residual tumour in the re-excision specimens. In the interval between initial excision and re-excision, there may be eradication of the residual tumour. The exact mechanisms for this are unclear, however, and re-excision remains the appropriate recommended course in the presence of involved surgical margins of periocular BCC, particularly when high-risk tumour subtypes are encountered.

PURPOSE: To determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published literature. PATIENTS AND METHODS: A retrospective case review of all patients undergoing orbital decompression for TED under the care of one orbital surgeon (SMS) between January 2009 and December 2015. A systematic literature review of orbital decompression for TED. RESULTS: Within the reviewed period, 93 orbits of 55 patients underwent decompression surgery for TED. There were 61 lateral (single) wall decompressions, 17 medial one-and-a-half wall, 11 two-and-a-half wall, 2 balanced two wall, and 2 orbital fat only decompressions. For the lateral (single) wall decompressions, mean reduction in exophthalmometry (95% confidence interval (CI) was 4.2 mm (3.7–4.8), for the medial one-and-a-half walls it was 2.9 mm (2.1–3.7), and for the two-and-a-half walls it was 7.6 mm (5.8–9.4). The most common complications were temporary postoperative numbness (29% of lateral decompressions, 17% of other bony decompressions, OR 0.50, 95% CI 0.12–2.11) and new postoperative diplopia (9% of lateral decompressions, 39% of other bony decompressions, OR 6.8, 95% CI 1. 5–30.9). Systematic literature searching showed reduction in exophthalmometry for lateral wall surgery of 3.6–4.8 mm, with new diplopia 0–38% and postoperative numbness 12–50%. For other bony decompressions, reduction in exophthalmometry was 2.5–8.0 mm with new diplopia 0–45% and postoperative numbness up to 52%. CONCLUSION: Differing approaches to orbital decompression exist. If the correct type of surgery is chosen, then safe, adequate surgical outcomes can be achieved.

Fireman Z. Biopsy forceps: reusable or disposable? J Gastroenterol Hepatol. 2006;21:1089–92. Article Google Scholar Lockington D, Macdonald E, Mantry S, Ramaesh K. A case for single use disposable corneal forceps: equipment reliability should be the primary concern. Br J Ophthalmol. 2010;94:388–9. Article Google Scholar NHS England. Carbon emissions: carbon footprinting study sustainable development commission. London: NHS England; 2008. Wormer BA, Augenstein VA, Carpenter CL, Burton PV, Yokeley WT, Prabhu AS, et al. The green operating room: simple changes to reduce cost and our carbon footprint. Am Surg. 2013;79:666–71. Article Google Scholar Lockington D, Dutton GN. Eyes, economics and the environment: should green issues drive changes in ophthalmic care?–no. Eye. 2010;24:1312–4. CAS Article Google Scholar Download references Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK Christine A Putri, Parushak Rezai, Jennifer Capel & Zanna Currie You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Christine A Putri. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Putri, C.A., Rezai, P., Capel, J. et al. Money, environment and eyelids. Eye (2020). https://doi.org/10.1038/s41433-020-01189-z Download citation Received: 17 July 2020 Revised: 12 September 2020 Accepted: 14 September 2020 Published: 22 September 2020 DOI: https://doi.org/10.1038/s41433-020-01189-z

Microphthalmic cysts are rare. Although small cysts can be left in situ to promote orbital expansion, large cysts require drainage or surgical excision. Complete surgical excision is notoriously difficult, and incomplete excision may result in cyst reformation. We describe a novel method of using fibrin glue to aid successful complete removal of a large recurrent microphthalmic cyst in a 6-year-old child who previously had multiple drainage and surgical attempts.

Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. We studied the association between MC1R variants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. We pooled individual data from 15 case-control studies conducted during 2005-2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. Six thousand eight hundred ninety-one CM cases and 5555 controls were included. CM risk was increased among MC1R variant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma (ALM), for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47-2.07) than intermittently (1.55, 95% CI 1.34-1.78) sun-exposed skin. CM risk was greater for those carrying 'R' vs. 'r' variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated with MC1R status. MC1R variants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Objective To evaluate the incidence and management of recurrent periocular sebaceous gland carcinoma at a tertiary ocular oncology service in the United Kingdom. Methods This was a retrospective cohort study of 62 patients with sebaceous gland carcinoma treated between 2004 and 2017. A total of 10 eyes were treated for local recurrence. The following variables were recorded: age and sex of patient; tumour location, histological subtype; recurrence type; treatment and outcome. Results Of the 62 cases with eyelid SGC, 10 (16%) had recurrences during the study period and satisfied inclusion criteria. There were six (60%) females and four males in the recurrent group. The mean time interval between initial excision and tumour recurrence was 37 months (median 23 months; range 4 to 84 months). Four patients received cryotherapy to the lids and conjunctiva to control recurrent disease and two patients were treated with topical or intralesional chemotherapy. Four patients (40%) underwent orbital exenteration during the study period. Metastasis occurred in 20% over a mean follow-up of 113 months (median 106; range 47–184 months). Conclusions The risk factors for local recurrence of SGC after wide excision with paraffin section control were reported, and an approach to these recurrent lesions was proposed. The results of this study will help guide surgeons dealing with the medical and surgical conundrum of recurrent disease. The risk of recurrence is highest in the first 2 years after initial excision.

Purpose: To describe the clinical and histopathological features of a conjunctival melanoma (CM) during early pregnancy. Procedures: A 37-year-old, 20-week pregnant primigravida was referred to the Sheffield Ocular Oncology Service with a rapidly growing lesion arising from the right superior conjunctival fornix, noted from the first trimester of pregnancy. This was associated with pain and bloody discharge. Incisional biopsy confirmed the clinical suspicion of invasive CM. She was treated by primary surgical excision and cryotherapy under local anaesthesia. Results: Histology of the excised specimen showed an invasive malignant melanoma with surrounding in situ conjunctival changes arising from a naevus. The melanoma was 10.5 mm thick, focally necrotic, and had a mitotic count of 11/mm2 focally. The patient responded well to surgical treatment. She gave birth to a healthy boy, and the placenta showed no evidence of metastatic melanoma. There has been no recurrence or distant metastasis during 5 years of follow-up. Conclusion: CM during pregnancy is extremely rare. Because of possible transformation to malignant melanoma, we recommend close monitoring of females known to have pigmented conjunctival lesions of the conjunctiva during pregnancy.

To analyze the genetic profile of 6 cases of primary orbital melanoma with clinicopathologic correlation.Retrospective noninterventional study to analyze the genetic profile of 6 cases of primary orbital melanoma and to correlate the genetic findings with prognosis and clinicopathologic features. Inclusion criteria were patients with primary orbital melanoma with no evidence of primary eyelid skin, conjunctival, uveal, or remote melanoma at extraocular sites.The study involved 6 primary orbital melanomas from 6 patients. Four patients were exenterated and 2 had incisional biopsies performed.Clinical notes and radiologic records were assessed to ascertain clinical tumor behavior. Sections were stained with hematoxylin-eosin and exposed to immunohistochemistry for S100, MelA, HMB45, Sox10, and BAP1. Melanoma DNA was exposed to array comparative genomic hybridization to assess gross chromosomal copy number changes. Point mutation assessment and Sanger sequencing were performed for GNAQ, GNA11, BRAF, NRAS, pTERT, SF3B1, and EIF1AX.These were the presence of gross chromosomal copy number changes and the presence of mutations in GNAQ, GNA11, BRAF, NRAS, pTERT, SF3B1, and EIF1AX; the presence of metastases and time period between diagnosis and death from melanoma; and correlation between the tumor genetic profile and the clinical behavior of the tumor.One of the 6 cases was clinically associated with oculodermal melanocytosis. Of the 6 patients, 3 died of melanoma metastases and 1 of unrelated causes; 2 remain alive at last review. Three of the 6 cases were histologically associated with a benign precursor lesion. All melanomas expressed S100, MelA, HMB45, and Sox10. One patient showed loss of BAP1 nuclear staining. The most frequent chromosomal gains across the 6 cases, in order of frequency, were 6p, 8q, 17q, 6q, and 20p. The most frequently lost regions were 1p, 9p, 16q, and 17p. One patient showed monsomy 3 and gain of 8q (and showed the BAP1 loss). Mutations were found in GNAQ (1 case), GNA11 (1 case), SF3B1 (2 cases), NRAS (2 cases), and pTERT (2 cases).The data point to 2 genetic groups for primary orbital conjunctiva melanoma-like and a uveal melanoma-like group. A larger study would help confirm this suggestion.

Purpose: To describe the ophthalmic and histopathological features of a female with granulomatous common variable immunodeficiency (CVID) who presented with upper-lid swelling. Procedures: The patient underwent a biopsy of the right upper lid/palpebral lacrimal gland with imaging showing a left-sided nasopharyngeal mass, multiple lymph nodes within the mediastinum, bilateral lung nodules and a peritoneal nodule in the right iliac fossa. The right upper-lid swelling progressed and was subject to a second biopsy. Results: The first right upper-lid biopsy revealed a diffuse large B-cell lymphoma (DLBCL), confirmed with clonal IgH gene rearrangement with PCR. The nasopharyngeal mass and lymph nodes were suspected clinically to be DLBCL. However, a biopsy of the nasopharyngeal mass showed Kaposi sarcoma (KS). The second biopsy of the right upper lid/palpebral lacrimal gland revealed KS with no evidence of DLBCL. Conclusion: This is the first documentation of periocular/orbital metachronous DLBCL and KS in a patient with granulomatous CVID. We discuss the role of fluctuating immunity in CVID to explain the spontaneous regression of the DLBCL and the varying clinical picture.

Purpose: Description of the clinical and histopathological features of unusual lacrimal gland intra-glandular duct cysts. Procedures: A 38-year-old male presented with bilateral upper lid lumpiness, which was worse on the left. Computed tomography scan showed bilateral multiple lacrimal gland cysts, which were larger on the left compared to the right. After two unsuccessful attempts to excise the largest cyst on the left side, it was removed at the third attempt using a novel technique that incorporated the use of fibrin glue to fill the remaining cavity. Results: The microscopy of the left-sided cyst comprised a cavity containing fibrin glue, lined by intra-lobular lacrimal gland duct epithelium. The cyst wall contained reactive lymphoid aggregates, plasma cells and eosinophils associated with fibrosis. Focally, there were small vessels affected by an acute vasculitis associated with eosinophils and a granulomatous component. Conclusions: We ascribe the cyst formation to the effects of tractional fibrosis secondary to focal vasculitis and to obstructive fibrosis of the lacrimal ductules. This case also described a novel use of Tisseel fibrin glue to assist intact removal of a lacrimal gland cyst.

$\textbf{Purpose}$ $\textit{BRCA1/2}$ mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of $\textit{BRCA1/2}$ mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of $\textit{BRCA1/2}$ mutations and implications for cancer risk prediction. $\textbf{Materials and Methods}$ We genotyped 1,802 male carriers of $\textit{BRCA1/2}$ mutations from the Consortium of Investigators of Modifiers of $\textit{BRCA1/2}$ by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of $\textit{BRCA1/2}$ mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. $\textbf{Results}$ In male carriers of $\textit{BRCA1/2}$ mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; $P$ = 8.6 × 10$^{-6}$)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; $P$ = 3.2 × 10$^{-9}$)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of $\textit{BRCA1}$ mutations and from 19% to 61% for carriers of $\textit{BRCA2}$ mutations, respectively. $\textbf{Conclusion}$ PRSs may provide informative cancer risk stratification for male carriers of $\textit{BRCA1/2}$ mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

PURPOSE To evaluate the use of excision and delayed reconstruction with rapid paraffin section analysis in patients with sebaceous carcinoma (SC) of the periocular region. METHODS A retrospective study of patients with SC. Patients were identified from a contemporaneously maintained database and medical notes reviewed. Data were collected on known risk factors. Standard management started with conjunctival mapping biopsies. The tumor was excised with a 3-mm clinical margin and sent in formalin for histopathological analysis. The patient went home with dressings and returned 3 days later. Further excision or reconstruction was performed as indicated. Follow-up data were collected. RESULTS Seventeen patients had excision and delayed reconstruction with paraffin section control. Ten had clear margins after 1 excision, and 7 were clear after 2 excisions. Reconstructive technique varied according to the defect. Three patients developed further tumor. One of these had a local recurrence treated with further excision and reconstruction. One developed a multicentric tumor with regional metastasis, and the third patient developed distant metastasis. Two patients died from SC. Average follow up was 5 years (2-9 years). CONCLUSIONS Excision and delayed reconstruction using paraffin section histopathological analysis are in widespread use for the management of basal cell carcinomas in the periocular region. While some authors advocate the use of Mohs' micrographic surgery in patients with SC, this technique has been questioned due to the possible misinterpretation of subtle intraepithelial pagetoid spread with frozen section analysis. To preserve the function of the eyelid and ease of reconstruction, it is important to try and preserve as much healthy tissue as possible while effecting a successful excision. Excision and delayed reconstruction offer an excellent option for the management of this rare and highly malignant tumor.

Incidental folliculotropic mycosis fungoides in a blepharoplasty specimen performed for dermatochalasis

Aim A retrospective and longitudinal review of the outcome of strabismus surgery for adults with large- and very-large-angle manifest exodeviations, using two-, three- and four muscle horizontal recti surgery with adjustable sutures. Methods A total of 26 consecutive adult patients undergoing surgery for socially noticeable strabismus comprising five primary, 16 consecutive, and five secondary constant exotropias with a mean near deviation of 58 prism dioptres and a mean distance deviation of 55Δ were evaluated preoperatively and at various time intervals postoperatively. Surgery involved two muscles in seven cases, three muscles in 13 cases, and four muscles in six cases; and 25 of 26 had adjustable sutures. There was a horizontal preoperative ocular movement deficit in 17 that was asymmetrical in four cases. Results Binocularity was restored in eight patients (31%), 20 (77%) were within 10Δ of orthotropia, and 24 (92%) were happy with their cosmesis. Two had symptomatic asymmetrical ocular motility deficits postoperatively following a two-muscle procedure and one required reoperation. A total of 19 patients undergoing three- or four-muscle surgery were asymptomatic postoperatively. A total of 22 patients had follow-up of 8 months or more. Conclusion In adults with large-angle manifest exodeviations, adjustable suture surgery involving three or more horizontal recti successfully restores primary position alignment, a high degree of patient satisfaction, and can be expected to be associated with a low incidence of symptomatic postoperative asymmetrical ocular movement deficits.

PURPOSE Uveal melanoma continues to present problems when attempting to predict disease progression. This study attempts to identify markers indicative of the biological characteristics of cells isolated from samples of uveal melanoma, including adhesion (ICAM-1), immune reactivity (MHC Class I and II), cell cycle control (c-erbB-2, c-myc) and apoptosis control (bcl-2, p53) using dual parameter (DNA/MoAb) flow cytometry. METHODS Sixty-three fresh tissue samples from choroidal melanomas were taken at enucleation. Samples were assayed for DNA content and cell cycle, the above antibodies together with positive (PHM-5) and negative (2 degrees FITC Ab) controls. The clinical parameters sex, age, tumour location, cell type, tumour volume and presence of metastases were compared with the results and analysed with the non-parametric Mann-Whitney U-t-test. RESULTS ICAM-1 expression proved to be the most clinically relevant, being present on a higher proportion of cells in tumours > 2000 mm3 (median 38, n = 19) compared with the smaller tumours < 2000 mm3 (median 17, n = 26) (p = 0.0015). Metastatic disease was present in 11 patients and did not correlate with any of the surface markers. C-myc, c-erbB-2 and MHC Class II expression were associated with cell type, all showing greater expression in spindle cell tumours than mixed/epithelial types. CONCLUSION These results show flow cytometry as a quick, easy method to provide a 'phenotypic profile' for these tumours, and identifies cell cycle control and adhesion molecule expression as important areas for further investigation. c-erbB-2 and bcl-2 positivity was typically seen on over 60% cells in each sample, indicating two potential targets for therapeutic intervention.

Purpose: To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment. Methods: After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months. Results: Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1 %), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly ( P Conclusion: Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

p53 gene alterations are among the most common events observed in colorectal cancer,and are accompanied frequently by DNA aneuploidy and high proliferative activity. The prognostic significance of such mutations remains controversial. We prospectively evaluated the prognostic significance of p53 mutations, DNA-ploidy, and S phase fraction (SPF) in a consecutive series of 160 colorectal cancer patients (median follow-up 71 months). Tumor DNA was screened for p53 mutations by PCR/single-strand conformational polymorphism/sequencing. DNA-ploidy and SPF were assessed by DNA flow cytometry. p53 mutations were detected in 68 of 160 (42.5%) cases. In 56% (38 of 68) of these, p53 mutations were found in conserved areas of the gene and in 44% (30 of 68 cases) outside the conserved regions. Eighteen of the 68 cases (26%) had mutations in the L3 loop, 11 of 68 (16%) in the L1 loop-sheet-alpha helix motif, and 39 of 68 (58%) outside L3 and loop-sheet-alpha helix. Seventy-five percent of the cases (120 of 160) showed DNA aneuploidy, whereas 18% of these (22 of 120) were multiclonal. The major independent predictors for both disease relapse and death were advanced Dukes' stage, p53 mutations affecting L3 loop, DNA-aneuploid tumors, and high SPF (18.5%). Our results show that mutations in L3 functional domain, more than any mutations, are important biological indicators to predict the outcome of patients indicating that these mutations have biological relevance in terms of colorectal cancer disease course.