Serum-free light chain test utilisation at a South African academic laboratory and comparison with serum protein electrophoresis results.

Background: Serum protein electrophoresis (SPE), urine protein electrophoresis and immunofixation electrophoresis were traditionally utilised for the diagnosis of monoclonal gammopathies. The quantitative serum-free light chain (SFLC) assay is reportedly more sensitive and has been introduced to recent clinical guidelines. Objective: This study aimed to investigate SFLC test utilisation and describe SPE findings in patients with abnormal SFLC ratios. Methods: A retrospective audit of SFLC analyses was conducted in Cape Town, South Africa, from May 2018 to April 2020. Agreement between abnormal SFLC ratios and SPE results was determined in a sub-group of patients screened for monoclonal gammopathies. Serum-free light chains were analysed using Freelite® Kappa and Lambda assays. Results: Of the 1425 patients included in the audit, 741 (52%) had abnormal SFLC ratios; 636 (45%) had increased and 105 (7%) had decreased SFLC ratios. In a sub-group analysis of 117 new patients with an abnormal SFLC ratio, 57 had a monoclonal protein (M-protein) on SPE (49%), and 60 (51%) did not. Four out of 60 patients without M-protein had a plasma cell dyscrasia, while renal impairment or inflammatory response accounted for the rest. Of the 57 patients with a M-protein and abnormal SFLC ratio, 41 (72%) had a plasma cell dyscrasia, seven (12%) had lymphomas and nine patients (16%) were unclassifiable. Conclusion: Serum-free light chains should be requested when there is a high index of clinical suspicion. Neither SFLC nor SPE should be performed in isolation when screening patients for monoclonal gammopathy, to ensure that no patient is missed. What this study adds: The study adds to the evidence on SFLC test utilisation. Serum protein electrophoresis alone may miss cases of light chain myeloma, while SFLC performed in isolation may produce false positive results in the setting of inflammatory disorders or renal impairment, leading to unnecessary further investigation.

Insulin-like growth factor (IGF) and hepatocyte growth factor (HGF) in follicular fluid cooperatively promote the oncogenesis of high-grade serous carcinoma from fallopian tube epithelial cells: Dissection of the molecular effects.

Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin-like growth factor (IGF2) and hepatocyte growth factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high-grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co-injection model, we observed that FF co-injection induced tumorigenesis of STIC-mimicking cells, FE25. Co-injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co-injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring-independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine-protein kinase Met (cMET)/mitogen-activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF-IGF2 could mediate clonogenicity and stemness activities via the IGF-1R/AKT/mammalian target of rapamycin and IGF-1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF-sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.

Effect of ovulation IGF and HGF signaling on the oncogenesis of murine epithelial ovarian cancer cell ID8.

The incidence and mortality of epithelial ovarian cancer (EOC) are increasing in Taiwan and worldwide. The prognosis of this disease has improved little in the last few decades due to insufficient knowledge of the etiology. Previous studies on the role of ovulation in the development of EOC have unveiled IGF2, HGF, and other carcinogens in ovulatory follicular fluid (FF) that exert transformation activities on the exposed fallopian tube fimbria epithelium. However, an orthotopic proof in an animal model is lacking. By using the murine ID8 EOC cells and the syngenic transplantation model, this study explored the effect of FF on the oncogenesis of mouse ovarian cancer. We found FF promoted clonogenicity and anchorage-independent growth of ID8 cells, largely through the IGF-1R and cMET signaling. In contrast, FF modestly promoted cell proliferation independent of the two signals and did not affect cell migration and invasion. Transplantation of ID8 cells into the ovarian bursa of C57BL6/J mice orthotopically grew ovarian tumors and metastasized to the peritoneum with ascites formation. The tumorigenic rate and severity of the disease were positively correlated with the level of IGF-1R and cMET receptors on the cell surface. Our data demonstrated that ovulation, through the signaling of IGF/IGF-1R and HGF/cMET, promotes oncogenic phenotypes in a murine EOC model. The results provide further proof of the carcinogenic effect of ovulation in the development of EOC.

The Double Engines and Single Checkpoint Theory of Endometriosis.

Endometriosis is a chronic disease characterized by the ectopic localization of the endometrial tissue in the peritoneal cavity. Consequently, it causes local pathological changes and systemic symptoms, affecting at least one in every ten women. This disease is difficult to diagnose early, it is prone to dissemination, is difficult to eradicate, tends to recur, and is regarded as "a cancer of no kill". Indeed, the development of endometriosis closely resembles that of cancer in the way of mutagenesis, pelvic spreading, and immunological adaptation. While retrograde menstruation has been regarded as the primary cause of endometriosis, the role of ovulation and menstrual stimuli in the development of endometriosis has long been overlooked. The development of ovarian and peritoneal endometrioses, similar to the development of high-grade serous carcinoma in the fallopian tube fimbriae with intraperitoneal metastasis, depends highly on the carcinogens released during ovulation. Moreover, endometriosis carries an extremely hypermutated genome, which is non-inferior to the ultra-mutated endometrial cancer. The hypermutation would lead to an overproduction of new proteins or neoantigens. Because of this, the developing endometriosis may have to turn on the PD-1/PDL-1 "self-tolerance" checkpoint to evade immune surveillance, leaving an Achilles tendon for an immune checkpoint blockade. In this review, we present the double engines and single checkpoint theory of the genesis of endometriosis, provide the current pieces of evidence supporting the hypothesis, and discuss the new directions of prevention and treatment.

Acute kidney injury without need for dialysis, incidence, its impact on long-term stroke survival and progression to chronic kidney disease.

INTRODUCTION: Patients who had a stroke are at increased risk of sepsis, dehydration and fluctuations in blood pressure, which may result in acute kidney injury (AKI). The impact of AKI on long-term stroke survival has not been studied well. OBJECTIVE: We aimed to identify incidence of AKI during acute stroke, follow-up period and its impact on long-term survival and development of chronic kidney disease (CKD). DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of patients who had a stroke admitted at the rehabilitation facility in Changi General Hospital, Singapore, between June 2008 and May 2017, with median follow-up of 141 (95% CI 120 to 163) months. OUTCOME MEASURES AND RESULTS OF UNIVARIATE ANALYSIS: Total 681 patients, median age (63.6) years, 173 (28%) died during follow-up. Elevated blood urea (3.02, 95% CI 2.17 to 4.22; p≤0.001) and creatinine (1.96, 95% CI 1.50 to 2.57; p≤0.001) during stroke affected survival adversely.Excluding patients with CKD, we analysed the remaining 617 patients. AKI was noted in 75 (12.15%) patients during the index admission, and it affected survival adversely (2.16, 95% CI 1.49 to 3.13; p<0.001). Of the patients with AKI, 21 of 75 (28%) progressed to CKD over a median follow-up of 40.7 months. CONCLUSIONS: We found AKI during stroke admission was associated with increased mortality as compared with those without AKI on univariate analysis. AKI without need of renal replacement therapy was also associated with progression to CKD in this cohort. This suggests that patients with AKI need to have their renal function monitored longitudinally for development of CKD.

Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases.

In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.

Cloning, expression, identification and characterization of borneol dehydrogenase isozymes in Pseudomonas sp. TCU-HL1.

Borneol is a bicyclic plant monoterpene. It can be degraded by soil microorganisms through the conversion of borneol dehydrogenase (BDH) and a known camphor degradation pathway. Recombinant BDH from Pseudomonas sp. TCU-HL1 was produced in the form of inclusion body. The refolded BDH1 tends to precipitate. Insoluble recombinant BDH1 was converted into a soluble form by adding glycerol in LB medium. The kcat and kcat/Km values of soluble form BDH1 for (+)-borneol turned out to be about 34-fold and 45-fold higher, respectively, than those of the refolded enzyme. On the other hand, a gene knockout mutant, TCU-HL1Δbdh, was constructed to investigate the possible presence of a second copy of the bdh gene in TCU-HL1 genome. A new gene, bdh2, encoding a BDH isozyme, was identified, and the recombinant BDH2 protein was produced in a soluble form. Both bdh1 and bdh2 genes are expressed in the crude extract of wild type TCU-HL1, as shown by RT-qPCR results. Both BDH isozymes prefer to degrade (+)-borneol, rather than (-)-borneol, probably because (+)-camphor is the main form present in nature.

Production of optically pure (-)-borneol by Pseudomonas monteilii TCU-CK1 and characterization of borneol dehydrogenase involved.

(-)-Borneol is a bicyclic plant secondary metabolite. Optically pure (-)-borneol can only be obtained from plants, and demand exceeds supply in China. In contrast, chemically synthesized borneol contains four different stereoisomers. A strain of Pseudomonas monteilii TCU-CK1, isolated in Hualien, Taiwan, can accumulate (-)-borneol in growth culture and selectively degrades the other three isomers when chemically synthesized borneol is used as sole carbon source. This (-)-borneol production method can be scaled-up for production of large quantities in the future. More importantly, laborious plant cultivation and harvest is no longer required. The main enzyme that appears in this degradation pathway, borneol dehydrogenase (BDH), and the genome sequence of TCU-CK1 are reported. The kcat/Km values of TCU-CK1 BDH on (+)- and (-)-borneol are 538.4 ± 38.4 and 17.7 ± 1.1 (s-1 mM-1), respectively. About ∼30 fold difference in the kcat/Km value between (+)-borneol and (-)-borneol was observed, in good agreement with the fact that TCU-CK1 prefers to degrade (+)-borneol, rather than (-)-borneol. A BDH isozyme was identified in a strain in which the primary BDH gene had been knocked out. (-)-Camphor can work as an inhibitor of BDH with a Ki of 1.03 ± 0.11 mM at pH 7.0, leading to the accumulation of (-)-borneol in culture. (Patent pending).

Structural characterization of borneol dehydrogenase from Pseudomonas sp. TCU-HL1.

During the microbial degradation of borneol, a bicyclic plant monoterpene, it is first converted into camphor by borneol dehydrogenase (BDH) and then enters a known camphor-degradation pathway. Previously, a recombinant Pseudomonas BDH was found in inclusion bodies when expressed in Escherichia coli. After refolding, it was still unstable and was difficult to concentrate. Here, the protein-expression conditions were improved by changing the medium from lysogeny broth to Terrific Broth, yielding a soluble form of the enzyme with higher activity. The protein was crystallized and its 3D structure was determined by X-ray diffraction. Like other known homologues such as quinuclidinone reductase, the protein forms a tetramer with subunits containing Rossmann folds. Structural comparison revealed major differences in the C-terminal helices and the associated loops. It is likely that these regions contain the determinants for substrate recognition.

Resolution of isoborneol and its isomers by GC/MS to identify "synthetic" and "semi-synthetic" borneol products.

Borneol is a plant terpene commonly used in traditional Chinese medicine. Optically pure (+)-borneol and (-)-borneol can be obtained by extraction from the plants Dipterocarpaceae and Blumea balsamifera, respectively. "Synthetic borneol" is obtained from the reduction of (±)-camphor to lead to four different stereoisomers: (+)-isoborneol, (-)-isoborneol, (+)-borneol, and (-)-borneol. In contrast, "semi-synthetic borneol" is produced from the reduction of natural camphor, (+)-camphor, to afford two isomers: (-)-isoborneol and (+)-borneol. We established a convenient method to identify them by treating the four stereoisomers with two chiral reagents, (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride ((R)-(+)-MTPA-Cl) and (1S)-(-)- camphanic chloride. The resulting derivatives from the above mentioned method were analyzed by gas chromatography. The enantiomers of (+)- and (-)-isoborneol were successfully separated from (+)- and (-)-borneol isomers in this study to make this a useful method in the identification of "synthetic" and "semi-synthetic" borneols. Furthermore, we also examined five different commercial borneols. During this course, a novel and unprecedented partial epimerization from isoborneol-camphanic ester to borneol-camphanic ester was observed. However, this phenomenon did not occur in isoborneol-MTPA esters epimerization to borneol-MTPA case under the same conditions. The DFT calculation of activation energies for both reactions was in a good agreement with the results obtained from GC analysis.

Post-stroke seizure-Do the locations, types and managements of stroke matter?

OBJECTIVE: To determine the incidence of post-stroke seizures and the associated risk factors in a government-restructured hospital in Singapore. METHODS: This retrospective study included consecutive patients (age ≥21 years) admitted to the stroke rehabilitation facility at Changi General Hospital, Singapore, between June 2008 and May 2017, with a minimum post-discharge follow-up of 6 months. Patients with known epilepsy central nervous system infection or tumor, a history of neurosurgery and or missing data were excluded from study. To determine the incidence of seizures, the patients' hospital records, including those for all initial and subsequent admissions and outpatient follow-ups, were reviewed. All prescribed medications were checked and documented. Seizures were diagnosed on the basis of clinical examination with or without electroencephalography. RESULTS: In total, 722 patients (women, 38%) with a mean age of 64 years were included. Of these, 48 (6.64%) experienced post-stroke seizures during a follow-up period of 6-108 months. The incidence of seizures was significantly higher in patients with hemorrhagic stroke (42%, p = 0.010), those with ischemic partial anterior circulation stroke (PACS) (27%, p = 0.025), those who underwent a neurosurgical procedure after stroke (p < 0.001), those with a low activated partial thromboplastin time (APTT) at admission (mean, 25.6; p = 0.015), and those using levodopa (21%, p < 0.001). Neurosurgical intervention after stroke (odds ratio [OR] 6.2, 95% confidence interval [CI] 2.9-13.1; p < 0.001), APTT (per-unit increase; OR 0.86, 95% CI 0.76-0.98; p = 0.028), and underlying ischemic heart disease (IHD; OR 2.2, 95% CI 1.08-4.60; p = 0.029) were found to be independent predictors of seizure occurrence after stroke. SIGNIFICANCE: Post-stroke seizure incidence from our study is 6.64%, with a median follow-up of 49 months. Among patients with stroke, those with underlying IHD, those who undergo a neurosurgical procedure, and those with a low APTT at admission need careful monitoring. Levodopa should be used with caution and withdrawn as soon as possible.

Strategies in overcoming racial and socio-cultural differences in the learning environment of post-graduate medical specialty training in South Africa.

This article was migrated. The article was marked as recommended. Study problem The training of postgraduate medical students in the multi-racial landscape of South Africa has faced challenges given the need for relationships in personal mentoring and learning through legitimate participation in the community of practice (CoP), as part of cognitive apprenticeship training. A high failure rate in the exit examination had stimulated interest into understanding the nature of the learning environment. Aim and objectives The study explored conceptions of former students in a medical specialty program regarding the nature of racial and socio-cultural diversities in their learning environment, influences on learning, and how they responded to them. Methodology A qualitative enquiry using in-depth interviews with semi-structured open-ended questions and thematic analysis with a social constructionist approach of epistemology used for data analysis and interpretation. Findings Students conceived race, language, departmental culture and social identity as barriers in their learning. The lack of structured formative training with feedback, evaluation, personal mentoring, and supervision also emerged. Through resilience, adaptability, and maturity qualified students overcame these difficulties. Conclusion Current and future students may benefit by developing resilience when dealing with racial and socio-cultural differences, and findings support the inclusion of cultural competence and a multi-lens approach in medical specialty curricula.

Borneol Dehydrogenase from Pseudomonas sp. Strain TCU-HL1 Catalyzes the Oxidation of (+)-Borneol and Its Isomers to Camphor.

Most plant-produced monoterpenes can be degraded by soil microorganisms. Borneol is a plant terpene that is widely used in traditional Chinese medicine. Neither microbial borneol dehydrogenase (BDH) nor a microbial borneol degradation pathway has been reported previously. One borneol-degrading strain, Pseudomonas sp. strain TCU-HL1, was isolated by our group. Its genome was sequenced and annotated. The genome of TCU-HL1 consists of a 6.2-Mbp circular chromosome and one circular plasmid, pTHL1 (12.6 kbp). Our results suggest that borneol is first converted into camphor by BDH in TCU-HL1 and is further decomposed through a camphor degradation pathway. The recombinant BDH was produced in the form of inclusion bodies. The apparent Km values of refolded recombinant BDH for (+)-borneol and (-)-borneol were 0.20 ± 0.01 and 0.16 ± 0.01 mM, respectively, and the kcat values for (+)-borneol and (-)-borneol were 0.75 ± 0.01 and 0.53 ± 0.01 s-1, respectively. Two plant BDH genes have been reported previously. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. IMPORTANCE: The degradation of borneol in a soil microorganism through a camphor degradation pathway is reported in this study. We also report a microbial borneol dehydrogenase. The kcat and kcat/Km values of lavender BDH are about 1,800-fold and 500-fold lower, respectively, than those of TCU-HL1 BDH. The indigenous borneol- and camphor-degrading strain isolated, Pseudomonas sp. strain TCU-HL1, reminds us of the time 100 years ago when Taiwan was the major producer of natural camphor in the world.

High prevalence of primary dyslipidaemia in black South African patients at a tertiary hospital in northern Gauteng, South Africa.

BACKGROUND: The prevalence of cardiovascular disease is projected to be 38.7% for the USA in 2020, including coronary heart disease at 8.6% and stroke at 3.6%. In South Africa (SA), premature deaths due to heart and blood vessel diseases in people of working age (35 - 64 years) have been predicted to increase by 41% between 2007 and 2030, with enormous negative economic impact. Atherosclerosis underlies much of the pathogenesis, which involves risk factors including dyslipidaemia. Secondary dyslipidaemia associated with diabetes mellitus, hypothyroidism, chronic renal disease, cholestasis, nephrotic syndrome, alcohol excess, drugs such as thiazide diuretics and antiretroviral agents may respond to treatment of underlying causes, but residual dyslipidaemia may in such cases be due to primary disorders of metabolism. Primary dyslipidaemias are uncommon and to a large extent underdiagnosed, especially in the black population of SA, reflecting a lack of clinical and laboratory awareness or expertise. Specific diagnoses enable effective intervention in the patients as well as the families. OBJECTIVE: To assess the burden and prevalence of dyslipidaemia in the SA black population at Dr George Mukhari Hospital in the north region of Gauteng. METHOD: A retrospective data analysis of 12-month lipid profiles comprising triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol and directly measured low-density lipoprotein (LDL) cholesterol (LDLC). RESULTS: There were 24 656 requests for 6 348 patients. The lipid cut-off levels were somewhat arbitrary but were based on the commonly used decision-making levels in the treatment guidelines. Severe hypercholesterolaemia (>7 mmol/L) was seen in 299 (4.7%) patients and extreme hypercholesterolaemia (>12 mmol/L) was seen in 30 (0.5%) patients. LDLC (>5 mmol/L) occurred in 80 (1.3%) patients and >10 mmol/L in 19 (0.3%) patients. A predominant triglyceride problem was seen in 578 (9.1%) patients with TG (>2 mmol/L) and TC (<5 mmol/L), whereas moderate hypertriglyceridaemia (>5 mmol/L) was present in 113 (1.8%) patients, and more severe hypertriglyceridaemia (>10 mmol/L) in 10 (0.2%). TC (>5 mmol/L) with LDL (>3 mmol/L) but TG in the normal range was seen in 369 (5.8%) patients, indicating a cholesterol-predominant problem. In contrast, LDLC (>3 mmol/L) and TG (>1.7 mmol/L) was seen in 249 (3.87%) representing mixed hyperlipidaemia. Paediatric patients with severe dyslipidaemia mostly suffered from nephrotic syndrome. CONCLUSION: A significant burden and a high prevalence of dyslipidaemias were present in adults in whom a monogenic disorder should be considered. The extent and severity of dyslipidaemia justify a special clinic and laboratory to ensure accurate diagnosis with effective intervention for patients and their families.

Use of surface enhanced blocking (SEB) electrodes for microbial cell lysis in flow-through devices.

By simultaneously subjecting microbial cells to high amplitude pulsed electric fields and flash heating of the cell suspension fluid, effective release of intracellular contents was achieved. The synergistic effect of the applied electric field and elevated temperature on cell lysis in a flow-through device was demonstrated for Gram-negative and Gram-positive bacteria, and Mycobacterium species. The resulting lysate is suitable for downstream nucleic acid amplification and detection without requiring further preparation. The lysis chamber employs surface enhanced blocking electrodes which possess an etched micro-structured surface and a thin layer of dielectric metal oxide which provides a large effective area and blocks transmission of electrical current. The surface enhanced blocking electrodes enable simultaneous suppression of the rapid onset of electric field screening in the bulk of the cell suspension medium and avoidance of undesired electrochemical processes at the electrode-electrolyte interface. In addition the blocking layer ensures the robustness of the cell lysis device in applications involving prolonged flow-through processing of the microbial cells.

Impact of laboratory accreditation on patient care and the health system.

Accreditation is emerging as a preferred framework for building quality medical laboratory systems in resource-limited settings. Despite the low numbers of laboratories accredited to date, accreditation has the potential to improve the quality of health care for patients through the reduction of testing errors and attendant decreases in inappropriate treatment. Accredited laboratories can become more accountable and less dependent on external support. Efforts made to achieve accreditation may also lead to improvements in the management of laboratory networks by focusing attention on areas of greatest need and accelerating improvement in areas such as supply chain, training, and instrument maintenance. Laboratory accreditation may also have a positive influence on performance in other areas of health care systems by allowing laboratories to demonstrate high standards of service delivery. Accreditation may, thus, provide an effective mechanism for health system improvement yielding long-term benefits in the quality, cost-effectiveness, and sustainability of public health programs. Further studies are needed to strengthen the evidence on the benefits of accreditation and to justify the resources needed to implement accreditation programs aimed at improving the performance of laboratory systems.

Globe-sparing surgery for medial canthal Basal cell carcinoma with anterior orbital invasion.

PURPOSE: To describe a case series of patients with anterior orbital invasion by medial canthal basal cell carcinoma (BCC) managed with non-exenterating surgery. DESIGN: International, multicenter, retrospective, noncomparative, consecutive case series. PARTICIPANTS: Twenty patients identified from the individual institutions' databases with histologically confirmed orbital invasion by periocular BCC. METHODS: Examination of charts, relevant imaging, and histopathologic data. MAIN OUTCOME MEASURES: Demographics; clinical characteristics and radiologic features; histopathologic features; surgical techniques for excision, reconstruction, and subsequent procedures; complications; visual acuity; and recurrence. RESULTS: Twenty patients were identified. Twelve of 20 patients (60%) had recurrent BCCs, with 1 patient having had prior radiotherapy for previously incomplete excision. Eighteen of 20 patients (90%) had a palpable mass, 16 of 20 patients (80%) had clinical involvement of the nasolacrimal system, and 1 of 20 patients (5%) had limited extraocular movements. Preoperative radiologic evidence of orbital invasion was found in 10 of 20 patients (50%). Histologic evidence of orbital invasion was present in every patient, the subtypes being infiltrative (9/20, 45%), nodular (4/20, 20%), micronodular (2/20, 10%), multifocal (1/20, 5%), and mixed (4/20, 20%); extratumoral perineural invasion was present in 1 patient (5%). Final margins were clear in 18 of 20 patients (90%), positive in 1 of 20 patients (5%), and unclear in 1 of 20 patients (5%). Reconstruction was by direct closure in 1 patient and by a variety of standard oculoplastic flaps and grafts in 19 of 20 patients (95%). Twelve of 20 patients (60%) had postoperative extraocular muscle movement restriction, and 15 of 20 patients (75%) had epiphora. Subsequent revision procedures were needed in 12 of 20 patients (60%), including insertion of a lacrimal bypass tube and revision of medial canthal position. At a mean follow-up of 38 months, 18 of 20 patients (90%) were still alive (2 deaths due to other causes) with 1 recurrence (exenterated). Postoperative visual acuity was within 2 Snellen lines of preoperative visual acuity in 17 of 20 patients (85%). CONCLUSIONS: With careful planning and margin control, conservative surgery in this highly selected group proved possible with a low rate of disease recurrence, albeit with a relatively short follow-up. Postoperative complications, such as epiphora and ophthalmoplegia, were largely expected; most patients underwent subsequent revision procedures to address these and other complications. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.