Surgery for pouch inflow limb-related complications: Crohn's disease or something else?

PURPOSE: A total proctocolectomy with subsequent creation of an ileal-pouch, such as a J-pouch or a Kock pouch, has been the most common surgery performed for ulcerative colitis (UC). A small portion of these patients will develop complications with the inflow limb into the pouch requiring operative intervention. The objective was to establish a better understanding as to the pathological mechanism by which these pouch inflow limb problems develop. METHODS: This was a retrospective cohort study conducted at a single tertiary care inflammatory bowel disease (IBD) center. A database was created of all the patients who underwent pouch-related procedures, following completion of their original pouch, between 2006 and 2018. The patients requiring operative resection for inflow limb complications were identified among this cohort. Operative and pathological data were collected. RESULTS: One hundred seventy-eight UC patients underwent surgeries on their pouches between 2006 and 2018. Sixteen patients required operative resection for inflow limb problems. Reoperations for inflow limb problems included inflow limb resection with pouch excision (n = 4) and inflow limb resection with pouch revision (n = 12). The pathology findings of the inflow limb were consistent with Crohn's disease in 9 patients (56%). Two other patients (total 69%) were eventually diagnosed with Crohn's disease due to other pathological specimens or perianal pathology. The remaining patients had chronic, non-specific enteritis/serositis. CONCLUSIONS: A small proportion of pouch patients will eventually require surgery for inflow limb complications. Among these, there was a high rate of Crohn's disease of the inflow limb and overall change in diagnosis to Crohn's disease (Plietz et al. in Official Journal of the American College of Gastroenterology | ACG 114:S453, 2019).

Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial.

OBJECTIVE: We hypothesized that the Oncotype Dx® 21-gene Recurrence Score (RS) could guide neoadjuvant systemic therapy (NST) to facilitate breast conserving surgery (BCS) for hormone receptor positive (HR+) breast cancers. METHODS: This study enrolled patients with HR+, HER2-negative, invasive breast cancers not suitable for BCS (size ≥ 2 cm). Core needle biopsy blocks were tested. For tumors with RS < 11, patients received hormonal therapy (NHT); patients with RS > 25 tumors received chemotherapy (NCT); patients with RS 11-25 were randomized to NHT or NCT. Primary endpoint was whether 1/3 or more of randomized patients refused assigned treatment. RESULTS: Sixty-four patients were enrolled. Of 33 patients with RS 11-25, 5 (15%) refused assignment to NCT. This was significantly lower than the 33% target (binomial test, P = 0.0292). Results for clinical outcomes (according to treatment received for 55 subjects) included successful BCS for 75% of tumors with RS < 11 receiving NHT, 72% for RS 11-25 receiving NHT, 64% for RS 11-25 receiving NCT, and 57% for RS > 25 receiving NCT. CONCLUSIONS: Using the RS to guide NST is feasible. These results suggest that for patients with RS < 25 NHT is a potentially effective strategy.

Lymphoepithelial Carcinoma of the Nasolacrimal Duct: Clinical, Radiologic, and Immunopathologic Features.

Undifferentiated lymphoepithelial carcinoma (exhibiting both begin lymphoid and malignant epithelial components) most commonly arises in the head and neck, especially in the nasopharynx. It may also be encountered in various ocular adnexal sites, including the nasolacrimal duct. A 63-year-old woman developed a swelling in the region of the right lacrimal sac accompanied by epiphora. CT scanning revealed an enlargement of the nasolacrimal duct from the lacrimal sac to the inferior nasal meatus. A biopsy during dacryocystorhinostomy for symptomatic epiphora revealed hypercellular sheets of small lymphocytes which were interpreted as evidence for a chronic dacryocystitis. Two years later the subtotally excised lesion had substantially grown in size. Repeat CT scans demonstrated an inferonasal anterior orbital mass with further enlargement of the nasolacrimal duct with a solid mass in its lumen, and bone erosion. The biopsy combined a rich background of lymphocytes within which were clusters of undifferentiated carcinoma cells that were cytokeratin and p63 positive. Critical review of the earlier biopsy led to the detection of the same cells, but in smaller numbers, that had been overlooked. An awareness of the possibility of lymphoepithelial carcinoma of the lacrimal sac/duct should improve diagnostic accuracy with the aid of immunohistochemistry. Radiation therapy is often successful in managing this highly sensitive malignant tumor.

A card-sorting tool to measure expert versus novice thinking in scientific research.

Undergraduate research and laboratory experiences provide a wide range of benefits to student learning in science and are integral to imbed authentic research experiences in biology labs. While the benefit of courses with research experience is widely accepted, it can be challenging to measure conceptual research skills in a quick and easily scalable manner. We developed a card-sorting task to differentiate between novice and expert conceptualization of research principles. There were significant differences in the way faculty/postdocs, graduate students, and undergraduate students organized their information, with faculty/postdocs more likely to use deep feature sorting patterns related to research approach. When provided scaffolding of group names reflecting expert-like organization, participant groups were better able to sort by that organization, but undergraduate students did not reach expert levels. Undergraduates with Advanced Placement experience were more likely to display expert-like thinking than undergraduates without Advanced Placement Biology experience and non-PEER (persons excluded because of their Ethnicity or Race) students displayed more expert-like thinking than PEER students. We found evidence of undergraduates in various stages of development toward expert-like thinking in written responses. This card-sorting task can provide a framework for analyzing student's conceptualizations of research and identify areas to provide added scaffolding to help shift from novice-like to expert-like thinking.

Soluble chitosan derivative treats wound infections and promotes wound healing in a novel MRSA-infected porcine partial-thickness burn wound model.

Burns are physically debilitating and potentially fatal injuries. The most common etiology of burn wound infections in the US is methicillin-resistant Staphylococcus aureus (MRSA), which is particularly recalcitrant when biofilms form. The current standard of care, silver sulfadiazine (SSD) is effective in reducing bacterial load, but less effective in improving burn wound healing. New treatments that can manage infection while simultaneously improving healing would provide a benefit in the treatment of burns. Porcine models are frequently used as a model for human wound healing but can be expensive due to the need to separate wounds to avoid cross contamination. The porcine model developed in this study offers the capability to study multiple partial thickness burn wound (PTBW) sites on a single animal with minimal crosstalk to study wound healing, infection, and inflammation. The current study evaluates a wound rinse and a wound gel formulated with a non-toxic, polycationic chitosan derivative that is hypothesized to manage infection while also promoting healing, providing a potential alternate to SSD. Studies in vitro and in this PTBW porcine model compare treatment with the chitosan derivative formulations to SSD. The wound rinse and wound gel are observed to disrupt mature MRSA biofilms in vitro and reduce the MRSA load in vivo when compared to that of the standard of care. In vivo data further show increased re-epithelialization and faster healing in burns treated with wound rinse/gel as compared to SSD. Taken together, the data demonstrate the potential of the wound rinse/gel to significantly enhance healing, promote re-epithelialization, and reduce bacterial burden in infected PTBW using an economical porcine model.

Wooden intraorbital foreign body injuries: clinical characteristics and outcomes of 23 patients.

PURPOSE: To describe the clinical characteristics, interventions, and visual outcomes of orbital injuries associated with wooden foreign bodies. METHODS: A retrospective case review of orbital injuries managed at Wills Eye Institute and Massachusetts Eye and Ear Infirmary was conducted between 1992 and 2006. RESULTS: The clinical course and management for a total of 23 intraorbital wooden foreign body injuries were reviewed. The distribution of wood included pencil (39%), tree branch/plant matter (35%), and other treated wood (26%). About half of the subjects (52%) presented with preoperative vision between 20/20 and 20/40. Almost all [corrected] of the subjects with preoperative vision between 20/20 to 20/40 retained vision in that range postoperatively (92%). [corrected] Time from injury to presentation was highly variable, ranging from 24 hours to 17 months (mean, 62 days; median, 3 days). Forty-three percent of subjects presented within 24 hours of injury. The site of foreign body found within the orbit was superior (26%; n = 6), medial 30% (n = 7), inferior (26%, n = 6), posterior (9%; n = 2), and lateral (4%; n = 1). Preliminary radiographic interpretation for foreign body was definite in 61% (n = 14), possible in 22% (n = 5), and absent in 13% (n = 3). CONCLUSIONS: Young men are at particularly high risk for wood intraorbital foreign body. There was a relatively equal distribution of wood type. The time from injury to presentation was variable, ranging from <1 day to over a year. Almost half of the subjects presented within 24 hours of injury. In patients with a known site of penetration, almost half occurred in the conjunctiva, notably without presence of eyelid laceration, emphasizing the need to check the conjunctiva and fornices closely. Preliminary radiographic readings often miss or are inconclusive in detecting the foreign body. The shape, location, serial examinations, and particularly the use of quantitative CT are extremely helpful in distinguishing retained wood foreign body from other low-density signals of air or fat.

Age- and fatigue-related markers of human faces: an eye-tracking study.

PURPOSE: To investigate the facial cues that are used when making judgments about how old or tired a face appears. DESIGN: Experimental study. PARTICIPANTS: Forty-seven subjects: 15 male and 32 female participants, ranging from age 18 to 30 years. METHODS: Forty-eight full-face digital images of "normal-appearing" patients were collected and uploaded to an eye-tracking system. We used an Applied Science Laboratories (Bedford, MA) Eye Tracker device associated with gaze-tracking software to record and calculate the gaze and fixation of the participants' left eye as they viewed images on a computer screen. After seeing each picture, participants were asked to assess the age of the face in the picture by making a selection on a rating scale divided into 5-year intervals; for fatigue judgments we used a rating scale from 1 (not tired) to 7 (most tired). MAIN OUTCOME MEASURES: The main outcome measure was gaze fixation, as assessed by tracking the eye movements of participants as they viewed full-face digital pictures. RESULTS: For fatigue judgments, participants spent the most time looking at the eye region (31.81%), then the forehead and the nose regions (14.99% and 14.12%, respectively); in the eye region, participants looked most at the brows (13.1%) and lower lids (9.4%). Participants spent more time looking at the cheeks on faces they rated as least tired than they did on those they rated as most tired (t = 2.079, P<0.05). For age judgments, the eye region (27.22%) and then the forehead (15.71%) and the nose (14.30%) had the highest frequencies of interest; in the eye region, the brows and lower lids also had the highest frequencies of interest (11.40% and 8.90%, respectively). Participants looked more at the brows (t = -2.63, P<0.05) and glabella (t = -3.28, P<0.01) in those faces they rated as looking the oldest. CONCLUSIONS: This study supports the hypothesis that age and fatigue judgments are related to preferential attention toward the eye region. Consequently, these results suggest that aesthetic or functional surgery to the eye region may be one of the most effective interventions in enhancing the appearance of an individual. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

In the eye of the beholder--skin rejuvenation using a light-emitting diode photomodulation device.

BACKGROUND: A light-emitting diode (LED) photomodulation system can produce pulses of amber light expected to induce structural skin changes and reverse the effects of photoaging. OBJECTIVE: To reproduce the encouraging results already published. METHODS AND MATERIALS: Facial skin was exposed to pulses of 588+/-10-nm-wavelength light from a photomodulation device for 40 seconds once a week for 8 weeks. Photographs, clinical assessment, and a subjective questionnaire were taken at baseline, at the last follow-up, and 1 month after that. Thirty-six patients' pre- and post-treatment photos were arbitrarily scrambled, and 30 independent blinded observers were asked to pick the post-treatment photo. Two time-point comparisons were evaluated. RESULTS: For every facial characteristic studied and for both time-point comparisons, patients reported highly statistically significant improvements. In extremely sharp contrast, neither the physician's assessment nor the independent observers' evaluation indicated any improvement. CONCLUSION: Although subjective findings are comparable between studies, we were unable to reproduce the objective results of efficacy previously reported. Patients genuinely believed that several of their facial features had improved, even though there was no detectable objective change. Our data therefore suggest that the LED photomodulation treatment from the device tested is a placebo.

Understanding the mechanism of radiation induced fibrosis and therapy options.

Radiation therapy has been increasingly employed as a tool to cure and palliate majority of solid tumors. Although radiotherapy has shown promising results in preserving structure and function of organs, it is associated with late side effects mainly manifested in the form of tissue fibrosis. Recent advances in molecular biology techniques has helped better understand the molecular mechanisms involved in radiation induced fibrosis. Currently, very few treatment modalities are available to treat the condition with moderate success rate. Stem cell therapies and particularly adipose tissue and adipose derived stem cells therapies have shown promising results in clinical applications. Identification of the key factors involved in the mitigation process will help to enhance the beneficial effects and develop new therapy approaches.

Myeloid Sarcoma with Megakaryoblastic Differentiation Arising in the Conjunctiva.

An 87-year-old woman not known to have either a lymphoma or leukemia developed a left multinodular, fish-flesh superior epibulbar and forniceal mass. A biopsy disclosed a blastic tumor with scattered multinucleated immature megakaryoblasts. Immunophenotyping of bone marrow cells revealed strong positivity for CD7, CD31, CD43, CD45, CD61, and CD117; CD71, myeloperoxidase, and lysozyme were also positive in scattered cells. Forty percent of the neoplastic cells were Ki-67 positive. Cytogenetic studies indicated a trisomy 8 (associated with worse prognosis) and a t(12; 17) translocation. Desmin, smooth muscle actin, pancytokeratin, CAM 5.2, adipophilin, tryptase, S100, SOX10, MART1, and E-cadherin were negative, ruling out a nonhematopoietic tumor. The conjunctival lesion was diagnosed as a myeloid sarcoma with megakaryoblastic differentiation, a rare variant. It probably arose from a myelodysplastic syndrome. This is the first case of its type to develop in the conjunctiva.

Screening and surveillance colonoscopy in chronic Crohn's colitis: results of a surveillance program spanning 25 years.

BACKGROUND & AIMS: Since 1980, we have followed 259 patients with chronic Crohn's colitis in a prospective colonoscopic surveillance program. Our initial results through August 1998 showed a 22% chance of developing definite dysplasia or cancer by the fourth surveillance examination. We now update the results of all examinations since September 1998 until April 2005. METHODS: All patients had at least 7 years of Crohn's colitis affecting at least one third of the colon. Patients were recalled every 1 to 2 years or sooner if dysplasia was found. Pathology was classified as normal, dysplasia (indefinite, low-grade [LGD], or high-grade [HGD]), or carcinoma. Lesions were classified as flat, polyp, or mass. RESULTS: A total of 1424 examinations were performed on 259 patients. Ninety percent had extensive colitis. The median age at diagnosis was 22 years (range, 2-61 y), and the median disease duration was 18 years (range, 7-49 y). On screening examination, definite dysplasia or cancer was found in 18 patients (7%). Thirteen had LGD, 2 had HGD, and 3 had cancer. On surveillance examinations, a first finding of definite dysplasia or cancer was found in an additional 30 patients (14%). Twenty-two had LGD, 4 had HGD, and 4 had cancer. The cumulative risk of detecting an initial finding of any definite dysplasia or cancer after a negative screening colonoscopy was 25% by the 10th surveillance examination. The cumulative risk of detecting an initial finding of flat HGD or cancer after a negative screening colonoscopy was 7% by the ninth surveillance examination. CONCLUSIONS: Periodic surveillance colonoscopy should be part of the routine management of chronic extensive Crohn's colitis.

Polymorphisms in drug metabolism genes, smoking, and p53 mutations in breast cancer.

Polymorphisms in phase I and phase II enzymes may enhance the occurrence of mutations at critical tumor suppressor genes, such as p53, and increase breast cancer risk by either increasing the activation or detoxification of carcinogens and/or endogenous estrogens. We analyzed polymorphisms in CYP1B1, GSTM1, GSTT1, and GSTP1 and p53 mutations in 323 breast tumor samples. Approximately 11% of patients exhibited mutations in p53. Women with mutations had a significantly younger age of diagnosis (P = 0.01) and a greater incidence of tumors classified as stage II or higher (P = 0.002). More women with mutations had a history of smoking (55%) compared to women without mutations (39%). Although none of the genotypes alone were associated with p53 mutations, positive smoking history was associated with p53 mutations in women with the GSTM1 null allele [OR = 3.54; 95% CI = 0.97-12.90 P = 0.06] compared to women with the wild-type genotype and smoking history [OR = 0.62, 95% CI = 0.19-2.07], although this association did not reach statistical significance. To test for gene-gene interactions, our exploratory analysis in the Caucasian cases suggested that individuals with the combined GSTP1 105 VV, CYP1B1 432 LV/VV, and GSTM1 positive genotype were more likely to harbor mutations in p53 [OR = 4.94; 95% CI = 1.11-22.06]. Our results suggest that gene-smoking and gene-gene interactions may impact the prevalence of p53 mutations in breast tumors. Elucidating the etiology of breast cancer as a consequence of common genetic polymorphisms and the genotoxic effects of smoking will enable us to improve the design of prevention strategies, such as lifestyle modifications, in genetically susceptible subpopulations.

Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer.

Polymorphisms in the cytochrome P450 1B1 (CYP1B1) and glutathione S-transferase (GST) drug metabolic enzymes, which are responsible for metabolic activation/detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one CYP1B1 119S allele (OR=0.53; 95% CI=0.20-1.40) and increased risk for those women harboring at least one CYP1B1 432V allele (OR=5.52; 95% CI=0.50-61.37). Stratified analyses demonstrated significant interactions in younger (age < or =60) Caucasian women with the CYP1B1 119SS genotype (OR=3.09; 95% CI=1.22-7.84) and younger African-American women with the GSTT1 null genotype (OR=4.07; 95% CI=1.12-14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at GSTP1 114 (OR=2.12; 95% CI=1.02-4.41). In Caucasian women, the combined GSTP1 105IV/VV and CYP1B1 119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04-3.72) and the three way combination of GSTP1 105IV/VV, CYP1B1 119AS/SS and GSTT1 null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27-12.40). These results suggest the importance of estrogen/carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation.

Recognizing the protruding eye.

UNLABELLED: It is currently unknown how much exophthalmos may be noticeable to an observer. The authors determined the threshold for detection of exophthalmos may be 4 millimeters. PURPOSE: To determine the threshold for detection of exophthalmos by an observer. METHODS: The Massachusetts Eye and Ear Infirmary Ophthalmic Plastics imaging database was used to select 28 photographs of patients with unilateral exophthalmos measuring between 1 to 11 mm for the study group and 28 photographs of patients without exophthalmos for the control group. One hundred ophthalmology attendings, residents, medical students, and technicians reviewed each photograph. Participants commented on whether the patient appeared "normal" or "abnormal." RESULTS: Eighty-one percent of the control patients were correctly identified as "normal." In comparison, 60% of patients with 1 mm of exophthalmos (p < 0.001), 53% of patients with 2 mm of exophthalmos (p < 0.001), 46% of patients with 3 mm of exophthalmos (p < 0.001), 35% of patients with 4 mm of exophthalmos (p < 0.001), and 40% of patients with 5 mm of exophthalmos (p < 0.001) were identified as "normal." The vast majority of patients (91.9%, p < 0.001) with 6 mm of exophthalmos were identified as "abnormal," and almost all patients (97.9%, p < 0.001) with more than 6 mm of exophthalmos were also described as having an "abnormal" appearance. CONCLUSIONS: Greater than half of the patients with 1-2 mm of exophthalmos appear as "normal" as the control patients. In comparison, the majority of patients with 4-5 mm of exophthalmos and nearly all the patients with 6 mm of exophthalmos and greater appear "abnormal." Our data suggests that the point at which exophthalmos becomes clinically perceptible to the majority of observers is 4 mm. There may be patients with 3 mm of exophthalmos and greater with orbital pathology being "missed" on cursory external examinations by general ophthalmologists, optometrists, and general practitioners.

Green bone.

OBJECTIVE: To describe the unusual finding of yellow-green-colored bone during routine orbital surgery, to detail its investigation, and to demonstrate its benign nature. METHODS: When green bone was found, specimens were sent for light and fluorescent microscopy, ultraviolet photography, and spectrophotometry. RESULTS: Yellow-green bone was encountered in 3 patients during orbital tumor excision or orbital fracture repair procedures. The only common cause was prior use of tetracycline during adolescence. All patients had healthy white dentition. In all cases, absence of neoplasia was demonstrated histologically. The bone fluoresced with a bright yellow-green color when exposed to 365-nm ultraviolet light. Histologic analysis demonstrated fluorescence located near the haversian canals. Spectrophotometry revealed absorption at 4 wavelengths specific to tetracycline: 230, 275, 380, and 440 nm. CONCLUSIONS: Fixation of tetracycline and ensuing fluorescence occurs mostly in areas of new bone growth and mineralization. This happens during childhood but also with bone remodeling associated with tumors or fractures. Once mineralized, teeth should therefore not be affected if tetracycline exposure occurs after ages 8 to 10 years. This paucity of external clues can lead to the surprising but innocuous surgical finding of green bone. Careful history and proper investigation can confirm its origin.