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This study investigated the possibility of using virtual reality perceptual-motor tasks as a screening tool for laparoscopic ability. We hypothesized that perceptual-motor skills assessed using virtual reality will correlate with the quality of simulated laparoscopic ventral hernia repair.Surgical residents (N = 37), performed 2 virtual reality perceptual-motor tasks: (1) force matching and (2) target tracking. Participants also performed a laparoscopic ventral hernia repair on a simulator and final product quality score, and endoscopic visualization errors were calculated. Correlational analysis was performed to assess the relationship between performance on virtual reality tasks and laparoscopic ventral hernia repair.Residents with poor performance on force matching in virtual reality-"peak deflection" (r = -0.34, P.05) and "summation distance" (r = -0.36, P.05)-had lower final product quality scores. Likewise, poor performance in virtual reality-based target tracking-"path length" (r = -0.49, P.05) and "maximum distance" (r = -0.37, P.05)-correlated with a lower final product quality score.Our findings support the notion that virtual reality could be used as a screening tool for perceptual-motor skill. Trainees identified as having poor perceptual-motor skill can benefit from focused curricula, allowing them to hone personal areas of weakness and maximize technical skill.

Background This paper explores a method for assessing intraoperative performance by modeling how surgeons integrate psychomotor, procedural, and cognitive skills to manage errors. Methods Audio-video data were collected from general surgery residents (N = 45) performing a simulated laparoscopic ventral hernia repair. Errors were identified using a standard checklist, and speech was coded for elements related to error recognition and management. Epistemic network analysis (ENA) was used to model the integration of error management skills. Results There was no correlation between number or type of errors committed and operative outcome. However, ENA models showed significant differences in the integration of error management skills between high-performing and low-performing residents. Conclusion These results suggest that error checklists and surgeons' speech can be used to model the integration of psychomotor, procedural, and cognitive aspects of intraoperative performance. Moreover, ENA can identify and quantify this integration, providing insight on performance gaps in both individuals and populations.

Background This study explores general surgery residents' decision making skills in uncommon, complex urinary catheter scenarios. Methods 40 residents were presented with two scenarios. Scenario A was a male with traumatic urethral injury and scenario B was a male with complete urinary blockage. Residents verbalized whether they would catheterize the patient and described the workup and management of suspected pathologies. Residents' decision paths were documented and analyzed. Results In scenario A, 45% of participants chose to immediately consult Urology. 47.5% named five diagnostic tests to decide if catheterization was safe. In scenario B, 27% chose to catheterize with a 16 French Coude. When faced with catheterization failure, participants randomly upsized or downsized catheters. Chi-square analysis revealed no measurable consensus amongst participants. Conclusions Residents need more training in complex decision making for urinary catheterization. The decision trees generated in this study provide a useful blueprint of residents' learning needs. Summary Exploration of general surgery residents' decision making skills in uncommon, complex urinary catheter scenarios revealed major deficiencies. The resulting decision trees reveal residents' learning needs.

Background This study sought to compare general surgery research residents' survey information regarding self-efficacy ratings to their observed performance during a simulated small bowel repair. Their observed performance ratings were based on their leadership skills in directing their assistant. Methods Participants were given 15 min to perform a bowel repair using bovine intestines with standardized injuries. Operative assistants were assigned to help assist with the repair. Before the procedure, participants were asked to rate their expected skills decay, task difficulty, and confidence in addressing the small bowel injury. Interactions were coded to identify the number of instructions given by the participants to the assistant during the repair. Statistical analyses assessed the relationship between the number of directional instructions and participants' perceptions self-efficacy measures. Directional instructions were defined as any dialog by the participant who guided the assistant to perform an action. Results Thirty-six residents (58.3% female) participated in the study. Participants who rated lower levels of decay in their intraoperative decision-making and small bowel repair skills were noted to use their assistant more by giving more instructions. Similarly, a higher number of instructions correlated with lower perceived difficulty in selecting the correct suture, suture pattern, and completing the entire surgical task. Conclusions General surgery research residents' intraoperative leadership skills showed significant correlations to their perceptions of skill decay and task difficulty during a bowel repair. Evaluating resident's directional instructions may provide an additional individualized intraoperative assessment metric. Further evaluation relating to operative performance outcomes is warranted.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

Neoplasms derived from lymphoid cells include precursor lymphoid neoplasms, mature B-cell neoplasms, plasma cell myeloma, mature T- and NK-cell neoplasms, and Hodgkin lymphoma. The morphology and immunophenotype of B-cell neoplasms correlate with various stages of normal B-cell differentiation and are currently used as a basis for their classification and nomenclature. Alterations in the major physiologic pathways in B cells such as the B-cell receptor signaling pathway, T-cell receptor pathway, NF-kB pathway, MAPK pathway, PI3K/AKT1, MTOR pathway, NOTCH signaling pathway, inhibition of apoptosis, impairment of differentiation to plasma cells, and epigenetic alterations play a major role in neoplastic transformation. Advances in understanding of the molecular pathogenesis of lymphomas in recent years, especially using next-generation sequencing, have enabled identification of novel diagnostic, prognostic, and predictive molecular biomarkers. Novel-targeted therapies based on these biomarkers have revolutionized the therapeutic landscape for relapsed and refractory lymphomas.

Background The aim of this study was to investigate whether junior surgical residents had successfully mastered bladder catheterization. Our hypothesis was that surgical residents would be overly confident in their abilities and underestimate the potential for case complexity. Materials and methods PGY 2-4 surgery residents ( n = 44) were given 15 min. to complete three of four bladder catheterization simulations. Participants reported their mastery by rating confidence using a 5-point Likert scale. Multiple linear regression analysis was used to test predictors of procedure performance. Results Participants made a total of 228 errors with an average of 5.1 errors (standard deviation = 2.6) per participant. The most common errors included not maintaining the sterile field (52.0%), failure to get urine return (20.3%), and inflating the catheter balloon before urine return (8.4%). Some residents committed the same error more than once. Presimulation confidence ratings ranged from “1” being not confident to “5” being extremely confident. Average presimulation confidence was 4.42 (range 1-5, standard deviation = 0.85). Sixteen (36%) residents ranked their presimulation confidence in problem-solving abilities as “moderately confident” or below, whereas 28 (64%) were “very confident” or above. The lower the resident's presimulation confidence in problem-solving, the more errors they committed during the simulation (beta = −0.33, t = −2.15, P = 0.04). Conclusions The residents did not perform as well as they anticipated when presented with more complicated bladder catheterization scenarios. Simulation can be used to identify and expose potential errors that may occur during complex presentations of basic procedures. This type of training and assessment may facilitate mastery.

Urinary catheter insertion is a common procedure performed in hospitals. Improper catheterization can lead to unnecessary catheter-associated urinary tract infections and urethral trauma, increasing patient morbidity. To prevent such complications, guidelines were created on how to insert and troubleshoot urinary catheters. As nurses have an increasing responsibility for catheter placement, resident responsibility has shifted to more complex scenarios. This study examines the clinical decision-making skills of surgical residents during simulated urinary catheter scenarios. We hypothesize that during urinary catheterization, residents will make inconsistent decisions relating to catheter choices and clinical presentations.Forty-five general surgery residents (postgraduate year 2-4) in Midwest training programs were presented with three of four urinary catheter scenarios of varying difficulty. Residents were allowed 15 min to complete the scenarios with five different urinary catheter choices. A chi-square test was performed to examine the relation between initial and subsequent catheter choices and to evaluate for consistency of decision-making for each scenario.Eighty-two percent of residents performed scenario A; 49% performed scenario B; 64% performed scenario C, and 82% performed scenario D. For initial attempt for scenario A-C, the 16 French Foley catheter was the most common choice (38%, 54%, 50%, P's 0.001), whereas for scenario D, the 16 French Coude was the most common choice (37%, P 0.01). Residents were most likely to be successful in achieving urine output in the initial catheterization attempt (P 0.001). Chi-square analyses showed no relationship between residents' first and subsequent catheter choices for each scenario (P's 0.05).Evaluation of clinical decision-making shows that initial catheter choice may have been deliberate based on patient background, as evidenced by the most popular choice in scenario D. Analyses of subsequent choices in each of the catheterization models reveal inconsistency. These findings suggest a possible lack of competence or training in clinical decision-making with regard to urinary catheter choices in residents.

The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P

Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.

Comparative data regarding the distribution of non-Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly-diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male-to-female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B-NHL (28·4%) and a higher proportion of HG B-NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B-cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.

Problem The current obstacles to paediatric junior doctors engaging in patient safety include poor compliance with the safety reporting process (Datix – only 2% completed by doctors locally) and lack of understanding in what the process is trying to achieve. There is also a ‘fear of failure culture’ so doctors are more likely not to admit to mistakes. High turnover of staff leads to problems with team dynamics and lack of ‘buy in’ into the departmental safety culture. Aims The aim is to foster an open safety culture, remove this fear of blame mentality and promote collective learning from error. I want to double the number of Datix reported by junior doctors within 6 months. Methods The interventions are going to be: departmental induction, monthly clinical governance meetings, and interprofessional simulation. Outcomes are going to be measured through a pre and post placement questionnaire and the numbers of Datix logged by paediatric junior doctors six months pre and six months post-intervention. Results 100% of doctors stated patient safety was ‘important’ or ‘very important’ to clinical care. 100% knew what a Datix was, but only 16% had filled one in during the previous six months. This was reflected in only 5 out of 139 Datix (3.6%) being filled in by junior doctors. After the planned interventions Datix completion by paediatric junior doctors improved to 10/126 (8.1%) – over a 2 fold increase from the previous six months. The aim for the next 12 months is to expand this safety engagement across the whole hospital establishing a ‘safety board’ to which an elected trainee from each speciality will be a part and establish a monthly grand round looking at a clinical incident or datix to promote an open ‘no blame’ approach that will become part of the hospital culture.

Background This study explores the long-term effectiveness of a newly developed clinical skills curriculum. Methods Students (N = 40) were exposed to a newly developed, simulation-based, clinical breast exam (CBE) curriculum. The same students returned one year later to perform the CBE and were compared to a convenience sample of medical students (N = 15) attending a national conferences. All students were given a clinical vignette and performed the CBE. CBE techniques were video recorded. Chi-squared tests were used to assess differences in CBE technique. Results Students exposed to a structured curriculum performed physical examination techniques more consistent with national guidelines than the random, national student sample. Structured curriculum students were more organized, likely to use two hands, a linear search pattern, and include the nipple-areolar complex during the CBE compared to national sample (p Conclusions Students exposed to a structured skills curriculum more consistently performed the CBE according to national guidelines. The variability in technique compared with the national sample of students calls for major improvements in adoption and implementation of structured skills curricula.

Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.

Background The aim was to validate the potential use of a single, early procedure, operative task as a predictive metric for overall performance. The authors hypothesized that a shortcut psychomotor assessment would be as informative as a total procedural psychomotor assessment when evaluating laparoscopic ventral hernia repair performance on a simulator. Methods Using electromagnetic sensors, hand motion data were collected from 38 surgery residents during a simulated laparoscopic ventral hernia repair procedure. Three time-based phases of the procedure were defined: Early Phase (start time through completion of first anchoring suture), Mid Phase (start time through completion of second anchoring suture), and Total Operative Time. Correlations were calculated comparing time and motion metrics for each phase with the final laparoscopic ventral hernia repair score. Results Analyses revealed that execution time and motion, for the first anchoring suture, predicted procedural outcomes. Greater execution times and path lengths correlated to lesser laparoscopic ventral hernia repair scores (r = -0.56, P = .0008 and r = -0.51, P = .0025, respectively). Greater bimanual dexterity measures correlated to Greater LVH repair scores (r = + 0.47, P = .0058). Conclusions This study provides validity evidence for use of a single, early operative task as a shortcut assessment to predict resident performance during a simulated laparoscopic ventral hernia repair procedure. With the continued development and decreasing costs of motion technology, faculty should be well-versed in the use of motion metrics for performance measurements. The results strongly support the use of dexterity and economy of motion (path length + execution time) metrics as early predictors of operative performance.

Background Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. Methods We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes, Haemophilus influenzae, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunisation. Results We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunisation with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 mg/ml (range, 0.05 to 664.7 mg/ml) in children with DM and 6.1 mg/ml (0.12 to 203.36 mg/ml) in children without DM (p=0.013). Over 85% of children had levels above the protective threshold after booster immunisation with no difference between groups. Conclusions There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared with that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.

Background The aim of this study was to assess performance measurement validity of our newly developed robotic surgery task trainer. We hypothesized that residents would exhibit wide variations in their intercohort performance as well as a measurable difference compared to surgeons in fellowship training. Materials and methods Our laboratory synthesized a model of a pelvic tumor that simulates unexpected bleeding. Surgical residents and fellows of varying specialties completed a demographic survey and were allowed 20 minutes to resect the tumor using the da Vinci robot and achieve hemostasis. At a standardized event in the simulation, venous bleeding began, and participants attempted hemostasis using suture ligation. A motion tracking system, using electromagnetic sensors, recorded participants' hand movements. A postparticipation Likert scale survey evaluated participants' assessment of the model's realism and usefulness. Results Three of the seven residents (postgraduate year 2-5), and the fellow successfully resected the tumor in the allotted time. Residents showed high variability in performance and blood loss (125-700 mL) both within their cohort and compared to the fellow (150 mL blood). All participants rated the model as having high realism and utility for trainees. Conclusions The results support that our bleeding pelvic tumor simulator has the ability to discriminate resident performance in robotic surgery. The combination of motion, decision-making, and blood loss metrics offers a multilevel performance assessment, analyzing both technical and decision-making abilities.

Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV-encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student's t-test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0-19 to 55% in age group 20-34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.

The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.

Objective Previous studies have found that both resident and staff surgeons highly value postoperative feedback; and that such feedback has high educational value. However, little is known about how to consistently deliver this feedback. Our aim was to understand how often surgical residents should receive feedback and what barriers are preventing this from occurring. Design Surveys were distributed to resident and attending surgeons. Questions focused on the current frequency of postoperative feedback, desired frequency and methods of feedback, and perceived barriers. Quantitative data were analyzed with descriptive statistics, and text responses were examined using coding. Setting University-based general surgery department at a Midwestern institution. Participants General surgery residents ( n = 23) and attending surgeons ( n = 22) participated in this study. Results Residents reported receiving and staff reported giving feedback for procedure-specific performance after 25% versus 34% of cases, general technical feedback after 36% versus 32%, and nontechnical performance after 17% versus 18%. Both perceived procedure-specific and general technical feedback should be given more than 80% of the time, and nontechnical feedback should happen for nearly 60% of cases. Verbal feedback immediately after the operation was rated as best practice. Both parties identified time, conflicting responsibilities, lack of privacy, and discomfort with giving and receiving meaningful feedback as barriers. Conclusions Both resident and staff surgeons agree that postoperative feedback is given far less often than it should. Future work should study intraoperative and postoperative feedback to validate resident and attending surgeons’ perceptions such that interventions to improve and facilitate this process can be developed.

Background Due to the increased use of peripherally inserted central catheter lines, central lines are not performed as frequently. The aim of this study is to evaluate whether a virtual reality (VR)–based assessment of fine motor skills can be used as a valid and objective assessment of central line skills. Methods Surgical residents (N = 43) from 7 general surgery programs performed a subclavian central line in a simulated setting. Then, they participated in a force discrimination task in a VR environment. Hand movements from the subclavian central line simulation were tracked by electromagnetic sensors. Gross movements as monitored by the electromagnetic sensors were compared with the fine motor metrics calculated from the force discrimination tasks in the VR environment. Results Long periods of inactivity (idle time) during needle insertion and lack of smooth movements, as detected by the electromagnetic sensors, showed a significant correlation with poor force discrimination in the VR environment. Also, long periods of needle insertion time correlated to the poor performance in force discrimination in the VR environment. Conclusions This study shows that force discrimination in a defined VR environment correlates to needle insertion time, idle time, and hand smoothness when performing subclavian central line placement. Fine motor force discrimination may serve as a valid and objective assessment of the skills required for successful needle insertion when placing central lines.

Extranodal NK/T-cell lymphoma, nasal type, is a rare type of non-Hodgkin lymphoma that is most common in Asia and is driven by Epstein-Barr virus infection. These tumors usually arise in the nasal region; in rare cases they can involve extranasal sites, most often skin, with involvement of the breast being rare. Lymphomas arising adjacent to breast implants are rare, and most cases reported to date have been anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma. Here we report a 41-year-old white woman with bilateral saline breast implants placed for cosmetic reasons who almost 9 years later developed painful swelling at the right-breast implant site. Excisional biopsy revealed lymphoma composed of monomorphic large cells associated with necrosis and angioinvasion. Immunohistochemical analysis showed an aberrant, NK/T-cell immunophenotype with the lymphoma cells being CD2+, CD3+, CD56+, partial CD30+, granzyme B, TIA-1+, CD4+, CD5+, CD7+, and CD8+. In situ hybridization analysis showed Epstein-Barr virus-encoded RNA within the neoplastic cells. Polymerase chain reaction analysis showed monoclonal T-cell receptor-γ chain gene rearrangement. These findings support the diagnosis of extranodal NK/T-cell lymphoma, nasal type. On the basis of our review of the literature, this case is unique. In addition, we believe this case is important to report, because it expands the spectrum of T-cell lymphomas that can be associated with breast implants and may be a forerunner of additional cases to follow.

The aim of this study is to report the relative frequencies of non-Hodgkin lymphoma (NHL) subtypes in Guatemala. A panel of five hematopathologists reviewed 226 consecutive biopsies and classified them according to the 2001 World Health Organization (WHO) classification. The 83 cases of diffuse large B-cell lymphoma (DLBCL) were further subclassified into germinal center B-cell-like (GCB) and non-GCB subtypes. Of the 226 cases, 194 (86%) were confirmed as NHL, including 169 (87%) B-cell and 25 (13%) T- or natural killer (NK)-cell NHL. The most common subtype was DLBCL (44.3%), and the most frequent subtype among T- and NK-cell NHL was extranodal NK/T-cell lymphoma, nasal type (7.8% of all NHL). A comparison of the frequencies of NHL subtypes between Guatemala and other parts of the world showed that Guatemala is most similar to the Middle East and Asia. However, there is no significant difference in the frequency of the DLBCL subtypes compared to North America and Europe.

Fifty-five consecutive cases of Hodgkin's lymphoma (HL), collected between 1996 and 1998 from Cairo, Egypt, were histologically subtyped, phenotyped, and then studied for the presence of Epstein-Barr virus (EBV). We used immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) and in situ hybridization stains for EBV-encoded small RNA (EBER-1) transcripts. Forty-five cases (82%) had classic HL (cHL), and ten cases (18%) had nodular lymphocyte predominant HL (NLPHL), with each group expressing its typical phenotype. LMP-1 stains were positive in 63% and 0% of cHL and NLPHL cases, respectively. EBER-positive Reed-Sternberg cells and variants were also present in 62% and 0% of each group, respectively. The cHL cases showed variable EBER positivity: nodular sclerosis, 58%; mixed cellularity, 100%; lymphocyte depletion, 100%; and unclassifiable, 67%. Our findings are similar to those from other developing countries and point towards a pathogenic role of EBV in cHL.

We report a 13-year-old adolescent girl, the youngest thus far, with "an indolent T-lymphoblastic" proliferation (~10%) that uniquely presented within recurrent, large inguinal lymph node masses in a predominating (90%) background of Castleman disease. These nodal masses were resected thrice; the patient is well 5 years after diagnosis without further treatment. Histologically, the features of Castleman disease, hyaline vascular type, were present. Importantly, the interfollicular T-lymphoblastic component occurred as multiple clusters and islands of variable shapes and sizes composed of small "lymphoblasts" indistinguishable from normal cortical thymocytes but without thymic epithelial cells. Immunohistochemically, these lymphoblasts were consistent with the intermediate stage of T-cell differentiation (TdT(+)CD34(-)CD99(+)CD1a(+)CD2(+)CD3(+)CD4(+)CD8(+)CD5(+)CD7(+)CD10(+) [subset]), with 80% Ki-67. Molecularly, the T cells were nonclonal. Our case provides evidence for the benign nature of this highly unusual and poorly understood entity; because the current terminology can be readily misinterpreted as an indolent lymphoblastic lymphoma, we suggest a new term accurately reflecting this entity.

This study aims to answer the question whether the World Health Organization (WHO) classification of non-Hodgkin's lymphoma (NHL) can be practised to international standards at the Lymphoma Registry (LR) established at the Tata Memorial Hospital, Mumbai, India. Furthermore, the study aims to identify differences in the distribution of NHL subtypes at this LR (likely to be representative of India) as compared to the rest of the world. A panel of 5 expert hematopathologists from the NHL Classification Project reviewed 200 consecutive NHL cases at the LR in January of 2001. These cases were accrued during August and September, 2000. On all cases, hematoxylin and eosin stains and appropriate immunostains were available for review. The diagnosis made by the host pathologist at the LR (KNN) and the initial diagnosis made by each of the expert hematopathologists was compared with the consensus diagnosis. A consensus diagnosis was made by the 5 experts in 197 cases. The agreement of the host pathologist with the consensus diagnosis was 82% and the agreement of the individual experts with the consensus diagnosis varied from 76-88% (mean 82%). According to the consensus diagnosis, 80% of NHLs were of B-cell type, 18% were of T-cell type, and the immunophenotype could not be determined in the remaining 2% of cases. In conclusion, the WHO classification of NHL was properly utilized at the Lymphoma Registry, Mumbai, India, and geographic differences were noted in the distribution of NHL subtypes at the LR as compared to the rest of the world. Precursor T lymphoblastic leukemia/lymphoma was more common in India (7%) than the rest of the world (1-4%), and indolent B-cell NHLs (29%) were less common than in the West. As compared to China and Japan, peripheral T-cell lymphoma (4.6%), extranodal NK/T cell lymphoma, nasal type (0.5%) and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) (2.6%) were less common, but follicular lymphoma (15%) and chronic lymphocytic leukemia/small lymphocytic lymphoma (5%) were more common. This suggests that the distribution of the B-cell and T-cell lymphomas in the Indian population, except for lymphoblastic lymphoma, lies in between the Western world (mainly Caucasian) and the Orientals.

Purpose To evaluate the safety and efficacy of liposomal doxorubicin (Myocet; Medeus Pharma Ltd, Herts,UK) when substituted for doxorubicin in the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with newly diagnosed AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Secondary objectives were to assess the impact of HIV viral control on response and survival, and to correlate MDR-1 expression with outcome. Patients and Methods Liposomal doxorubicin at doses of 40, 50, 60, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone every 21 days. All patients received concurrent highly active antiretroviral therapy. NHL tissues were evaluated for multidrug resistance (MDR-1) expression. Results Twenty-four patients were accrued. 67% had high or high-intermediate International Prognostic Index scores; the median CD4 lymphocyte count was 112/mm3 (range, 19/mm3 to 791/mm3). No dose-limiting toxicities were observed at any level, with myelosuppression being the most frequent toxicity. Overall response rate was 88%, with 75% complete responses (CRs), and 13% partial responses. The median duration of CR was 15.6+ months (range, 1.7 to 43.5+ months). Effective HIV viral control during chemotherapy was associated with significantly improved survival (P = .027), but CRs were attained independent of HIV viral control. MDR-1 expression did not correlate with response, suggesting that the liposomal doxorubicin may evade this resistance mechanism. Conclusion Liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is active in AIDS-NHL, with complete remissions achieved in 75% independent of HIV viral control or tissue MDR-1 expression. HIV viral control is associated with a significant improvement in survival. Additional studies are warranted.

In this report, the Association of Directors of Anatomic and Surgical Pathology (ADASP) provides guidelines for the reporting of lymphoid neoplasms. The World Health Organization Classification of Tumors of the Haematopoietic and Lymphoid Tissues is the preferred international standard for diagnostic criteria (disease definition) and nomenclature. Ancillary studies are often required, and the Association recommends that immunophenotypic and genotypic information be integrated into the final report, to the extent possible.

Mantle cell lymphoma (MCL) comprises 7% of non-Hodgkin lymphomas. It can grow in several different architectural patterns including mantle zone, mantle cell nodular, follicular colonization, and diffuse. Cytologically, the mantle cell nuclei can range from round to slight to markedly irregular (classic), to blastoid, and to pleomorphic. They rarely have moderate amounts of cytoplasm and mimic marginal zone B cells. We present a most unusual case of MCL that displays mantle zone, mantle cell nodular, follicular colonization, marginal, inverse follicular, and interfollicular patterns. In the areas showing mantle zone, nodular, and follicular colonization, the mantle cells have round to slightly irregular nuclear contours, and show a high mitotic rate. In the areas displaying an interfollicular, inverse follicular, and marginal zone patterns, the mantle cells show selective transformation to large blastoid cells resembling lymphoblasts. The mitotic rate in these areas is exceedingly high. Immunophenotypically, both cytologic components are positive for CD20, CD5, CD43, and cyclin D1, confirming the MCL diagnosis.

We evaluated the association between common immune system-altering experiences and non-Hodgkin lymphoma (NHL) risk using a case-control study of 162 like-sex twin pairs discordant for NHL, identified from the International Twin Study. Information on medical history and evidence of childhood exposure to microbes was obtained by questionnaire from 1998 to 2002. Conditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Intra-twin-pair agreement between twins on individual exposures was high (76%-97%). A negative association between NHL and seasonal hay fever (odds ratio (OR) = 0.28, 95% confidence interval (CI): 0.10, 0.75) and certain allergies (OR = 0.29, 95% CI: 0.13, 0.68) was observed. The number of atopic diseases was negatively associated with NHL (P for trend = 0.0003). A history of infectious mononucleosis was negatively associated with NHL risk (OR = 0.35, 95% CI: 0.14, 0.90). NHL risk was associated with more frequent childhood exposure to microbes during early life (P for trend = 0.04). No differences in association by NHL subtype were observed, although statistical power for these comparisons was low. These observations support the hypothesis that immune-related exposures, especially atopy, are associated with decreased NHL risk. Use of the within-twin-pair study design mitigates confounding by genome, family structure, and unmeasured characteristics of early childhood factors.

The relative distribution of non-Hodgkin lymphoma (NHL) subtypes differs markedly around the world. The aim of this study was to report this distribution in Algeria. A panel of four hematopathologists classified 197 consecutive cases according to the World Health Organization classification, including 87.3% B-cell and 12.7% T- or natural killer (NK)-cell NHLs. This series was compared with similar cohorts from Western Europe (WEU) and North America (NA). Algeria had a significantly higher frequency of diffuse large B-cell lymphoma (DLBCL: 52.8%) and a lower frequency of follicular lymphoma (FL: 13.2%) compared with WEU (DLBCL: 32.2%; FL: 20.0%) and NA (DLBCL: 29.3%; FL: 33.6%). The frequency of mantle cell lymphoma was lower in Algeria (2.5%) compared with WEU (8.3%). Smaller differences were also found among the NK/T-cell lymphomas. In conclusion, we found important differences between Algeria and Western countries, and further epidemiologic studies are needed to explain these differences.

Bone marrow involvement is reported in approximately 25% of patients with newly diagnosed acquired immunodeficiency syndrome–related lymphoma (ARL). Studied were 291 patients with ARL, diagnosed and treated at one medical center between 1984 and 1998. Clinical, immunologic, and pathologic characteristics of patients with bone marrow involvement were compared with those of patients without marrow involvement. Bone marrow involvement was present in 55 patients (19%). Small noncleaved lymphoma was diagnosed in 38% of the entire group and was the most common pathologic subtype in patients with bone marrow involvement (55% versus 34%;P = .008). Analysis of complete blood counts revealed a median hemoglobin level of 10.6 g/dL in both marrow-positive and marrow-negative groups. In contrast, a platelet count lower than 100 000/μL was more common in patients with bone marrow involvement (27% versus 11%; P = .02). Patients with marrow involvement were more likely to have leptomeningeal (cerebrospinal fluid [CSF]) lymphoma than patients whose marrows were uninvolved (24% versus 7%; P

Anaplastic large-cell lymphoma (ALCL) is a heterogeneous process that may have a T-cell, B-cell, or indeterminant (null) phenotype and which may or may not express the anaplastic lymphoma kinase (ALK) oncoprotein. Because the clinical significance of these variants of ALCL is unclear, we evaluated the cases of ALCL-T/null and ALCL-B identified in the Non-Hodgkin's Lymphoma Classification Project. We evaluated 1,378 cases of non-Hodgkin's lymphoma (NHL), and a consensus diagnosis of ALCL-T/null was made in 33 patients (2.4%) with a diagnostic accuracy of 85%. Compared to 96 patients with other forms of peripheral T-cell lymphoma (PTCL), those with ALCL-T/null were significantly younger, less likely to have advanced-stage disease or bone marrow involvement, more likely to have a low International Prognostic Index score, and had a significantly better survival. Among those with ALCL-T/null, there were no significant differences in the clinical features or survival on the basis of ALK expression. A consensus diagnosis of ALCL-B was made in 15 patients (1.1%), and the diagnostic accuracy was 67%. However, compared to 366 patients with other forms of diffuse large B-cell lymphoma (DLBCL), those with ALCL-B were no different with regard to clinical features or survival. We conclude that patients with ALCL-T/null have favorable prognostic features and excellent survival and should be separated from those with other forms of PTCL for prognostic and therapeutic purposes. In contrast, patients with ALCL-B appear to be similar to those with other forms of DLBCL.

Over time, the epidemiologic and demographic characteristics of AIDS have changed in the United States, while the use of highly active antiretroviral therapy has changed the natural history of the disease. The goal of the study was to ascertain any changes in the epidemiologic, immunologic, pathologic, or clinical characteristics of AIDS-related lymphoma (ARL) over the course of the AIDS epidemic. Records of 369 patients with ARL diagnosed or treated at a single institution from 1982 through 1998 were reviewed. Single institutional data were compared to population-based data from the County of Los Angeles. Significant changes in the demographic profile of patients with newly diagnosed ARL have occurred, with the later time intervals associated with a higher prevalence in women (P = .25), in Latino/Hispanic individuals (P

To ascertain the results of standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) in HIV-infected patients with newly diagnosed Hodgkin's disease (HD), a nonrandomized, prospective, multiinstitutional clinical trial was conducted by the AIDS Clinical Trials Group (ACTG), in HIV-infected patients with Hodgkin's disease. All patients received the standard ABVD regimen, with granulocyte-colony-stimulating factor (G-CSF). Antiretroviral therapy was not used. Between May, 1992 and August, 1996, 21 patients were added to the study and treated. The median CD4 count was 113 cells/mm 3 , and 29% had a history of a clinical AIDS-defining condition before diagnosis of HD. Systemic B symptoms were present in 90% at diagnosis. Stage IV HD was present in 67%, with bone marrow involvement in 12 (57%). Nodular sclerosis HD was present in 38%, with mixed cellular disease in 31%. Among all patients entered and treated, complete remission (CR) was attained in 9 (43%; 90% confidence interval [CI], 24%-63%), whereas partial response occurred in 4 (19%), leading to an overall objective response rate of 62% (90% Cl, 42%-79%). Despite routine use of G-CSF, 10 patients (47.6%) experienced life-threatening neutropenia, with absolute neutrophil counts

BACKGROUND Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog with cytotoxic activity against both resting and proliferating cells. Clinical studies with cladribine have reported antitumor activity against various hematologic malignancies. METHODS The authors studied responses to cladribine among patients with low and intermediate grade non-Hodgkin's lymphoma that had been refractory to or relapsed after prior chemotherapy. Cladribine was given intravenously over 2 hours at a dose of 0.14 mg/kg daily for 5 consecutive days, repeated every 4 weeks. RESULTS Twenty-eight patients (16 males, 12 females) with a median age of 58 years (range, 41-75 years) were accrued. Twenty-three patients had low grade and 5 had intermediate grade lymphoma. Stage IV disease was present in 22 (79%), and 17 (61%) had systemic B-symptoms. The majority (57%) had received 2 or more prior chemotherapy regimens (median, 2; range, 1-5); 6 had had prior fludarabine therapy. Major responses were documented in 32% (9 of 28 patients), with 4 complete remissions (CR) and 5 partial remissions (PR) after a median of 4 cycles (range, 1-9). One CR occurred in one patient with intermediate grade diffuse large cell lymphoma, and three of six patients who had had prior fludarabine therapy experienced CR or PR with cladribine. Severe hematologic toxicities included reversible neutropenia, protracted thrombocytopenia, and lymphopenia. Other reported adverse effects included mild-to-moderate fatigue, nausea, and diarrhea. CONCLUSIONS Cladribine is an active single agent in the treatment of patients with refractory or relapsed advanced stage indolent lymphoma, with major responses in one third of patients. Cancer 1998;83:2370-2376. © 1998 American Cancer Society.

Pathfinder is an Expert System that assists pathologists in making accurate diagnoses in the domain of lymph-node pathology. Pathfinder provides a differential diagnosis based on the initial histological feature(s) observed by the pathologist, and suggests to the user additional histological features for observation that are likely to narrow the differential diagnosis.To evaluate the diagnostic accuracy of pathologists with and without the Pathfinder.Thirty HE stained slides from 30 lymph node biopsy specimens on which a Consensus diagnosis was made by two experts were reviewed by 19 pathologists to evaluate Pathfinder. After a period of training, 10 pathologists using Pathfinder (Interactive Computer Method) and 9 pathologists using the Routine Method (diagnosis without computer) determined a differential diagnosis for 15 slides (Test 1). Pathologists were then crossed over, trained, and evaluated the remaining 15 slides (Test 2). For each test, the proportion of "correct" diagnoses was compared between methods. In addition, the information integration attributes (making logical diagnosis given a set of specific histologic features) of Pathfinder and pathologists were compared. Finally, feature identification and quantification skills of pathologists were determined and correlated with the percent correct diagnosis.The diagnostic accuracy using Pathfinder was greater than that using the Routine Method (40% v 32%, P = .02). Diagnostic accuracy for the group of pathologists who made diagnosis using the Routine Method in Test 1 increased when they made diagnosis using Pathfinder in Test 2 (27% to 44%, P.0001). The proportion of correct diagnosis for the group of pathologists who used Pathfinder in Test 1 remained virtually unchanged when they gave up Pathfinder in Test 2 (35% to 37%). The percentage of incompatible feature identification ("atypical proliferation" diagnosis) was significantly lower after using Pathfinder (P.0001). In addition, information integration attributes of Pathfinder were significantly superior than that of the pathologists (P.0001).Pathfinder is a valuable tool that assists pathologists in making accurate diagnosis because it has superior attributes than pathologists to integrate information and to screen for observations incompatible with any specific disease.

Continuous class pattern recognition is a new analytic method that differs from existing techniques by recognizing and exploiting the continuous relationship among classes along diagnostic scales. Continuous class pattern recognition was applied to a wide variety of image processing features extracted from lymph node biopsy images that were digitized using a Coulter diff3/50 automated research microscope. The resultant classifiers correctly subtyped 89% of a set of 37 follicular lymphomas, compared to individual pathologist rates that ranged from 57% to 81%. This study demonstrates that continuous class pattern recognition can significantly reduce this diagnostic error rate.

BACKGROUND Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment. METHODS Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy. RESULTS CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1–61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic “B” symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006). CONCLUSIONS Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic “B” symptoms, whereas changes in serum IL-6 may correlate with response. Cancer 1996;78:517-26.

The role of zidovudine and other antiretroviral agents in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related lymphomas has been somewhat controversial. In an attempt to elucidate the precise role of antiretroviral agents in the subsequent development of AIDS-related lymphoma, we performed a population-based, case-control study of human immunodeficiency virus (HIV)-seropositive patients with intermediate- or high-grade lymphoma in Los Angeles County, California, in which information regarding use of antiretroviral medications was ascertained. Diagnostic biopsy material was reviewed to confirm intermediate-or high-grade lymphoma. A structured interview, conducted with all cases and controls, included information about use of zidovudine and other antiretroviral agents. A total of 112 HIV-infected homosexual/bisexual men with lymphoma were matched to 112 homosexual/bisexual men with asymptomatic HIV infection; 49 of the lymphoma cases were also matched to 49 additional controls with AIDS, as defined by conditions other than lymphoma. Positive histories of zidovudine use were reported by 44 (39%) lymphoma cases, 24 (21%) asymptomatic HIV controls, and 21 (42%) AIDS controls. The average duration of zidovudine use up to 12 months before lymphoma diagnosis was 19.0 +/- 13.0 months (mean +/- SD) for the lymphoma cases, 12.6 +/- 10.5 months for the asymptomatic controls, and 11.0 +/- 7.1 months for the AIDS controls. When comparing the 49 HIV-positive lymphoma cases with their 49 matched AIDS controls, all of whom were diagnosed with AIDS during the same time period, the matched relative odds of lymphoma associated with prior use of zidovudine was 0.43 (95% confidence interval [CI] = 0.17 to 1.12). In comparing all 112 lymphoma cases with 49 AIDS controls, the unmatched relative odds of lymphoma associated with zidovudine use was 0.93 (95% confidence interval = 0.47 to 1.83). One lymphoma case and no AIDS control cases had a history of didanosine use; no lymphoma case or AIDS control cases had taken zalcitabine. We conclude that zidovudine is not associated with an increased risk of development of lymphoma among HIV-infected homosexual or bisexual men.

Relatives of young adults with Hodgkin's disease are at increased risk of Hodgkin's disease, and lines of evidence implicate both inheritance and environment.We have identified and followed 432 sets of twins affected by Hodgkin's disease. The number of cases of Hodgkin's disease observed before the age of 50 years in the healthy monozygotic and dizygotic twins of the patients with Hodgkin's disease was compared with the number expected from national age-specific incidence rates.None of the 187 pairs of dizygotic twins became concordant for Hodgkin's disease, whereas 10 of the 179 pairs of monozygotic twins did; in 5 of these pairs, the second case appeared after the original ascertainment. During the observation period, 0.1 (monozygotic) and 0.1 (dizygotic) cases in the unaffected twins were expected. Monozygotic twins of patients with Hodgkin's disease thus had a greatly increased risk (standardized incidence ratio, 99; 95 percent confidence interval, 48 to 182), whereas no increase in the risk for dizygotic twins of patients with Hodgkin's was observed.Genetic susceptibility underlies Hodgkin's disease in young adulthood.

The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non- Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates for innovative therapy.

Purpose The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) –cell lymphomas. Patients and Methods Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. Results Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 109/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065). Conclusion AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.

The distribution of subtypes of non-Hodgkin lymphoma (NHL) in Latin America is not well known. This Chilean study included 207 consecutive cases of NHL diagnosed at five cancer centers in the capital, Santiago, and one center in Vina del Mar. All cases were reviewed and classified independently by five expert hematopathologists according to the 2001 World Health Organization classification of NHL. A consensus diagnosis of NHL was reached in 195 of the 207 cases (94%). B-cell lymphomas constituted 88% of NHL, and diffuse large B-cell lymphoma (DLBCL, 38.5%) and follicular lymphoma (25.1%) were the most common subtypes. There was a high frequency of marginal zone B-cell lymphoma (10.3%), as well as of extranodal natural killer (NK)/T-cell lymphoma, nasal type (2.6%) and adult T-cell leukemia/lymphoma (0.5%). Extranodal presentation was seen in 74 of the 195 cases (38%) and the most common extranodal presentation was in the stomach (37.6%). The most common gastric lymphoma was DLBCL (54.5%) followed by mucosa-associated lymphoid tissue (MALT) lymphoma (41%). Overall, the frequency of NHL subtypes in Chile is between that reported in Western and Eastern countries, which is probably a reflection of the admixture of ethnicities as well as the environment and socioeconomic status of its population.

Few large, international series of enteropathy-associated T-cell lymphoma (EATL) have been reported. We studied a cohort of 62 patients with EATL among 1153 patients with peripheral T-cell or natural killer (NK)–cell lymphoma from 22 centers worldwide. The diagnosis was made by a consensus panel of 4 expert hematopathologists using World Health Organization (WHO) criteria. Clinical correlations and survival analyses were performed. EATL comprised 5.4% of all lymphomas in the study and was most common in Europe (9.1%), followed by North America (5.8%) and Asia (1.9%). EATL type 1 was more common (66%) than type 2 (34%), and was especially frequent in Europe (79%). A clinical diagnosis of celiac sprue was made in 32.2% of the patients and was associated with both EATL type 1 and type 2. The median overall survival was only 10 months, and the median failure-free survival was only 6 months. The International Prognostic Index (IPI) was not as good a predictor of survival as the Prognostic Index for Peripheral T-Cell Lymphoma (PIT). Clinical sprue predicted for adverse survival independently of the PIT. Neither EATL subtype nor other biologic parameters accurately predicted survival. Our study confirms the poor prognosis of patients with EATL and the need for improved treatment options.

Pathfinder is an expert system that assists surgical pathologists with the diagnosis of lymph-node diseases. The program is one of a growing number of normative expert systems that use probability and decision theory to acquire, represent, manipulate, and explain uncertain medical knowledge. In this article, we describe Pathfinder and our research in uncertain-reasoning paradigms that was stimulated by the development of the program. We discuss limitations with early decision-theoretic methods for reasoning under uncertainty and our initial attempts to use non-decision-theoretic methods. Then, we describe experimental and theoretical results that directed us to return to reasoning methods based in probability and decision theory.