Safety and efficacy of oral anticoagulants in extreme weights.

BACKGROUND: The 2021 International Society on Thrombosis and Haemostasis' (ISTH) recommends standard doses of apixaban and rivaroxaban regardless of high body mass index (BMI) and weight, but had not compare DOACs head-to-head in obesity or address underweight patients. METHODS: Our aim is to evaluate the safety and efficacy of DOACs in underweight and obese patients compared to warfarin. The primary endpoints include incidence of thromboembolic and bleeding events. Descriptive statistics was used for continuous variables. The Kruskal-Wallis test was used to compare the four-groups for continuous measures and the chi-square test or Fisher's exact test was used to analyze categorical data. The chi-square test or Fisher's exact test, was used for categorical variables, and the Mann-Whitney test (the non-parametric counterpart to the two-sample t-test) for continuous data. RESULTS: Of 2940 patients receiving anticoagulation for venous thromboembolism (VTE) treatment or atrial fibrillation (AF), 492 met eligibility criteria. Within each group, 248 patients received warfarin, 101 received apixaban, 100 received rivaroxaban and 43 received dabigatran. Patients were characterized in 4 body mass index (BMI) categories, in which 80 were underweight and 412 were obese. CONCLUSIONS: When each DOAC was compared to warfarin in rates of VTE, apixaban showed statistically significant lower rate of VTE (p = 0.0149). However, no statistical significance was identified in the rate of VTE between DOACs combined vs. warfarin (p = 0.1529). When each DOAC was compared to warfarin, apixaban showed the lowest rate of overall bleeding (p = 0.0194). However, no statistical difference in the rate of bleeding was observed between DOACs combined vs. warfarin (p = 0.3284). Patients with extreme body weights requiring anticoagulation for VTE and AF may safety benefit from DOAC therapy. This evaluation showed apixaban with the lowest rate of VTE and bleeding compared to warfarin, rivaroxaban, and dabigatran. These results provide experience for the clinician to use DOACs, particularly apixaban, in underweight and obese populations.

Long term outcomes of robotic-assisted abdominal wall reconstruction: a single surgeon experience.

INTRODUCTION: Robotic abdominal wall reconstruction (RAWR) is one of the most significant advances in the management of complex abdominal wall hernias. The objective of this study was to evaluate long term outcomes in a cohort of patients that underwent complex RAWR in a single center. METHODS: This was a longitudinal retrospective review of a cohort of 56 patients who underwent complex RAWR at least 24 months prior by a single surgeon at a tertiary care institution. All patients underwent bilateral retro-rectus release (rRRR) with or without robotic transversus abdominis release (rTAR). Data collected include demographics, hernia details, operative and technical details. The prospective analysis included a post-procedure visit of at least 24 months from the index procedure with a physical examination and quality of life survey using the Carolinas Comfort Scale (CCS). Patients with reported symptoms concerning for hernia recurrence underwent radiographic imaging. Descriptive statistics (mean ± standard deviation or median) were calculated for continuous variables. Chi-square or Fisher's exact test as deemed appropriate for categorical variables, and analysis of variance or the Kruskal-Wallis test for continuous data, were performed among the separate operative groups. A total score for the CCS was calculated and analyzed in accordance with the user guidelines. RESULTS: One-hundred and-forty patients met the inclusion criteria. Fifty-six patients consented to participate in the study. Mean age was 60.2 years. Mean BMI was 34.0. Ninety percent of patients had at least one comorbidity and 52% of patients were scored ASA 3 or higher. Fifty-nine percent were initial incisional hernias, 19.6% were recurrent incisional hernias and 8.9% were recurrent ventral hernias. The mean defect width was 9 cm for rTAR and 5 cm for rRRR. The mean implanted mesh size was 945.0 cm2 for rTAR and 362.5 cm2 for rRRR. The mean length of follow-up was 28.1 months. Fifty-seven percent of patients underwent post-op imaging at an average follow-up of 23.5 months. Recurrence rate was 3.6% for all groups. There were no recurrences in patients that underwent solely bilateral rRRR. Two patients (7.7%) that underwent rTAR procedures were found with recurrence. Average time to recurrence was 23 months. Quality of life survey demonstrated an overall CCS score of 6.63 ± 13.95 at 24 months with 12 (21.4%) patients reporting mesh sensation, 20 (35.7%) reporting pain, and 13 (23.2%) reporting movement limitation. CONCLUSION: Our study contributes to the paucity of literature describing long term outcomes of RAWR. Robotic techniques offer durable repairs with acceptable quality of life metrics.

Oxalobacter formigenes treatment confers protective effects in a rat model of primary hyperoxaluria by preventing renal calcium oxalate deposition.

In primary hyperoxaluria, increased hepatic oxalate production sometimes leads to severe nephrocalcinosis and early end-stage kidney disease. Oral administration of Oxalobacter formigenes (O. formigenes), an oxalate-degrading bacterium, is thought to derive oxalate from systemic sources by inducing net enteric oxalate secretion. Here, the impact of O. formigenes on nephrocalcinosis was investigated in an ethylene glycol rat model mimicking hepatic oxalate overproduction in primary hyperoxaluria. Eighteen rats were administered ethylene glycol (0.75% in drinking water) for 6 weeks, of which 9 were treated by oral gavage with O. formigenes and 9 received vehicle. Five control rats did not receive ethylene glycol or O. formigenes. Plasma and urinary oxalate levels, calcium oxalate crystalluria, urinary volume, fluid intake, and serum creatinine were monitored during the study. On killing, nephrocalcinosis was quantified. Ethylene glycol intake induced pronounced hyperoxalemia, hyperoxaluria, calcium oxalate crystalluria and nephrocalcinosis. Concomitant O. formigenes treatment partially prevented the ethylene glycol-induced increase in plasma oxalate and completely prevented nephrocalcinosis. Urinary oxalate excretion was not reduced by O. formigenes treatment. Nevertheless, absence of crystals in renal tissue of O. formigenes-treated ethylene glycol animals indicates that the propensity for oxalate to crystallize in the kidneys was reduced compared to non-treated animals. This is supported by the lower plasma oxalate concentrations in O. formigenes-treated animals. This study shows a beneficial effect of O. formigenes treatment on ethylene glycol-induced hyperoxalemia and nephrocalcinosis, and thus supports a possible beneficial effect of O. formigenes in primary hyperoxaluria.

Diagnostic criteria for temporomandibular disorders: Diagnostic accuracy for general dentistry procedure without mandatory commands regarding myalgia, arthralgia and headache attributed to temporomandibular disorder.

The clinical examination in diagnostic criteria for temporomandibular disorders (DC/TMD) is a strict procedure and comprises mandatory commands. However, learning and using these mandatory commands in general practice have proven to be difficult and their use of DC/TMD is minimal. To investigate whether reliability on a diagnostic level for DC/TMD diagnoses differs between examiners using the mandatory commands or not. Six examiners were divided into two groups: one using the mandatory commands in DC/TMD for the clinical examination and one who did not use the mandatory commands. A reliability assessment was performed twice, one occasion for each group of examiners. The assessment was performed according to the guidelines from the International Network for Orofacial Pain and Related Disorders Methodology. Each group of examiners thereby examined 16 subjects (11 TMD patients and 5 healthy individuals) each, and the diagnostic agreement (reliability) as compared to diagnoses derived by a reference standard examiner was calculated with Cohen' s kappa coefficient. The DC/TMD diagnoses myalgia, arthralgia and headache attributed to TMD were included in the reliability assessment. There was no significant difference regarding diagnostic agreement reliability between the examiners using or not using the mandatory DC/TMD commands. This study indicates that not using the mandatory commands in DC/TMD in general practice does not impair the diagnostic reliability regarding the diagnoses myalgia, arthralgia and headache attributed to TMD compared to including the commands.

Effects of medications on post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: Drug-induced pancreatitis accounts for about 2% of acute pancreatitis. The aim of this study is to determine whether propofol and other medications are associated with increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: A retrospective study was conducted at a single tertiary care hospital. All patients who underwent ERCP from 2001 to 2004 were included. Diagnosis of acute post-ERCP pancreatitis was based on a consensus definition. RESULTS: A total of 506 patients underwent ERCP. The total incidence of post-ERCP pancreatitis was 7.1%. There was no significant difference in post-ERCP pancreatitis between patients who received propofol compared to patients who received midazolam and fentanyl (9.0 vs. 5.9%, p = 0.18). Patients receiving an angiotensin receptor blocker were approximately 4 times more likely to develop post-ERCP pancreatitis (OR = 4.1, 95% CI 1.6-10.9). Patients younger than 65 years and smokers also had higher risk of developing acute post-ERCP pancreatitis than those who were older than 65 years (OR = 3.9, 95% CI 1.7-9.1) and non-smokers (OR = 2.8, 95% CI 1.3-6.2). CONCLUSIONS: Propofol is a safe sedative drug for ERCP without additional risk of developing acute post-ERCP pancreatitis. Use of angiotensin receptor blockers, smoking and younger age are independent risk factors for post-ERCP pancreatitis.

Low-grade fibromyxoid sarcoma is difficult to diagnose by fine needle aspiration cytology: a cytomorphological study of eight cases.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon neoplasm with bland morphology and an indolent clinical course, although metastases may develop in approximately 5-10% of the cases. The diagnosis of LGFMS can be difficult to render from fine needle aspiration cytology (FNAC) alone because of morphological overlap with other spindle cell and myxoid lesions. OBJECTIVE: To determine cytological criteria for LGFMS by reviewing FNAC aspirates in eight cases and to compare the findings with those in subsequent histological sections. METHODS: FNAC slides were reviewed from eight patients with subsequently excised tumours diagnosed as LGFMS. Of these patients, six also had core needle biopsies (CNB). Cytogenetic and/or molecular analysis was carried on all tumours. RESULTS: The patients were six men and two women ranging in age from 26 to 78 years. Tumours arose in the deep soft tissues of the thigh (n = 5), shoulder girdle (n = 1) or upper arm (n = 1) and one in the subcutaneous tissue of the abdominal wall. Cytological features included clusters of bland spindle and round/polygonal cells embedded in a collagenous and myxoid matrix along with dissociated, uniform or slightly/moderately pleomorphic spindle cells, bare nuclei and fragments of collagen and myxoid tissue in varying proportions. Unequivocal sarcoma was diagnosed in two aspirates, but mitoses were absent in all cases. In three cases, the diagnosis was inconclusive with regard to benignity or malignancy, while three were erroneously diagnosed as benign spindle cell lesions. Although the diagnosis was suggested on three of six CNB, these presented similar diagnostic problems. CONCLUSIONS: There were no cytomorphological findings in FNAC to allow for a clear cut separation of LGFMS from other spindle cell or myxoid lesions, but high-grade sarcoma could be excluded. Surgical (incisional or excisional) biopsy or, alternatively, examination of RT-PCR for the FUS/CREB3L or FUS/CREB3L1 fusion transcripts may be necessary to obtain a correct diagnosis.

A pilot study of activity-based therapy in the arm motor recovery post stroke: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of activity-based therapies using arm ergometer or robotic or group occupational therapy for motor recovery of the paretic arm in patients with an acute stroke (< or =4 weeks) admitted to an inpatient rehabilitation facility, and to obtain information to plan a large randomized controlled trial. DESIGN: Prospective, randomized controlled study. SETTING: Stroke unit in a rehabilitation hospital. SUBJECTS: Thirty patients with an acute stroke (< or =4 weeks) who had arm weakness (Medical Research Council grade 2 or less at the shoulder joint). INTERVENTION: Occupational therapy (OT) group (control) (n = 10), arm ergometer (n = 10) or robotic (n = 10) therapy group. All patients received standard, inpatient, post-stroke rehabilitation training for 3 hours a day, plus 12 additional 40-minute sessions of the activity-based therapy. MAIN MEASURES: The primary outcome measures were discharge scores in the Fugl-Meyer Assessment Scale for upper limb impairment, Motor Status Scale, total Functional Independence Measure (FIM) and FIM-motor and FIM-cognition subscores. RESULTS: The three groups (OT group versus arm ergometer versus robotic) were comparable on clinical demographic measures except the robotic group was significantly older and there were more haemorrhagic stroke patients in the arm ergometer group. After adjusting for age, stroke type and outcome measures at baseline, a similar degree of improvement in the discharge scores was found in all of the primary outcome measures. CONCLUSION: This study suggests that activity-based therapies using an arm ergometer or robot when used over shortened training periods have the same effect as OT group therapy in decreasing impairment and improving disability in the paretic arm of severely affected stroke patients in the subacute phase.

The complex cytological features of synovial sarcoma in fine needle aspirates, an analysis of four illustrative cases.

OBJECTIVE: The cytological features of conventional monophasic spindle cell and biphasic synovial sarcoma have been defined in detail in several large series. The cytology of rare morphological variants, especially the subtypes of poorly differentiated synovial sarcoma, are insufficiently evaluated and diagnostically difficult to define. The objective of the present study was to call attention to the variable cytology of rare variants of synovial sarcoma. Furthermore, adjunctive diagnostic methods, necessary for a correct diagnosis, are discussed. METHODS: Aspirates from four synovial sarcomas, with cytological features, which differed from those of conventional synovial sarcoma and from each other, were retrieved from our files and re-evaluated. RESULTS: In three of the cases a correct diagnosis was not obtained from routinely stained aspirates. In the fourth case, the correct diagnosis was established by a combination of cytomorphology, immunocytochemistry and fluorescence in situ hybridization (FISH) performed on the aspirated material. CONCLUSION: Ancillary diagnostic methods are necessary in the examination of aspiration smears from synovial sarcoma, especially of morphological variants with a cytomorphology that differs from conventional spindle-cell monophasic and biphasic tumours. Immunocytochemistry and molecular genetic examinations (reverse transcriptase polymerase chain reaction or FISH) are the methods of choice.

Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma.

BACKGROUND: Numerous studies have reported on the association between coeliac disease and the otherwise uncommon enteropathy-type T cell lymphoma (ETTL). A systematic risk assessment of more prevalent lymphoma entities, such as B cell and non-intestinal lymphomas, in coeliac disease has not been performed. AIMS: In light of the increasing number of patients diagnosed with coeliac disease and the unknown aetiology of malignant lymphomas, we aimed to estimate the distribution and risk of lymphoma subtypes in coeliac disease. METHODS: We reviewed and reclassified 56 cases of incident malignant lymphomas occurring in a Swedish population based cohort of 11,650 patients hospitalised with coeliac disease. The observed numbers of lymphoma subtypes were compared with those expected in the Swedish population. RESULTS: The majority (n=32, 57%) of lymphomas in the cohort were not intestinal T cell lymphomas. Significantly increased risks were observed for B cell non-Hodgkin lymphoma (NHL) (standardised incidence ratio (SIR) 2.2 (95% confidence interval (CI) 1.2-3.6); 11 non-intestinal and five intestinal) and for lymphomas of non-intestinal origin (SIR 3.6 (95% CI 2.3-5.2), 11 B and 14 T cell). Furthermore, 44% of patients with B cell NHL had a history of other autoimmune/inflammatory diseases. The relative risks for T cell NHL (SIR 51 (95% CI 35-68); n=37) and for primary gastrointestinal lymphomas (SIR 24 (95% CI 16-34); five B and 25 T cell) were markedly increased, as anticipated. CONCLUSION: Most lymphomas complicating coeliac disease are indeed related to the disease and are not of the ETTL-type. There was a remarkable aggregation of autoimmune/inflammatory disorders, female sex, coeliac disease, and B cell lymphoma.

Assessment of biological prognostic factors provides clinically relevant information in patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic effects of four biological markers, BCL2, TP53, Ki-67, and P-glycoprotein, and their possible clinical relevance in addition to the international prognostic index (IPI) in diffuse large B-cell lymphoma (DLBCL). A total of 405 patients with aggressive lymphoma, stage II-IV, between 18 and 67 years, were randomized in a trial comparing CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). Of these, 267 cases were classified as DLBCL, with adequate paraffin blocks available in 207 cases, enabling immunohistochemical assessment of the expression of BCL2, TP53, P-glycoprotein, and Ki-67. In a multivariate analysis, stratified for IPI, high BCL2 expression (>10%) low (<60%) expression of Ki-67, and high TP53 protein expression (>75%) were shown to provide additional prognostic information with regard to overall or failure-free survival. We found no association between expression of P-glycoprotein and outcome. Assessment of BCL2 positivity might be introduced as part of the routine investigation in patients with DLBCL, but further studies are necessary to confirm the clinical relevance of Ki-67 and TP53 expression.

Prognostic information in soft tissue sarcoma using tumour size, vascular invasion and microscopic tumour necrosis-the SIN-system.

We have earlier devised a system for soft tissue sarcoma (STS), based on three negative prognostic features: large tumour size, vascular invasion, and microscopic tumour necrosis, the SIN-system. Tumours which exhibit 2 or 3 of these features are categorised as high-risk, the others as low-risk. We have now tested this system for reproducibility both as regards recognition of its components, and as regards prognostic strength in patients from another institution. We have also compared it with the American Joint Committee on Cancer (AJCC) system. 200 patients with STS were analysed, all had been treated by surgery, in 97 patients combined with radiotherapy. The median follow-up for the 117 survivors was 10 (1.5-27) years. Without knowledge of the clinical data, three groups of pathologists independently reviewed original slides from all of the tumours. Based on the factors, the tumours were classified as high-risk or low-risk. The prognostic strength was compared using the results obtained by the different observers. Concordance in recognition of vascular invasion, tumour necrosis, and overall grading was seen in 156 (78%), 154 (77%), and 167 (84%) of the 200 tumours, respectively. Based on the different observers' grading, the cumulative 5-year metastasis-free survival rate (MFSR) varied for patients with low-risk tumours between 0.85 and 0.80, and for patients with high-risk tumours between 0.48 and 0.43. The Kappa-value for grading between all three groups of observers was 0.77. The SIN-system gave more clinically useful prognostic information than the AJCC system. Useful prognostic information in STS can be obtained by using tumour size, vascular invasion and microscopic tumour necrosis. This system provides two distinct prognostic groups, and has a high reproducibility.

Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery.

Patients with anaplastic thyroid carcinoma can rarely be cured, but every effort should be made to prevent death due to suffocation. Between 1984 and 1999, 55 consecutive patients with anaplastic thyroid carcinoma were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin, and when feasible surgery. Radiotherapy was carried out for 5 days a week. The daily fraction until 1988 was 1.0 Gyx2 (A) and 1989-92 1.3 Gyx2 (B). Thereafter 1.6 Gyx2 (C) was administered. Radiotherapy was administered to a total target dose of 46 Gy; of which 30 Gy was administered preoperatively in the first two protocols (A and B), while the whole dose was given preoperatively in the third protocol (C). The therapy was otherwise identical. Twenty mg doxorubicin was administered intravenously weekly. Surgery was possible in 40 patients. No patient failed to complete the protocol due to toxicity. In only 13 cases (24%) was death attributed to local failure. Five patients (9%) 'had a survival' exceeding 2 years. No signs of local recurrence were seen in 33 patients (60%); 5 out of 16 patients in Protocol A, 11 out of 17 patients in Protocol B, 17 out of 22 patients in Protocol C (P=0.017). In the 40 patients undergoing additional surgery, no signs of local recurrence were seen in 5 out of 9 patients, 11 out of 14 patients and 17 out of 17 patients, respectively (P=0.005).

Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours.

BACKGROUND: The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours. METHODS: FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients. RESULTS: Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients. CONCLUSION: FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.

Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.

The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.

Distinct cytologic features of spindle cell lipoma. A cytologic-histologic study with clinical, radiologic, electron microscopic, and cytogenetic correlations.

BACKGROUND: Spindle cell lipoma (SCL) is a relatively uncommon, benign tumor that usually presents in the subcutaneous fat of adult men. Although some studies have addressed the histologic findings of SCL, only a few descriptions of aspiration cytology findings have been published. The cytologic features are poorly defined, and aspirates from SCL may cause diagnostic problems, because SCL shares some features with other fatty/spindle cell or myxoid lesions, benign as well as malignant. METHODS: Twelve patients underwent fine-needle aspiration (FNA) cytology as the primary diagnostic modality before surgery. FNA findings were evaluated and correlated with histologic features. In addition, radiologic, electron microscopic, and cytogenetic findings were analyzed. The objective of this study was to determine cytologic criteria of SCL by reviewing cytologic specimens in 12 patients with SCL who underwent FNA cytology. RESULTS: All of the tumors arose in adults, and 10 tumors developed in the subcutaneous tissue of the neck, back, or shoulder girdle. Two patients presented with tumors in atypical locations; one in the tongue and one in the cheek. Cytologically, all 12 tumors were characterized by a mixture of mature adipocytes, uniform spindle cells, and collagen bundles and/or fibers in varying proportions. The presence of a myxoid matrix and of mast cells was less specific and occurred in six aspirates. CONCLUSIONS: SCL has a characteristic cytologic appearance that, together with clinical data, helps to exclude low-grade liposarcoma as well as other spindle cell and myxoid lesions.

Cytologic findings in granular cell tumors, with emphasis on the diagnosis of malignant granular cell tumor by fine-needle aspiration biopsy.

BACKGROUND: Granular cell tumors (GCTs) are uncommon tumors of putative schwannian derivation that are rarely malignant. Although recent studies have addressed a histologic correlation with malignant behavior, similar studies have not been done on cytologic material. METHODS: The authors evaluated 3 malignant GCTs and 17 benign GCTs (comprising 17 fine-needle aspiration biopsy samples and 3 samples from direct scrapes) for the following cytologic features: hyperchromasia; coarse chromatin; nuclear-to-cytoplasmic (N/C) ratio; nuclear pleomorphism; and vesicular nuclei with enlarged nucleoli, mitoses, necrosis, and spindle cell morphology. RESULTS: Hyperchromasia, coarse chromatin, increased N/C ratio, nuclear pleomorphism, and vesicular nuclei with enlarged nucleoli and spindle cell morphology were associated the most closely with malignancy when they were present throughout the cytologic sample. All were diffusely present in three of three malignant tumors, except vesicular nuclei and spindle cell morphology, which were present diffusely in two tumors and focally in one tumor. By contrast, although one to five of these features were present focally in 8 of 17 benign GCTs, none was present diffusely in any benign GCTs, with one exception, which had a combination of focal nuclear pleomorphism and hyperchromasia together with diffuse vesicular nuclei, large nucleoli, and coarse chromatin. The N/C ratio in this tumor was not increased, and there were no spindle cells or mitoses. Mitoses were present in 2 of 3 malignant GCTs and absent from all 17 benign GCTs. Necrosis was not seen in any tumors. CONCLUSIONS: Malignant GCTs have characteristic cytologic features that differ from those of benign GCTs. However, morphologic heterogeneity precludes definitive classification of some tumors by cytologic features alone.

Histopathological and cell biological factors of ductal carcinoma in situ before and after the introduction of mammographic screening.

With the introduction of mammographic screening the incidence of ductal carcinoma in situ (DCIS) has increased to 10-15% of all breast cancers. The aim of this study was to investigate whether there were any morphological and cell biological differences between DCIS detected during the pre-screening (n = 39) as opposed to the screening period (n = 120). We could not demonstrate any statistically significant differences between the pre-screening and the screening period with regard to nuclear grade, presence of necrosis, the Van Nuys classification system, growth pattern, or cell biological factors (estrogen and progesterone receptors, c-erbB-2, p53, DNA ploidy status, Ki67, and Auer classes). These findings suggest that DCIS tumors detected during the two time periods have a similar malignant potential. DCIS detected during the screening period was further divided into the prevalence period versus the period thereafter, and symptomatic versus screening-detected asymptomatic cases. More cases with diffuse growth patterns were seen during the prevalence period than after the prevalence period, and screening-detected asymptomatic DCISs were more often 15 mm or smaller in diameter than DCISs detected symptomatically.

Clinical impact of molecular and cytogenetic findings in synovial sarcoma.

Synovial sarcoma is an aggressive soft-tissue tumor that accounts for up to 10% of soft-tissue sarcomas. Cytogenetically, synovial sarcoma is characterized by the t(X;18)(p11;q11), found in more than 95% of the tumors. This translocation results in rearrangements of the SYT gene in 18q11 and one of the SSX1, SSX2, or SSX4 genes in Xp11, creating a SYT/SSX1, SYT/SSX2, or SYT/SSX4 chimeric gene. It has been shown that patients with SYT/SSX1 fusion genes have a shorter metastasis-free survival than do patients with SYT/SSX2. Previous studies have also suggested that clonal evolution may be associated with disease progression. In the present study, RT-PCR analysis showed that all 64 examined synovial sarcomas from 54 patients had SYT-SSX chimeric genes. SYT/SSX1 was found in 40 tumors from 33 patients, SYT/SSX2 in 23 tumors from 20 patients, and SYT/SSX4 in one case. Two patients had variant SYT/SSX2 transcripts, with 57 bp and 141 bp inserts, respectively, between the known SYT and SSX2 sequences. Patients with tumors with SYT/SSX1 fusions had a higher risk of developing metastases compared to those with SYT/SSX2 fusions (P = 0.01). The reciprocal transcripts SSX1/SYT and SSX2/SYT were detected using nested PCR in 11 of the 40 samples with SYT/SSX1 and 5 of the 23 samples with SYT/SSX2, respectively. Among 20 blood samples, SYT/SSX1 and SYT/SSX2 were detected in one sample each. The t(X;18), or variants thereof, was found cytogenetically in all patients but three. Among 32 primary tumors, the t(X;18) or a variant translocation was the sole anomaly in 10. In contrast, of the seven metastatic lesions that were investigated prior to radiotherapy, only one had a t(X;18) as the sole anomaly; all other tumors displayed complex karyotypes. Cytogenetic complexity in primary tumors was, however, not associated with the development of metastases. Tumors with SYT/SSX2 less often (4/12 vs. 7/15) showed complex karyotypes than did tumors with SYT/SSX1, but the difference was not significant. Combining cytogenetic complexity and transcript data, we found that the subgroup of patients with tumors showing simple karyotypes and SYT/SSX2 fusion had the best clinical outcome (2/8 patients developed metastases), and those with tumors showing complex karyotypes together with SYT/SSX1 fusion the worst (6/7 patients developed metastases). This corresponded to 5-year metastasis-free survival rates of 0.58 and 0.0, respectively (P = 0.02).

Clinicopathologic re-evaluation of 100 malignant fibrous histiocytomas: prognostic relevance of subclassification.

PURPOSE: Malignant fibrous histiocytoma (MFH) has been regarded as the most common soft tissue sarcoma (STS) in adults. Yet its true nature and the validity of this diagnostic concept have increasingly been questioned. Available data suggest that most patients with MFH can be subclassified into specific STS types, but the clinical relevance of such categorization has been argued. In a retrospective study, we reclassified 100 tumors of the extremity and trunk wall primarily diagnosed as MFH and analyzed the outcome. PATIENTS AND METHODS: Patients were adults (median age, 70 years; range, 32 to 94 years). The median tumor size was 8 cm (range, 1 to 30 cm), and the thigh was the most common tumor location (n = 31). Median follow-up was 8 years (range, 3 to 16 years). The overall 5-year metastasis-free survival rate was 0.64. The tumors were reanalyzed histologically, immunohistochemically, and, where available, ultrastructurally, and were classified according to strict diagnostic criteria. Patients were staged according to the American Joint Committee on Cancer system, and prognoses were compared among different groups of the reclassified diagnoses, paying special attention to myogenic tumors. RESULTS: In 84 of 100 tumors, a specific line of differentiation was either proved or strongly suggested. The most common diagnoses were myxofibrosarcoma (n = 22) and leiomyosarcoma (n = 20). Overall, 30 tumors could be grouped as some form of myogenic sarcoma. These tumors had a worse prognosis, even within the same American Joint Committee on Cancer stage, and a shorter time to metastasis than nonmyogenic tumors. CONCLUSION: This retrospective study confirms that most so-called MFH can be subclassified by defined criteria; it provides evidence that such classification is clinically important. Specifically, pleomorphic STS showing myogenic differentiation are significantly more aggressive, a finding that allows planning future therapeutic trials.