Fred Ullrich

ALK− anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project

The International Peripheral T-Cell Lymphoma Project is a collaborative effort designed to gain better understanding of peripheral T-cell and natural killer (NK)/T-cell lymphomas (PTCLs). A total of 22 institutions in North America, Europe, and Asia submitted clinical and pathologic information on PTCLs diagnosed and treated at their respective centers. Of the 1314 eligible patients, 181 had anaplastic large-cell lymphoma (ALCL; 13.8%) on consensus review: One hundred fifty-nine had systemic ALCL (12.1%) and 22 had primary cutaneous ALCL (1.7%). Patients with anaplastic lymphoma kinase-positive (ALK(+)) ALCL had a superior outcome compared with those with ALK(-) ALCL (5-year failure-free survival [FFS], 60% vs 36%; P = .015; 5-year overall survival [OS], 70% vs 49%; P = .016). However, contrary to prior reports, the 5-year FFS (36% vs 20%; P = .012) and OS (49% vs 32%; P = .032) were superior for ALK(-) ALCL compared with PTCL, not otherwise specified (PTCL-NOS). Patients with primary cutaneous ALCL had a very favorable 5-year OS (90%), but with a propensity to relapse (5-year FFS, 55%). In summary, ALK(-) ALCL should continue to be separated from both ALK(+) ALCL and PTCL-NOS. Although the prognosis of ALK(-) ALCL appears to be better than that for PTCL-NOS, it is still unsatisfactory and better therapies are needed. Primary cutaneous ALCL is associated with an indolent course.

Obstetric anesthesia workforce survey : Twenty-year update

A dvances and changes in any medical specialty are often defined and detected by surveys. This is particularly true in obstetric anesthesia, especially given the complications arising from medicolegal, financial, maternal, and fetal considerations. Economic pressures, payment variations, decreased numbers of anesthesia providers, patient expectations, and technical aspects have challenged obstetric anesthesia practice. This 2001 obstetric anesthesia workforce survey was performed in conjunction with the Society from Obstetric Anesthesia and Perinatology to estimate and assess current trends and identify potential areas for improvement. A stratified random sample frame of 1300 hospitals was selected. The institutions were stratified based on geographic region and number of births for that year (stratum I, >1500 births; II, 500–1499 births; and III, 100–500 births). Three key labor and delivery personnel were identified at each institution that responded to the initial query. These personnel included from each hospital the chief of anesthesiology, the chief of obstetrics, and the labor and delivery manager. The number of hospitals providing obstetric care decreased from 4163 in 1981 to 3545 in 1992, to 3160 in 2001. A substantial decrease in stratum III facilities occurred between 1992 and 2001 (1603 down to 1081). A total of 378 of the 1300 initially sampled hospitals responded to the request for contact information (29% overall response). In the anesthesiology survey, the response rate was 57% and that for the obstetrics survey was 45%. In the labor and delivery manager survey, the rate of response was 75%. An overall increase in the percent of maternity cases using regional analgesia for labor was noted across all strata. The use of epidural analgesia for labor increased compared with previous surveys; spinal analgesia was used in <10% of cases. Patient-controlled epidural analgesia was used in about 33% of stratum I and II hospitals but in only 18% of stratum III hospitals. For cesarean delivery, use of spinal anesthesia increased and use of epidural anesthesia decreased across all strata. Combined spinal-epidural anesthesia was used in <10% of cesarean deliveries in all strata. Availability of in-house regional analgesia during labor was reported by only 3% of the smallest hospitals. In-house coverage was available in 77% of stratum II hospitals, and only 3% of stratum III hospitals reported that regional analgesia for labor was unavailable. Across all strata in 2001, an anesthesiologist was slightly more often directly involved in the care of patients receiving regional analgesia for labor compared with 1981 and 1992 survey data. In stratum III hospitals, 34% of regional analgesics for labor were administered by independently practicing certified nurse anesthetists, with 14% administered by these personnel under the medical direction of nonanesthesiologist physicians. Pediatricians performed an average of 42% and 48% of neonatal resuscitations during cesarean deliveries in stratum I and II hospitals, respectively. Vaginal birth after cesarean delivery (VBAC) was allowed in 98% and 92% of stratum I and II hospitals, but only 68% of stratum III institutions. Only 25% to 30% of all patients attempted it across all strata. Based on the American College of Obstetricians and Gynecologists practice bulletin on VBAC, 40% of stratum III hospitals no longer perform VBAC, and stratum I and II hospitals reported a reduction in VBAC attempts. Across all strata, at least 60% of VBACs were successful. Most institutions in all strata required anesthesia providers to be in-house during epidural infusion. Between 63% and 94% of hospitals required providers to be in-house when women were attempting VBAC with regional analgesia. Although almost all hospitals allowed ambulation during labor, only about 50% allowed ambulation during epidural or combined spinal-epidural analgesia. Interestingly, only a very small percentage of patients actually ambulated. Across all strata, <10% of hospitals allowed labor floor nurses (LFNs) to reinstitute epidural infusions. LFNs could adjust infusion rates in 28% and 7% of stratum II and I hospitals, respectively. LFNs were allowed to administer epidural boluses in 13% and 3% of stratum II and I hospitals, respectively. Collection rates for professional fees for anesthesia for labor, vaginal and cesarean deliveries, and other surgical procedures steadily decreased from 1981 to 2001. Collection rates for cesarean delivery declined from 76% in 1981 to 70% in 1992 to 66% in 2001. Respective anesthesia collection rates for labor and vaginal delivery were 67%, 68%, and 60%, and for other surgical procedures, 85%, 74%, and 68%. Stratum I hospitals had the largest percentage of health maintenance organization payers, and stratum II and III institutions the largest percentage of Medicaid payers. Percentage payment of actual charges was similar among all groups of payers across all sizes of hospitals. The 2001 survey results indicate that, despite staffing and payment challenges in obstetric anesthesia care, availability of services and anesthesia personnel have improved.

Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project

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.

Marginal Zone B-Cell Lymphoma: A Clinical Comparison of Nodal and Mucosa-Associated Lymphoid Tissue Types

PURPOSE In the International Lymphoma Study Group classification of lymphoma, extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT) type is listed as a distinctive entity. However, nodal MZL is listed as a provisional entity because of questions as to whether it is truly a disease or just an advanced stage of MALT-type MZL. To resolve the issue of whether primary nodal MZL without involvement of mucosal sites exists and whether it is clinically different from extranodal MALT-type lymphoma, we compared the clinical features of these two lymphomas. PATIENTS AND METHODS Five expert hematopathologists reached a consensus diagnosis of MZL in 93 patients. Seventy-three were classified as having MALT-type MZL because of involvement of a mucosal site at the time of diagnosis, and 20 were classified as having nodal MZL because of involvement of lymph nodes without involvement of a mucosal site. RESULTS A comparison of the clinical features of nodal MZL and MALT-type MZL showed that more patients with nodal MZL presented with advanced-stage disease (71% v 34%; P =. 02), peripheral lymphadenopathy (100% v 8%; P <.001), and para-aortic lymphadenopathy (56% v 14%; P <.001) than those with MALT-type MZL. However, fewer patients with nodal MZL had a large mass (> or = 5 cm) than those with MALT-type MZL (31% v 68%; P =.03). The 5-year overall survival of patients with nodal MZL was lower than that for patients with MALT-type MZL (56% v 81%; P =.09), with a similar result for failure-free survival (28% v 65%; P =.01). Comparisons of patients with International Prognostic Index scores of 0 to 3 showed that those with nodal MZL had lower 5-year overall survival (52% v 88%; P =.025) and failure-free survival (30% v 75%; P =.007) rates than those with MALT-type MZL. CONCLUSION Nodal MZL seems to be a distinctive disease entity rather than an advanced stage of MALT-type MZL because the clinical presentations and survival outcomes are different in these two types of MZL. Clinically, nodal MZL is similar to other low-grade, node-based B-cell lymphomas, such as follicular and small lymphocytic lymphomas.

Influence of margins on overall survival after hepatic resection for colorectal metastasis: A meta-analysis

Objective: The aim of our study was to conduct a meta-analysis of reports published on hepatic resection for colorectal liver metastasis (CRLM) and determine whether a negative margin of 1 cm or more confers a survival advantage over subcentimeter negative margins. Background: Surgical margin is an important prognostic factor in patients undergoing hepatic resection for CRLM. Although there is a consensus that positive margins portend a worse outcome than negative margins, the extent of negative margins remains controversial. Methods: A PubMed search was conducted to identify articles on hepatic resection for CRLM. The 357 initially located articles were screened to identify 90 articles of interest. The texts of these 90 articles were completely reviewed to finalize 18 articles for inclusion in the study on the basis of absolute and relative inclusion criteria. Patients with positive margins were excluded from the meta-analysis. Meta-analysis was performed using STATA 9.2 statistical software. Results: A total of 4821 patients with negative margins from the 18 studies were included in the meta-analysis. The overall 5-year survival for all patients was 41% [95% confidence interval (CI), 40%-43%]. The overall 5-year survival for the ≥1 cm negative margin subgroup was 46% (95% CI, 44%-48%) when compared with 38% (95% CI, 36%-40%) for less than 1 cm negative margin subgroup. The odds ratio for 1-cm or more negative margins was found to be 0.773 (95% CI, 0.638-0.938; P = 0.009) when compared with less than 1 cm negative margins. Conclusions: The results of this meta-analysis demonstrate that in patients undergoing hepatic resection for CRLM, a negative margin of 1 cm or more confers a survival advantage when compared with subcentimeter negative margins.

Sclerosing rhabdomyosarcomas in children and adolescents: A clinicopathologic review of 13 cases from the Intergroup Rhabdomyosarcoma Study Group and Children's Oncology Group

In recent reports, investigators have described a variant of adult sclerosing rhabdomyosarcoma (RMS) that is characterized by a hyalinizing, matrix-rich stroma. To determine whether this variant occurs in children, we investigated this phenomenon in a recent series of 1207 pediatric patients who had RMS accessioned by the Intergroup Rhabdomyosarcoma Study Group, now part of Children’s Oncology Group. Thirteen patients had features of sclerosing RMS; 9 had been diagnosed with alveolar RMS (ARMS), 3 with embryonal RMS (ERMS), and 1 with a spindle cell RMS. Primary sites included head and neck (6 patients), extremities (5 patients), scrotum (1 patient), and retroperitoneum (1 patient). Patients’ ages ranged from 0.3 to 16 years. All tumors showed positivity for myogenin, MyoD, and desmin, but only 2 patients demonstrated the strong myogenin staining typically seen in ARMS. Three patients diagnosed with ARMS demonstrated embryonal-appearing foci, and 3 of 4 patients who had nonalveolar tumors had ARMS-like foci. Standard reverse transcriptase–polymerase chain reaction performed on RNA isolated from frozen sections showed 1 ARMS with a positivity for PAX3-FKHR with four patients classified as having ARMS and 1 as having spindle cell RMS were negative for both ARMS fusion transcripts (PAX3- and PAX7-FKHR). Cytogenetic testing in 2 patients who had ARMS-like foci demonstrated mild hyperdiploidy in both patients and a near-tetraploid clone in 1 patient. Sclerosing RMS may arise in children, have mixed ERMS-ARMS histology, originate from the head and neck, and lack strong myogenin staining.

Preoperative Nomogram to Predict Risk of Perioperative Mortality Following Pancreatic Resections for Malignancy

IntroductionThe majority of pancreatic resections for malignancy are performed in older patients with major comorbidities. The aim of this study was to develop a preoperative nomogram based on the presence of comorbidities to predict risk of perioperative mortality.Materials and MethodsThe National Inpatient Sample database was queried to identify patients that underwent pancreatectomy for malignancy. The preoperative comorbidities identified as predictors were used, and a nomogram was created. Sample A (2000–2004) was utilized to develop the model, and sample B (2005) was utilized to validate this model.ResultsThe overall actual observed perioperative mortality rate for samples A and B was 6.3% and 5.2%, respectively. The mean total points calculated for sample A by the nomogram was 131.7 that translates to a nomogram-predicted mortality rate of 4.9%, which is similar to the actual mortality. The mean total points for sample B was 128.1, which translates to a nomogram-predicted mortality rate of 4.6%. The similarity of mortality rates as predicted by the nomogram and a concordance index of 0.76 shows good agreement between the data and the nomogram.ConclusionThis preoperative nomogram has been shown to accurately predict the risk of perioperative mortality following pancreatectomy for malignancy.

Clinical significance of follicular lymphoma with monocytoid B cells

Although follicular lymphoma (FL) is very common in the Western world, very little information is available regarding the frequency and significance of monocytoid B cells (MBC) in FL. We recently completed a clinicopathologic study of 1,378 cases of non-Hodgkins lymphoma. In this study, a research data sheet was designed to conduct research on several types of lymphomas, one part of which was evaluating the presence of intrafollicular clear cells and extrafollicular MBC in 326 cases diagnosed as FL by one of the pathologists (B.N.N.). For each case diagnosed as FL, the presence of intrafollicular clear cells or extrafollicular MBC was scored as pure FL (no intrafollicular clear cells or extrafollicular MBC), FL with intrafollicular clear cells, FL with less than 5% MBC, and FL with greater than 5% MBC. Of 326 cases classified as FL, 252 (77%) had no intrafollicular clear cells or extrafollicular MBC and therefore were called pure FL. In 36 cases (11%), intrafollicular clear cells were seen, but no extrafollicular MBC. There were no clinical differences between such cases and the 252 cases of pure FL. In eight cases of FL (2%), MBC clusters were rare (<5%). In contrast, 30 cases of FL (9%) had a prominent (>5%) proliferation of extrafollicular MBC; these 30 cases had a significantly shorter failure-free survival (P = .001) and overall survival (P = .04) than the 252 cases of pure FL. The shorter survival of these 30 cases appeared to be independent of the international prognostic index (IPI), stage, and treatment. The FFS of this group remained shorter than that of cases with pure FL when the analysis was restricted to patients treated with Adriamycin-containing regimens and either a favorable (0 to 3) IPI score (P = .001) or advanced stage (III/IV) disease (P = .015). In conclusion, FL with a prominent (>5%) MBC component constitutes a substantial proportion (9%) of FL and has distinctive morphology, and these patients have a significantly shorter survival than those with pure FL.

Comparison of outcomes based on treatment algorithms for rhabdomyosarcoma of the bladder/prostate: combined results from the Children's Oncology Group, German Cooperative Soft Tissue Sarcoma Study, Italian Cooperative Group, and International Society of Pediatric Oncology Malignant Mesenchymal Tumors Committee

The purpose of this study was to determine patient characteristics and outcomes for bladder/prostate (BP) rhabdomyosarcoma (RMS) using an international cohort of prospectively treated patients comparing different treatment algorithms. Data were collected from 379 patients (1979–1998) treated on protocol; Intergroup Rhabdomyosarcoma Study, IRS‐IV (n = 239 patients), International Society of Pediatric Oncology Malignant Mesenchymal Tumors (MMT) Committee MMT‐84 and ‐89 (n = 74), Italian Cooperative Group, RMS‐79 and RMS‐88 Studies (n = 37) or German Cooperative Soft Tissue Sarcoma Study CWS‐91 protocols (n = 29). A total of 322 (85%) patients had localized embryonal RMS (ERMS) and 27 had metastatic disease. Thirty patients (21 local disease; 9 metastatic) had nonembryonal BP RMS. Patients with localized ERMS had large tumors (64% >5 cm) that were invasive (54%) with uninvolved regional lymph nodes (N0, 93%). The 5‐year failure‐free survival (FFS) was 75% and the overall survival (OS) was 84%, with 89% of deaths attributed to disease. Treatment failures were usually local disease recurrence (60%). Predictors of FFS included T‐stage (invasiveness), size, and histology. FFS was decreased for patients not receiving initial radiotherapy but this did not translate into a decreased OS. The 21 patients with localized nonembryonal BP RMS had a FFS and OS of 47%. The 36 patients with metastatic disease were more likely to be older and had large tumors that were invasive with alveolar histology and regional lymph node involvement. The 5‐year FFS and OS were 41 and 44%, respectively. In conclusion, the majority of BP RMS patients had localized ERMS with a resultant good prognosis using current treatment algorithms. There were differences in FFS between treatment protocols but this did not result in an altered OS.

Clinical practice patterns of managing low-risk adult febrile neutropenia during cancer chemotherapy in the USA

PurposeThe purpose of the study was to determine oncologists’ current practice patterns for antibiotic management of low-risk fever and neutropenia (FN) after chemotherapy.Materials and methodsA self-administered survey was developed to query management practices for low-risk FN patients and sent to 3,600 randomly selected American Society of Clinical Oncology physician members; hypothetical case scenarios were included to assess factors influencing decisions about outpatient treatment.ResultsOf 3,560 actively practicing oncologists, 1,207 replied (34%). Outpatient antibiotics are used by 82% for selected low-risk FN patients (27% used in them >65% of their patients). Oral levofloxacin (50%), ciprofloxacin (36%), and ciprofloxacin plus amoxicillin/clavulanate (35%) are common outpatient regimens. Fluoroquinolone prophylaxis is used by 45% of oncologists, in a subset of afebrile patients at low risk for FN; growth factors are used adjunctively by 48% for treating low-risk FN. Factors associated with choosing outpatient treatment were: frequency of use in oncologists’ own practices, absence of hematologic malignancy, lower patient age, no infiltrate on X-ray, no prior serious infection, shorter expected FN duration, lower creatinine levels, and shorter distance of patient’s residence from the hospital.ConclusionsUS oncologists, who responded are willing to prescribe outpatient oral antibiotic treatment for low-risk FN, although practices vary considerably and are based on favorable clinical factors. However, practices are often employed that are not recommended for low-risk patients by current guidelines, including fluoroquinolone prophylaxis, adjunctive and/or prophylactic growth factors, and use of levofloxacin for empiric therapy. Educational efforts are needed to better guide cost-effective and supportive care.