Historical Case Series Research Articles

Timing of gonadectomy in adult women with complete androgen insensitivity syndrome (CAIS): patient preferences and clinical evidence

Adult women with complete androgen insensitivity syndrome (CAIS) are increasingly likely to defer or decline gonadectomy despite counselling about malignancy risk. The objectives of this study were to review the evidence on the risk of gonadal malignancy in adult women with CAIS and to explore women's reasons for deferring gonadectomy. A case series and literature review. Sixteen women with CAIS over the age of 18 years who have elected to defer gonadectomy. Sixty-two relevant papers were identified. Of these, 14 confirmed that tumours had been reported in 98 adults. Taking into account the limitations of combining historic case series, this review estimates a risk of gonadal malignancy of 14% (range 0% and 22%) in adults with CAIS. The most common reasons women offered for deferring gonadectomy included inconvenience of surgery, concern about surgical risk and reluctance to take hormone replacement therapy. Perceived benefits for retaining gonads in women with CAIS are prompting more women to keep their gonads in situ. An accurate estimate for adult malignancy risk is unavailable, and the risks currently quoted may be falsely reassuring.

Incidência do pênfigo vulgar ultrapassa a do pênfigo foliáceo em região endêmica para pênfigo foliáceo: análise de série histórica de 21 anos

There are two main clinical subsets of pemphigus: pemphigus vulgaris and pemphigus foliaceus. Clinical and epidemiological changes related to both types of pemphigus have been observed in the last years. To analyze a 21-year historical case series of pemphigus vulgaris and pemphigus foliaceus in the northeast region of the state of Sao Paulo, where pemphigus foliaceus is endemic. In this descriptive study, data related to annual incidence and age of onset of symptoms compatible with pemphigus vulgaris or pemphigus foliaceus were analyzed, comparing both forms, in the period from 1988 to 2008. The overall results cover a period of 21 years, with 103 cases of pemphigus vulgaris and 163 cases of pemphigus foliaceus. An evaluation of the trend lines regarding incidence has shown that pemphigus foliaceus is decreasing while pemphigus vulgaris is increasing. There was great variation in the age ranges, with persistence of the minimum range, from 10 to 20 years old, for pemphigus foliaceus (mean age = 32.1 years old), and clear downward in the minimum age for pemphigus vulgaris (mean age = 41.5 years old), especially from the middle of the first decade of the total period studied. The incidence of pemphigus vulgaris has been exceeding that of pemphigus foliaceus since 1998. The results of this case series comprehending 21 years corroborate the change in the epidemiology of both clinical forms of pemphigus in Brazil, raising new hypotheses for their etiology and pathogenesis.

Outcome predictors of pediatric extracorporeal cardiopulmonary resuscitation.

Extracorporeal cardiopulmonary resuscitation (ECPR) allows clinicians to potentially rescue pediatric patients unresponsive to traditional cardiopulmonary resuscitation (CPR). Clinical and laboratory variables predictive of survival to hospital discharge are beginning to emerge. In this retrospective, historical cohort case series, clinical, and laboratory data from 31 pediatric patients (<21 years of age) receiving ECPR from March 2000 to April 2006 at our university-affiliated, tertiary-care children’s hospital were statistically analyzed in an attempt to identify variables predictive of survival to hospital discharge. Seven patients survived to hospital discharge (23%), and 24 patients died. Survival was independent of gender, age, and CPR duration. ECPR survival was, however, associated with a lower pre-ECPR phosphorus concentration (P = 0.002) and a lower pre-ECPR creatinine concentration (P = 0.05). A classification tree analysis, using, in part, a pre-ECPR phosphorus concentration threshold and a CPR ABG base excess concentration threshold, yielded a 96% nominal accuracy of predicting survival to hospital discharge or death. A large, multicenter, prospective cohort study aimed at validating these predictive variables is needed to guide appropriate ECPR patient selection. This study reveals the potential survival benefit of ECPR for pediatric patients, regardless of CPR duration prior to ECPR cannulation.

History of parathyroid gland surgery: an historical case series

The history of the parathyroid glands is a fascinating one full of famous medical names. The discovery of the glands was followed by laborious research into their anatomy, embryology and pathology and into the physiology of calcium metabolism; this led to the manufacture of hormone substitutes and, finally, to the refinement of surgical techniques. The glands were first identified in 1850 by Sir Richard Owen, conservator of the Hunterian Museum, but it was not until 1880 that the term 'glandulae parathyroideae' was first used. The physiology of parathyroid hormone and calcium metabolism eluded physicians and the forefathers of thyroid surgery alike for several decades more. Patients were treated as curiosities and were documented as untreatable medical patients or as inexplicable thyroid surgery complications. Halsted noticed the 'disastrous results from the loss of the glands' and the resulting tetany, as did Billroth. It is the patients, however, who best illustrate the journey of discovery. In this review, we discuss three cases, highlighting their contributions.

Hematuria de origen papilar o medular: entidad de difícil diagnóstico

Renal haemangiomas of renal papillary or medullar origin are a difficult diagnosis entity, being one of the most frequent processes of chronic episodes of hematuria, secondary to benign disease, mainly in young patients. The objective of this paper is to show the difficulty of this diagnosis and the need to suspect it in cases with clinical history similar to the ones described in these cases. We report 4 cases of spontaneous hematuria of renal origin, with clinical presentation as renal colic, from the historical case series of the Fundacion Jimenez Díaz-Capio, the last two from the years 2005-6. We present the diagnostic and therapeutic methodology employed, including angio-CT and flexible ureterorenoscopy (URS) as well as various treatment options. Hematuria was identified as "essential" when any relation with tumor or lithiasic pathologies was ruled out, and of renal origin when the source was clearly pointed. We interpreted it was related to angiomas or microangiomas of papillary or medullar origin. In one case, the vascular malformation was interpreted as an arterial venous fistula (AVF) at that level. Hematuria stopped spontaneously in two cases after exploratory URS. The eldest historical case required surgical expiration of the caliceal structures. Years ago, following the professional development of Urology as speciality, conventional surgery was carried out in all these cases, of very difficult diagnosis, with a very small number of cases undergoing a conservative approach based on the examination of renal cavities trying to observe and find the bleeding point. Most cases underwent complete or partial nephrectomy. Currently, the possibility of exploration of all renal cavities with the flexible ureterorenoscope enables a better diagnosis of the lesions and a more conservative treatment. The ultimate diagnosis of renal papillary angioma is the pathologic diagnosis, without pathognomonic data in the imaging tests. This pathology is thought of at the end of the diagnostic workup, and when the papillary area is identified as the source of bleeding. The historical case series, with the pathologic findings from nephrectomy specimens, permits us to point out this entity as papillary angioma, in patients with similar clinical presentation.

P2: Bariatric surgery in adolescents: An historic case series

The epidemic of morbid obesity is increasingly impacting the adolescent population. It is important to review past program experiences to demonstrate both weight and health improvement and to plan future prospective studies.

Efficacy of Warfarin Reversal in Orthopedic Trauma Surgery Patients

We determine the efficacy of active reversal of warfarin anticoagulation with intravenous vitamin K compared to withholding warfarin in patients requiring urgent orthopedic trauma surgery. This was a prospective cohort with immediate prehypothesis consecutive retrospective comparative case series conducted at a level 1 university hospital trauma unit. Forty-eight consecutive patients between 1998 and 2004 in a study composed of a prospective cohort were compared with a retrospective consecutive case series of warfarinized orthopedic trauma patients requiring urgent surgery. The prospective arm directly followed the historic case series from which the hypothesis was generated. Vitamin K administration. Primary outcome was time to surgery. Secondary outcomes were problems with active reversal, length of time for warfarin stabilization after surgery, and complications. The mean time to surgery in warfarinized patients not given vitamin K was 111.9 hours; in the intervention group, it was 67.4 hours, giving a mean difference of 44.5 hours (P = 0.01). Vitamin K reduced the international normalized ratio (INR) to less than 2.0 in 74% of patients within 24 hours. There were no complications of vitamin K administration. A dose of vitamin K costs approximately 1/1000 of a hospital bed day cost. A loading dose of warfarin on the second postoperative day took approximately 1 day longer to reach an INR of greater than 2.0 in the intervention patients than in those who had not been given vitamin K. Warfarin reversal with vitamin K was successful and facilitated earlier surgery in all patients; the first dose was effective in approximately three quarters of patients. It is cost-effective, with no side effects caused in this study.

Influence of the Number of Malignant Regional Lymph Nodes Detected by Endoscopic Ultrasonography on Survival Stratification in Esophageal Adenocarcinoma

The nodal staging of esophageal cancer accounts for the absence or presence of metastatic lymph nodes (N0 or N1, respectively). Surgical data suggest that patients have worse survival when esophagectomy specimens contain higher numbers of regional malignant lymph nodes. It has been proposed that the staging system for esophageal cancer be modified to include the number of malignant lymph nodes. The aim of this study was to determine the influence of the number of malignant-appearing regional lymph nodes detected on endoscopic ultrasonography (EUS) on survival in patients with esophageal adenocarcinoma. Historical case series involved patients with esophageal adenocarcinoma who underwent EUS staging at a single center between 1994 and 2004. Endoscopy reports were reviewed to determine the number of malignant-appearing periesophageal lymph nodes seen on EUS examination. Subjects were categorized as having 0, 1-2, or >2 periesophageal lymph nodes. A regional cancer registry prospectively obtained survival data. Among 85 patients with esophageal adenocarcinoma, the Kaplan-Meier curves showed distinct survival advantages in those with fewer malignant-appearing regional lymph nodes (P=.0008). The median survivals were 66 months, 14.5 months, and 6.5 months for 0, 1-2, and >2 malignant-appearing lymph nodes, respectively. Survival was also influenced by celiac lymph nodes and tumor length, both of which were associated with increased number of malignant nodes. The number of malignant-appearing periesophageal lymph nodes detected by EUS is associated with improved survival stratification in patients with esophageal adenocarcinoma and should be considered in the presurgical staging of esophageal cancer.

A model to predict delivery of reduced chemotherapy dose intensity in the first three cycles of treatment among patients with non-Hodgkin's lymphoma and breast cancer

6100 Background: Reduction of chemotherapy dose intensity is common among patients receiving treatment for non-Hodgkin's lymphoma (NHL) and breast cancer. A recent publication suggests that neutropenia is a cause of dose modifications, and that maintaining chemotherapy dose intensity in the initial cycles may be associated with improved outcomes. We evaluated possible risk factors associated with delivery of reduced chemotherapy dose intensity in the first 3 cycles of treatment among a sample of patients with NHL or breast cancer. Methods: A historical case series of 1617 patients (704 NHL and 913 early-stage breast cancer) who received initial chemotherapy at 16 community and academic oncology practices between 1991 and 1999 were studied. Reduced average relative dose intensity (ARDI) was defined as at least a 20% or 15% reduction in dose intensity for NHL and breast cancer patients, respectively. Stepwise logistic regression was used to select risk factors significantly associated with a reduction in ARDI. Results: 427 of 1617 patients (26%) received reduced ARDI within the first 3 cycles of chemotherapy. Factors significantly associated with delivery of reduced ARDI in a multiple logistic regression model included age greater than or equal to 65 years (odds ratio [OR] 2.4; 95% CI 1.8–3.2), presence of heart, renal, or hepatic comorbidity (OR 2.2; 95% CI 1.6–3.2), low body surface area (OR 1.3; 95% CI 1.1–1.7), and no preemptive growth factor in cycle 1 (OR 1.7; 95% CI 1.0–2.6). Patients with NHL were less likely to have a reduction in ARDI (OR 0.6; 95% CI 0.4–0.8). Conclusions: Increased age, comorbidity (heart, renal or hepatic), low body surface area, and no preemptive growth factor in cycle 1 were associated with increased risk for delivery of reduced chemotherapy dose intensity in cycles 1 through 3 after controlling for differences in diagnosis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen, Inc.; Schering-Plough Amgen, Inc. Amgen, Inc.

A model to predict chemotherapy-related severe or febrile neutropenia in cycle one among breast cancer and lymphoma patients

8068 Background: Chemotherapy used to treat cancer may produce severe (absolute neutrophil count ≤250/mm3) or febrile neutropenia (SFN), which often results in fever, infection, and hospitalization. This can lead to dose delays or reductions in subsequent chemotherapy cycles and/or early termination of therapy. Recent studies suggest most patients who experience SFN do so early in the course of chemotherapy, in particular during the first cycle. Several recent risk models for neutropenia have identified baseline patient characteristics that predict the occurrence of neutropenia. The ability to identify patients at risk for developing neutropenia early in their therapy might help guide appropriate hematopoietic growth factor use. We evaluated possible risk factors associated with cycle 1 SFN among a sample of patients with NHL or breast cancer. Methods: A historical case series of 1,617 patients (704 NHL and 913 early-stage breast cancer) who received initial chemotherapy at 16 community and academic oncology practices between 1991 and 1999 were selected for study. SFN was defined as absolute neutrophil count ≤250/mm3 or febrile neutropenia. Results: A total of 461 patients (29%) experienced at least one SFN episode; 268 (58%) of these patients (167 [59%] with NHL and 101 [56%] with breast cancer) had SFN in cycle 1. Risk factors associated with cycle 1 SFN included age ≥65 years (Odds ratio [OR] 2.08; 95% CI: 1.48–2.92), baseline hemoglobin <12.0 g/dL (OR 1.90; 95% CI: 1.41–2.58), presence of heart, renal, or liver disease (OR 2.12; 95% CI: 1.03–4.36), NHL (OR 1.64; 95% CI: 1.16–2.32), planned full chemotherapy dose intensity (OR 2.74; 95% CI: 1.55–4.84), and no growth factor in the first 5 days of cycle 1 (OR 1.82; 95% CI 1.07–3.08). Conclusions: Data routinely available to the clinician can help identify patients at risk for SFN in cycle 1. In our model assessing chemotherapy-related SFN in breast cancer and lymphoma, patients ≥65 were twice as likely to have SFN in Cycle 1. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Inc. Amgen, Inc.; Schering-Plough Amgen, Inc. Amgen, Inc.

Anemia in stage II and III breast cancer patients treated with adjuvant doxorubicin and cyclophosphamide chemotherapy.

The incidence and severity of prechemotherapy anemia and chemotherapy-induced anemia experienced by women treated with adjuvant doxorubicin and cyclophosphamide (AC) therapy for stage II and III breast cancer are described. Medical charts of 310 breast cancer patients who received chemotherapy at eight oncology practices during 1997 through 2001 were reviewed in this historical case series study. Prechemotherapy anemia was defined as a baseline hemoglobin value <12 g/dl. An anemic event during chemotherapy (used to define chemotherapy-induced anemia) was defined as either a drop in hemoglobin level below the threshold (< or = 10 g/dl), the receipt of a blood transfusion(s), or treatment with epoetin alfa. Overall, 40.0% of patients experienced moderate to severe anemia (i.e., their hemoglobin levels dropped to <10 g/dl) and 31.3% (97/310) were anemic prechemotherapy. Of the patients with mild anemia prechemotherapy, 61.9% developed moderate to severe anemia during chemotherapy. Only 47.4% (46/97) of those patients received epoetin alfa therapy during chemotherapy. Of the patients with normal prechemotherapy hemoglobin levels (> or = 12 g/dl), 88.3% developed some degree of anemia (<12 g/dl) during chemotherapy and 27.7% (59/213) developed moderate to severe anemia (<10 g/dl). Anemic events were experienced by 41.8% (89/213) of the patients with normal prechemotherapy hemoglobin levels. We conclude that a significant proportion (31.3%) of stage II and III breast cancer patients are anemic prechemotherapy and that the incidence of anemia increases substantially from prechemotherapy through the postchemotherapy period. This evidence appears to warrant earlier evaluation of anemia and an intervention in the prechemotherapy stage.

Chemotherapy-induced moderate to severe anemia in intermediate-grade non-Hodgkin’s lymphoma patients

This study investigated the incidence of anemia in chemotherapy-treated intermediate-grade non-Hodgkin’s lymphoma (IGNHL) patients. A historic case series design was used. The study data were obtained from 12 oncology practices that participated in the Oncology Practice Pattern Study (OPPS). The analysis focused on 353 IGNHL patients with normal baseline (prechemotherapy) hemoglobin (Hb) (≥12.0 g/dL). These patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone combination) therapy (at some point) from 1993 through 1999. Anemia was found to be prominent during chemotherapy. About 24% of the patients with a normal baseline Hb level dropped below 10.0 g/dL and 49% dropped to 10.0 -11.9 g/dL, at some point during chemotherapy. As anemia treatment data were unavailable, it is likely that some of these patients received therapy to boost their Hb levels, rendering our results conservative. A logistic regression model revealed that in patients with normal baseline Hb, age ≥60, female gender, lower baseline Hb level, and lymphoma histology classified as the Working Formulation (WF) E or H were significant predictors of a drop in Hb below 10.0 g/dL during chemotherapy. Chemo-therapy-induced anemia is frequently observed in lymphoma patients. It is possible to identify adverse baseline patient characteristics associated with higher risk of chemotherapy-induced anemia and carefully monitor such patients. Additional studies in community oncology practice are warranted to validate these findings and improve our understanding of the problems of anemia in chemotherapy treated non-Hodgkin’s lymphoma (NHL) patients.

Recommendations for the management of unruptured intracranial aneurysms

Optimal management of patients with unruptured intracranial aneurysms (UIAs) remains controversial. Recent studies have found conflicting data regarding the natural history and the treatment outcome of UIAs. Based on the recommendations published by the American Heart Association, the Section of Vascular Neurosurgery of the German Society of Neurosurgery has formed a task force to summarize the available data and to develop a practical framework for the management of UIAs. For UIAs, only evidence from nonrandomized historical cohort comparisons and case series without control subjects are available, supporting only grade C recommendations (options), but no standards (grade A) and no guidelines (grade B). The present recommendations have been developed as a neurosurgical, neuroradiological and neurological consensus. They are based on the existing data of both treatment risks and the risks of the natural history of UIAs.

Chemotherapy-induced moderate tolife-threatening anemia in early-stage breast cancer

Purpose. We evaluated the incidence and severity of anemia experienced by women treated with doxorubicin and cyclophosphamide (AC) therapy for early-stage breast cancer are described. We also explored the possibility of identifying clinical characteristics that will allow early identification of women more likely to develop anemia and may require anemia treatment. Methods. This study used a historic case series from 13 oncology practices that participated in the Oncology Practice Pattern Study. The analysis focused on 411 patients who received AC chemotherapy from 1993 through 1999. Seventeen percent of the study population was excluded from the analysis due to missing data. Anemia was defined as a hemoglobin (Hb) value of &lt; 12 g/dL. Hb ≤10 g/dL was considered the threshold value for treatment. Results. Among patients receiving AC, 18.0% was anemic prior to chemotherapy. Overall, 14.9 -16.9% of women with early-stage breast cancer who started AC chemotherapy with a normal Hb (≥12 g/dL) developed anemia. Nearly 11% developed severe to life-threatening anemia (Hb &lt; 8 g/dL). Data on blood transfusions and erythropoietic therapy were unavailable. Multivariate logistic regression analysis showed that patients who started with a normal prechemotherapy Hb and dropped to ≤10 g/dL at some point during chemotherapy were more likely to be ≥65 years of age, have a low body surface area (&lt; 1.78), and have four or more positive nodes. Conclusion. The incidence of anemia increased substantially from baseline to post-chemotherapy. The data suggested the importance of monitoring and managing Hb levels of patients at increased risk for developing chemotherapy-induced anemia.

The Impact of Age on Delivered Dose Intensity and Hospitalizations for Febrile Neutropenia in Patients with Intermediate-Grade Non-Hodgkin's Lymphoma Receiving Initial CHOP Chemotherapy: A Risk Factor Analysis

The purpose of this historical case series study was to evaluate the association of age on delivered dose intensity of initial CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and the occurrence of hospitalizations for febrile neutropenia for patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Findings are reported for 12 managed community and academic practices. Medical records of 930 NHL patients not enrolled on clinical trial protocols were reviewed. We reported on 577 of the study patients (62%) who received initial CHOP chemotherapy. Median age of the patients was 65.1 years. Older patients (age ≤ 65 years) had more hospitalizations for febrile neutropenia (28% vs. 16%; P < 0.05) than younger patients (age, 18-64 years). In patients with advanced-stage NHL (stage III/IV), older patients received fewer cycles of CHOP (< 6 cycles, 35% vs. 22%; P < 0.05) than younger patients. Older patients were planned for lower average relative dose intensity (ARDI = 80%; P < 0.05) and had more heart disease and comorbid conditions (P < 0.05) than younger patients. Multiple logistic regression models showed that older patients were more likely to receive a lower dose intensity (ARDI ≥ 80%; odds ratio = 2.46, 95% confidence interval [CI]: 1.62-3.72) during their first 3 cycles of therapy and to experience more hospitalizations for febrile neutropenia (odds ratio = 2.17, 95% CI: 1.43-3.30). We found the dose intensity of delivered CHOP chemotherapy for elderly patients to be less than standard CHOP therapy and the risk of hospitalizations for febrile neutropenia to be greater than in younger patients. Prospective clinical trials examining supportive care measures, such as colony-stimulating factor, for elderly NHL patients are recommended.

Prevalence and predictors of severe acute pancreatitis in patients with acquired immune deficiency syndrome (AIDS).

Recent case control data suggested that a severe course of acute pancreatitis in HIV+ patients was 1) common (50% of cases), 2) poorly predicted by Ranson's criteria (sensitivity 41%), and 3) accurately predicted by a diagnosis of AIDS (positive predictive value 67%). However, the definition of severity included length of stay in hospital and excluded commonly accepted markers (local complications, systemic complications, and need for surgery). The aim of this study was to determine 1) the prevalence of severity and 2) the value of these predictors with regard to severity, as defined by commonly accepted standardized criteria in patients with AIDS and acute pancreatitis. A retrospective review identified 50 patients with AIDS exhibiting clinical, laboratory, and/or radiological features of acute pancreatitis. Only five patients followed a severe course as defined by accepted markers. Of these patients, 29 had values available for at least nine of 11 of Ranson's criteria (sensitivity 80%, specificity 54%). Points were awarded most commonly for decreased serum Ca2+ (n = 14) and elevated serum LDH (n = 7). In patients with AIDS and acute pancreatitis at our institutions, 1) the prevalence of severity and 2) the sensitivity of Ranson's criteria with regard to severity is comparable to that reported in large historical case series of immunocompetent patients. Pseudohypocalcemia and/or elevation in LDH are frequent, likely due to the catabolic infectious disease state.

Prevalence and predictors of severe acute pancreatitis in patients with acquired immune deficiency syndrome (AIDS)

OBJECTIVE: Recent case control data suggested that a severe course of acute pancreatitis in HIV+ patients was 1) common (50% of cases), 2) poorly predicted by Ranson’s criteria (sensitivity 41%), and 3) accurately predicted by a diagnosis of AIDS (positive predictive value 67%). However, the definition of severity included length of stay in hospital and excluded commonly accepted markers (local complications, systemic complications, and need for surgery). The aim of this study was to determine 1) the prevalence of severity and 2) the value of these predictors with regard to severity, as defined by commonly accepted standardized criteria in patients with AIDS and acute pancreatitis. METHODS: A retrospective review identified 50 patients with AIDS exhibiting clinical, laboratory, and/or radiological features of acute pancreatitis. RESULTS: Only five patients followed a severe course as defined by accepted markers. Of these patients, 29 had values available for at least nine of 11 of Ranson’s criteria (sensitivity 80%, specificity 54%). Points were awarded most commonly for decreased serum Ca 2+ (n = 14) and elevated serum LDH (n = 7). CONCLUSIONS: In patients with AIDS and acute pancreatitis at our institutions, 1) the prevalence of severity and 2) the sensitivity of Ranson’s criteria with regard to severity is comparable to that reported in large historical case series of immunocompetent patients. Pseudohypocalcemia and/or elevation in LDH are frequent, likely due to the catabolic infectious disease state.