Katherine T. Morris

Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Objective Measurements

PURPOSE Sentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND). PATIENTS AND METHODS At median follow-up of 5 years, lymphedema was assessed in 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined. RESULTS Of the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P < .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P < .0001). Risk factors associated with measured lymphedema were greater body weight (P < .0001), higher BMI (P < .0001), and infection (P < .0001) or injury (P = .02) in the ipsilateral arm since surgery. CONCLUSION When compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.

A comparison of complementary therapy use between breast cancer patients and patients with other primary tumor sites

BACKGROUND Interest in complementary therapies in the United States is rising. We sought to characterize the use of complementary therapies among our cancer patients in our community and analyze differences in use between patients with breast versus those with other primary tumor sites. METHODS A survey of 1,935 randomly selected patients from the tumor registry was performed. A questionnaire was mailed to 935 breast cancer patients and 1,000 patients with other primary site diagnoses. RESULTS There were 617 responses (288 breast, 329 other). Seventy-five patients (75%) reported use of a complementary modality. Top therapies used were nutrition (63%), massage (53%), and healing herbs (44%). The most common reason for use, immune modulation (73%), was similar in both groups. Therapy was used consistently by 84% of breast patients versus 66% of others (P = 0.003). CONCLUSION A significant number of cancer patients are using complementary therapies. Breast cancer patients are far more likely to be consistent users compared with other tumor sites.

Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Patient Perceptions and Precautionary Behaviors

PURPOSE Sentinel lymph node (SLN) biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. This study was undertaken to examine patient perceptions of lymphedema and use of precautionary behaviors several years after axillary surgery. PATIENTS AND METHODS Nine hundred thirty-six women who underwent SLN biopsy (SLNB) alone or SLNB followed by axillary lymph node dissection (SLNB/ALND) between June 1, 1999, and May 30, 2003, were evaluated at a median of 5 years after surgery. Patient-perceived lymphedema and avoidant behaviors were assessed through interview and administered a validated instrument, and compared with arm measurements. RESULTS Current arm swelling was reported in 3% of patients who received SLNB alone versus 27% of patients who received SLNB/ALND (P < .0001), as compared with 5% and 16%, respectively, with measured lymphedema. Only 41% of patients reporting arm swelling had measured lymphedema, and 5% of patients reporting no arm swelling had measured lymphedema. Risk factors associated with reported arm swelling were greater body weight (P < .0001), higher body mass index (P < .0001), infection (P < .0001), and injury (P = .007) in the ipsilateral arm since surgery. Patients followed more precautions if they had measured or perceived lymphedema. CONCLUSION Body weight, infection, and injury are significant risk factors for perceiving lymphedema. There is significant discordance between the presence of measured and patient-perceived lymphedema. When compared to SLNB/ALND, SLNB-alone results in a significantly lower rate of patient-perceived arm swelling 5 years postoperatively, and is perceived by fewer women than are measured to have it.

Laparoscopic management of accessory spleens in immune thrombocytopenic purpura

AbstractBackground: A disparity exists between the incidence of accessory spleens reported in the open (15–30%) versus the laparoscopic (0–12%) literature. This disparity implies that a percentage of laparoscopic patients will require a reoperation for accessory splenectomy. We present our experience with the laparoscopic management of accessory spleens discovered after primary splenectomy for idiopathic thrombocytopenic purpura (ITP). Methods: Seventeen patients who underwent primary splenectomy for ITP were reviewed (1 open, 16 laparoscopic). In the laparoscopic group, the incidence of accessory spleens was 3 in 16 (19%). In 1 of these 3 patients, the accessory spleen was found and removed at the initial operation, whereas in 2 of the 16 patients (13%), the accessory spleens were missed. A third patient, whose initial operation was open, presented with recurrent thrombocytopenia after primary splenectomy. After recurrent thrombocytopenia developed, radio nuclide spleen scans were performed showing accessory spleens in all three patients. These three patients underwent accessory splenectomy using a four-port laparoscopic approach. Results: Laparoscopic accessory splenectomy was successfully performed in all three patients. Location of accessory spleens correlated with the spleen scan in each case. Mean operation time was 180 min. There were no conversions to open surgery and no complications. All patients were discharged from the hospital on postoperation day 1. The three patients had a good clinical response and were weaned effectively from their steroid medications. Conclusions: Patients undergoing a laparoscopic splenectomy for chronic ITP have a higher probability of requiring a reoperation for a missed accessory spleen. To minimize missing an accessory spleen, a systematic search should be made at the beginning of the laparoscopic operation. We have found that preoperation imaging with heat-treated erythrocyte scans is valuable for locating accessory spleens before reoperation. When reoperation for accessory splenectomy is necessary, a laparoscopic approach is safe and effective.

The rational use of computed tomography scans in the diagnosis of appendicitis

BACKGROUND Recently, limited abdominal computed tomography (CT) scans have been reported (Rao, New England Journal of Medicine, 1998) to have accuracy as high as 98%. We compare our hospitals CT accuracy ordered by emergency room (ER) physicians with that of experienced surgeons provided only with the ER history and physical examination in the evaluation of appendicitis. METHODS All charts of patients 16 years or older with limited CT scans ordered by ER from January 1, 1996, through February 28, 1998, were reviewed. CT scans ordered when appendicitis was not in the differential were excluded from analysis. Pathology and clinical follow-up were criterion standards. Four surgeons reviewed ER history and physical and placed them into one of three categories: appendectomy, observe to rule out appendicitis, or discharge with follow-up (included admitting to another service or treating for another disorder). RESULTS A total of 526 charts were reviewed; 129 met the criteria for the study. The accuracy of CT scans as used by our ER was not as high as reported in the literature. In addition, surgeon accuracy approached that of the CT scan even without the ability to evaluate the patients in person. Noncontrast CTs were ordered before surgical evaluation in contrast to the Rao protocol, likely reducing their accuracy. CONCLUSIONS Ordering CT scans to evaluate for appendicitis prior to surgical evaluation is of limited value.

Prevention of local recurrence after surgical debulking of nodal and subcutaneous melanoma deposits by hypofractionated radiation

Background: Local recurrence (LR) after surgical debulking of nodal or subcutaneous melanoma deposits defeats the purpose of operation and may worsen prognosis if the procedure was performed for stage III disease. To decrease LR rates in this setting, we extended the previously described role of hypofractionated radiation for melanoma deposits of the neck to all situations where the patient was felt to be at high risk for postoperative relapse after resection of bulky disease.Methods: Hypofractionated external beam radiation was administered in 6-Gy doses for 5 fractions (total dose 30 Gy, given over a median of 15 elapsed days) to 42 resected melanoma deposit sites in 41 patients.Results: Stages of the 41 patients at the time of treatment were: 22 stage III and 19 stage IV. All patients had complete gross resection of disease at the radiation site before radiation. Mean time between operation and initiation of radiation was 4 weeks. The 42 sites of treatment included 27 neck, 9 axilla, 3 groin, and 3 subcutaneous deposits. There were no treatment-related deaths; side effects were minimal and self-limited. Transient erythema, desquamation, fibrosis, telangiectasias, and mucositis, parotiditis, and xerostomia (for head and neck radiation) were reported, but no patient required interruption of therapy for these events. Of the 42 treated sites, only 2 recurred in the treatment field (one neck, one axilla) during the mean follow-up time of 22.4 months, for a treatment failure rate of 4.8%. This represents improved local control compared with patients treated with surgery alone at our institution and with published recurrence rates.Conclusions: The addition of hypofractionated radiation therapy after resection of nodal and subcutaneous melanoma deposits at a variety of sites is a rapid and well-tolerated method of providing excellent local control.

Simple Measurement of Intra-abdominal Fat for Abdominal Surgery Outcome Prediction

OBJECTIVE To assess the effect of increasing body mass index, intra-abdominal fat, and outer abdominal fat on outcome in patients undergoing major hepatectomy. DESIGN Cohort study. SETTING Memorial Sloan-Kettering Cancer Center. PARTICIPANTS We studied patients aged 19 to 86 years undergoing major hepatic resection between June 18, 1996, and November 6, 2001. Complications were extracted from a prospective database at a tertiary cancer center. INTERVENTION A total of 349 patients were grouped according to body mass index for analysis. Preoperative abdominal computed tomographic scans were examined and measurements of perinephric fat (as a surrogate for intra-abdominal fat) and outer abdominal fat taken at uniform anatomical locations. MAIN OUTCOME MEASURES We compared 30-day mortality and morbidity figures, length of stay, and operating times. RESULTS Body mass index had an influence on operative time (P = .02) but no significant effect on mortality, frequency of any complications, frequency of severe complications, or length of stay (P = .80, P = .89, P = .16, and P = .81, respectively). Outer abdominal fat had no significant effect on any of the 5 outcome measures. Perinephric fat measurements had a significant effect on most outcome measures (P = .004 for mortality, P = .003 for frequence of complications, P < .001 for frequence of severe complications, and P = .001 for length of stay). CONCLUSIONS Outer appearances of obesity do not correlate with poor outcomes for major upper abdominal operations. A simple measurement of perinephric fat, as a surrogate for intra-abdominal fat, on preoperative imaging gives a more useful risk assessment for patients undergoing major upper abdominal operations.

Stromal Cells Induce Th17 during Helicobacter pylori Infection and in the Gastric Tumor Microenvironment

Gastric cancer is associated with chronic inflammation and Helicobacter pylori infection. Th17 cells are CD4+ T cells associated with infections and inflammation; but their role and mechanism of induction during carcinogenesis is not understood. Gastric myofibroblasts/fibroblasts (GMF) are abundant class II MHC expressing cells that act as novel antigen presenting cells. Here we have demonstrated the accumulation of Th17 in H. pylori-infected human tissues and in the gastric tumor microenvironment. GMF isolated from human gastric cancer and H. pylori infected tissues co-cultured with CD4+ T cells induced substantially higher levels of Th17 than GMF from normal tissues in an IL-6, TGF-β, and IL-21 dependent manner. Th17 required interaction with class II MHC on GMF for activation and proliferation. These studies suggest that Th17 are induced during both H. pylori infection and gastric cancer in the inflammatory milieu of gastric stroma and may be an important link between inflammation and carcinogenesis.

A new score for the evaluation of palpable breast masses in women under age 40.

BACKGROUND The purpose of this study was to develop a rapid and accurate diagnostic test for palpable breast masses in women under age 40. METHODS Masses were evaluated utilitzing a modified triple test score (MTTS), which assigned scores of 1 point for benign, 2 points for suspicious, or 3 points for malignant findings from physical examination, ultrasonography, and fine needle aspiration. The MTTS was the sum of the three scores and was correlated with biopsy or follow-up. RESULTS Among 113 masses, 100 scored 3 points, 8 scored 4 points; all were benign. Three scored 5 points; 1 was malignant. Two scored >or=6 points: both were malignant. CONCLUSIONS The MTTS has 100% diagnostic accuracy when other than 5 points. Masses scoring <or=4 points are benign. Masses scoring >or=6 points may proceed to definitive therapy. Masses scoring 5 points (3%) require biopsy. This approach avoids open biopsy in the majority of cases, while capturing all malignancies.

Identification of a Novel Bcl-2-interacting Mediator of Cell Death (Bim) E3 Ligase, Tripartite Motif-containing Protein 2 (TRIM2), and Its Role in Rapid Ischemic Tolerance-induced Neuroprotection

We have previously shown that the cell death-promoting protein Bcl-2-interacting mediator of cell death (Bim) is ubiquitinated and degraded following a neuroprotection-conferring episode of brief ischemia (preconditioning). Here, we identify the E3 ligase that ubiquitinates Bim in this model, using a proteomics approach. Using phosphorylated GST-Bim as bait, we precipitated and identified by mass spectrometry tripartite motif protein 2 (TRIM2), a RING (really interesting new gene) domain-containing protein. The reaction between TRIM2 and Bim was confirmed using co-immunoprecipitation followed by immunoblotting. We show that TRIM2 binds to Bim when it is phosphorylated by p42/p44 MAPK but does not interact with a nonphosphorylatable Bim mutant (3ABim). 12-O-tetradecanoylphorbol-13-acetate activation of p42/p44 MAPK drives Bim ubiquitination in mouse embryonic fibroblast cells and is associated with an increased interaction between TRIM2 and Bim. One hour following preconditioning ischemia, the binding of Bim to TRIM2 increased, consistent with the time window of enhanced Bim degradation. Blocking p42/p44 MAPK activation following preconditioning ischemia with U0126 or using the nonphosphorylatable 3ABim reduced the binding between Bim and TRIM2. Immunodepletion of TRIM2 from cell lysates prepared from preconditioned cells reduced Bim ubiquitination. Finally, suppression of TRIM2 expression, using lentivirus transduction of shRNAmir, stabilized Bim protein levels and blocked neuroprotection observed in rapid ischemic tolerance. Taken together, these data support a role for TRIM2 in mediating the p42/p44 MAPK-dependent ubiquitination of Bim in rapid ischemic tolerance.