Predictive Model of Lake Photic Zone Temperature Across the Conterminous United States.

As the average global air temperature increases, lake surface temperatures are also increasing globally. The influence of this increased temperature is known to impact lake ecosystems across local to broad scales. Warming lake temperature is linked to disruptions in trophic linkages, changes in thermal stratification, and cyanobacteria bloom dynamics. Thus, comprehending broad trends in lake temperature is important to understanding the changing ecology of lakes and the potential human health impacts of these changes. To help address this, we developed a simple yet robust random forest model of lake photic zone temperature using the 2007 and 2012 United States Environmental Protection Agency's National Lakes Assessment data for the conterminous United States. The final model has a root mean square error of 1.48°C and an adjusted R2 of 0.88; the final model included 2,282 total samples. The sampling date, that day's average ambient air temperature and longitude are the most important variables impacting the final model's accuracy. The final model also included 30-days average temperature, elevation, latitude, lake area, and lake shoreline length. Given the importance of temperature to a lake ecosystem, this model can be a valuable tool for researchers and lake resource managers. Daily predicted lake photic zone temperature for all lakes in the conterminous US can now be estimated based on basic ambient temperature and location information.

Analyzing long-term water quality of lakes in Rhode Island and the northeastern United States with an anomaly approach.

Addressing anthropogenic impacts on aquatic ecosystems is a focus of lake management. Controlling phosphorus and nitrogen can mitigate these impacts, but determining management effectiveness requires long-term datasets. Recent analysis of the LAke multi-scaled GeOSpatial and temporal database for the Northeast (LAGOS-NE) United States found stable water quality in the northeastern and midwestern United States; however, sub-regional trends may be obscured. We used the University of Rhode Island's Watershed Watch Volunteer Monitoring Program (URIWW) dataset to determine if there were sub-regional (i.e., 3000 km2) water quality trends. URIWW has collected water quality data on Rhode Island lakes and reservoirs for over 25 yr. The LAGOS-NE and URIWW datasets allowed for comparison of water quality trends at regional and sub-regional scales, respectively. We assessed regional (LAGOS-NE) and sub-regional (URIWW) trends with yearly median anomalies calculated on a per-station basis. Sub-regionally, temperature and chlorophyll a increased from 1993 to 2016. Total nitrogen, total phosphorus, and the nitrogen:phosphorus ratio (N:P) were stable. At the regional scale, the LAGOS-NE dataset showed similar trends to prior studies of the LAGOS-NE with chlorophyll a, total nitrogen, and N:P all stable over time. Total phosphorus did show a very slight increase. In short, algal biomass, as measured by chlorophyll a in Rhode Island lakes and reservoirs increased, despite stability in total nitrogen, total phosphorus, and the nitrogen to phosphorus ratio. Additionally, we demonstrated both the value of long-term monitoring programs, like URIWW, for identifying trends in environmental condition, and the utility of site-specific anomalies for analyzing for long-term water quality trends.

Clinical patterns of metastasis.

In human solid cancer, lymph node status is the most important indicator for clinical outcome. Recent developments in the sentinel lymph node concept and technology have resulted in a more precise way of examining micrometastasis in the sentinel lymph node and the role of lymphovascular system in the facilitation of cancer metastasis. Different patterns of metastasis are described with respect to different types of solid cancer. Expect perhaps for papillary carcinoma and sarcoma, the overwhelming evidence is that solid cancer progresses in an orderly progression from the primary site to the regional lymph node or the sentinel lymph node in the majority of cases with subsequent dissemination to the systemic sites. The basic mechanisms of cancer metastasis through the lymphovascular system form the basis of rational therapy against cancer. Beyond the clinical patterns of metastasis, it is imperative to understand the biology of metastasis and to characterize patterns of metastasis perhaps due to heterogeneous clones based on their molecular signatures.

Molecular analysis in evaluating the sentinel node in malignant melanoma.

The most powerful predictor of cancer mortality in solid tumors is the status of regional lymph nodes. If the presence or absence of regional nodal metastases will determine which patient receives formal dissection or which patient enters adjuvant therapy, then a technique is needed to accurately screen lymph node samples for occult disease. Routine histopathologic examination commonly underestimates the number of patient with metastases. The use of reverse transcription-polymerase chain reaction (RT-PCR) method increased the detection of nodal metastases exponentially. Studies have shown that RT-PCR is a sensitive, reproducible, and efficient technique with prognostic significance. If identification of micrometastases through RT-PCR can lead to improved clinical outcome, then this more accurate method of staging would become the new standard in cancer care.

The role of lymphoscintigraphy in the management of the patient with breast cancer.

INTRODUCTION: Regional nodal status is the most powerful predictor of recurrence and survival in women with breast cancer. Lymphatic mapping and sentinel lymph node (SLN) biopsy have been found to accurately predict the regional nodal status. Preoperative lymphoscintigraphy has been used in melanoma patients to identify the basins at risk for metastases when primary sites are located in watershed areas of the body. This study was performed to define the role of lymphoscintigraphy for axillary nodal staging in women with breast cancer. Specifically, can preoperative lymphoscintigraphy define a population of women with breast cancer who have multidirectional drainage or who do not drain to the axilla and need no axillary dissection? METHODS: 516 patients with invasive breast cancer were accrued in a national breast lymphatic mapping trial sponsored by the U.S. Department of Defense. Preoperative lymphoscintigraphy images were produced using filtered technetium-99 sulfur colloid. Lymphatic drainage to axillary and internal mammary sites was noted. RESULTS: Drainage to an axillary SLN was found in 335 (65%) patients, and internal mammary or extra-axillary drainage was noted in 52 (10%) patients. By using sensitive hand-held probes and vital blue dye intraoperatively, the overall success rate of finding an axillary SLN was 85%. Of the 335 patients who had an axillary SLN identified with imaging, all had successful SLN biopsy procedures. Although no SLNs could be imaged in 181 patients, 153 (85%) of these patients had an axillary SLN identified with intraoperative mapping. For 28 patients in which lymphoscintigraphy was negative and intraoperative mapping was unsuccessful, complete axillary node dissection was performed, and 13 (46%) of these patients were found to have metastatic disease in the basin. CONCLUSIONS: Preoperative lymphoscintigraphy can identify those women with primary breast cancers who have extra-axillary regional basin drainage such as internal mammary. The ability to image an axillary SLN was associated with a high success rate of being able to find the node intraoperatively with a combination mapping technique. In a high percentage of patients with negative lymphoscintigraphy, the SLN was identified with more sensitive hand-held probes. Therefore, patients who have a negative preoperative lymphoscintigraphy and intraoperatively are found to have no "hot" spot in the axilla with the hand-held probe still need an axillary node dissection, because 46% of these patients contain metastatic disease in the axilla.

Learning curves and breast cancer lymphatic mapping: institutional volume index.

INTRODUCTION: To date, studies of breast cancer lymphatic mapping (LM) have analyzed success with respect to individual surgeons. However, LM and sentinel lymph node biopsy (SLNBx) are procedures that require institutional multidisciplinary cooperation between the departments of radiology, pathology, and surgery. Thus, it is important to evaluate these procedures with respect to the institution. This study examines 30 institutions to clarify the value of the institutional volume index (IVI) (cases/month) to the outcome of LM and SLNBx in breast cancer. METHODS: From July 1997 to July 1999, 30 institutions participated in the Department of Defense national breast LM trial. All participants underwent a 2-day training course for surgeons, nuclear medicine physicians, and pathologists. The records for each institution were prospectively accrued and submitted to a database. The false negatives, failure rates, and IVI were calculated for each institution. A logistic regression model plots the relationship between IVI and institutional failure rate. Using a multivariate analysis, mapping failure was analyzed as a function of case number with respect to the individual surgeon and the institution as a whole. RESULTS: False negative results were demonstrated in only 5 (4%) cases among all institutions and were excluded from further analysis due to small numbers. Mapping failures were found in all but 7 of the 30 institutions whose data were complete. There were 71 mapping failures among 74 surgeons over 555 cases, which yielded an overall failure rate of 12.79% (71 555). The logistic regression model revealed an inverse relationship between IVI and institutional failure rate. However, the multivariate analysis revealed that the individual surgeon performance was the most significant factor in determining institutional mapping success. CONCLUSION: Failure to map can be a function of multiple factors including surgical skill, surgical volume index, and injection method of the SLN patient, all under the quality control of an institution. The surgical failure rate on the other hand is a function of surgical skill, surgical volume, and injection methods. While differences in mapping success exist across institutions, this disparity is not due to factors associated with the institution as a whole, but lie with the individual surgeon.

The clinical relevance of molecular staging for melanoma.

The presence of metastatic disease in the regional nodal basin is the most important prognostic indicator for patients with malignant melanoma. The metastatic status of the sentinel lymph node (SLN), defined as the first node in the basin to drain a primary tumor, has been shown to represent that of the entire basin. Since routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease, a more sensitive assay for detecting tumor cells is needed. We have previously shown that a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) was able to define a population of patients at higher risk for both recurrence and death, compared with routine H&E histology. Recently, we have compared "molecular staging" of patients by RT-PCR with conventional S-100 immunohistochemistry (IHC) staining of the SLNs. In these studies, SLN specimens were bivaled, and half of each specimen was examined by routine histology, including both H&E and S-100 IHC. The other half of each specimen was analyzed by a nested RT-PCR assay. H&E histology alone detected metastatic disease in 36 of 233 (16%) patients tested. Serial sectioning and IHC detected micrometastatic disease in another 16 patients, thus increasing the proportion of patients with nodal disease to 22%. RT-PCR detected micrometastatic disease in 114 of 181 patients who were negative by conventional methods, further increasing the proportion of patients with evidence of nodal disease to 70% overall. The clinical significance of these findings is still uncertain. The value of additional therapy (including elective lymph node dissection and interferon therapy) for patients who are positive only by the molecular method is currently being investigated by the national multi-center Sunbelt Melanoma Trial.

Clinical relevance of molecular staging for melanoma: comparison of RT-PCR and immunohistochemistry staining in sentinel lymph nodes of patients with melanoma.

OBJECTIVE: To determine the clinical significance of a molecular assay based on the reverse transcriptase polymerase chain reaction (RT-PCR) for the presence of micrometastatic melanoma cells in sentinel lymph nodes (SLNs). SUMMARY BACKGROUND DATA: Routine histologic examination of lymph nodes often underestimates the presence of micrometastatic disease. The authors have previously shown that an RT-PCR assay designed to detect melanocyte-specific expression of the tyrosinase gene could be used to define a population of patients at higher risk for both recurrence and death compared with routine hematoxylin and eosin (H&E) histology. In this study, the authors used the tyrosinase RT-PCR assay in a patient population examined by a more detailed histologic analysis, including S-100 immunohistochemistry. METHODS: Patients underwent lymphatic mapping and SLN biopsy. SLN specimens were bivalved, and half of each specimen was serially sectioned and examined by routine H&E histology and S-100 immunohistochemistry. The other half of each specimen was analyzed by a nested RT-PCR assay. RESULTS: Hematoxylin and eosin histology detected metastatic disease in 36 (16%) of the 233 patients tested. S-100 immunohistochemistry detected micrometastatic disease in another 16 patients, and 114 (63%) of 181 patients with histology-negative nodes had positive findings on RT-PCR. There were significant differences between PCR-positive and PCR-negative patient groups in Breslow thickness, Clark level, and the presence of ulceration of the primary tumor, factors that have been shown to correlate with recurrence and survival. CONCLUSIONS: These results suggest that RT-PCR can increase the sensitivity of detection of metastatic melanoma cells in SLNs over the current standard methods, including H&E histology and S-100 immunohistochemistry. Further long-term follow-up is needed to detect actual differences in recurrence and overall survival.

Metastatic melanoma to regional lymph nodes.

There is an epidemic of melanoma in the United States and throughout most parts of the word. Recent advancements in the management of this disease has provided the patient with more options. The emerging technology of lymphatic mapping and sentinel node biopsy results in a more conservative, less morbid procedure to obtain nodal staging information. At the same time, providing the pathologist the 1-2 nodes from the basin most likely to contain metastatic disease, allows for a more detailed examination of the sentinel lymph node. This more detailed examination may include serial sectioning, immunohistochemical staining or even molecular biology techniques based on RT-PCR to provide more accurate staging. National trials are ongoing to examine the clinical relevance of the disease that is detected and the 'upstaging' that occurs with more sensitive assays for occult metastases.

Molecular staging for melanoma and breast cancer.

Despite increased sensitivity of PCR techniques, routine H&E histology and, in some cases, immunohistochemistry remain the gold standards for the detection of micrometastatic disease. Highly sensitive and specific molecular assays such as RT-PCR provide an ideal way to detect micrometastatic disease in tissues or blood at risk for metastases. RT-PCR has been shown to increase detection of micrometastases, especially in patients with breast cancer and melanoma. These assays have the potential to provide valuable tumor staging and progression information and thus determine the need for further surgery, adjuvant chemotherapy, and antigen-specific immunotherapy. As investigators gain more experience using molecular assays, the results of these assays will be more likely to guide clinical staging and decision making.

Historical perspectives and future applications.

Lymphatic Mapping and sentinel lymph node biopsy are developing into a new field of minimally invasive surgery. These procedures were brought about by the necessity to better stage patients while minimalizing morbidity. Their application is reaching several aspects of surgery and becoming a major foundation in the armamentarium of the general surgeon.

Molecular staging of malignant melanoma: correlation with clinical outcome.

CONTEXT: For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases. OBJECTIVE: To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma. DESIGN: A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months. SETTING: A major university-based melanoma referral center at a National Cancer Institute-designated cancer center. PATIENTS: A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases. MAIN OUTCOME MEASURE: Melanoma recurrence and overall survival. RESULTS: Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival. CONCLUSIONS: The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.

The Role of Selective Lymphadenectomy in Breast Cancer.

BACKGROUND: Axillary node dissection is considered a standard staging procedure in patients with breast cancer. The procedure is associated with significant morbidity and provides pathologists with many lymph nodes to evaluate. METHODS: A total of 174 women participated in a trial that included preoperative lymphoscintigraphy and intraoperative lymphatic mapping using a combination of a vital blue dye and radiocolloid mapping. RESULTS: The intraoperative lymphatic mapping correctly identified a sentinel lymph node (SLN) in 160 (92%) of 174 patients. One skip metastasis (0.7%) occurred in 136 women who had a subsequent complete node dissection. CONCLUSIONS: Lymphatic mapping and SLN biopsy using a combination of mapping techniques provide accurate nodal staging for women with breast cancer. With this technique, approximately 70% to 80% of women with no axillary metastases could be spared the morbidity of a complete node dissection.

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer.

OBJECTIVES: To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla. DESIGN: A prospective trial. PARTICIPANTS: Sixty-two patients with newly diagnosed invasive breast cancers. INTERVENTION: Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection. MAIN OUTCOME MEASURE: The metastatic distribution in the axilla was determined in patients with occult nodal disease. RESULTS: The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P<.001). CONCLUSIONS: This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.

delta 9-Tetrahydrocannabinol (THC) modulates IL-1 bioactivity in human monocyte/macrophage cell lines.

We have previously observed that delta 9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, increased supernatant interleukin-1 (IL-1) bioactivity in cultures of mouse resident peritoneal macrophages stimulated with lipopolysaccharide (LPS). In this study, experiments were performed to determine whether THC treatment similarly affected phagocytes of human origin. The results showed that THC increased the levels of supernatant IL-1 bioactivity of two human monocytic cell lines, but only if the cells were differentiated with phorbol myristate acetate. Undifferentiated cells displayed decreased IL-1 bioactivity in response to THC. However, under conditions in which THC augmented supernatant IL-1 bioactivity from THP-1 cells, ELISA studies showed that the levels of IL-1 alpha and IL-1 beta were unchanged and decreased, respectively. Furthermore, supernatant interleukin-6 (IL-6) levels were decreased, but tumor necrosis factor (TNF-alpha) levels were increased by THC treatment. These results show that THC treatment modulates cytokine production and/or release by mouse and human macrophages and the drug effects on IL-1-like bioactivity in the supernatants of the human THP-1 cells are due to increased levels of other cytokines, such as TNF-alpha, rather than IL-1 itself.