Thesis (Ph. D.)--University of Hawaii at Manoa, 2001. / Includes bibliographical references (leaves 127-162).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.

Thesis (M.D.) -- Dept. of Surgery, University of Adelaide, 1981. / Typescript (photocopy).

Thesis (M.S.) -- University of Adelaide, Dept. of Surgery, 2000. / Corrigenda inside back cover. Bibliography: leaves 161-178.

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a variety of South African Hospitals: a retrospective study Purpose: To examine the number of lymph nodes present in specimens submitted for histological examination from a variety of South African hospitals; the identification of factors that influence nodal yield and node positivity; determining whether oncological clearance is improved based on the number of nodes examined in high volume centers versus low volume centres; the establishment of guidelines on where surgery for colorectal cancer should ideally be performed. Patients and methods: Pathology reports of resected specimens of colorectal adenocarcinoma in the database of the National Health Laboratory Service Johannesburg laboratory from 2000 to 2005, were examined for patient demographics, referring hospital, tumour specific features of T-stage, degree of differentiation, lymphovascular invasion and adenocarcinoma subtype (mucinous versus non-mucinous), number of lymph nodes identified, number of nodes positive and whether preoperative radiotherapy was administered. Hospitals were grouped into four groups of Charlotte Maxeke Johannesburg Academic Hospital, Helen Joseph Hospital, private hospitals and non-academic public hospitals. Patients were grouped according to the number of lymph nodes retrieved into the following groups: not recorded, no nodes identified,1-7 nodes identified, 8-12 nodes, 13-18 nodes, and greater than 18 nodes identified. Additionally, patients were subdivided into those with nodal metastasis and those without, and into colon and rectal cancer respectively. Multivariate analysis was performed via StatSoft, Inc. (2008) STATISTICA (data analysis software system), version 8.0 on the different lymph node groups versus the abovementioned covariates. Results: Of the 365 patients identified, the mean number of lymph nodes examined per resected specimen was 8.9 (±6.2SD), with significant differences noted between the different resection subtypes (p < 0.001). No statistically significant difference in mean number of nodes identified could be seen between the various hospitals. Alarmingly, in the group of patients where no metastatic nodes could be identified, the recommendation of 12 or more nodes examined per specimen was upheld in only 29% of cases. Factors associated with positive lymph nodes in this study include T-stage, degree of differentiation and lymphovascular invasion by the tumour. No significant benefit in terms of finding metastasis nodes could be demonstrated by examining more than 18 nodes. Conclusions and recommendations: This study highlights a substandard nodal assessment in colorectal cancer specimens overall, including the academic hospitals. More than 70% of node negative patients in this series may have been understaged. Close liaison between the surgeon and examining pathologist is recommended. In the presence of the identified high risk factors for nodal involvement and a substandard nodal assessment, additional measures i.e. fat clearance and immunohistochemistry need employment. A prospective study assessing quality of surgery is necessary, as is the creation of a central database to improve overall quality of cancer care.

Objective: To evaluate the age-related changes in active pumping in thoracic duct (TD) from 24-month-old Fisher-344 rats comparing with TD pumping in 9-month rats. Methods: Lymphatic diameters, contraction amplitude and frequency, ejection fraction, and fractional pump flow were determined in isolated TD preparations. Western blot analyses were performed to evaluate relative levels of eNOS and iNOS in 9- and 24-month-old TD. Results: Stretch-dependent regulation was altered in aged TD especially at higher levels of pressure: the negative inotropy, negative chronotropy and diminished minute pumping (2- to 3-fold decrease) were observed. Physiological NO/imposed-flow-dependent inhibition was completely abolished in aged TD, yet NO-synthase blockade by l-NAME (10-4 M) increased pumping in a flow-independent manner. Western blot analyses indicated that the relative levels of eNOS were decreased ∼ 7-fold in the 24-month-old TD when compared with 9-month-old TD; whereas iNOS levels were increased ∼ 10-fold in 24-month-old TD. Conclusions: These data provide the first evidence that stretch- and imposed-flow-dependent regulatory mechanisms are greatly altered in aged TD. These alterations of active pumping mechanisms in TD appear to be related with age-related disturbances in NO-dependent regulatory pathways, and may reflect diminished lymphatic muscle contractility as well as altered lymphatic endothelium function.

Indiana University-Purdue University Indianapolis (IUPUI) / Endometrial cancer is the most common gynecologic cancer in the United States, and patients with early-stage endometrioid adenocarcinoma have a favorable prognosis. Over the past decade, the gynecologic oncology community has debated whether potential harms of systematic lymph node dissection (LND) outweigh potential benefits for these patients. To minimize number of nodes removed, sentinel lymph node dissection (SLND) is under investigation as an alternative. However, ongoing uncertainty of LND/SLND best practices may result in variations in disease management and discrepant outcomes. Methods Three retrospective cohort studies examined LND/SLND use in patients with endometrioid adenocarcinoma. Two examined temporal and geographic variations, respectively, utilizing the Surveillance, Epidemiology, and End Results (SEER) 18 dataset for the years 2004 through 2015. The third used the SEER-Medicare dataset from 2003 through 2016 to quantify and compare the risk of developing 6-month post-surgical lymphedema, lymphocele, hemorrhage, ileus, infection, thrombosis, and all-cause death by number of lymph nodes removed (0, 1-4, 5-9, or 10+). Results Time trend analyses found LND increased from 2004 through 2008, followed by a significant decline through 2015. SLND was rare and did not increase significantly. Significant geographic variation existed for LND use but not SLND. Per 1,000 patients, analyses of 6-month post-surgical complications found 6.5 experienced lymphedema, 3.9 experienced lymphocele, 15.7 experienced hemorrhage, 28.7 experienced ileus, 37.1 experienced infection, 18.6 experienced thrombosis, and 19.8 died. Controlling for size of primary tumor, tumor grade, comorbidities, race/ethnicity, age at diagnosis, adjuvant chemotherapy, and radiotherapy, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) showed greater risk for ileus (HR: 1.53; 95% CI: 1.24-1.90), infection (HR: 1.52; 95% CI: 1.25-1.83), and thrombosis (HR: 1.41; 95% CI: 1.09-1.82) when comparing removal of 10+ nodes versus 0 nodes. Conclusion Overall, these studies found significant temporal and geographic variation in LND, as well as increasing risk of post-surgical complications associated with increasing numbers of lymph nodes removed. Should continued research into SLND find strong evidence that it effectively detects cancer spread, patients may benefit through decreased risk of post-surgical ileus, infection, and thrombosis.