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N N Williams

Publications and source records attributed to N N Williams.

At least 19 recordsLinked to original sources
PubMed2001

Fragile histidine triad expression delays tumor development and induces apoptosis in human pancreatic cancer.

The fragile histidine triad (FHIT) gene is a tumor suppressor gene that is altered by deletion in a large fraction of human tumors, including pancreatic cancer. To evaluate the potential of FHIT gene therapy, we developed recombinant adenoviral and adenoassociated viral (AAV) FHIT vectors and tested these vectors in vitro and in vivo for activity against human pancreatic cancer cells. Our data show that viral FHIT gene delivery results in apoptosis by activation of the caspase pathway. Furthermore, Fhit overexpression enhances the susceptibility of pancreatic cancer cells to exogenous inducers of apoptosis. In vivo results show that FHIT gene transfer delays tumor growth and prolongs survival in a murine model mimicking human disease.

Acid Anhydride Hydrolases↗
PubMed2001

Crohn's disease of the colon.

The surgical treatment of Crohn's disease of the colon is distinct from that used in treating ulcerative colitis. Crohn's disease often involves the small bowel and is not "cured" by colorectal resection. The popular ileo-anal pouch procedures used in the management of ulcerative colitis generally are not used for the treatment of Crohn's colitis, because of higher complication rates. Commonly performed operations include ileostomy, segmental colon resection, subtotal colectomy, and proctocolectomy. The general surgeon, therefore, is provided with many options when faced with complications of Crohn's colitis. This article examines the attributes of and results reported for each of these options.

Colectomy↗
PubMed2001

Long term survival after pancreatic resection for pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.

Adenocarcinoma↗
PubMed2000

Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas.

PURPOSE: To determine the clinical outcomes and potential impact of adjuvant chemoradiation in patients undergoing surgical resection of ampullary carcinoma. PATIENTS AND METHODS: Between 1988 and 1997, 39 patients underwent pancreaticoduodenectomy for ampullary adenocarcinomas. Clinical and pathologic factors, adjuvant therapy records, and disease status were obtained from chart review. Thirteen (33%) patients received adjuvant chemoradiation. Radiation therapy was delivered to the surgical bed and regional nodes to a median dose of 4,860 cGy with concurrent bolus or continuous infusion of 5-fluorouracil. Outcomes measures included locoregional control, disease-free survival, and overall survival. Univariate analysis was used to assess the impact of various patient- and tumor-related factors and the use of adjuvant therapy. Twenty (51%) patients with tumor invasion into the pancreas (T3) or node-positive disease were classified in a "high-risk" subgroup. RESULTS: After a median follow-up of 45 months for survivors, overall 3-year survival was 55%. Survival was significantly worse for patients with positive nodes (23% vs. 73%, p < 0.001) and high-risk status (30% vs. 80%, p = 0.002). Disease-free survival was 54% at 3 years. There were 3 postoperative deaths, and these patients (all high risk) are excluded from further analysis on adjuvant therapy. In univariate analysis, the use of adjuvant chemoradiation had no clear impact on local-regional control or overall survival. However, by controlling for risk status in multivariate analysis, the use of adjuvant therapy reached statistical significance for overall survival (p = 0. 03). Among the high-risk patients, 7 (77%) of 9 patients receiving adjuvant therapy remained disease-free during follow-up compared with only 1 (14%) of 7 patients not receiving adjuvant therapy (p = 0.012). CONCLUSION: Despite the relatively favorable prognosis of ampullary carcinomas compared with other pancreaticobiliary tumors, patients with nodal metastases or T3 disease are at high risk for disease relapse. The use of adjuvant chemoradiation may improve long-term disease control in these patients.

Adenocarcinoma↗
PubMed2000

Hand-assisted laparoscopic vertical banded gastroplasty: early results.

BACKGROUND: Minimally invasive hand-port-assisted laparoscopic vertical banded gastroplasty has the potential to reduce postoperative complications after bariatric surgery. METHODS: We analyzed the postoperative course of 46 hand-port-assisted laparoscopic vertical banded gastroplasties (LVBG) completed between January 1998 and April 1999. RESULTS: The operating time for the LVBG was shorter (140.8 +/- 6.0 vs 180.2 +/- 6.3 min; p < 0.05). Individuals were able to ambulate sooner (1.36 +/- 0.09 vs 2.44 +/- 0.16 days; p < 0.05), and start oral intake earlier (2.7 +/- 0.27 vs 3.7 +/- 0.17 days; p < 0.05) than the open vertical banded gastroplasty (VBG) controls. Three staple line leaks were detected in this group. Two leaks resolved without clinical sequelae, but one patient developed intraabdominal sepsis. This complication extended the average hospital stay to 6.8 +/- 2.00 days, as compared to 7.71 +/- 0.18 days for historical controls. By discounting this patient from the analysis, we arrive at a more representative length of hospitalization of 4.82 +/- 0.34 days (p < 0.05). CONCLUSIONS: LVBG offers a good alternative to the standard open VBG. Although this procedure has a relatively short learning curve, it should be done at centers with an interest in bariatric surgery.

Adult↗
PubMed1994

Stereotactic cytology in a regional breast-screening programme.

Stereotactic localization and fine-needle aspiration are new procedures for the management of non-palpable mammographic abnormalities. In this prospective study, stereotactically guided cytology with immediate reporting was performed before biopsy in a consecutive series of 166 patients with screen-detected non-palpable abnormalities. All specimens were obtained by multiple stereotactically guided passes with a 22-G Franzén needle and graded as: 1, acellular or inadequate; 2, benign; 3, atypical, probably benign; 4, probably malignant; or 5, malignant. After definitive surgery all tumours were staged according to the Union Internacional Contra la Cancrum classification. Of 71 patients with malignancy, 56 were correctly diagnosed by cytology before operation. Twelve patients with malignancy had grade 1 cytology and 50 of the 52 with grade 2 cytology had benign disease. This study confirms that stereotactic cytology is a valuable diagnostic test in a breast-screening programme.

Aged↗
PubMed1994

Proliferating cell nuclear antigen: a new prognostic indicator in renal cell carcinoma.

Renal cell carcinoma is a tumor, the prognosis and behavior of which remain poorly understood. Proliferating cell nuclear antigen levels have been shown to act as an independent prognostic variable in a variety of malignancies. Proliferating cell nuclear antigen was evaluated in 59 cases of renal cell carcinoma, and the results were correlated with existing clinicopathological variables and survival. Proliferating cell nuclear antigen index (percentage of tumor cells positive for proliferating cell nuclear antigen) did not correlate with stage, grade or ploidy. To assess survival, tumors with proliferating cell nuclear antigen indexes of greater than and less than 60% were compared. The 24 patients with a high index (greater than 60%) had a significantly worse survival than did 35 with a low index (less than 60%, p < 0.001). Therefore, the prognostic potential of proliferating cell nuclear antigen in renal cell carcinoma is promising and may be of clinical value in the management of patients with renal cell carcinoma.

Adult↗
PubMed1994

The pros and cons of laparoscopic cholecystectomy and extracorporeal shock wave lithotripsy in the management of gallstone disease.

The recent introduction of laparoscopic cholecystectomy (LAPC) has revolutionised the surgical treatment of gallstone disease. However, it has also raised doubts about the future role of extracorporeal shock wave lithotripsy (ESWL) in the treatment of gallstones. In this study, we compared patients treated successfully with ESWL and dissolution therapy with patients treated by LAPC. Out of 67 patients, 50 had successful clearance with ESWL while 50 out of 54 had successful LAPC. We evaluate treatment duration, recurrence rate (ESWL) and cost of treatment in both groups. All patients had uncomplicated symptomatic gallstones. The inclusion criteria were similar in both groups with the exception of patients with non-functioning gallbladders who were excluded from ESWL. The results of the study show that although ESWL is noninvasive and associated with minimal morbidity, it is also costly and has a high failure and recurrence rate. In contrast, laparoscopic cholecystectomy, while requiring short-term hospital stay and debility, seems to be a safe and effective alternative with an advantage in terms of cost and duration of treatment.

Adult↗
PubMed1993

In situ ESWL for ureteric calculi: the optimum treatment?

In situ ESWL for ureteric calculi is associated with good stone clearance rates but is it without significant morbidity? A review of 189 patients with single ureteric calculi (150 upper ureter, 39 lower ureter calculi) revealed an 89% stone clearance for upper ureteral calculi and 80% stone clearance for lower ureteral calculi. However 11% of patients with upper ureteral calculi and 20% of patients with lower ureteral calculi required additional intervention for complications or failed treatment. In situ ESWL may not be the optimum therapy for all ureteric calculi especially those in the lower ureter.

Adolescent↗
PubMed1992

Growth-factor-independence and invasive properties of colorectal carcinoma cells.

During serial passage of the colorectal carcinoma cell line SW1116 in athymic nude mice, we selected 2 variants that metastasized to the lungs and liver. The metastatic capacity of these in vivo variant cell lines was associated with their ability to (1) grow under growth-factor-deprived conditions, (2) invade and transgress a reconstructed basement membrane with high effectiveness, and (3) produce higher activities of the substrate-degrading enzymes collagenase and plasminogen activator as compared to parental cells. To assess the relative contribution of growth-factor-independence and high levels of invasiveness/motility to the metastatic phenotype, variants of 6 colorectal carcinomas were selected in vitro by adaptation to a growth-factor-free culture medium followed by selection of highly invasive cells in chemoinvasion assays. Four out of 6 cell lines selected for growth-factor-independence showed significantly higher levels of invasiveness through reconstructed membranes, suggesting co-segregation of growth-factor-independence and high levels of invasiveness in vitro. Using an in vitro chemoinvasion assay, 2 poorly and 1 highly invasive cell line were further selected for invasiveness. After 6 selection passages, all cell lines were highly invasive and showed high motility rates. However, when injected s.c. into athymic nude mice to test their metastatic capacity in vivo, double-selected variant cell lines did not form spontaneous metastases. Our results indicate that growth-factor-independence and high levels of invasiveness, although associated with the metastatic phenotype, are not sufficient for experimental metastasis formation of colorectal carcinoma cells in vivo.

Animals↗
PubMed1992

Laparoscopic common bile duct exploration.

Laparoscopic cholecystectomy is now the standard approach to gallbladder disease. While laparoscopic cholecystectomy offers many advantages over the conventional laparotomy procedure one of its drawbacks is that a synchronous common bile duct exploration, for so long a cornerstone of management of choledocholithiasis, is not yet widely practised laparoscopically. Endoscopic sphincterotomy or open surgery, with their attendant hazards and morbidity, remain the most common approaches. A flexible choledochoscope with an operating channel may in future facilitate laparoscopic management of choledocholithiasis but as yet this is not widely available. We report the removal of a common duct stone by dormia basket extraction through the cystic duct at laparoscopic cholecystectomy.

Aged↗
PubMed1992

A study of regional distribution of renal blood flow using quantitative autoradiography.

Quantitative autoradiography utilizing [14C]iodoantipyrine was used to measure regional renal blood flow in anesthetized rats. This technique allowed blood flow in any region of the kidney to be measured with a resolution of 100 microns. There was no significant difference between flow to polar and middle regions of the renal cortex [875 +/- 57 vs. 926 +/- 71 (SE) ml.100 g-1 x mm-1]. Areas of high optical density in renal cortex corresponded to peritubular capillaries. Mean cortical blood flow was three times greater than mean medullary blood flow. Outer medullary blood flow was uniform but significantly higher than inner medullary blood flow (272 +/- 16 vs. 45 +/- 7 ml.100 g-1 x mm-1; P < 0.001).

Animals↗
PubMed1991

Endoscopic management of common duct stones with laparoscopic cholecystectomy.

In the first year from October 1990 since starting the procedure 65 laparoscopic cholecystectomies were carried out on one surgical service. There were 4 planned open cholecystectomies and 8 laparoscopic procedures converted during the same period: 7 of these were in the first 3 months with only 1 of the last 53 being opened. Surgery was carried out during the same admission in 22 patients presenting as emergencies: acute cholecystitis (9), colic (6), pancreatitis (3), jaundice (4). Two patients had later laparotomies for complications; one patient bled from the umbilical stab and with ongoing peritonism had a pelvic haematoma drained on day 5 and a second was opened following a bile leak caused by a displaced cystic duct clip--both recovered uneventfully. Peroperative cholangiography was performed in 13 patients; 2 were positive (15%) and had ERCP papillotomy 3 days post op without complication. One patient who presented with pancreatitis had ERCP performed post-op without incident. Seven patients had laparoscopic cholecystectomy following papillotomy for common duct stones. The gallbladder was extracted per umbilicus in 45 (3 wound infections) and per right subcostal stab in 20 (no infections). Mean hospital stay was 48 hours (1-4 days) in uncomplicated cases. In conclusion, the learning curve is associated with higher conversion rates. Extraction through pliable hypochondrial muscles is easier and may be safer and less traumatic. Perioperative endoscopic papillotomy is safe and effective for choledochal stones.

Adult↗
PubMed1991

Natural killer cell stimulatory factor (NKSF) augments natural killer cell and antibody-dependent tumoricidal response against colon carcinoma cell lines.

The therapy of colorectal cancer may be improved by biologic response modifiers that enhance natural killer (NK) cell and antibody-dependent tumoricidal mechanisms. This study examined the effect of a recently discovered cytokine purified from the supernatant of an Ebstein-Barr virus-transformed B-lymphoblastoid cell line (RPMI-8866), natural killer cell stimulatory factor (NKSF), on NK and antibody-dependent cellular cytotoxicity (ADCC) of human colon adenocarcinoma cell lines. Human peripheral blood lymphocytes were cultured for 24 hr in the presence or absence of NKSF (3.6 pM) or interleukin-2 (1 nM). The cultured lymphocytes were analyzed for lytic potential toward chromium-51-labeled colon carcinoma targets SW 1116, 498 LI, and WC 1. ADCC was measured by incubating chromium-51-labeled SW 1116 or WC 1 targets with the monoclonal antibody CO17-1A, an IgG2a antibody reactive with gastrointestinal cancer-associated cell antigen, or control mouse IgG prior to testing NKSF-treated or control PBL effectors in a 6-hr cytotoxicity assay. NKSF significantly enhanced NK cytolysis of colon carcinoma and NK-resistant lymphoma cell lines, and on a molar basis was approximately 300 times more potent than interleukin-2 in generating NK cytotoxicity. Furthermore, NKSF significantly augmented lymphocyte-mediated ADCC against colon carcinoma targets, and the combination of NKSF with the antibody CO17-1A had an additive effect on lymphocyte tumoricidial capacity. Thus, NKSF may have a potential role in the treatment of colon cancer.

Animals↗
PubMed1990

Flow cytometry and prognostic implications in patients with solid tumors.

Flow cytometric DNA content analysis is a rapid, quantitative method of determining the DNA ploidy status and proliferative index of a given tumor. Abnormal DNA content, or aneuploidy, has been recognized as a marker of malignancy and is present in about 70 per cent of solid tumors. In the majority of solid tumors, the consensus is that the presence of an aneuploid tumor predicts a poorer over-all survival rate and a shorter disease-free interval, indicating that patients with diploid tumors have a more favorable prognosis than those with aneuploid tumors. The prognostic implications of an abnormal DNA content, therefore, suggest either a higher risk of relapse, a worsening of survival rate or a risk for progression of disease in stages I and II carcinoma of the breast, carcinoma of the colon and rectum, superficial carcinoma of the bladder and malignant melanoma. Thus, the assessment of cellular DNA content should be regarded as an additional prognostic determinant and should play an ancillary role in the decisions regarding the management of patients with malignant disease. With the introduction of more sophisticated technology, it will be possible to simultaneously assay for DNA ploidy and cell cycle distribution in addition to a series of tumor markers, such as CEA, and various products of oncogenes, thus providing further understanding of the heterogeneity of solid tumor cells.

Biomarkers, Tumor↗
PubMed1989

Infusional versus systemic chemotherapy for liver metastases from colorectal cancer.

It is clear from these studies that intrahepatic arterial infusion of floxuridine produces significantly higher response rates than does systemic infusion of the same drugs. Nevertheless, survival is the most important consideration when comparing two methods of treatment, and at present, there is only a slightly improved survival rate in those patients who receive intrahepatic infusional therapy. However, palliation of the patient and the effect on the quality of life should be taken into account, and these high response rates suggest an effective palliative measure to be offered to patients with this advanced disease. It is hoped that in the future the development of methods to identify those patients who will respond to this form of therapy, together with new ways to increase drug uptake by the tumors, will translate the better response rates achieved into better survival rates.

Adult↗
PubMed1989

Heparin kinetics in vascular surgery.

Currently there is little information available about the efficacy of heparin during vascular surgery or of the effects of surgical trauma on heparin kinetics. This study was undertaken to evaluate the kinetics of heparin therapy during vascular surgery. Nine patients undergoing major vascular surgery (one carotid, one common iliac and seven aortic operations) were studied both preoperatively and intra-operatively, each patient acting as his own control. Following determination of control activated partial thromboplastin time (APTT) and plasma heparin levels, heparin (100 u/kg body weight) was administered intravenously. Heparin dosage ranged form 4500 units to 8600 units with a mean dose of 6500 units. Plasma heparin and APTT levels were then measured at 10 minute intervals for 1 hour and 20 minute intervals for a second hour. The mean pre-operative and intra-operative APTT levels at ten minutes attained maximal values of 6.6 +/- 3.7 and 8.8 +/- 1.7 times the control respectively. At the end of 2 hours the mean APTT remained greater than 2.5 times the control in both groups. Mean plasma heparin level was 0.83 +/- 0.04 units at 10 minutes and was almost identical in both groups. Heparin level was not a reliable indicator of anticoagulant effect as most patients achieved the same levels but had markedly differing APTT results. The results of this study suggest that excessive doses of heparin may be used in vascular surgery and that surgical trauma does not significantly alter sensitivity to heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗