Biomedical subjects

K C Soo

Publications and source records attributed to K C Soo.

At least 37 records · Page 2Linked to original sources

PubMed2000

Significance of a positive oesophageal margin in stomach cancer.

BACKGROUND: A positive oesophageal margin is frequently encountered in total and proximal gastrectomies. It is controversial as to whether a positive oesophageal margin in gastrectomy predisposes to anastomotic dehiscence and loco-regional recurrence. Its independent impact on survival has not been fully addressed. METHODS: A retrospective review of 137 total and proximal gastrectomies for adenocarcinoma was undertaken. Independent prognostic factors were identified in a bivariate and Cox proportional hazards regression model. RESULTS: The prevalence of positive oesophageal margin was 18.2%. A positive oesophageal margin was not associated with increased anastomotic leak (8.0 vs 10.7%; P = 0.51), operative morbidity (32.0 vs 27.7%; P = 0.85) or 30-day mortality (8.0 vs 5.4%; P = 0.48) rates when compared with a negative margin. In addition, it did not predispose to anastomotic (13.0 vs 10.4%; P = 0.47) or regional (22.7 vs 24.5%; P = 0.51) recurrences. In the multivariate analysis the TNM stage and status of the oesophageal margin were the only independent prognostic factors for survival. CONCLUSIONS: A positive oesophageal margin is an independent poor prognostic factor for long-term survival in stomach cancer. All efforts should therefore be made to clear the oesophageal margin in total and proximal gastrectomies.

Adenocarcinoma↗

PubMed2000

Management of intraparotid facial nerve schwannomas.

BACKGROUND: The purpose of the present paper was to review the management of intraparotid facial nerve schwannoma so as to discuss its clinical presentation, evaluate the various possible diagnostic investigations, and compare the various surgical options and outcome. METHODS: Case series was undertaken of five (1.3%) patients with facial nerve schwannoma out of 400 consecutive parotidectomies at Singapore General Hospital. RESULTS: There were three men and two women with an age range of 29-65 years. Three patients presented with painless parotid lumps while two had painful parotid swellings. None had facial nerve paresis. Only one patient had preoperative diagnosis suspicious of schwannoma by fine-needle aspiration cytology (FNAC). Diagnoses were made intraoperatively. Four patients had excision with cable grafting of the nerve defect. achieving facial nerve grade II-IV (House-Brackmann scale). One patient who underwent enucleation of tumour with nerve preservation achieved grade II. CONCLUSIONS: Preoperative diagnosis is difficult but it is important for discussion of the extent and options of surgery. Fine-needle aspiration cytology holds promise in making a preoperative diagnosis. Enucleation with nerve preservation where possible seems to offer better facial function whereas nerve excision with cable graft can give satisfactory results.

Adult↗

PubMed2000

Changes in prostaglandin and nitric oxide levels in the hyperdynamic circulation following liver resection.

BACKGROUND AND AIMS: Significant changes in hepatic haemodynamics occur after major hepatectomy, but the pathogenesis of this phenomenon is unclear. This study investigates the serum profile of prostaglandin and nitric oxide in the hepatic and systemic circulation before and after hepatectomy and the temporal relationship of these to changes in the hepatic blood flow. METHODS: Blood samples were collected from the internal jugular, portal and hepatic veins of six Yorkshire pigs (17-25 kg) before, immediately after and 48 h after partial hepatectomy. RESULTS: Serum levels of prostacyclin I2 (PGI2) and prostaglandin E2 (PGE2) from the systemic circulation, the portal circulation and from the hepatic veins were found to differ considerably even before hepatectomy. After the hepatectomy was performed, there was a significant rise in PGI2 levels in the systemic circulation (P=0.027). Hepatic blood flow and cardiac output were measured before hepatectomy, 24 and 48 h after hepatectomy in another six pigs. A significant increase in hepatic blood flow (P=0.029) occurred after the hepatectomy and this was accompanied by a concomitant increase in the cardiac output (P=0.042). The increase in PGI2 concentration in the systemic circulation after hepatectomy appears to accompany the development of hyperdynamic hepatic and systemic circulations. No significant change was found in circulating PGE2 levels in the systemic, portal and hepatic veins at the three collection intervals (i.e. pre, post and 48 h after hepatectomy). The PGE2 levels in the hepatic vein, however, were significantly higher from than in the portal vein (P=0.028). No significant changes were observed in the level of nitric oxide. CONCLUSION: This study demonstrates an increase in the total hepatic blood flow after hepatectomy together with a threefold increase in prostacyclin in the systemic circulation. The liver was identified as the main source of circulatory prostaglandin.

Animals↗

PubMed2000

A non-invasive isotope dilution technique for quantifying hepatic blood flow using radiolabelled red blood cells.

Clinically significant changes in hepatic haemodynamics accompany the development of portal hypertension, hepatocellular carcinoma, liver metastases and liver cirrhoses, and after major liver resection. Hepatic blood flow parameters, such as hepatic arterial flow (HAF), hepatic portal flow (HPF), total hepatic blood flow (THBF) and hepatic perfusion index (HPI), are useful adjuncts to the diagnosis of liver pathology, the evaluation of disease progress and prognostication. Here, we describe a non-invasive method that combines the measurement of these parameters in a single study in real time. Red blood cells from eight pigs were labelled with 99Tc(m) using an in-vitro method and re-injected into the pigs. Data acquisition over the heart, lungs, liver and kidneys was started immediately and a blood sample was obtained 15 min post-injection. Hepatic arterial flow was determined from the ratio of the maximum gradients between the integrated time-activity curve of the left ventricle and the first-pass time-activity curve of the liver before the peak of the kidneys time-activity curve. The hepatic perfusion index was determined by comparing the slope of the liver time-activity curve before and after the kidney peak. Hepatic portal flow was determined from the hepatic arterial flow and the hepatic perfusion index, and total hepatic blood flow was determined as the sum of arterial and portal flow. The results were compared against those obtained from a clearance method using 99Tc(m)-DISIDA. The average hepatic perfusion index was 0.38, and the average hepatic arterial flow and hepatic portal flow were 168.3 +/- 52.9 and 274.6 +/- 60.1 ml x min(-1) respectively. The average total hepatic blood flow was 442.8 +/- 53.5 ml x min(-1), while the total hepatic flow determined by 99Tc(m)-DISIDA clearance was 419.7 +/- 62.6 ml x min(-1). No significant difference in total hepatic blood flow was found between the two methods. The results of this study show that it is possible to obtain all hepatic haemodynamics data in a single study using a non-invasive method.

Animals↗

PubMed2000

Results of surgical resection of oesophageal carcinoma in Singapore.

INTRODUCTION: The 5-year survival rate after resection of oesophageal cancer is still poor, reported to be between 5% to 34% in the literatures. We conducted this retrospective study to determine the prognostic factors and long-term survival rate for surgical resection of oesophageal carcinoma in Singapore. MATERIALS AND METHODS: Sixty-seven consecutive patients who underwent surgical resection of oesophageal carcinoma from January 1989 to December 1996 were reviewed. RESULTS: Majority of the patients were Chinese (94%), males (81%) with a history of dysphagia (96%), cigarette smoking (84%) and alcohol ingestion (58%). The median age at surgery was 63.6 (range 29 to 81) years. Sixty-four patients had squamous cell carcinoma of the oesophagus and 3 patients had adenocarcinoma. The lower one-third of the oesophagus was the most common site (48.6%) followed by the middle third (46%). Postoperative complications included pneumonia (43.3%), vocal cord paralysis/paresis (19.4%) and anastomotic leakage (17.9%). Thirty-day postoperative mortality was 7.5%. There was an almost equal number of patients undergoing transhiatal (34 patients) and transthoracic approach (33 patients). There was no significant difference in postoperative complications and survival outcome for both approaches. The median survival was 15.3 months after surgery. Tumour features such as depth of involvement and TNM stage were useful in predicting survival (P < 0.05, log-rank test). CONCLUSIONS: We conclude that the poor outcome of surgical resection (5-year survival rate was 18% by Kaplan-Meier survival plots) was mainly attributed to late presentation (80% patients had T3 or T4 tumour).

Adenocarcinoma↗

PubMed2000

Adverse operative risk factors for perforated peptic ulcer.

INTRODUCTION: Mortality from perforated peptic ulcer still remains high as a result of more perforations in the elderly who are generally more ill. We conducted this retrospective study to determine the adverse operative risk factors for perforated peptic ulcers. MATERIALS AND METHODS: Two hundred and six consecutive patients operated for perforated peptic ulcers from 1 January 1993 to 31 December 1997 were reviewed. RESULTS: Majority (n = 194) of the patients had perforations at the pyloroduodenal region and the remaining 10 patients had perforated benign gastric ulcers. The median age at surgery was 58 years (range 18 to 91 years). Forty-four patients (21.4%) were more than 70 years old. The 30-day operative mortality rate was 10.7% (n = 22). Advanced age (> 70 years), female gender, concurrent major medical illness, perforation developed while hospitalised for other medical illnesses, prolonged perforation (> 24 hours) and preoperative hypotension (systolic blood pressure < 90 mmHg) were indicators for operative mortality by univariate analysis. By logistic regression analysis, only concurrent major medical illness, prolonged perforation and preoperative hypotension were independent adverse risk factors. The operative mortality rate for patients with 0, 1, 2 and 3 independent adverse risk factors were 0%, 11%, 30% and 88%, respectively. CONCLUSIONS: As concurrent medical illness is a non-modifiable factor and preoperative hypotension is usually resulting from treatment delay and inadequate resuscitation, emphasis should place on shortening the time to surgery as well as prompt resuscitation.

Adolescent↗

PubMed2000

Extended resection of locally advanced (T4) stomach cancer.

INTRODUCTION: The surgical management of locally advanced (T4) stomach cancer remains controversial and many still question the benefits of an extended resection. The aims of this study were to examine the morbidity and mortality associated with extended resection and also to determine the survival benefit. MATERIALS AND METHODS: A retrospective review of all stomach cancer operations performed from 1989 to 1998 was carried out and the relevant case histories retrieved and analysed. RESULTS: Out of the 980 stomach cancer operations performed, 784 (80%) had tumour resection and 20 (2.5%) also had extended resection of adjacent involved organs. These 20 patients had a 10% postoperative morbidity and the operative mortality was 15%. The survival ranged from 2 to 35 months (median 17 months). CONCLUSIONS: Extended resection of T4 stomach cancer is feasible and carries an acceptable operative morbidity and mortality. However, there is poor survival benefit and it should only be performed in a selected group of patients.

Adult↗

PubMed1999

An improved model of galactosamine-induced fulminant hepatic failure in the pig.

Fulminant hepatic failure is a serious condition with very high mortality. Development of new therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of fulminant hepatic failure in the pig by administration of an aminosugar d-galactosamine hydrochloride. Galactosamine in a dose of 1.0 g/kg was dissolved in 5% dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of galactosamine or D5W alone, under general anesthesia. Neurological data were recorded at the same intervals before inducing anesthesia. Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of galactosamine, with death resulting from fulminant hepatic failure characterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histology showed massive hepatocellular necrosis in all seven galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans.

Animals↗

PubMed1999

Liver regeneration after partial hepatectomy is non-uniform: flow cytometric bromodeoxyuridine incorporation and cell cycle studies in a porcine model.

The rate of hepatocyte regeneration at different anatomical locations of the remnant liver after partial hepatectomy was assessed in porcine hepatocytes by bromodeoxyuridine (BrdUr) incorporation and cell cycle kinetics using flow cytometric analysis. Partial hepatectomy was performed in five Yorkshire pigs. A single intravenous injection of BrdUr at 50 mg/kg was administered on the 2nd post-operative day and the animals were sacrificed 1 h later. The remnant liver tissue was harvested and divided into four equal zones, from the liver periphery towards the surgical cut-edge. Biopsy samples were obtained from the centre of each of these zones and similarly from identical anatomical locations in two control pigs that had undergone sham surgery. Hepatocyte nucleus suspension was prepared, double labelled with anti-BrdUr and propidium iodide and analysed by a flow cytometer. The cells in S-phase was used as the parameter to measure the regeneration status. A gradient increase in S-phase from the periphery to the cut edge was observed in all five pigs that had undergone partial hepatectomy. The percentage of S-phase cells in all four zones from the hepatectomy group was significantly higher when compared with that in the controls. Liver regeneration after partial hepatectomy was not uniform but was greatest adjacent to the surgical cut edge and decreased towards the periphery of the liver.

Animals↗

PubMed1999

Epidemiology of Warthin's tumour of the parotid gland in an Asian population.

BACKGROUND: Recent studies have documented a number of changing demographic features in the occurrence of Warthin's tumour (adenolymphoma) of the parotid gland. In order to analyse its epidemiology in an Asian population, a retrospective study was performed on all parotid neoplasms (n = 289) operated on between 1988 and 1998. PATIENTS AND METHODS: A total of 209 consecutive patients were selected for study, 136 with pleomorphic adenomas (one bilateral) and 73 with Warthin's tumours (seven bilateral). Patients were analysed with regard to tumour incidence, age, sex and race. Smoking as an aetiological factor in the development of Warthin's tumour was also studied. RESULTS: Warthin's tumour formed 25 per cent of parotid tumours and its ratio to pleomorphic adenomas was 1 : 1.9. Multicentricity was found in 14 patients (19 per cent). The male : female ratio for Warthin's tumours was 4.6 : 1. The proportion of Warthin's tumours did not show any increasing trend relative to pleomorphic adenomas. The racial distribution of Warthin's tumours showed an increased incidence among Chinese and a reduced incidence among Malays and Indians. The adjusted odds ratio for sex and age favouring an association between smoking and Warthin's tumour was 39.5 (95 per cent confidence interval 10.5-149. 0; P < 0.0001). CONCLUSION: The incidence of Warthin's tumour is considerable among Asians although there is still male predominance. There is no rising incidence of Warthin's tumour; the trend parallels the declining smoking rate in the population. The lower incidence among ethnic groups with dark skin seems to suggest concomitant genetic factors other than environmental factors alone in histogenesis. Smokers have a 40-fold greater risk than non-smokers of developing a Warthin's tumour.

Adenolymphoma↗

PubMed1999

Five micro-curie urea breath test for the diagnosis of Helicobacter pylori infection: evaluation in a South-East Asian population.

BACKGROUND: Helicobacter pylori is an important pathogen responsible for significant morbidity and mortality. Its prevalence varies widely in different geographical locations and is especially high in parts of Asia. METHODS: A double-blind study was carried out to evaluate the use of the 5 microCi (185 KBq) [14C]-urea breath test ([14C]-UBT) in a South-East Asian population by validating its diagnostic accuracy against histology and the CLO test. RESULTS: The sensitivity and specificity of the [14C]-UBT was 100% when compared against the CLO test. When histology was used as the 'gold standard', the sensitivity and specificity were 100% and 97.2%, respectively. There was no overlap or indeterminate values between positive and negative results on the [14C]-UBT. CONCLUSIONS: Among South-East Asian populations where the prevalence of H. pylori infection is high, the high sensitivity of the 5 microCi [14C]-UBT makes it a very important test in the detection of H. pylori.

Adult↗

PubMed1999

The pattern of nodal recurrence following definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The pattern of nodal metastasis in previously untreated nasopharyngeal carcinoma (NPC) has been studied and reported. In order to analyse the pattern of recurrent nodal disease in previously treated NPC, a retrospective study on 68 patients who underwent radical neck dissection for regionally recurrent NPC was conducted. METHODS: Seventy-four neck dissections were performed on 68 patients who developed nodal recurrence after a mean disease-free interval of 39.2 months. None of the patients had evidence of local or systemic disease at the time of surgery. Histopathological reports of the 74 neck dissections were analysed with regard to the number of positive nodes as well as the number of involved nodal levels. RESULTS: Of the 65 neck dissection specimens with analysable data, 31 showed metastatic disease at a single nodal level with a mean number of positive nodes of 1.2, while 34 showed metastatic disease at multiple levels with a mean number of positive nodes of 6.6. Nodal recurrence occurred at level II with the greatest frequency (78.5%). Of the 31 specimens with single level nodal involvement, 21 (67.7%) occurred at level II. Isolated involvement at the other levels did occur, but was uncommon (range 3-16%). Of the 34 specimens with multiple level nodal involvement, 30 (88.2%) showed involvement at level II. Once more than one level was involved, the frequency of involvement at any given level was at least 30%. CONCLUSION: The predominant involvement at level II and the high frequencies of involvement at all levels support the use of a classical radical neck dissection in treating recurrent nodal disease in NPC.

Carcinoma↗

PubMed1999

Bile duct injuries during laparoscopic cholecystectomy: a collective experience of four teaching hospitals and results of repair.

BACKGROUND: Laparoscopic cholecystectomy has been performed in Singapore since 1990 and, up until the end of 1997, a total of 4445 procedures had been performed in the four major teaching hospitals. Although bile duct injuries were thought to have increased following the introduction of laparoscopic cholecystectomy, there have been no reviews done on the incidence of these injuries in the Singapore context. METHODS: The present retrospective review aimed to audit the rate of bile duct injuries in the four major teaching hospitals in Singapore and to document the results of management of these injuries. RESULTS: Of the 4445 procedures performed, there were 19 (0.43%) cases of bile duct injuries. These involved the common hepatic duct (n = 8), common bile duct (n = 10), and the right hepatic duct (n = 1). The underlying gall bladder pathology included non-inflamed gall bladders (n = 10), acute cholecystitis (n = 4), Mirrizzi's syndrome (n = 3) and mucocele of the gall bladder (n = 2). Transection of the duct accounted for the majority of the injuries. Eleven bile duct injuries were identified at the time of operation. These were primarily repaired over a T tube (n = 4) or by a bilio-enteric bypass (n = 7). The remainder were diagnosed at a median of 7 days (range: 1-556 days) after surgery with a presentation of jaundice or pain. These were repaired by bilio-enteric anastomosis (n = 7) and closure over a T tube (n = 1). Three patients developed strictures subsequently, two following bilio-enteric repair after delayed diagnosis and one following immediate primary repair over a T tube. One patient developed intrahepatic stones and required a left lateral segmentectomy. CONCLUSIONS: The experience of a 0.43% bile duct injury rate is comparable to the best results from most large series in the West. Inflammation at Calot's triangle is an important associated factor for injury. Early recognition and prompt repair affords good results, and hepaticojejunostomy is recommended as the repair of choice.

Adult↗

PubMed1999

The viability of liver graft for transplantation after prolonged warm ischaemia.

Maximum duration of warm ischaemia within which the liver graft is viable for transplantation remains undefined. Published data on porcine allogeneic liver transplantation (LTx) using non heart beating donors (NHBDs) are conflicting because technical details like the hepatic artery status, systemic heparinisation of donor animals and duration of rewarming were not addressed. We described a novel porcine model which simulate conditions of transplantation from NHBDs. The pigs were divided into three groups of 6 each. Groups I, II and III were subjected to 60, 90 and 120 minutes of warm ischaemia, respectively. Liver viability was assessed using four parameters: serum liver function tests (serum bilirubin and transaminase), dynamic liver function test i.e. the monoethylglycinexylidide (MEGX) formation test, morphological assessment and animal survival. All animals in groups I and II (90 minutes of warm ischaemia or less) survived but 50% of animals in group III died of massive liver failure. Given that rewarming period required in actual allogeneic LTx is about 60 minutes, the safe period for intervention in NHBDs is determined to be about 30 minutes. Allogeneic porcine LTx using NHBDs with 30 minutes of cardiac arrest were performed in 5 animals. All of them survived.

Alanine Transaminase↗

PubMed1999

Splenic angiosarcoma--an unusual cause of bleeding gastrointestinal tract.

Splenic angiosarcoma is a rare malignant vascular tumour with about 100 reported cases to date. The presentation of splenic angiosarcoma is highly variable, frequently causing diagnostic difficulty. It usually presents with splenomegaly, abdominal pain and occasionally with a microangiopathic type of anaemia. Here we report an additional case of primary angiosarcoma of the spleen presenting as a problem of bleeding from the gastrointestinal tract.

Gastrointestinal Hemorrhage↗

PubMed1999

Focused abdominal sonography for trauma (FAST).

This study aims to examine the feasibility of applying the focused ultrasound examination (FAST) in the initial assessment of the trauma patient. Its advantage over diagnostic peritoneal lavage lies in the speed in which it can be performed, its non-invasiveness and repeatability. Over the period January 1997 to July 1998, the FAST examination (Acuson 128XP/10, 3.5 MHz probe) was used to assess the presence of haemopericardium or haemoperitoneum in 38 multi-trauma patients admitted to the Singapore General Hospital. The sample comprises mainly males (82%) with a mean age of 34 years (range 17 to 77 years). The mechanism of injury was predominantly blunt (95%). Mean Injury Severity Score (ISS) was 22. Eleven patients presented in shock and 16 patients had abdominal tenderness on examination. A single surgeon did the examination, which was performed during the secondary survey phase of resuscitation. Time taken for the FAST examination averaged 2.3 +/- 1.3 minutes. The results of the examination were compared to diagnostic peritoneal lavage, CT scan, operative findings, serial examination and/or post-mortem findings. Overall sensitivity was 67% and specificity 97%. Although the FAST examination missed the small amount of free fluid seen in the CT scan of 2 patients, these patients did not have to undergo laparotomy as their abdominal examination was normal. We conclude that the FAST examination is feasible and should be part of a general surgeon's armamentarium in the initial assessment of trauma.

Abdomen↗

PubMed1998

Tamoxifen alters levels of serum insulin-like growth factors and binding proteins in postmenopausal breast cancer patients: a prospective paired cohort study.

BACKGROUND: Recent data suggest that tamoxifen may act by altering serum levels of insulin-like growth factors (IGFs) and their binding proteins (BPs). This prospective paired cohort study evaluated the influence of tamoxifen on serum levels of IGFs and BPs in postmenopausal patients with breast cancer. METHODS: Blood was collected from 32 postmenopausal patients with breast cancer before and during tamoxifen therapy for at least 6 months. All patients had undergone primary surgery. Serum concentrations of IGF-I, IGF-II, BP-1, and BP-3 were determined by immunoradiometric assays, and Western ligand blots provided a semiquantitative measurement of BP-2, BP-3, and BP-4. Statistical analysis was performed by paired Student's t-test. RESULTS: Mean serum IGF-1 level was significantly lower after tamoxifen treatment (pretreatment: 116.2 ng/mL+/-13.6 [SEM] vs. posttreatment: 77.5 ng/mL+/-7.8; P=.003). In contrast, mean IGF-II levels increased from 651.5+/-62.2 ng/mL to 812.5+/-35.1 ng/mL during treatment (P=.006). Posttreatment levels of BP-1 (92.9 ng/mL+/-7.5) were significantly higher compared to the pretreatment values (28.1 ng/mL+/-4.7; P <.001). Serum concentration of BP-3 also was elevated (pretreatment: 2228.1 ng/mL+/-145.2 vs. posttreatment: 3539.1 ng/mL+/-172.3; P <.001). Densitometric measurements showed a similar significant increase in BP-3 (P <.001) as well as BP-4 (P=.017) after hormonal therapy. Levels of BP-2 were not influenced by tamoxifen treatment. CONCLUSIONS: These significant alterations in serum concentrations of IGFs and BPs with tamoxifen therapy suggest that the IGF system is a potential mechanism by which tamoxifen exerts its growth inhibitory effect on breast carcinomas.

Aged↗

PubMed1998

Altered serum levels of insulin-like growth-factor binding proteins in breast cancer patients.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for breast cancer cell lines and has been proposed to be an important factor in breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding proteins might increase susceptibility to breast cancer. This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP). METHODS: Serum was collected from 90 patients (63 with breast cancer and 27 with benign breast disease) after an overnight fast and before surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays. In a subset of 66 patients, Western ligand blots were also performed for a semiquantitative measurement of functioning BP levels. A forward stepwise logistic regression model to adjust for other confounding variables (age, menopausal status, parity, age at menarche, use of oral contraceptives, history of breast biopsy, family history of breast cancer, hormone replacement therapy, and body-mass index) was used in the multivariate analysis. RESULTS: Serum IGF-1 levels were similar in cases and controls. However, levels of BP3 (p < 0.001), BP4 (p < 0.01), and BP1 (p < 0.05) were significantly associated with risk of breast cancer. The level of BP3 was the most significant factor predictive of breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066 ng/ml was 0.18 (95% CI, 0.05-0.55). Correspondingly, women with BP1 levels higher than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07-0.68) for breast cancer. When considering only cancer patients (n = 63), decreasing levels of BP4 (p < 0.01) and increasing levels of BP1 (p < 0.02) were significantly associated with progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5-37.4). Better grade of tumor (well and moderately differentiated) was observed in patients with higher levels of BP3 (p < 0.03). CONCLUSIONS: Distinct differences in BP profiles exist among patients with breast cancer and also among those with high-grade, hormonal receptor-negative tumors. These findings suggest that the bioavailability of IGF-1 as mediated by its binding proteins may participate in both breast carcinogenesis and selection of more aggressive breast carcinomas.

Age Factors↗