The expression of p16 (INK4a) and Ki-67 in relation to high-risk human papilloma viral load and residual disease after conization with positive margins.

The purpose of this study was to investigate the correlations between high-risk human papillomavirus (HPV) load and p16 (INK4a) or Ki-67, and to identify biomarkers that may predict residual disease after conization with positive margins. The following samples were analyzed: 49 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 12 CIN 2 conization specimens and 37 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to p16 (INK4a) and Ki-67. Hybrid Capture II testing was used to detect high-risk HPV DNA. The mean HPV loads within each of the p16 (INK4a)-staining cases were 9.5 (relative light units/positive control) RLU/PC for negative staining, 531.8 RLU/PC for 1+ staining, 140.2 RLU/PC for 2+ staining, and 545.1 RLU/PC for 3+ staining. HPV loads differed significantly according to p16 (INK4a) expression (P = 0.0021). The mean HPV loads within Ki-67 staining cases were 28.2 RLU/PC for 1+ staining, 189.6 RLU/PC for 2+ staining, and 563.3 RLU/PC for 3+ staining. HPV loads differed significantly according to Ki-67 expression (P = 0.0259). The expression of p16 (INK4a) (P = 0.0012) and Ki-67 (P = 0.0006) were significantly associated with the CIN grade. In univariate and multiple logistic regression analysis, age, parity, cytology, lesion grade in the cone, high-risk HPV load, and the expression of p16 (INK4a) and Ki-67 were not significantly associated with residual lesions after conization with positive margins (P > 0.05). In conclusion, high-risk HPV load showed significant differences according to the expression of p16 (INK4a) and Ki-67, while none of the prognostic factors were significantly associated with residual disease after conization with positive margins.

The expression of epidermal growth factor receptor, vascular endothelial growth factor, matrix metalloproteinase-2, and cyclooxygenase-2 in relation to human papilloma viral load and persistence of human papillomavirus after conization with negative margins.

The aim of this study was to investigate the correlations between human papillomavirus (HPV) load and vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2), and to identify biomarkers that may predict high-risk HPV clearance or persistence after conization with negative margins. The following samples were analyzed: 77 paraffin-embedded specimens from patients with cervical intraepithelial neoplasia (CIN), including 27 CIN 2 conization specimens and 50 CIN 3 conization specimens. Immunohistochemical analysis was performed with antibodies to VEGF, EGFR, MMP-2, and COX-2. Hybrid capture II testing was used to detect HPV DNA. VEGF expression was significantly associated with HPV load (rho = 0.27186, P = 0.0191), while COX-2 expression was significantly and inversely associated with HPV load (rho = -0.34309, P = 0.0028). In univariate analysis, HPV load (P = 0.0112) and VEGF expression (P = 0.0274) were significantly associated with high-risk HPV clearance or persistence after conization with negative margins. In multiple regression analysis, high viral load (relative light unit/positive control > 500) and positive VEGF expression were significantly associated with high-risk HPV persistence after conization with negative margins (odds ratio [OR]: 9.915, CI: 1.891-51.994; OR: 6.661, CI: 1.208-36.722, respectively). In conclusion, VEGF expression is related to HPV load, while COX-2 expression is inversely related to HPV load, and immunohistochemical analysis of VEGF expression and HPV viral load are a significant and an independent prognostic indicator of high-risk HPV persistence after conization with negative margins.

Risk factors for the progression or persistence of untreated mild dysplasia of the uterine cervix.

To identify the factors that may predict the progression or persistence of untreated mild dysplasia of the uterine cervix, we performed a retrospective review of 118 patients with histologically verified mild dysplasia who underwent colposcopic biopsies between January 1999 and December 2003. Regression to normal occurred in 70.3%, progression to moderate dysplasia or worse occurred in 11.0%, and persistence of mild dysplasia occurred in 18.7%. In regression/progression analysis, progression of untreated mild dysplasia was 34.5% (10/29) in patients with high viral loads (> or =100 relative light units/positive control [RLU/PC]) and 4.5% (3/67) in those with low viral loads (1 to <100 RLU/PC) and negative human papillomavirus (HPV) tests (P < 0.001). Women with high viral loads had a 13-fold greater chance of progression of untreated mild dysplasia than those with low viral loads and negative HPV tests (CI: 2.494-95.297; P = 0.0022). Those associated with both positive smear and positive HPV test (12/45 = 26.7%) were at a greater risk of progression of untreated mild dysplasia as compared with those with positive smear and negative HPV (0/17 = 0.0%) or those with negative smear and positive HPV test (1/18 = 5.6%). Those with high viral loads and both with positive smear and positive HPV test should be followed closely because of their increased risk of progression of untreated mild dysplasia.

Finger-assisted stretching technique for cesarean section.

OBJECTIVE: To compare the perioperative outcomes of two cesarean section methods, the finger-assisted stretching technique (FAST), based on a modified Joel-Cohen method, with the traditional technique. METHODS: A retrospective review of the records of 416 women who underwent cesarean sections at Guro Hospital, Seoul, Korea, between May 1993 and December 2001 was performed. Of the 416 women, 283 underwent cesarean sections with FAST and 133 with the traditional technique. RESULTS: Operative time was significantly shorter with FAST (15.3 vs. 42.6 min, P<.05), and FAST was associated with lower blood loss (601 vs. 928 mL, P<.05) and shorter hospital stay (3.7 vs. 6.5 days, P<.05). There were no significant differences in wound infection, voiding difficulty, and postoperative adhesions between the two methods. CONCLUSION: These results suggest that FAST may be the better technique.

Natural history of low-grade squamous intraepithelial lesion.

OBJECTIVE: To determine guidelines for management of CIN1 by evaluating its natural history. METHODS: One hundred fifty-eight patients were diagnosed with CIN1 had colposcopy follow-up with or without cytology every three months. RESULTS: Colposcopically directed biopsy confirmed progression to CIN2 or CIN3 in 17 of 158 (10.7%) patients, persistence of CIN1 in 87 (55%) patients, regression to normal in 54 (34.2%) patients during the 5-year follow-up period. The percentage of abnormal Pap tests were 39%, 64%, and 71% in the regression, persistent, and progression groups, respectively. The percentage of HPV-positive tests were 16%, 29%, 65% in regression, persistent, and progression groups, respectively. CONCLUSIONS: Of the patients who were diagnosed with CIN1 and monitored by colposcopy for 60 months, 34% had disease regression, 55% had persistent disease, and 11% had progressive disease. HPV DNA testing is more informative than the Pap test in the prediction of disease progression.

Hybrid cardiac revascularisation surgery.

Currently, 3 methods of myocardial revascularisation are available for the treatment of coronary artery disease: i) coronary artery bypass grafting (CABG); ii) percutaneous transluminal coronary angiography (PTCA), and iii) transmyocardial laser revascularisation (TMR). Until recently, these procedures were performed exclusive to one another. We report 2 cases of minimally invasive direct coronary artery bypass grafting with subsequent PTCA, and 1 case of staged PTCA followed by TMR performed at our institution. We discuss the role of hybrid procedures in the current era of treatment of ischaemic heart disease.

Detection of epidermal growth factor receptor in the serum of patients with cervical carcinoma.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of malignancies, including breast, lung, gastric, and cervical carcinoma. Its overexpression has been associated with disease progression or poor prognosis in patients with cervical carcinoma. In the present study, the levels of EGFR were determined in serum from 38 patients with cervical carcinoma [invasive or recurrent carcinoma (n = 26) and carcinoma in situ (CIS; n = 12)] and 38 healthy female controls using ELISA. The mean serum level for EGFR in patients with invasive or recurrent carcinoma (165 +/- 60 fmol/ml) was significantly elevated (P < 0.0001) compared with that of healthy controls (66 +/- 17 fmol/ml) and also higher (P = 0.015) than that of patients with CIS (126 +/- 25 fmol/ml). In addition, there was a significant difference in the mean serum levels of EGFR between patients with CIS and healthy controls (P < 0.0001). Thirty-five patients (92%) with cervical carcinoma [invasive or recurrent (n = 24) and CIS (n = 11)] had elevated serum, EGFR levels above the cutoff value of 100 fmol/ml (defined as 2 SD above the mean of the controls). In conclusion, the serum EGFR level was elevated in a significant proportion of patients with cervical carcinoma, and it demonstrated an increasing tendency according to disease progression from normal tissue through CIS to invasive cervical carcinoma. Therefore, it may have a potential usefulness as a biological marker of cervical carcinoma.

Coronary artery bypass surgery in the elderly.

This review of all patients operated on for isolated coronary artery disease from January 1985 to June 1989, was undertaken to determine the impact of advancing age on their final outcome following coronary artery bypass grafting. Three hundred and seventy patients were studied, 147 (39.7%) were less than 55 years old, 141 (38.1%) between 55 and 64 years, 55 (14.6%) between 65 and 69 years and 28 (7.6%) were aged 70 years and above. There were 10 deaths (2.7%) and 99 complications (26.8%). Using univariate analysis, advance age, the presence of some concomitant diseases, poor left ventricular function and left main stem disease were found to be significant risk factors. Patients with four or more grafts and those who underwent emergency or urgent surgery were also at greater risk of developing complications including death. Multivariate regression analysis revealed that increasing age beyond 65 years was an independent risk factor. Inspite of the above findings, it is recommended that elderly patients with uncontrollable unstable angina should not be denied surgery in view of their improved quality of life after surgery.

Permanent cardiac pacing in Malaysia. An update.

Updated data on permanent cardiac pacing in Malaysia is presented. Over the past 3 1/2 years (1976-1980), 75 patients underwent insertion of pacemakers giving an annual incidence of about 20 cases as compared with a total of 21 cases in the previous 8 years (1968-1977). Many of the features reported in an earlier paper in 1977 viz mode of presentation, age and sex distribution and indications for pacing remain unchanged. Over this period only 4 patients required lead replacement. Since concentrating mainly on the use of epicardial leads implanted via a subxiphoid approach, complications have been remarkably low. The problem of availability of pacemakers has been averted. Cost remains a major consideration when recommending one pacemaker in preference over another. The details concerning clinical features, indications for pacing, complications and other problems encountered in the management of these patients are discussed.

The efficacy of potassium-induced cardioplegia and topical hypothermia in the correction of congenital cardiac lesions.

Myocardial metabolic, structural and functional preservation were evaluated in 44 patients who underwent open heart surgery under cardiopulmonary bypass, potassium cardioplegia and topical hypothermia. The duration of cardiac arrest varied from 14 to 87 minutes. Myocardial high-energy phosphates were not only adequately preserved but actually exceeded the control values during periods of cardiac arrest. Glycogen levels were decreased moderately and one to three fold increases in lactate/pyruvate ratios were detected. Myocardial ultrastructure was well preserved. Postoperative clinical recovery of the patients was excellent. The only patient who died from a low output syndrome showed no evidence of myocardial damage. The results of this study serve to illustrate the beneficial effects of potassium cardioplegia and topical hypothermia on myocardial preservation during prolonged periods of ischaemic cardiac arrest, as used for the correction of congenital cardiac lesions.

What is an ideal cardioplegic solution?

Some form or other of chemical cardioplegia is used by most cardiac surgeons today as a means of intra-operative myocardial protection. Innumerable clinical papers supporting each of these solutions have emerged but actual experimental evidence of their efficacy is scarce. Experimental models were developed at the University Hospital, Kuala Lumpur to facilitate the testing of commonly used cardioplegic solutions in vivo and in vitro. This paper summarises the experimental and clinical data obtained as regards biochemical and electronmicroscopic changes. From the results, it can be concluded that the solution used at the University Hospital was safe and effective. An extension of the use of these experimental models could perhaps delineate the exact composition required to constitute an ideal cardioplegic solution.

Effect of potassium-induced cardioplegia in hypothermia on myocardial energy, ammonium, and intermediary metabolism in man.

Cardiac muscle biopsy specimens were obtained from 33 patients undergoing open-heart surgery under K+-induced ischemic arrest in hypothermia (cardioplegic right atrial and right ventricular muscles) or under hypothermic ischemic arrest without K+-cardioplegia (noncardioplegia right atrial muscle), and sequential patterns of changes in the myocardial metabolism were studied by standard enzymatic techniques. The concentrations of the high energy phosphates were not only adequately preserved but actually exceeded the initial values in the cardioplegic muscles during the 40-min period of the ischemic arrest. In addition, elevated ammonia levels were neutralized by these muscles, and excessive variations in the myocardial intermediary metabolism were prevented. The levels of ATP were also adequately preserved by the noncardioplegic right atrial muscle during the 12-min period of ischemic arrest. But this protection was achieved at the expense of a 20% reduction in the myocardial creatine phosphate levels and other associated severe intracellular metabolic derangements. Changes in the myocardial intermediary metabolism, at the end of 12 min of ischemic arrest and at the end of 40 min of K+-cardioplegic arrest, were almost identical. The results of these studies suggest that, in contrast to the hypothermic arrest alone, K+-cardioplegia in hypothermia offers a superior myocardial metabolic preservation over an extended period of time.

Haemangiopericytoma: problems in diagnosis and management.

Three cases of haemangiopericytoma with diverse modes of presentation are reported. The difficulties with clinical diagnosis are emphasized. There is no consensus on the best mode of treatment, and we have chosen radical surgical excision in the first instance, but have not hesitated to employ radiotherapy or chemotherapy as adjunctive treatment if the need has arisen. The clinical behaviour of this tumour is unpredictable; therefore the prognosis for life must remain uncertain.