Piglet model for studying esophageal regrowth after resection and interposition of a silicone stented small intestinal submucosa tube.

PURPOSE: To investigate the use and subsequent healing of a silicone stented small intestinal submucosa (SIS) tube as a full-circumference replacement following surgical resection of the esophagus in piglets. MATERIAL AND METHODS: Three centimeters of the intrathoracic esophagus was replaced with a silicone stented SIS tube (Cook Medical) in 6 growing piglets. The esophageal stent was retained for 4 weeks. Esophageal dilations were performed, if needed, after stent removal. RESULTS: The piglets were sacrificed 1-17 weeks after surgery. Recurrent dilations were needed after stent removal. Histology showed that the gap between the resection margins was filled with new loose connective tissue consisting of fibroblasts and few inflammatory cells. In this tissue, intense angiogenesis was seen at the early time points, which then gave way to the proliferation of immature-looking smooth-muscle-like cells in the submucosa, which appeared to stem from the pericytes of the ingrowing capillaries. CONCLUSIONS: Through using a stented SIS tube as a circumferential esophageal replacement in a piglet model, this study suggests that pericytes from ingrowing capillaries may play a role in the remodeling of the SIS mesh. It remains to be seen if this process gives a favorable end result because stricture formation after stent removal remains a problem.

Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment.

PURPOSE: Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed. PATIENTS AND METHODS: We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality. RESULTS: For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter. CONCLUSION: Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.

The influence of a serine protease inhibitor, nafamostat mesilate, on plasma coagulation, and platelet activation during experimental Extracorporeal Life Support (ECLS).

INTRODUCTION: During extracorporeal circulation the contact between blood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to assess the effect of a serine protease inhibitor--Nafamostat mesilate (FUT-175)--on coagulation and on platelets during experimental extracorporeal circulation. METHODS: Two identical Extra Corporeal Life Support (ECLS) circuits were primed with fresh, heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrations were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h + 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as an initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusion, and analysed for platelet count, plasma betathromboglobulin (beta-TG), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, thrombin/antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1). RESULTS: Significantly higher platelet membrane GPIb expression and lower plasma beta-thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activation. Also, a reduced activation of the coagulation system was observed in the "FUT-circuits", as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated. CONCLUSION: FUT-175 reduces the activation of platelets and plasma coagulation in an in vitro ECLS model.

Can we predict the long-term function of the subclavian flap angioplasty?

Neonatal operations have improved the prognosis for newborn children with aortic coarctation. The 30-day mortality of 123 neonates with isolated coarctation of the aorta collected from nine series was found to be 0.8%. The subclavian flap angioplasty was the most frequently used surgical procedure in this collected series. This technique is relatively new, however, and many questions have yet to be answered. In this study we have done subclavian flap repair in newborn pigs and followed them up to adult ages. The pigs were killed 28 or 44 weeks postoperatively, and the aortas were reexamined. All flaps had grown symmetrically in width and length and parallel to the growth of the descending thoracic aorta. The flaps were macroscopically intact. Signs of degenerative processes were not found. The wall thickness of the subclavian flap increased by growth of the individual fibroelastic lamellar units in the tunica media. This adaptation to the increased wall stress occurred early in life. The wall strength of the flap also increased by thickening of the intimal layer. We conclude that the subclavian flap is well suited to function as a part of the aorta in adult life.

Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion.

BACKGROUND: Hemorrhage is a major complication experienced in 10% to 35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS-induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of nitric oxide on the ECLS-induced platelet consumption and activation. METHODS: Two identical in vitro ECLS circuits were primed with fresh, heparin-treated human blood and circulated for 24 hours. Nitric oxide (15, 40, or 77 ppm) was added to one of the oxygenators in each pair. Eight paired experiments were performed. Platelet count, plasma beta-thromboglobulin, platelet serotonin content, plasma nitrate, plasma cyclic guanosine monophosphate, and platelet membrane glycoprotein Ib were assayed before the start and at 0.5, 1, 3, 12, and 24 hours of perfusion. RESULTS: Plasma nitrate and plasma cyclic guanosine monophosphate levels were significantly higher in the nitric oxide circuits than in the control circuits (p < 0.01). Higher platelet counts (p < 0.01) and lower beta-thromboglobulin levels (p < 0.01) were observed in the nitric oxide circuits compared with the control circuits. However, no significant differences in platelet serotonin content or platelet membrane glycoprotein Ib density were noted between the circuits. CONCLUSIONS: Nitric oxide probably reduces platelet consumption and platelet activation during ECLS.

Cytogenetic findings in 111 ovarian cancer patients: therapy-related chromosome aberrations and heterochromatic variants.

The chromosomes of 111 ovarian cancer patients were studied in G- and C-banded slides from peripheral blood lymphocyte (PBL) cultures for chromosome damage caused by chemotherapy and radiotherapy and for asymmetry of the constitutive heterochromatin of chromosomes 1, 9, and 16. We also monitored the survival of these patients to determine whether any secondary neoplasia induced by the therapy and report the findings of our investigations. Melphalan (MEL) was the only drug used in single-drug chemotherapy. The incidence of chromosome abnormalities in melphalan-treated cells (25%) was higher than in the control group (17%). The incidence of structural changes was also higher (10.5%) in the MEL-treated group than in controls (6%). After treatments with combinations of drugs, the incidence of structural changes remained at the same level (11%). In the patients receiving combined treatment with MEL and radiation, the rate of structural changes increased dramatically (24%). The overall rate of chromosome aberrations in this group was also higher (50%). Combination of two or more drugs and radiation produced only 14% structural chromosome changes. The overall rate of chromosome aberrations was also low (20%) in this group. Of 111 patients studied, only 33 were alive 6 years after initiation of the study. Of the surviving patients, eight had rearranged chromosomes in the first analysis. After 5 years, new blood samples were collected from these patients and chromosome analyses showed abnormal karyotypes in all eight patients. All chromosome abnormalities in the second analysis were completely unrelated to those in the first analysis, however. Whether the chromosome changes in the second analysis were due to therapy or to other unknown factors could not be determined. Data on C-banding and the distribution of inversions indicated that 91% of the patients had C-band heteromorphisms of chromosomes 1, 91% had heteromorphisms of chromosome 9, and 69% had heteromorphisms of chromosome 16. Furthermore, inversions were observed in chromosome 1 (41% of patients), chromosome 9 (28% of patients), and chromosome 16 (5% of patients).

Endometrial carcinoma; ovarian dysfunction--a risk factor in young women.

From a referral area comprising one-fifth of the Swedish female population we investigated possible risk factors for endometrial cancer (EC) in different age groups. Seventy-seven women aged 31-45 with EC were collected retrospectively, and 99 women aged 46-65 were consecutively collected. Both groups were compared to referents randomly selected from a population based study from the city of Göteborg. The referents consisted of 1746 women aged 39-65 years. All cases were studied by hospital record and 82% of the women aged 31-45 years and 85% of those aged 46-65 years were studied by an extensive questionnaire. Among the referents 1409 (81%) were investigated by the above-mentioned questionnaire. Hirsutism, increased body mass index (BMI) and hypertension were significantly more common in both EC groups compared to referents. Nulliparity and infertility were significantly more common in the young EC group. Referents used combined oral contraceptives significantly more often than women developing EC. There was, however, no difference between the groups with respect to the duration of medication with combined oral contraceptives. There was a significant negative correlation between cigarette smoking and the development of EC. These findings indicate that untreated ovarian dysfunction like that present in polycystic ovarian disease (PCO) with unopposed estrogen action on the endometrium is associated with EC in younger women, and that smoking may protect against EC by an 'anti-estrogenic' effect.

Transventricular dilation for critical aortic stenosis in neonates.

Critical aortic stenosis (CAOS) is not compatible with life when the ductus arteriosus closes. We have treated 11 consecutive cases with isolated CAOS. Symptom presentation was in the early neonatal period and diagnosis was made noninvasively at a mean age of 4 days. All were operated on with transventricular dilation (TVD) at a mean age of 4.7 days. There was no early mortality. There were two late deaths due to fibroelastosis. Both had the smallest aortic anulus diameter (5 mm). Two other patients had aortic root replacement, one at the age of 6.5 weeks due to intractable heart failure, and the other at the age of 3 months due to increasing gradient. In these two cases elective surgery was made possible by a successful TVD in the early neonatal period. TVD in this material was not associated with any early mortality, which makes this procedure a good alternative in the treatment of CAOS.

The effect of cardiopulmonary bypass on blood cell filterability in children undergoing cardiac surgery.

BACKGROUND: The extended use of cardiopulmonary bypass (CPB) in cardiac surgery is limited because of damage to blood which in adults has been assessed by alterations in blood cell rheology. Blood trauma assessment in children is difficult because of the restrictions in sample volume and frequency but needs to be established from time to time in order to study the tolerance to new surgical and extracorporeal techniques. MATERIALS AND METHODS: Fourteen pediatric patients undergoing cardiac surgery with CPB for congenital heart disease corrections were studied. Whole blood, red blood cell and white blood cell rheology (filterability) were monitored before, during and after CPB using the St. George filtrometer that used small amounts of blood. RESULTS: The results showed that all the rheologic parameters were altered during the blood trauma of CPB and were outside the reference values before, during and after CPB. CONCLUSIONS: This suggested that blood cell rheologic disturbances did not recover soon after CPB and this may be of interest in long term follow-up to understand responses and recovery patterns to disease and interventions associated with pediatric heart surgery using CPB.

Tumor marker CA 125 level and ovarian volume at different cycle day periods and in postmenopause.

The value of using CA 125 for screening of ovarian carcinoma is still under debate. It is important to be aware of possible physiological variation in serum levels of this antigen. This study aimed at finding out whether there were any differences in CA 125 levels in serum at different cycle day periods of fertile women and postmenopausal women. In 106 women, CA 125 and ovarian volume were measured at different cycle day periods and in postmenopausal women. The highest levels were found in cycle day (CD) 1-9, i.e. 22 units/ml and the lowest in postmenopausal women i.e. 6.7 units/ml. No correlation could be found between the CA 125 levels and ovarian volume as measured by vaginal sonography.

Blood platelet activation and membrane glycoprotein changes during extracorporeal life support (ECLS). In vitro studies.

The aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeal system. Two different perfusion pumps were compared, a roller pump (Polystan) and a centrifugal pump (Biomedicus). A continuous increase in glycoprotein (GP)1b-negative platelets was observed in both circuits. A marked increase of plasma beta-thromboglobulin thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. The plasma concentration of glycocalicin increased in parallel with a reduced platelet surface expression of GP1b, suggesting that the loss of GP1b is caused by proteolysis rather than by a downregulation of this receptor protein. It is concluded that ECLS results in a pronounced platelet degranulation and causes changes of important membrane receptors which might explain some of the bleeding problems observed in patients treated with ECLS. No significant difference was noted between the roller pump and the centrifugal pump. Trial of strategies, e.g., protease inhibitors and nitric oxide to revert this untoward effect of ECLS are highly warranted.

Dysphagia in adults operated on for esophageal atresia--use of a symptom score to evaluate correlated factors.

INTRODUCTION: Dysphagia is not unusual following repair of esophageal atresia (EA). The lack of a uniform definition has led to a variance when it comes to reporting the prevalence of dysphagia among patients operated on for EA. Our aim is to estimate the occurrence and degree of dysphagia, using a numerical score with its statistical versatility independent of a specific definition. The results are used to find early risk factors of dysphagia within this patient group. The results are also used to see whether we can find a correlation between dysphagia and symptoms of gastroesophageal reflux (GER) and quality of life (QoL). METHODS: 79 consecutive survivors operated on for EA in Gothenburg between 1968 and 1983 were located. Hospital charts were reviewed and patients received questionnaires on dysphagia, symptoms of GER and QoL. Dysphagia was measured by a numerical score, symptoms of GER were extracted using a predetermined questionnaire (GerdQ), and QoL was determined using the generic questionnaire SF-36. RESULTS: 73 patients (92.4%) returned the questionnaires. In order to make the study group as homogeneous as possible with regard to the malformation we choose to study the 63 patients representing the vast majority: those with Gross type C. 36 patients (57%) had symptoms of dysphagia to varying degrees. We did not find any aggravating factors in their hospital charts nor did we find any correlation to the most recent demographics. There was a significant difference in dysphagia scores when we compared Gross type C to the often more complex type A (p<0.05). We did not find any correlation to heartburn but a strong correlation to regurgitation with an OR of 2.8 (95% CI: 1.2-6.6). The QoL was good for this patient group, and we did not find any correlation between QoL and the dysphagia score. CONCLUSIONS: The dysphagia score provides easy-to-use results when it comes to evaluating the potential influence of dysphagia. Dysphagia is common within this patient group. Patients operated on for EA Gross type A seem to do worse when it comes to dysphagia. Regurgitation is associated with dysphagia, which could imply that GER is an aggravating factor. Further studies to support this finding will show whether there is a correlation between the dysphagia score and the results of 24-h pH-monitoring. If so, this could mean that treating GER might decrease dysphagia, at least in this patient group.

Prognostic value of steroid hormone receptors for 5-year survival in stage II endometrial cancer.

BACKGROUND AND METHODS: In a prospective study, the 5-year survival of 57 patients with Stage II endometrial cancer was correlated to the estrogen (ER) and progesterone (PR) receptor concentrations using the dextran-coated charcoal (DCC) technique. The cutoff level was 3 fmol/mg of protein for ER and 6 fmol/mg of protein for PR. RESULTS: An histopathologic examination of the tumor tissue samples before treatment demonstrated that 16% of the cases (9 patients) were well-differentiated (Grade 1), 45% (26 patients) moderately differentiated (Grade 2), and 39% (22 patients) poorly differentiated (Grade 3). Only 3 were ER negative, whereas 19 were PR negative. The mean concentrations for ER and PR were 106 and 162 fmol/mg of protein, respectively. All patients received standard treatment, including preoperative irradiation. The total 5-year survival rate was 82% (47 of 57 patients). Deep myometrial invasion was important in Grade 3, but not in Grades 1 and 2; in these two grades, all five patients with deep infiltration survived. There was a correlation between receptor concentration and grade, with a significant difference between Grades 1 and 2 versus Grade 3. All patients who were ER negative survived, as did all patients who were PR negative in Grades 1 and 2. Of the patients with Grade 3 disease who died, four of six (67%) were PR negative. Of the patients with Grade 3 disease who survived, 10 of 16 (63%) were PR negative. CONCLUSIONS: Patients who survived for 5 years did not have significantly different ER and PR concentrations than those who died. The mean ER and PR concentrations in patients who survived were 99 and 159 fmol/mg of protein, respectively, compared with 108 and 178 fmol/mg of protein, respectively, for those who died.

Primary adenocarcinoma of the uterine cervix. A clinical study.

In a retrospective clinical study, 67 matched cases of primary adenocarcinoma and squamous cell carcinoma of the cervix were compared. The mean age, weight, and menopausal age of women with adenocarcinoma of the cervix were in excess of the corresponding figures for squamous cell carcinoma. There was a significantly (P less than 0.05) larger number of diabetics and nulliparous women amongst the patients with adenocarcinoma of the cervix. Blood group A was significantly (P less than 0.05) more frequent in patients with cervix cancer. Treatment choice was independent of the tumors histological type. The five-year survival rates for adenocarcinoma of the cervix were 83.3% (Stage IB), 60.0% (Stage IIA), and 45.5% (Stage IIB). The corresponding five-year survival rates for squamous cell carcinoma were 90.0%, 73.3%, and 40.9%. There were indications that adenocarcinoma of the cervix was less radiosensitive than squamous cell carcinoma. Estrogen substitution following treatment of adenocarcinoma of the cervix did not adversely affect the outcome.

Resection+carotid flap plasty. A new surgical technique for newborn children with coarctation of the aorta and critical hypoplasia of the aortic arch.

Coarctation of the aorta with critical hypoplasia of the aortic arch is a ductus dependent malformation-complex often combined with severe intracardiac malformations with a common denominator: there is a predominance of the pulmonary circulation and a flow restriction through the ascending aorta. Coarctation of the aorta with critical hypoplasia of the aortic arch may be looked upon as a malformation bordering on hypoplastic left heart syndrome. The degree of aortic arch hypoplasia seems to mirror the severity of the intracardiac malformation. The first objective in reconstructing these hearts is to create an unobstructed flow through the aortic arch. Resection of the coarcted segment combined with carotid flap plasty is a surgical alternative which fulfils this objective. We have used the technique in premature-born and severely ill neonates where one-step total correction was considered contraindicated. Thirteen neonates were operated upon, there were no cerebral consequences referable to the carotid artery ligation and no recoarctations.

Spinal cord injury after subclavian flap aortoplasty. An experimental study in piglets.

Paraplegia is a rare but much feared complication of corrective surgery for coarctation of the aorta. The problem was studied in 31 newborn pigs submitted to subclavian flap aortoplasty. The aortic cross-clamping time ranged from 9-25 min. Twenty-three piglets with clamping times 9-18 min were neurologically intact, whereas eight with aortic clamping for 18-25 min became paraplegic. The clinical implications for newborn children with symptomatic aortic coarctation are discussed with regard to these experimental findings.

Endometrial cancer stage II: 190 cases with different preoperative irradiation.

In a retrospective study, the 5-year survival in 190 patients with endometrial adenocarcinoma stage II was evaluated in relation to different preoperative radiotherapy techniques. In one group, group A, 111 patients received low dose rate radium to the cervix region and in a second group, group B, 79 patients received high dose rate 60Co treatment using the after-loading technique. Both groups received intracavitary radium using the standard Heyman technique. There were no statistically significant differences in survival, after correction for intercurrent disease, between the two groups. The overall 5-year survival corrected by intercurrent disease was 79% for group A and 80% for group B. The histological grade survival in group A was 94% in grade 1, 83% in grade 2, and 60% in grade 3 and in group B, 100% in grade 1, 80% in grade 2, and 59% in grade 3. A correlation was found between histological grade, uterine sound, and survival in both groups. Only in grade 3 was deep infiltration found to have a worse prognosis. No metastasis in regional lymph nodes was found, but distant metastasis was a problem in grade 3. A significant overrepresentation of nullipara could be found among the 190 patients and was pronounced for grade 1. Our results indicate that vaginal radium application can be replaced by high dose rate 60Co in the treatment of stage II endometrial adenocarcinoma, with no decrease in the 5-year survival rate.

Prognostic value of DNA ploidy and S-phase fraction in endometrial cancer stage I and II: a prospective 5-year survival study.

Knowledge of reliable prognostic factors is essential in cancer treatment. Especially when intensified treatment is to be considered to improve the overall result, it is desirable to identify well-defined high-risk groups. In a prospective study DNA ploidy and S-phase fraction were measured in 88 patients with endometrial cancer stage I and II. Fresh tumor samples were analyzed using flow cytometry prior to treatment. Diploid tumors represented 84% of the cases, and aneuploid represented 16%. The mean S-phase fraction in diploid tumors was 10%, as compared with 22% in aneuploid tumors. The follow-up time was 5 years in all cases. The survival rate for patients with diploid tumors was 92% and for aneuploid tumors 36%. In the surviving patients, the mean S-phase fraction was 10.4%, a significant difference from 19.9% in the nonsurviving patients (P < 0.001). The highest mortality was found when aneuploidy was combined with an S-phase fraction over 20%, with only 11% survival for 5 years. In diploid tumors with an S-phase fraction below 20%, the survival rate was 92%. In a stepwise regression analysis, S-phase fraction was found to be of the most important prognostic value, followed by myometrial invasion and stage of the tumor and ploidy. Grade was not found to be of any important significance.