CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer.

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32-2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise.

TATI (tumor associated trypsin inhibitor) and cancer antigen 125 (CA 125) in patients with early-stage endometrial cancer.

BACKGROUND: In patients with gynecologic malignancies, a 6 kD polypeptide known as the tumor-associated trypsin inhibitor (TATI) is present in high concentrations, both in the urine and the serum. This study attempts to evaluate the usefulness of pretreatment serum levels of TATI (cutoff level 21 ng ml-1) and CA 125 (cutoff levels 35 U ml-1 and 65 U ml-1) in the prediction of early endometrial cancer. PATIENTS AND METHODS: One hundred twenty-seven patients with stage I and II endometrial carcinomas, 110 healthy women and 258 women with benign pelvic pathologies were evaluated. The data obtained were correlated with the tumor stage and tumor grade. RESULTS: Overall, TATI showed a sensitivity of 31% and a specificity of 81%. The sensitivity and specificity of CA 125 > 35 U ml-1 was 25% and 86%, respectively. When both serum tumor markers were combined the sensitivity increased to 48% (CA 125 > 35 U ml-1), with a specificity of 71%. A correlation with the depth of myometrial infiltration was found for neither of the tumor markers under investigation. In addition, neither TATI nor CA 125 correlated well with tumor grade. The combination of TATI and CA 125 had a high positive predictive value (84%) when no other gynecologic pathologies were present. Furthermore, if TATI and CA 125 levels are within normal ranges and gynecological examination does not show other abnormalities besides vaginal bleeding, endometrial carcinoma appears to be very unlikely. CONCLUSION: We concluded that, while TATI and CA 125 may not be recommended as a screening method for the detection of endometrial cancer, the combination of TATI and CA 125 is a valuable additional tool for further evaluation of women with suspected uterine cancer.

Serum levels of the tumour-associated trypsin inhibitor in patients with endometriosis.

OBJECTIVE: To show that in patients with endometriosis a 6 kD polypeptide, the tumour-associated trypsin inhibitor (TATI), can occur at elevated concentrations in serum. DESIGN: In a prospective study TATI serum levels were assessed prior to surgery in 368 consecutive patients suffering from benign gynaecological diseases (e.g. pelvic pain, infertility, elective sterilisation, uterine fibroids and pelvic masses) with (n = 71) and without (n = 297) endometriosis, who underwent laparoscopy or laparotomy for diagnosis and/or treatment. RESULTS: The TATI serum levels of patients suffering from endometriosis were significantly different from those in the control group and showed a positive correlation with the stage of endometriosis. The sensitivity of TATI was 0.34 with a specificity of 0.85 for all cases of endometriosis, with an increase of sensitivity (0.67) and slight decrease of specificity (0.82), considering only a group of Stage III/IV patients. Excluding patients with benign ovarian cysts, the specificity of TATI was 0.91 and 0.85, respectively. The combination of TATI and CA125 showed an increase of sensitivity to 0.59 for all cases of endometriosis and 0.89 for patients with Stage III/IV endometriosis. CONCLUSIONS: The sensitivity of TATI as a screening method for endometriosis is too low, but considering its high specificity, TATI in combination with CA125 could provide an additional diagnostic tool in diagnosis and follow up of patients with endometriosis.

Pseudopericardial effusions in heart transplant recipients.

BACKGROUND: The objective of this study was to determine the nature of sonographically observed band-shaped, homogeneous, almost echo-free structures located ventral to the right ventricle of the heart in heart transplant recipients. METHODS: A total of 212 consecutive heart transplant recipients was evaluated sonographically. RESULTS: In 18 of the 212 patients (8.5%) band-shaped structures were detected, and these structures were proved with computed tomography or magnetic resonance imaging to be caused by mediastinal fat. CONCLUSIONS: A sonographically demonstrable, almost echo-free band-shaped structure located ventral to the heart should not be misinterpreted as localized pericardial effusion.

Influence of delayed diagnosis on established prognostic factors in endometrial cancer.

To evaluate the influence of delayed diagnosis on prognostic factors in endometrial cancer, we conducted a retrospective chart analysis based on the data of 116 postmenopausal patients with FIGO stage I-IV endometrial carcinoma. The interval from the first episode of post-menopausal vaginal bleeding to definitive, histological diagnosis (bleeding interval) was compared with tumor stage and various histomorphologic features in endometrial cancer. The mean bleeding interval was 12.7 +/- 17.8 weeks in 74 patients with FIGO stage IA, IB endometrial carcinoma and 35.2 +/- 69.3 weeks in 42 patients with stage IC-IV disease (t-test, p: 0.011). FIGO stage IA, IB disease was diagnosed in 23/26 (88%) patients with a bleeding interval <4 weeks, and in 22/34 (64%) and 29/56 (51%) patients with bleeding intervals of 4-8 weeks and >8 weeks, respectively (Chi-square 10.358, p=0.006). The correlation with histologic grade, lymph-node status, vessel invasion and histologic subtypes did not reach statistical significance. Our data confirm the clinical impression that postmenopausal vaginal bleeding is an early symptom in patients with endometrial cancer, and that advanced disease in the majority of cases might come from delayed diagnosis in women with poor compliance.

The application of fibrin glue after axillary lymphadenectomy in the surgical treatment of human breast cancer.

Experimental studies point out that a reduction of lymph flow can be obtained by the local application of fibrin glue following axillary lymphadenectomy in the surgical treatment of breast cancer. In a prospective study the influence of human fibrin glue on postoperative axillary lymph secretion and the period of drainage of the wound cavity were evaluated. In 40 patients, 5 ml of fibrin glue (Tissucol) was applied to the wound cavity by the use of a spray applicator (Tissumat) immediately after axillary dissection of the lymph nodes. For drainage of the wound area Redon suction-drains were used. The daily amount of postoperative lymph secretion was measured and drains were removed at a lymph secretion of less than 20 ml. 40 patients who underwent surgery and axillary lymphadenectomy without subsequent application of fibrin glue sourced as control group. No significant difference concerning the total amount of lymph secretion, the mean period of drainage or the incidence of lymphatic cysts was observed. In our study, the expected occlusion of the wound cavity by the application of fibrin glue after axillary lymphadenectomy did not lead to any advantage when compared with the control group.

Hystero-salpingo scintigraphy: a routine investigation in sterile women?

Based on the spontaneous migration of radioactive tracer from the posterior vaginal fornix to the ovaries and peritoneal cavity, several attempts were made to assess hystero-salpingo scintigraphy (HSS). The low acceptance rate by sterile women of routine investigation of tubal function may be due to a fear of radiation exposure and unpleasant examination procedures. Our protocol for HSS adopts a low dose of radioactive tracer (0.2-0.3 mCi), a defined mode of application (between the external and internal os of the cervical canal) and a short imaging time (60 min). From 1990 to 1992, we investigated 60 fallopian tubes in 32 sterile women by HSS, hystero-salpingography (HSG) and/or chromopertubation during laparoscopy (LPSC). The results of HSG and HSS corresponded in 15 of 49 fallopian tubes, LPSC and HSS in 9 of 24. None of the 32 patients had become pregnant naturally during the average observation period of 17 months. Two patients became pregnant after in-vitro fertilization. HSS, performed according to our protocol, causes less pain and results in a lower dose of radiation than HSG (about 50%). It is well accepted by patients and is easy to perform. As an investigation of tubal function, HSS may serve as an additional examination technique in cases of presumed tubal sterility.

[Conisation in stage Ia cervix cancer]. / Die Konisation beim Zervixkarzinom im Stadium Ia.

Between 1975 and 1988, a total of 78 patients suffering from cervical cancer stage Ia were treated by conisation based on a positive smear. According to FIGO, these 78 patients consisted of 53 (67.9%) stage Ia1 and 25 (32.1%) stage Ia2 cases. Complete removal of the tumour by conisation was achieved in 51 patients. In 23 cases (29.5%) the margin of resection was reached by a carcinoma in situ, in 4 cases (5.1%) invasive carcinoma was found. Conisation was not followed by further surgery in 10/51 patients with complete tumour removal. One patient (1/23) with incomplete removal underwent surgery elsewhere. In the other 67/78 patients following hysterectomy, the pathologist diagnosed three cases of cervical cancer, 11 cases of carcinoma in situ and 53 cases (67.9%) without pathological findings. Carcinoma in situ after hysterectomy was found in only 2 cases (4.9%) with primarily free resection margins of the conus. Among the 27 patients with carcinoma in situ or invasive carcinoma reaching the conus margin, 9 cases of carcinoma in situ and 3 invasive carcinomas were diagnosed histologically after hysterectomy and one patient underwent surgery elsewhere. In this study, the value of conisation as single therapy of cervical cancer stage Ia1 and stage Ia2 with good prognosis (depth of infiltration of < 3 mm and no invasion of blood vessels) is discussed and the importance of thorough and exact histological examination is emphasised.

The branching angles in computer-generated optimized models of arterial trees.

The structure of a complex arterial tree model is generated on the computer using the newly developed method of "constrained constructive optimization." The model tree is grown step by step, at each stage of development fulfilling invariant boundary conditions for pressures and flows. The development of structure is governed by adopting minimum volume inside the vessels as target function. The resulting model tree is analyzed regarding the relations between branching angles and segment radii. Results show good agreement with morphometric measurements on corrosion casts of human coronary arteries reported in the literature.

Exercise chronotropy in patients with normal and impaired sinus node function after cardiac transplantation.

The chronotropic response during graded, symptom limited exercise was investigated in 32 cardiac transplant recipients a mean of 49 +/- 18 days after transplantation. All patients had systematic evaluation of postoperative donor sinus node (SN) function and the cardioacceleratory response was compared according to the SN function. Twenty-one patients had normal postoperative SN studies (corrected SN recovery time < 520 msec, group I) while the SN function was impaired postoperatively in the remainder (n = 11, group II; corrected SN recovery time 4,149 +/- 6,283 msec in 5 patients, junctional escape rhythm in 6 patients). All patients had regained sinus rhythm at time of the exercise test. Patients in group II had lower basal sinus rates at the beginning of exercise (91.5 +/- 11 vs 101.4 +/- 7 beats/min, P < 0.02). This lower chronotropy was maintained over every incremental step (F rate between groups = 30, P = 0.0001, F rate vs workload = 15, P = 0.0001 by two-way ANOVA) and resulted in a significantly lower heart rate at individual peak exercise (108.3 +/- 20 vs 124.2 +/- 13 beats/min, P < 0.02). A total of 14/16 patients in group I but only 2/16 patients in group II accomplished a peak heart rate > or = 120 beats/min (P = 0.009). The workload achieved did not differ between the groups (107 +/- 29 vs 102 +/- 32 watts, P > 0.5). These data show a lower SN chronotropy during rest and at peak exercise in cardiac transplant recipients with postoperative SN deficiency and apparent normalization of SN function.

Normal AV node function in patients with sinus node dysfunction after cardiac transplantation.

Postoperative atrioventricular nodal (AVN) function was compared in 55 patients with normal and 50 patients with impaired sinus node (SN) function after cardiac transplantation (corrected SN recovery time > 520 msec or sinus arrest +/- escape rhythm). Fifty-two patients had fixed atrial pacing at cycle lengths between 600 and 430 msec, and 53 patients at cycle lengths from 600 to 300 msec between postoperative weeks 1 to 3. Relative (stimulus-R interval; AVNRRP) and effective AVN refractory period (AVNERP) were determined in 53 patients at a cycle length of 500 msec. Only one of 105 recipients had high degree AVN conduction disturbance characterized by a Wenckebach phenomenon at cycle length < 630 msec in the first postoperative week. Three patients with normal and two patients with impaired SN function had Wenckebach cycle lengths > 430 msec while the Wenckebach cycle lengths were < or = 430 msec in the remainder (p = NS). Resting PQ interval (146 +/- 18 vs 162 +/- 32; p = 0.09), Wenckebach cycle length (350 +/- 53 vs 362 +/- 50 msec), AVNRRP (356 +/- 38 vs 367 +/- 37 msec), and AVNERP (217 +/- 48 vs 244 +/- 49 msec) did not differ significantly between patients with normal and impaired SN function. AVN conduction did not deteriorate during 318 +/- 130 days of follow-up (PQ at follow-up 154 +/- 17 and 158 +/- 22 msec, patients with normal and impaired SN function, respectively). One DDD pacemaker was placed for AVN conduction disturbance while 22 pacemakers were implanted for SN deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer-optimization of vascular trees.

Arterial branchings closely fulfill several "bifurcation rules" which are deemed to optimize blood flow. The question is whether these local criteria in conjunction with a general optimization principle can explain the overall structure of an arterial tree. We present a model of an arterial vascular tree which is grown on the computer by successively adding terminal vessel segments. Each new terminal segment is connected to the optimum site within the preexisting tree, and the new bifurcation is optimized geometrically. After each step of adding and optimizing, the whole tree is rescaled to meet invariant boundary conditions of pressure and flow at each terminal site. Thus, local geometric optimization is used to induce simultaneously an optimized global structure. The comparison between the model and real coronary arterial trees shows good agreement regarding structural appearance, morphometric parameters, and pressure profiles.

Inducible atrial flutter and fibrillation after orthotopic heart transplantation.

Inducible atrial flutter (two patients) and fibrillation (two patients) were observed in a series of 35 heart transplant patients who underwent evaluation of sinus node function including premature atrial stimulation. The sinus node function was entirely normal in both patients with inducible atrial flutter. In contrast it was profoundly abnormal in the patients with inducible atrial fibrillation. Atrial fibrillation was no longer inducible as the sinus node function became borderline normal. These observations suggest extensive electrical atrial abnormality, including the sinus node, in patients with atrial fibrillation, and temporary pacing should be available when considering cardioversion in patients with atrial fibrillation early after heart transplantation. Atrial flutter, in contrast, may be inducible in the absence of any sinus node abnormality and without any evidence of rejection.

Hemodynamic and hemorheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy.

The purpose of the present study was to evaluate the specific role of hemorheologic and hemodynamic parameters for spontaneous echo contrast and thrombus formation in vivo. We therefore investigated the association between the presence of left atrial spontaneous echo contrast and thrombus formation by transesophageal echocardiography and multiple clinical, hemodynamic, and hemorheologic parameters in 70 patients with idiopathic dilated cardiomyopathy. Transesophageal echocardiography showed left atrial spontaneous echo contrast and left atrial thrombi in 33% and 19% of patients, respectively. Patients with left atrial spontaneous echo contrast had a lower cardiac index (2.1 +/- 0.9 versus 2.6 +/- 0.9 L/min/m2; p < 0.02), a lower left atrial (21 +/- 8 versus 38 +/- 10 cm/sec; p < 0.001) and left atrial appendage flow velocity (17 +/- 14 versus 39 +/- 13 cm/sec; p < 0.001), a larger left atrial diameter (53 +/- 6 versus 46 +/- 10 mm; p < 0.002), and more often presented with atrial fibrillation (62% versus 32%; p < 0.02). Plasma fibrinogen concentration (4.0 +/- 1.1 versus 3.5 +/- 0.7 gm/L; p < 0.02) and plasma viscosity (1.83 +/- 0.10 versus 1.76 +/- 0.15 mPa.sec; p < 0.05) were higher in patients with spontaneous echo contrast. Multivariate analysis revealed an association between the presence of spontaneous echo contrast and left atrial flow velocity p < 0.0001) and plasma viscosity (p < 0.01). In patients with left atrial (appendage) thrombus or a history of embolism, left atrial appendage flow velocity was lower (15.0 +/- 8.2 versus 29.6 +/- 14.5 cm/sec; p < 0.005) and spontaneous echo contrast was more frequently observed (52% versus 23%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The electrophysiology of cardiac allograft rejection: independent effects of rejection and perioperative ischemia on the sinus node recovery phenomenon after cardiac transplantation.

We characterized the effect of cardiac allograft rejection on the sinus node (SN) recovery response from overdrive suppression. A total of 54 corresponding data sets (SN recovery time [SNRT]/endomyocardial biopsy [EMB]) was available in 24 transplant recipients with normal SNRT. Data were pooled in the rejection vs the no-rejection group (n = 16 vs n = 38, respectively). During cardiac rejection (defined as a 7-day period starting 3 days prior to and lasting until 3 days after the EMB) the SNRT curves were moderately, but significantly shifted towards higher values (F = 13.4, p = .0003). All changes occurred within accepted normal limits for the SNRT. Multivariate analysis indicated independent effects of donor heart ischemic time (p = .0005) on SNRT in addition to that of rejection. After accounting for that influence of ischemic time respective F values regarding the influence of rejection on the SNRT excursions were 10.8 (ischemic time < 100 min, p = .0014) and 4.36 (ischemic time > or = 100 min, p = .039). This study shows that cardiac allograft rejection significantly delays the SN recovery response from overdrive suppression. These changes, however, are subtle and, hence, are an unlikely explanation for the often grossly abnormal postoperative SN function.

Long-term intrinsic pacemaker function in patients paced for sinus node deficiency after cardiac transplantation.

Fifteen cardiac transplant recipients requiring permanent pacing (AAI, n = 9; VVI, n = 6; rate responsive devices, n = 11) for postoperative sinus node (SN) insufficiency underwent evaluation of long-term SN function 240 to 1,461 days after transplantation. The intrinsic rhythm at the time of discharge was sinus in 7 patients; junctional escape in 6 patients; and pacemaker dependent in 2 patients. At follow-up, 5 patients had regained regular sinus rhythm, accounting for a total of 11 patients in sinus rhythm while 4 patients were in junctional bradycardia. The SN recovery time as determined by the permanent pacemaker was normal (< 1,500 msec) in only 1/8 patients in whom it was determined, although 4 of these 8 patients were temporarily overriding the pacemaker during ambulatory monitoring. Patients with pathological SN recovery times included 3 patients with late return of sinus rhythm and 4 patients who had recovered normal sinus rhythm before their discharge from the hospital. Three patients developed late symptoms despite apparent early normalization and underwent delayed pacemaker implantations on postoperative days 35, 52, and 225, respectively. We conclude that, in patients requiring pacemaker implantation after cardiac transplantation, normalization of SN function cannot be inferred from just return of sinus rhythm, regardless of whether it occurs early or late. These findings may have implications when a pacemaker exchange or explantation is being considered.

Sinus node dysfunction after orthotopic cardiac transplantation: postoperative incidence and long-term implications.

We investigated incidence, normalization rates, and clinical significance of sinus node (SN) dysfunction after cardiac transplantation. Thirty-nine of 90 patients systematically evaluated presented with impaired SN function in the postoperative period. Of these, 22 normalized their SN function during follow-up while 17 remained impaired after 3 months. The proportion normalized was higher in patients with prolonged SN recovery time (11/16, 68.8%) and those reverting from escape rhythm to sinus rhythm until discharge (5/8, 62.5%) when compared to patients in escape rhythm throughout the postoperative period (5/11, 45.5%) or pacemaker dependence (1/4, 25%). There was no reliable postoperative predictor of normalization and necessity of long-term pacing. A postoperative heart rate consistently less than 70 beats/min (irrespective of the native rhythm) was significantly related to outcome (P = 0.01), but revealed unacceptable sensitivity (61.5%) and specificity (81%). After all, both patients with severe symptoms (near syncopes and syncope), were derived from this group. These two patients, who had been discharged in sinus rhythm, had late pacemakers implanted. An additional 17 patients had early pacemaker placement, only seven of which were constantly paced during follow-up. Given the low normalization rates, patients with postoperative escape rhythm are those most likely to benefit from pacemaker therapy over the long term. Even those in, or reverting back to, sinus rhythm until discharge may experience severe symptoms, particularly in the setting of a postoperative rate consistently less than 70 beats/min since this indicates a relatively lower probability of recovery.