EGFR, HER-2 and COX-2 levels in colorectal cancer.

AIMS: Receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER-2 and cyclooxygenase-2 (COX-2) are promising molecular targets for cancer therapy and/or prevention. The aim was to evaluate EGFR, HER-2 and COX-2 mRNA and protein expression in colorectal cancer patients. METHODS AND RESULTS: EGFR, HER-2 and COX-2 protein levels were evaluated by immunohistochemistry in malignant tissue, dysplastic tissue and normal mucosa samples from 124 cases with primary colorectal carcinoma. Moreover, the corresponding mRNA levels were assessed by quantitative reverse transcriptase-polymerase chain reaction in 46 colorectal carcinomas. There was strong correlation between mRNA and protein expression for EGFR (P < 0.001), HER-2 (P < 0.004) and COX-2 (P < 0.007). EGFR levels did not correlate with stage of the disease or tumour differentiation. HER-2 and COX-2 levels increased in advanced stages and in differentiated carcinomas. Furthermore, a correlation between HER-2 and COX-2 expression was revealed in neoplastic tissue. CONCLUSIONS: EGFR as well as HER-2 and COX-2 overexpression represent important alterations that are related to the molecular pathways underpinning colorectal carcinogenesis. Further investigation is required to evaluate the impact of these markers on the management of patients with colorectal cancer.

Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy.

The current prospective study sought to trace the incidence and severity of cisplatin plus paclitaxel (DDP+P)-induced neuropathy and to determine its clinical and electrophysiological pattern. Furthermore, it was attempted to describe its evolution by following up the course of peripheral neuropathy (PN) during chemotherapy as well as 3 months after its discontinuation. Thirteen adult patients scheduled to be treated with six courses of cumulative DDP+P-based regimens for a non-myeloid malignancy participated in this study. These patients were clinically and electrophysiologically monitored at baseline, during chemotherapy and 3 months after its discontinuation. The severity of PN was summarized by means of a modified PN score. Evidence of PN was disclosed in nine of the 13 patients (69.2%). The mean PN score for patients that manifested some grade of PN was 17.3 +/- 6.1 (range 9-28). All longitudinal comparisons concerning the motor conduction velocities (MCV) variables failed to reach significance. By contrast, comparisons of the mean changes at baseline and each of the follow-up studies revealed a significant decrease in all sensory action potentials examined. The follow-up evaluation performed 3 months after the discontinuation of chemotherapy showed that the DDP+P-induced neuropathy persists and progresses over time. Our results indicate that the majority of patients treated with a DDP+P-based regimen at full dose intensities would manifest an axonal, predominately sensory PN, of mild to moderate severity, which would persist for several months after the discontinuation of chemotherapy.

Primary adrenal tuberculosis: role of computed tomography and CT-guided biopsy in diagnosis.

A case of isolated, bilateral, adrenal tuberculosis is presented. A 25-year-old male was admitted to the hospital due to lumbar pain, fever, weight loss and anorexia. Abdominal ultrasonography and computed tomography demonstrated bilateral adrenal enlargement. Laboratory investigations were remarkable for adrenal insufficiency. The Mantoux reaction was positive but there was no evidence of lung or urinary infection. CT-guided biopsy of the left adrenal gland was performed and established the diagnosis of adrenal tuberculosis.

Paranephric abscess during pregnancy: a case for a low-dose interventional CT.

A young pregnant woman hospitalized in our department with sepsis due to a paranephric abscess, and treated successfully with a nephrostomy under the guidance of low-dose CT, is presented. Based on this successful and safe treatment for the fetus, it is proposed that low-dose CT can be applied without any risk to pregnant women with special urological problems such as paranephric and splenic abscesses, dysmorphic and ectopic or horseshoe kidneys.

Can high resolution computed tomography predict lung function in patients with chronic obstructive pulmonary disease?

High-resolution computed tomography (HRCT) is a useful method for quantifying the extent of emphysema. Few reports have mentioned the relationships between HRCT scans and pulmonary function tests in chronic obstructive pulmonary disease (COPD). For diagnosis, COPD requires chronic airflow limitation and emphysema and/or chronic bronchitis. We examined 20 who were previous smokers with middle to moderate COPD. All were normocapnic with mean arterial oxygen pressure (PaO2) 77,52 +/- 16,789 mmHg. Forced spirometry, somatic plethysmography and cardiopulmonary exercise test were performed in each patient. HRCT was performed in both full inspiration and full expiration at three levels through the upper (at the aortic arch), lower (2 cm above the diaphragm), and middle lung (midpoint between upper and lower) levels. During expiration all pulmonary function parameters correlated with the HRCT grade in the middle right and left part of the lungs. The middle right part of the lung during expiration correlated statistically significant with MVV (r = -0.681, p = 0.001), forced vital capacity (FVC) (r = -0.477, p = 0.027), forced expiratory volumein 1 sec (FEV1) (r = -0.632, p = 0.002), resistance (r = 0.674, p = 0.001), residual volume (RV) (r = 0.733, p = 0.001), total lung capacity (TLC) (r = 0.696, p = 0.001), functional residual capacity (FRC) (r = 0.752, p = 0.001) and peak oxygen consumption during exercise (VO2) (r = -0.493, p = 0.023). The middle left part of the lung during expiration correlated statistically significant with MVV (r = -0.673, p = 0.001), FVC (r = -0.493, p = 0.027), FEV1 (r = -0.629, p = 0.003), resistance (r = 0.593,p = 0.005), RV (r = 0.601, p = 0.005), TLC (r = 0.546, p = 0.012), FRC (r = 0.594, p = 0.006) and peak VO2 (r = -0.525, p = 0.015). Forced expiratory volume in 1 sec (FEV1), which is a well-established measure of airflow obstruction, correlated with the HRCT grade (1) in the middle left part of the lung during inspiration (r = -0.468, p = 0.035) and during expiration (r = - 0.629, p = 0.003) (2) in the lower right lung during inspiration (r = -0.567, p = 0.007) and during expiration (r = -0.558, p = 0.008) (3) in the lower left lung during inspiration (r = -0.542, p = 0.011) and during expiration (r = -0.558, p = 0.008) (4) in the upper right lung during expiration (r = -0.469, p = 0.037) (5) in the upper left lung during expiration (r = -0.463, p = 0.035) and (6) in the middle right lung during expiration (r = -0.632, p = 0.002). According to our results HRCT was a valuable tool for evaluating the severity of COPD--especially the middle right and left part of the lungs, during expiration--and correlated well with pulmonary function tests.

Virtual endoscopy in the diagnosis of an adult double tracheal bronchi case.

We report a case of ipsilateral double tracheal bronchi supplying a tracheal lobe in a 42-year-old man, who presented with a 10-year history of recurrent respiratory infections. Diagnosis was established by chest computed tomography (CCT), virtual endoscopy and bronchoscopy. Both bronchi were surgically resected along with the right upper lobe of the lung and the associated tracheal lobe. To our knowledge, this is the first report of ipsilateral double tracheal bronchi in the adult life to be diagnosed and treated on the basis of modern radiological techniques and especially virtual endoscopy findings.

Mitomycin C and vinblastine in anthracycline-resistant metastatic breast cancer: a phase II study.

The purpose of this phase II study was to evaluate the clinical efficacy of mitomycin C and vinblastine in patients with anthracycline-resistant metastatic breast cancer. This single-center, non-randomized trial enrolled 39 patients. Eligible patients must have received at least three chemotherapy regimens with epirubicin or CAF and had treatment failure while on chemotherapy or within 6 months of completing therapy. Treatment consisted of mitomycin C at a starting dose of 8 mg/m2 on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen was repeated every 6 weeks with a 20% dose escalation of both drugs after the first cycle in the absence of grade III hematologic or other toxicity. On an intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95% confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had stable disease. The median time to disease progression was 6.21+/-4.26 months (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was 10.76+/-7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients had a significantly better survival than those with stable and progressive disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III) developed in 28.9% and 26.3% of the patients, respectively. One patient with grade III granulocytopenia developed fever and infection that required hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is an effective and well-tolerated regimen for anthracycline resistant cancer.

Serious complications of tuberculous epididymitis.

Tuberculous epididymitis is a rare entity associated with minor complications. We present two cases of tuberculous epididymitis associated with serious complications (bilateral psoas abscesses and Addison's disease with psoas abscess). A review of the literature disclosed six additional cases associated with serious complications (Addison's disease, inappropriate antidiuretic hormone secretion, central nervous system involvement) which are discussed and compared to these cases. We conclude that tuberculous epididymitis represents a grave sequela of genital tract involvement and may be associated with serious and even fatal complications.

Percutaneous treatment of large symptomatic renal cysts.

PURPOSE: To evaluate the efficacy of alcohol in combination with tetracycline for the treatment of symptomatic renal cysts. PATIENTS AND METHODS: Twenty-four patients age 45 to 77 years (mean 66 years) with a large (5-13-cm; mean 7.5-cm) symptomatic renal cyst associated with flank pain were treated by aspiration under ultrasound guidance and injection of alcohol and tetracycline. Patients were followed with ultrasonography at 1, 6, and 12 months and once a year thereafter. RESULTS: The aspirated volume ranged from 65 to 1500 mL (mean 360.5 mL). Two patients experienced mild pain during alcohol injection, but the procedure was completed successfully. One patient reported severe pain after tetracycline injection. The tetracycline was immediately aspirated, and the procedure was then aborted. The remaining patients were relieved of their symptoms after treatment, and they remained symptom free during a mean follow-up of 20 months (range 7-36 months). CONCLUSIONS: The combination of alcohol and tetracycline is safe and effective and offers a very favorable minimally invasive therapeutic alternative for the treatment of symptomatic renal cysts.

An experimental approach of the Doppler perfusion index of the liver in detecting occult hepatic metastases: histological findings related to the hemodynamic measurements in Wistar rats.

Image-directed colour Doppler sonography has been successfully introduced for the detection of hepatic haemodynamic changes in the presence of liver metastases. The aim of our study was to correlate these haemodynamic changes with the liver histology at the time of measurement. We experimentally induced liver metastases in 30 male Wistar rats by inoculating Walker 256 tumour subcutaneously. The animals were assigned into three groups of ten and were studied sonographically at 4, 7 and 15 days after tumour implantation. Another group of ten normal animals were used as controls. Portal vein and hepatic artery measurements included resistance index (PVRI, HARI) and flow volume (PVFV, HAFV). Doppler perfusion index (DPI) of the liver was calculated as the ratio of HAFV/PVFV + HAFV. Liver histology followed each Doppler measurement. Metastases were first encountered on day 4, as small groups of cells in the connective tissue of the porta hepatis and the portal triads without apparent vascular association. Distinct elevation of HAFV and DPI was recorded in comparison with the controls (p = 0.0004 and p = 0.0005, respectively). PVFV reduction was subtle. Up to day 15 there were no significant changes in the measurements. Our data suggest that HAFV and DPI can efficiently detect early liver metastases and this is in accordance with existing clinical reports. Haemodynamic changes seem to originate from the early non-vascular phase of the metastases.

Scintigraphic imaging of sarcomatous tumors with [(111)In-DTPA-phe-1]-octreotide.

The objective of the present study was to investigate the efficacy of (111)In-DTPA-octreotide (OC) for in vivo scintigraphic imaging of these relatively uncommon tumors. Thirteen patients (9 males, 4 females, mean age 59 years) with known sarcomatous lesions were studied. All patients had known lesions as demonstrated by previous investigation with other modalities, e.g. CAT, MRI. Following intravenous injection of 10 microg of OC labeled with 2.8-4.2 mCi (111)In, planar imaging was done at 6 +/- 1 and 22 +/- 2 h, respectively. Histologic verification was obtained in all cases, either from fine needle aspiration or from surgically removed tissue. Positive imaging was observed in 12/13 cases (92.3%). One scan was false-negative (7.7%). Occult lesions were demonstrated in two patients. The histologic typing and the scintigraphy results were: fibrosarcoma (1+/1), embryonic rhabdomyosarcoma (1+/1), leiomyosarcomas (3+/3), liposarcomas (2+/2), uterine sarcomas (2+/2), HIV (-) Kaposi sarcoma (1+/1), osteosarcoma (1+/1), chondrosarcoma (1-/1) and neurogenous sarcoma (1+/1). OC appears to have properties that lead to a new indication for its use. Other possible applications relate to the therapeutic use of octreotide either unlabeled or labeled with a beta-emitting radionuclide, as well as its use in radioimmunoguided surgery. Regarding the latter, our preliminary results are encouraging.

Radioimmunoscintigraphy in patients with ovarian cancer.

The targeting potential of three different monoclonal antibodies (MAbs) was assessed in patients with ovarian cancer. HMFG1, OC-125 and H17E2 labelled with 111In or 123I were evaluated prospectively for their ability to localize ovarian tumour. Forty two patients with ovarian cancer, aged 40-78 years (median = 58 years) were studied using OC-125 (n = 9), HMFG1 (n = 11) and H17E2 (n = 22). Imaging data were compared with the CT and the surgical findings. Presence of tumour was confirmed in 35/42 (83%) patients (8/9 OC-125, 10/11 HMFG1 and 17/22 H17E2) and correlated well with the conventional radiology diagnostic methods. One patient with a negative H17E2 scan and a large abdominal mass detected at laparotomy revealed a PLAP-negative tumour on immunohistochemistry. Scintigraphy revealed the presence of active disease, confirmed by laparotomy/laparoscopy in 6/8 patients considered to be in clinical remission. The sensitivity of the method was high enough and the diagnostic contribution of this approach should be further evaluated.

Non-invasive estimation of pulmonary arterial hypertension in chronic obstructive pulmonary disease.

The feasibility and reliability of the combination of several noninvasive methods using a multivariate method of analysis to predict pulmonary artery hypertension (PAH) is evaluated in 20 patients with chronic obstructive pulmonary disease. These methods comprised arterial blood gases (Pao2, Paco2), pulmonary functional parameters (FEV1), echo-Doppler parameters (tricuspid regurgitation jets, acceleration time on pulmonary valve), computed tomography measurements (transhilar distance, hilar thoracic index, and measurement of the descending branch of the right pulmonary artery to the lower lobe). A multiple stepwise regression analysis (including one Doppler parameter, two parameters of arterial blood gases, and one functional parameter) revealed a coefficient of determination (R2) equal to 0.954 for mean pulmonary artery pressure (MPAP) with a standard error of estimate (S.E.E.) of 5.25 mmHg. A stepwise regression analysis including computed tomography and radiographic parameters revealed an R2 equal to 0.970 for PAP with a S.E.E. of 4.26 mmHg. Logistical regression analysis classified correctly 80% of patients with PAH using noninvasive methods such as the diameter of the main pulmonary artery and the diameter of the left pulmonary arterial branch calculated by computed tomography. Not only the presence of PAH but also the level of MPAP can be estimated by the combination of multiple stepwise and logistical regression analyses.

Treatment of patients with severe acute necrotizing pancreatitis based on prospective evaluation.

BACKGROUND/AIMS: To examine the impact of a prospectively applied diagnostic and treatment protocol in patients with severe acute necrotizing pancreatitis. METHODOLOGY: During a 4-year period (1993-1996), 26 patients were treated for necrotizing pancreatitis, as documented by contrast-enhanced computed tomography (CE-CT). All patients were prospectively treated by medical means. Patients with persistent systemic inflammatory response syndrome underwent fine-needle aspiration for bacterial cultures. In case of positive results operative intervention was followed, while in negative results the conservative management was continued. Fine-needle aspiration was repeated every 5-7 days if systemic inflammatory response syndrome persisted or worsened. Sixty-five patients hospitalized during the preceding 11 years (1982-1992), when such a treatment was not constantly applied, served as controls. RESULTS: Infected pancreatic necrosis was demonstrated in 7 of the 26 patients (27%) and was treated by open drainage and/or post-operative lavage with a mortality rate of 14.2%. Thirteen patients in whom fine-needle aspiration was not necessary and 6 with negative cultures after fine-needle aspiration (73%) followed conservative treatment and the mortality rate was 5.2%. The total mortality rate of 7.7% was significantly lower than the mortality rate of 26.2% observed in the control group (p = 0.05). CONCLUSIONS: Recent evolution made in the management of severe necrotizing acute pancreatitis can lead to better results in the context of a strictly applied treatment protocol. Such protocols may improve mortality and serve as controls in future study.

Management of non resectable malignant esophageal stricture and fistula.

OBJECTIVE: The palliation of dysphagia caused by esophageal carcinoma and other inoperable tumours obstructing the esophagus presents a challenge for the thoracic surgeon, in particularly when associated with fistula (F). In a prospective study over the last 5 years, we have evaluated the effectiveness of different approaches and types of prostheses to solve the above problem. METHOD: Thirty three patients (mean age: 63.5 years, range 42-76, M/F:24/9) with inoperable tumours obstructing the esophagus underwent intubation and/or palliative surgery according to the following protocol: (1) Preoperative esophagography; (2) endoscopy and biopsy; (3) dilatation and insertion of prosthesis usually under general anaesthesia; and (4) re-evaluation the following day, in 30 days and as required thereafter. Prosthesis used were: Atkinson 3, Wilson-Cook (plain) 12, Wilson-Cook (cuffed) 4, Strecker (metallic self-expandable) 13. The patients were divided in three groups according to the extension of the disease: group A (n = 19) plain malignant strictures, group B (n = 5) strictures with respiratory Fs, group C (n = 9) strictures with mediastinal or pleural Fs. RESULTS: All patients of group A had successful palliation irrespectively of prosthesis used and site of obstruction. One patient required two stents. There was no death and 50% survival at 6 months was 70%. In group B, a cuffed prosthesis successfully closed two bronchoesophageal Fs, while three patients underwent retrosternal bypass surgery. There was one death on the 26th postoperative day. In group C, one Strecker, two plain Wilson-Cook and two cuffed Wilson-Cook stents, although initially succeeded, in due course, failed to block the Fs in five patients who subsequently underwent bypass surgery with one death. With four patients both leak and dysphagia were significantly improved with the use of self-expandable stents therefore, not requiring surgery. Overall, there were two deaths but no failure in palliating dysphagia. Longer survival was 20 months. Patients with fistulae had poorer prognosis as compared to those suffering from plain malignant stricture (P = 0.01). CONCLUSIONS: Plain malignant inoperable oesophageal strictures can be successfully palliated with intubation. Complicated with fistula strictures, however, are difficult to manage and have a poor prognosis. Due to the fact that bypass surgery is associated with an increased mortality, it should be kept for those with late stent failures and fistula recurrences.

Fibrin glue for sealing the needle track in fine-needle percutaneous lung biopsy using a coaxial system: Part II--Clinical study.

PURPOSE: Following percutaneous lung biopsy (PLB), we used fibrin glue as a sealant in 26 patients for the purpose of decreasing the incidence of pneumothorax. METHODS: All 26 patients (group A) had chronic obstructive pulmonary disease (COPD). The results for group A were compared with a control group of 32 patients (group B), also with COPD and in whom fibrin glue was not used. All biopsies were conducted under computed tomography (CT) using a coaxial needle system consisting of 19-gauge and 22-gauge needles. RESULTS: Pneumothorax developed in five patients (19.2%) in group A and in one instance, drainage was required (3.8%). In group B, pneumothorax developed in 13 patients (40.6%) and in six instances (18.8%) drainage was required. Comparing the use of chest-tube drainage in the two groups, a statistical significance was observed, p < 0.0025). No adverse reactions related to the fibrin glue were observed. CONCLUSION: Our results indicate that fibrin glue is a safe sealing material for lung PLB and serves to decrease the incidence and, in particular, the severity of pneumothorax, especially in high-risk patients.

Fibrin glue for sealing the needle track after percutaneous lung biopsy: Part I--Experimental study.

PURPOSE: Evaluate the effectiveness of fibrin glue for the embolic occlusion of needle tracks following percutaneous lung biopsy (PLB). METHODS: Twenty-six rabbits underwent computed tomography (CT)-guided PLB using a coaxial system consisting of 19- and 22-gauge needles. Thirteen rabbits were used as controls (group A). In 13 other rabbits (group B), fibrin glue labelled with I131 fibrinogen and contrast medium was injected into the track. Both groups were examined by CT for the presence and severity of pneumothorax (mild: less than 20%; severe: more than 20%). Group B was also examined scintigraphically and their lungs were studied histologically. RESULTS: In group A, pneumothorax developed in eight animals (61.6%) and was severe in six (46.1%) whereas in group B, pneumothorax developed in five animals (38.5%) and was severe in one (7.7%). Though the difference between the two groups in overall incidence of pneumothorax was not significant (p > 0.1), it was significantly higher (p < 0.025) for severe pneumothorax in group A. No signs of systemic embolism were observed. CONCLUSIONS: Based on this animal model, fibrin glue is a safe and useful sealant following PLB and reduces the incidence of severe pneumothorax.