Pg Lindgren

Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs.

The extent of apoptosis identified by in situ DNA nick end labelling (TUNEL) on tissue samples obtained from patients with neuroendocrine tumors was correlated with the clinical outcome in patients treated with high-dose somatostatin analog (lanreotide 12 mg/day), n = 8, or other biotherapy including interferon-alpha (IFN-alpha), n = 4, low-dose somatostatin analog (octreotide or lanreotide), n = 3, or a combination of both, n = 1. Biopsies were obtained before the start of treatment and/or after 6 months and 12 months. After 6 months of treatment, 5 patients receiving high-dose somatostatin analog showed a biochemical response (decrease in different neuroendocrine tumor markers) and 4 of these showed an increase in apoptotic index (AI: percentage of apoptotic cells) by 1.94 +/- 1.71%. At 12 months, AI was also increased in patients with a biochemical response (4.22 +/- 3.93%). However, none showed a decrease in tumor size on computerized tomography (CT) and none of the patients treated with low-dose somatostatin analog or IFN-alpha showed any significant increase in AI during treatment. In an experimental model, nude mice were xenografted with the neuroendocrine cell line (BON-1). From the 2nd day of tumor implantation, they received treatment with either placebo, high-dose octreotide, IFN-alpha, or a combination of both, for 28 days. In mice receiving treatment with high-dose octreotide (300 microg/kg, t.i.d) there was a threefold increase in apoptotic cells as compared to the placebo group (p = 0.0084), while the combination group had few cells with ultra-structural changes indicating apoptosis and the IFN-alpha treated group showed no significant changes. However, tumor growth inhibition was more pronounced in the combination group (p = 0.0011). This probably denotes that tumor growth inhibition could be achieved more efficiently by blocking the cell cycle than by inducing apoptosis. We concluded that treatment with high-dose somatostatin analogs may induce apoptosis in neuroendocrine tumors, while this is not found during treatment with low-dose somatostatin analogs or IFN-alpha. We also found that an increase in AI during high-dose somatostatin analog treatment was correlated with the biochemical response, but not with the tumor size as detected by CT in patients or with the tumor mass in the experimental model.

Efficiency of percutaneous core biopsy in pancreatic tumor diagnosis

BACKGROUND Radiologic diagnosis of pancreatic tumors exhibits limited precision. The aim of this study was to investigate the outcome and complications of pancreatic core biopsy in patients with suspected pancreatic neoplasms. METHODS One hundred patients underwent ultrasonography-guided core biopsy of 1.2 mm external diameter. Medical charts were examined for biochemical and clinical signs of complications. Final diagnosis was settled by operation, autopsy, and clinical signs of the disease including survival with at least 2.3 years of follow-up. RESULTS Histopathologic biopsy evaluation showed correct discrimination between exocrine and endocrine tumors and nonneoplastic conditions in 89 patients. No false-positive cancer diagnosis was found, and guidance on nature of primary tumors was obtained for eight of eight metastases. The sensitivity was 91% for exocrine and 87% for endocrine pancreatic tumors, and negative predictive values of these diagnoses were 83% and 97%, respectively. No clinically significant complications were noted. CONCLUSIONS Core biopsy is an attractive alternative to diagnostic laparotomy in unresectable pancreatic cancer and efficiently provides diagnosis of endocrine tumors and pancreatic metastases in conjunction with rare complications. Benign biopsy findings cannot be used to exclude presence of primary or metastatic pancreatic neoplasms.

Operative tumour yield obviates preoperative pancreatic tumour localization in multiple endocrine neoplasia type 1

Abstract. The efficiency of pancreatic tumour localization was prospectively evaluated in 12 consecutive patients with multiple endocrine neoplasia type 1 (MEN1), who were subjected to extirpation of 56 islet cell neoplasms of 0.2–4 cm in diameter (mean 0.8 cm) during pancreatic resection and enucleation. Computed tomography, angiography of the coeliac trunc and superior mesenteric artery, and percutaneous ultrasound correctly localized 7–12% of the tumours and 21–37% of the 19 lesions measuring at least one centimetre in diameter. Transhepatic portal vein sampling correctly located tumour sites in the proximal or distal portions of the pancreas in four out of six patients, but demonstrated unsatisfactory specificity. Intra‐operative ultrasound and bidigital palpation of the pancreas had overall sensitivities of 86 and 45%, respectively, and eight lesions below 0.3 cm in diameter remained undetected with intraoperative ultrasound. It is concluded that diagnosis of endocrine pancreatic neoplasms is biochemical in MEN1 and that broad screening of tumour markers efficiently reveals pancreatic involvement decades before the development of a clinically overt disease. Intra‐operative ultrasound is a requisite for pancreatic endocrine surgery in MEN1, and it obviates the need for conventional pancreatic imaging unless a pre‐operative search for metastatic disease and anatomical aberrations is considered important.

Nuclear DNA Distribution in Neuroendocrine Gastroenteropancreatic Tumors Before and During Treatment

The nuclear DNA contents of tumor cells in 73 patients with endocrine gastrointestinal tumors, 19 patients with endocrine pancreatic tumors (EPT) and 54 patients with malignant carcinoid tumors were determined before and after treatment. The DNA profiles were divided into diploid and aneuploid. In untreated patients, 9 out of 10 (90%) primary EPT and all 9 primary malignant carcinoid tumors (100%) were diploid. Tumor cell imprints from liver metastases of patients with untreated EPT showed aneuploidy in 5 of 11 cases, but only in 7 out of 46 DNA records from patients with untreated carcinoid liver metastases. DNA alteration from diploid to aneuploid profiles occurred in 2 patients with endocrine pancreatic tumors who had received chemotherapy. A change from diploid to aneuploid records was also seen in 7/23 (30%) carcinoid tumors after treatment. The DNA patterns before and after treatment did not show any correlation with survival or treatment response.

Artifacts in 3D rotational angiography. an experimental study

Purpose: To investigate artifacts in three‐dimensional rotational angiography (3D‐RA) in an experimental model and to evaluate which parameters influence their distribution. Material and Methods: 3D‐RA was carried out in a circular vessel phantom filled with contrast medium. Two different rotational angulations were used: 160° causing 64 images and 180° causing 90 or 120 images. The images were transferred to one workstation for reconstruction of axial slices and then to another workstation for 3D reconstructions. The 3D reconstructions were compared with standardized threshold settings. Results: The artifacts occurred where the vessel had a longer path parallel to the rotation plane and became increasingly pronounced when the threshold level was raised. The artifacts decreased in size when rotation angle and number of projections were increased. Conclusion: The quality of the 3D reconstructions from RA was degraded by beam‐hardening and sampling artifacts. The sampling artifacts were diminished by increasing both the rotation angle and the number of projections. The distortions in the 3D reconstructions caused by beam‐hardening remain to be resolved. The threshold values also had a considerable influence on the 3D reconstructions.

Ultrasound-guided biopsies of neuroendocrine metastases : comparison of 0.9 and 1.2 mm biopsy-gun needle biopsies

Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles to evaluate the respective diagnostic accuracy of the 2 needle sizes. The influence of treatment-related fibrosis on the histopathological diagnosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. This difference, however, seems more related to needle guiding difficulties with the 0.9 mm needle than to insufficient tissue yield. When the tumour was hit with both the 0.9 and the 1.2 mm needle the tissue yield was inferior with the 0.9 mm needle in only one of 16 cases. The increased amount of fibrous tissue due to interferon treatment did not seem to negatively influence the diagnostic accuracy.

Computed tomography, ultrasonography and gamma camera scintigraphy after renal transplantation.

In routine postoperative observations on 31 transplanted kidneys, computed tomography (CT), ultrasonography (US) and gamma scintigraphy (GS) were compared with respect to diagnosis of abscess or lymphocele in the vicinity of the transplant, rejection and outflow obstruction. The results showed that US was the most reliable procedure for detecting fluid-filled cavities. In cases of graft rejection, GS was of most value. In demonstrating outflow obstruction, there was no definite difference between the three methods.