Changes of colonic mucosal microcirculation and histology in two colitis models: an experimental study using intravital microscopy and a new histological scoring system.

This study investigated capillary blood flow (CBF) and pathomorphological alterations in the mucosa of different bowel segments at different times after disease onset in rats with colitis induced by either trinitrobenzensulfonic acid (TNBS) or mitomycin-C. CBF was determined by intravital microscopy using fluorescein-labeled erythrocytes. The histological degree of inflammation was assessed by a new scoring system. Severe acute histological changes were found in the distal colon 24 hr after induction of TNBS colitis (score: 8.9+/-1.0). CBF was increased (2.9+/-0.05 vs. 2.6+/-0.04 nl/min in healthy controls). The histological alterations persisted until day 3 (8.5+/-0.9) when CBF significantly decreased (1.8+/-0.05 nl/min). After 15 days, moderate acute inflammation was still detectable histologically (5.4+/-1.3), but CBF had returned to normal values. In mitomycin-C colitis, changes developed mainly in the proximal colon: After three days, there was mild inflammation (2.8+/-1.2) with normal CBF (2.5+/-0.1 nl/min). After seven days, the inflammation had increased (4.8+/-1.1), while CBF had decreased (1.5+/-0.06 nl/min). These changes persisted for six weeks (5.3+/-0.7; 1.2+/-0.05 nl/min). These data suggest that disturbed colonic microcirculation may play an important role in the pathogenesis of inflammatory bowel disease regardless of the histopathomorphological alterations.

Treatment of colorectal liver metastases by adenoviral transfer of tissue inhibitor of metalloproteinases-2 into the liver tissue.

Metastatic disease is the leading cause of death in cancer patients. Here, we describe a novel gene therapeutic strategy for prevention of metastatic spread by providing a suitable defense mechanism for the target organ. The production of metalloproteinase (MMP) enzymes by cancer cells is critical for local invasion and for infiltration of metastatic cells into distant sites. Using a nude mouse model of colorectal liver metastasis, we have overexpressed the MMP inhibitor, tissue inhibitor of MMP-2 (TIMP-2) in the liver prior to, or following, tumor challenge by metastatic LS174T cells in vivo. Transduction of approximately 50% of hepatocytes resulted in 95% reduction in metastasis after tumor challenge compared with controls. Furthermore, TIMP-2 gene transfer into livers with preexisting metastatic spread resulted in a 77% reduction in tumor cell growth. Our data imply that MMP activity of metastatic cancer cells is required for spread and subsequent tumor growth and that enhancing antiproteolytic defense mechanisms in target organs represents a novel form of cancer gene therapy.

Primary tracheal leiomyosarcoma.

We present the clinical course of a 56-year-old female patient with a primary tracheal leiomyosarcoma. The diagnostic approach and pathological classification of this seldom described tumour remains extremely difficult. We discuss the symptoms as well as the diagnostic and therapeutic procedures, including multimodal chemotherapy with organ-preserving surgery leading to complete remission.

Effect of the somatostatin analog octreotide on gastric mucosal function and histology during 3 months of preoperative treatment in patients with acromegaly.

OBJECTIVE: To study the effects of the somatostatin analog octreotide on gastric mucosal function and histology during short-term (3 months) preoperative treatment in patients with acromegaly. DESIGN: Open design clinical study. METHODS: 10 patients were studied before treatment with octreotide (pre-tx), on day 1 of 300 microg octreotide/day (d300), after 1 week on 300 (w300), 600 (w600) or 1500 (wl500) microg octreotide/day, and after an additional 2.5 months on 1500 microg octreotide/day (M3). An 8h gastrin profile was obtained and ambulatory intragastric 23h pH-metry carried out at the indicated time points. Gastroscopy was performed at pre-tx and M3 and multiple mucosal biopsy specimens taken. RESULTS: The mean serum gastrin concentration at first declined during octreotide therapy to a nadir at w1500, then recovered despite ongoing therapy (probably in response to reduced gastric acidity) and was similar to pre-tx values at M3 (mean+/-S.E.: 87+/-26, 50+/-11 and 98+/-46ng/l for pre-tx, w1500 and M3 respectively; P<0.05, pre-tx vs w1500). Gastric acidity had also declined at d300(P<0.05, d300 vs pre-tx), then recovered (despite the increase in the octreotide dose), but declined again at M3 (mean pH (95% confidence interval): 2.4 (1.7-3.2), 3.3 (2.4-4.3), 2.6 (1.8-:3.5, n=8) and 2.9 (1.6-4.2, n=7) at pre-tx, d300, w1500 and M3 respectively). The gastrin concentration at M3, although similar to pre-tx values, remained inadequately low for the reduced gastric acidity. The reduction in gastric acidity was marked during the daytime (0900-2200 h; P<0.01, d300 vs pre-tx and P=0.028, M3 vs pre-tx). However, while the stimulated postprandial gastric acid secretion was reduced at d300 (P<0.01, d300 vs pre-tx) and at M3 (n=7; P=0.027, M3 vs pre-tx), fasting and preprandial acidity was not affected. During the night, gastric acidity was reduced from 2200 to 0300 h, but the reduction was less marked than during the daytime. Paradoxically, the physiological intermittent late nocturnal reduction in acidity ('pH peaks' (0300-0800 h)) was abolished rather than enhanced. No patient acquired new Helicobacter pylori infection. The mean gastritis scores for antrum and body (n=8, Sidney classification) increased marginally from 1.7 to 1.9 (chronicity) and from 0.7 to 0.9 (atrophy), while the activity score was slightly reduced from 1.2 to 1.0. CONCLUSIONS: Three months of preoperative octreotide treatment profoundly and persistently altered gastric mucosal function (gastrin suppression, reduced acidity), but caused only minor variations in the pre-existing gastritis scores.

Stage I primary malignant mixed müllerian tumor of the fallopian tube. Report of a case with five-year survival after minimal surgery without adjuvant treatment.

BACKGROUND: Sarcomas of the fallopian tube are rarities in gynecologic oncology, consisting of < 1% of all genital sarcomas. CASE: A 70-year-old woman with a stage I malignant mixed müllerian tumor (MMMT) (International Federation of Gynecology and Obstetrics classification of fallopian tube carcinomas) did not undergo radical surgery or adjuvant treatment because of the patient's refusal of them. The patient underwent only abdominal hysterectomy with bilateral salpingo-oophorectomy. She was discharged feeling well and without abnormal clinical findings. Sixty months after primary surgery there were no signs of recurrence. CONCLUSION: This case suggests the possibility of a good prognosis in early-stage MMMT, especially if there is no deep infiltration of the fallopian tube muscle layer or lymphatic permeation and if the peritoneal cytology is negative. The important feature of this report is the five year disease-free survival after nonradical surgery for prognostically favorable MMMT.

[Differential diagnosis of distal peripheral nerve compression syndrome of the tibial nerve. Case report of primitive neuroectodermal tumor]. / Zur Differentialdiagnose distaler peripherer Kompressionssyndrome des N. tibialis. Fallbericht eines primitiven neuroektodermalen Tumors.

Tumors of the tibial nerve are not sufficiently taken into account in the diagnosis of tarsal tunnel syndromes (TTS). They may present with atrophy of the plantar flectors and with disturbances of sensory functions, but far more commonly with pain. Diagnosis is often only achieved after 1-2 years. Taking tumors into account when examining patients presenting with TTS may lead to a more rapid diagnosis and to improvement in patients' prognoses. We present the case of a 37-year-old female in whom a primitive neuroectodermal tumor (PNET) was found to be the cause of long-standing pain in the right foot.

Nephrotoxicity of antiinfective drugs.

Antiinfective drugs may show the same mechanisms of nephrotoxicity as other drugs, and these can be subgrouped into vascular, tubulotoxic, tubulo-obstructive, and immunologic effects. While vascular effects of antiinfective drugs are rare, tubulotoxicity is a well known phenomenon, especially in connection with aminoglycosides and amphotericin B as well as cephalosporins, pentamidine, foscarnet, and cidovir. The tubulo-obstructive effect caused by precipitation of the drug and first observed after treatment with sulfonamides in the 1940s, has become a renascent problem now that high doses of sulfonamides are being given to immunocompromised patients (sulfadiazine, cotrimoxazole). Moreover, this effect has also been associated with newer antiviral drugs like acyclovir and indinavir. We describe a transplant patient who received high doses of cotrimoxazole for pneumocystis carinii pneumonia and lost transplant function mainly due to bioptically proven glomerular and tubular crystallization with tubular degeneration caused by sulfamethoxazole. Acute interstitial nephritis is the main immunologic effect of antiinfective drugs (especially rifampicin but also cephalosporins, quinolones, sulfonamides, and penicillins). Immune stimulation by cytokine treatment (mainly interferon-alpha) involves several kinds of autoimmune renal diseases like acute interstitial nephritis or glomerulonephritis as well as interstitial and vascular rejection of renal transplants.

IgA nephropathy in a patient with Behçet's syndrome--case report and review of literature.

A 25-yr-old Turkish patient who presented with oral and genital ulcers, erythema nodosum and peripheral arthritis was diagnosed as having Behçet's syndrome (BS). The patient had normal renal function, but persistent proteinuria with 3 g protein loss/day. Renal biopsy revealed glomerulonephritis (GN) with IgA deposits in the membrane. Co-occurrence of BS and IgA nephropathy (IgAN) has only been reported once to date. In contrast to the statements in most current textbooks on BS, the review of the literature presented here suggests that renal involvement is not infrequent, but serious kidney disease is a rather rare event in Behçet's disease.

Bronchiolitis obliterans organizing pneumonia and chronic graft-versus-host disease in a child after allogeneic bone marrow transplantation.

We report an 8-year-old boy who developed cough and respiratory failure 7 months after bone marrow transplantation (BMT) coinciding with the onset of chronic graft-versus-host disease (GVHD). Lung function data, imaging studies, lung biopsy and bronchoalveolar lavage were consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia. While this has been reported in association with chronic graft-versus-host disease in one adult case previously, we report the simultaneous occurrence of BOOP and chronic GVHD in a child after bone marrow transplantation for the first time.

[Cystosarcoma phylloides of the breast. A retrospective analysis of 12 cases]. / Das Cystosarcoma phylloides der Brust. Eine retrospektive Analyse von zwölf Fällen.

INTRODUCTION: Phyllodes tumours, also known as cystosarcoma phyllodes (CSP), are rare fibroepithelial tumours with an incidence of 0.3-1.0% of all breast neoplasms. CSP tends to recur locally and metastasizes haematogenously. The treatment of CSP remains controversial. The present study demonstrates the recent experiences in diagnosis, therapeutical management and clinical follow-up of this disease. MATERIALS AND METHODS: Twelve female patients who developed CSP from 1982 to 1994 were recalled for clinical assessment and examined for local recurrence or metastatic disease. All histological samples from cases of CSP were evaluated by a single pathologist who was blinded to the patients' histories. The tumours were classified according to international criteria of three types of tumour status: benign CSP, borderline type tumours and malignant tumours. RESULTS: The average age of disease was 46 years. Three patients had benign tumours. There was one borderline type of tumour and eight malignancies. Six patients with malignant CSP underwent mastectomy and axillary dissection. In two cases of malignant CSP simple mastectomy was performed. In two cases of malignancy the operation was followed by radiation therapy. The borderline type of tumour and the benign CSP were treated by tumour removal, segmental resection or subcutaneous mastectomy. In one case of benign CSP two more benign recurrencies ocurred 18 months after the initial operation. Preoperative determination of the tumour marker CEA was normal. The tumour marker CA 15-3 was only elevated in one case. The growth fraction varied from 5-40%. In 8/8 patients the oestrogen and progesterone receptors were negative. We could not find any correlation between the development of cystosarcoma phyllodes and oral contraceptives, nicotine use, diabetes mellitus, age of menarche, allergies, or family history of cancer. CONCLUSION: The clinical finding of a large, firm, non-tender, well-defined, mobile tumour with gradual growth should lead to a suspicion of a phyllodes tumour. Our results and the review of the current literature lead to the following therapeutic recommendations: 1. Benign phyllodes tumour warrants wide local excision with a 2 cm tumour-free zone. 2. Borderline malignant phyllodes tumours should be treated via simple mastectomy. 3. Axillary dissection is recommended only if nodes are palpable. 4. Adjuvant radiation is necessary, if wide local spread of the tumour is present and a resection of the lesion with a 2 cm tumour-free zone is not possible. Close follow-up is mandatory.