Interobserver variations in reporting of prostatic adenocarcinoma using core biopsy specimens: a retrospective study from a tertiary referral hospital in Saudi Arabia.

In recent years, greater numbers of prostate biopsy cores are being submitted for histopathological assessment, with a concomitant increase in workload for the pathologist. This retrospective study aimed to assess the concordance and interobserver variation between histopathologists in reporting prostatic adenocarcinoma using material obtained from prostatic core biopsy specimens. A total of 810 prostatic needle core biopsy specimens obtained from 100 patients with suspected prostatic adenocarcinoma were retrieved from the archival material at King Khalid University Hospital, Riyadh, and classified independently by 3 experienced histopathologists who were blinded to the original diagnosis. There was considerable interobserver agreement between the pathologists, with unweighted kappa scores ranging from 0.69-0.85. We would encourage other hospital pathologists to review periodically the uniformity of diagnoses in an attempt to improve their practices in prostate gland pathology.

Interobserver variations in reporting of prostatic adenocarcinoma using core biopsy specimens: a retrospective study from a tertiary referral hospital in Saudi Arabia

In recent years, greater numbers of prostate biopsy cores are being submitted for histopathological assessment, with a concomitant increase in workload for the pathologist. This retrospective study aimed to assess the concordance and interobserver variation between histopathologists in reporting prostatic adenocarcinoma using material obtained from prostatic core biopsy specimens. A total of 810 prostatic needle core biopsy specimens obtained from 100 patients with suspected prostatic adenocarcinoma were retrieved from the archival material at King Khalid University Hospital, Riyadh, and classified independently by 3 experienced histopathologists who were blinded to the original diagnosis. There was considerable interobserver agreement between the pathologists, with unweighted kappa scores ranging from 0.69-0.85. We would encourage other hospital pathologists to review periodically the uniformity of diagnoses in an attempt to improve their practices in prostate gland pathology

Ces dernières années, le nombre d'échantillons de microbiopsie de la prostate soumis à une analyse histopathologique à augmenté, ainsi que la charge de travail concomitante du pathologiste. La présente étude rétrospective visait a évaluer la concordance et la variation inter-observateurs parmi les histopathologistes dans la notification de l'adénocarcinome prostatique à partir d'échantillons de microbiopsie prostatiques. Au total, 810 échantillons prostatiques de microbiopsie au trocart de 100 patients chez qui un adénocarcinome prostatique était suspecté, ont été extraits des archives de l'hôpital universitaire King Khalid à Riyad, puis classifies indépendamment par trois histopathologistes expérimentés qui ignoraient le diagnostic initial. La concordance entre les observateurs pathologistes était élevée, avec des scores kappa non pondérés compris entre 0,69 et 0,85. Nous encourageons d'autres pathologistes hospitaliers à examiner périodiquement l'uniformité des diagnostics afin d'améliorer leurs pratiques dans la pathologie de la prostate

يتم في السنوات الأخرة إرسال أعداد أكر من الخزعات اللبية للبروستات من أجل التقييم الهيستوباثولوجي، مع مايصاحب ذلك من زيادة في عبء العمل بالنسبة لاختصاصي الباثولوجيا. وقد هدفت هذه الدراسة الاستعادية إلى تقييم التوافقوالاختاف بن الفاحصن من اختصاصيي الهيستوباثولوجيا في الإباغ عن السرطانة الغدية في البروستات باستخدام مواد تمالحصول عليها من عينات خزعات لبية من البروستات. فقد تم جلب ما مجموعه 810 عينات لخزعات لبية بالإبرة من البروستاتتم الحصول عليها من 100 مريض يشتبه بإصابتهم بسرطانة غدية في البروستات، وذلك من المواد الأرشيفية في مستشفى جامعة الملكخالد بالرياض، وتم تصنيفها - بشكل مستقل - من قِبَل ثلاثة من اختصاصيي الهيستوباثولوجيا ذوي الخرة، والذين عُمِّي عليهمالتشخيص الأصي. فكان هناك اتفاق كبر بن الفاحصن من اختصاصيي الباثولوجيا، ترافَقَ مع أحراز كابا غر مرجِّحة تراوح مابن 0.69 و 0.85 . وخلص الباحثان إلى تشجيع اختصاصيي الباثولوجيا في مستشفيات أخرى عى أن يراجعوا - بشكل دوري - تَوَافُقالتشخيصات في محاولة لتحسن ممارساتهم في مجال باثولوجيا غدة البروستات

The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats.

The iron chelating activity of deferoxamine (DFO) has been exploited to obtain protection against the peroxidative damage in rat heart which was induced by the administration of an acute dose of doxorubicin (DXR, 25 mg x kg(-1), i.v.). The peroxidative lesions were evaluated both biochemically and histopathologically, 48 h after DXR administration. Abnormal biochemical changes including a marked increase in the levels of serum creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH), as well as elevated serum creatinine, blood urea nitrogen and transaminases (ALT and AST) levels were observed. Myocardial tissue from DXR treated rats showed a marked increase in malondialdehyde (MDA) production and depletion of reduced glutathione (GSH) contents. Similar results were also observed in both kidney and liver tissues. Pretreatment of rats with DFO, given i.p. 30 min prior to DXR injection, substantially reduced the peroxidative damage in the myocardium, hepatic and renal tissues and markedly lowered the serum CK-MB, LDH and the other biochemical variables. The protective effects obtained by DFO administration, however, were not complete and did not reach those of the control group. The significant protection against DXR-induced cardiomyopathy by DFO was evident from the histopathological findings observed by light microscopy. DFO at a dosing level equivalent to 10-fold of that of DXR was useful to obtain protective effects. Higher DFO dosing levels did not, however, show more improvement in the DXR-induced cardiotoxicity and at the same time exhibited hepatoxicity which was confirmed by microscopical examination. These results strongly suggest that DFO protects against acute DXR-induced cardiotoxicity in a dose-dependent manner with recognizing the presence of mild DFO-related biochemical and cytological hepatic toxicity.

Endobronchial inflammatory pseudotumor of the lung.

Inflammatory pseudotumor (also called plasma cell granuloma, histiocytoma and x-anthofibroma) is a benign, slow growing lesion which may present with cough, dyspnea, hemoptysis and unresolving pneumonia or can be discovered radiographically as a localised lesion. It has been reported in individuals up to 70 years old, but approximately two-thirds have developed in individuals under 30 years of age. The sex incidence is approximately equal. Inflammatory pseudotumors of the lung are usually peripheral lesions but may occasionally be endobronchial. We report the case of an endobronchial inflammatory pseudotumor in a 17-year-old girl who presented with unresolving right-sided pneumonia. Appropriate radiological, bronchoscopic and histopathological investigations lead to accurate pre-operative diagnosis and early complete surgical resection through a limited right main bronchus incision (bronchotomy). The patient made good postoperative recovery and an excellent prognosis is anticipated.

Chemopreventive effect of Ginkgo biloba extract against benzo(a)pyrene-induced forestomach carcinogenesis in mice: amelioration of doxorubicin cardiotoxicity.

Ginkgo biloba extract (EGb) is a natural product that possesses antioxidant and anticlastogenic properties. The current study was conducted to investigate the effect of EGb on benzo(a)pyrene (BP)-induced forestomach neoplasia, and to explore its possible beneficial effects against doxorubicin (Dox)-induced cardiotoxicity. Tumor was induced in female Swiss albino mice by oral administration of 1 mg BP, twice weekly for four weeks. EGb was given, at a daily oral dose of 150 mg kg(-1), two weeks before and during BP administration. Dox was given ip at a dose of 1.5 mg kg(-1), once weekly, for four weeks, during BP administration. EGb and Dox were given as combined or monotherapies. Results of the present investigation revealed that EGb blunted forestomach tumor multiplicity, as compared to control tumor bearing group. It also exhibited high activity to induce cytosolic glutathione S-transferase and glucose-6-phosphate dehydrogenase (G6PDH) in liver, as well as replenished hepatic glutathione that have been inhibited or depleted by tumorigenesis. Furthermore, it normalized nitric oxide (NO) serum level, without any observed alteration in neither the activity of liver microsomal NADPH-cytochrome P-450 reductase nor serum level of tumor necrosis factor-alpha (TNFalpha). Similar results have been obtained with Dox, but it failed to affect G6PDH activity, while increased serum TNFalpha and NO levels. The combined therapy did not add further to the anticarcinogenic effect of Dox, however it succeeded in ameliorating the deleterious effects of Dox on the heart; as evidenced by the reduction of cardiac lipoperoxidation, with modulation of Dox-induced pathological changes. Therefore, EGb confers a beneficial chemopreventive effect against BP-induced gastric carcinogenesis in mice, and possesses a salutary ameliorating potential on the cardiotoxic effects of Dox.

Effects of gemcitabine on cisplatin-induced nephrotoxicity in rats: schedule-dependent study.

The effects of gemcitabine (dFdC) on the lipid peroxidation and kidney histopathology in the nephrotoxicity of an antitumour drug cisplatin (CDDP) were studied in rats. dFdC was administered intraperitoneally (i.p.) at single doses of 90 mgkg(-1) while CDDP was administered i.p. at single doses of 6 mgkg(-1). Both drugs were injected either alone or sequentially in combination. In one case, CDDP preceded dFdC by 4 h and 24 h and in the other case, dFdC preceded CDDP by 4 h and 24 h. Seven days after CDDP administration, the nephrotoxicity was manifested biochemically by elevation of serum creatinine, blood urea nitrogen and an increase in the kidney weight as a percentage of total body weight. In addition, marked decreases in serum albumin and calcium levels were observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde (MDA) production level and kidney glutathione (GSH) content, which were increased and depleted, respectively. Administration of dFdC 4 h and 24 h after CDDP administration did not significantly change the indices of CDDP-induced nephrotoxicity or the kidney platinum concentration levels in comparison with those animals treated with CDDP alone. On the contrary, administration of dFdC 4 h and 24 h prior to CDDP administration significantly aggravated CDDP-induced nephrotoxicity which was manifested by severe increases in the serum creatinine and blood urea nitrogen levels as well as kidney weight as a percentage of total body weight. In addition, kidney tissue showed severe GSH depletion and increases in the MDA production and platinum concentration levels. Moreover, treatment of rats with dFdC 24 h prior to CDDP resulted in much more aggravation of CDDP-induced nephrotoxicity in comparison with those animals treated with dFdC 4 h prior to CDDP. Histopathological examination demonstrated tubular atrophy, tubular necrosis and drug-induced nuclear changes in the CDDP-treated group. However, pretreatment of rats with dFdC 4 h and 24 h prior to CDDP revealed extensive interstitial nephritis, renal tubular atrophy and tubular necrosis with 'sloughing off' of the lining cells, especially with those rats treated with dFdC 24 h prior to CDDP. These results might suggest that administration of dFdC prior to CDDP enhanced the lipid peroxidation in kidney tissue and aggravated CDDP-induced nephrotoxicity.

Fine needle aspiration cytology of mesenchymal hamartoma of the liver. A case report.

BACKGROUND: Mesenchymal hamartoma (MH) of the liver constitutes the third or fourth most common tumor of the liver in childhood and occurs most commonly in the first two years of life. MHs of the liver are seldom aspirated, and reports on the role of fine needle aspiration (FNA) in the diagnosis of MH are scarce. Clinically, cytologically and even histologically, MH can be mistaken for a number of reactive and neoplastic hepatic lesions that may occur in children under 2 years of age. CASE: A 10-month-old Pakistani female presented with a history of a right-sided, nonpainful abdominal swelling. Abdominal computed tomography showed a large, partly solid and partly cystic, heterogeneous hepatic mass. FNA cytology showed clusters of both epithelial and mesenchymal/spindle-shaped cells with pieces of loose connective tissue. A cytologic differential diagnosis of mesenchymal hepatic hamartoma and hepatoblastoma of the possible mixed mesenchymal/epithelial subtype was rendered. The histopathologic diagnosis of the resected tumor mass was benign mesenchymal hamartoma of the liver. CONCLUSION: In children under 2 years of age who present with partly solid and partly cystic hepatic masses, the possibility of MH of the liver should be considered. FNA has a role in the diagnosis of MH. The cytopathologist should be aware of the patient's age, radiologic features and cytologic appearances of this rare, benign neoplasm. Histologic examination of tru-cut biopsies and immunohistochemical stains can help to exclude other pediatric neoplasms that may show cytologic features similar to or mimicking those of MH.

Transurethral vaporization-resection of the prostate versus standard transurethral prostatectomy: comparative changes in histopathological features of the resected specimens.

OBJECTIVES: Transurethral vaporization resection of the prostate (TUVRP) is a recent modification of the standard transurethral resection of the prostate (TURP). TUVRP uses a band electrode coupled to a high electrocuting energy to achieve simultaneous resection, vaporization and coagulation of the prostate. We evaluated the histopathological resection specimens of patients treated with TUVRP to see whether the higher energy used will result in thermal artifacts that will interfere with the pathological evaluation of the prostate, and compared the results to TURP specimens. MATERIAL AND METHODS: The histopathological specimens of 50 patients that underwent TUVRP or TURP were reviewed. Artifactual pathological patterns that were identified in the specimens included: abnormal cellular orientation and spindling, artifactual cellular detachment from the underlying basement membrane, atypical cytological changes or areas of stromal coagulative necrosis. Each identified pattern was awarded 1 point. The severity of cautery artifact was graded into mild, moderate or severe according to the sum of points in each specimen. RESULTS: Mild cautery artifact changes were noted in 1 patient who underwent TURP. Moderate changes were noted in 21 patients in each TURP and TUVRP groups while severe changes were noted in 4 and 3 patients undergoing TUVRP and TURP respectively. There were no statistically significant differences between the groups with regard to the severity of the cauterization- induced changes. CONCLUSIONS: The quality of histopathological specimens produced by TUVRP is similar to the standard TURP. It seems that the higher energy use in electrovaporization technique does not result in greater thermal injury to the tissues possibly because of the cooling effect of the irrigation fluids used intraoperatively.

Protective effect of aminoguanidine, a nitric oxide synthase inhibitor, against carbon tetrachloride induced hepatotoxicity in mice.

The present study was undertaken to evaluate the effect of aminoguanidine (AG) on carbon tetrachloride (CCl4)-induced hepatotoxicity. Treatment of mice with CCl4 (20 microl/kg, i.p.) resulted in damage to centrilobular regions of the liver, increase in serum aminotransferase and rise in lipid peroxides level 24 hours after CCl4 administration. Pretreatment of mice with AG (50 mg/kg, i.p.) 30 minutes before CCl4 was found to protect mice from the CCl4-induced hepatic toxicity. This protection was evident from the significant reduction in serum aminotransferase, inhibition of lipid peroxidation and prevention of CCl4-induced hepatic necrosis revealed by histopathology. Aminoguanidine, a relatively specific inhibitor of inducible nitric oxide synthase, did not inhibit the in vitro lipid peroxidation. Taken together, these data suggest a potential role of nitric oxide as an important mediator of CCl4-induced hepatotoxicity.

Invasive mucormycosis in benign gastric ulcer.

Fungal elements are frequently noted overlying the base of chronic peptic ulcers of the stomach and it has been suggested that the fungi enhance the degree of necrosis and that these cases have protracted disease and deeper ulcers with more perforations. It has also been postulated that the number of fungal elements might be increased in the stomach of patients who are receiving potent medications such as H2-receptor antagonists to reduce gastric acidity, but there have not been adequate control studies, and the deleterious effects from the presence of the fungi in these cases have not been substantiated. We present a very rare case of invasive mucormycosis (phycomycosis) occurring in the base of a chronic gastric ulcer in a 55 years old diabetic male. This case was clinically and radiologically been mistaken for a gastric carcinoma. In addition, the ulcer was complicated by perforation and fungal septicemia with subsequent fatal outcome. The clinical, radiological and histopathological features are described together with a literature review of other reported fungal gastric ulcers.

Colorectal spirochetosis.

Colorectal spirochetosis is a very rare pathologic condition that was been described several decades ago; however, its clinical significance is debatable in causing problems to human beings. We describe the first 2 documented cases of colorectal sprirochetosis in Saudi Arabia and discuss the different views about this entity and it's clinical significance.

Morphologic patterns of male infertility in Saudi patients. A University Hospital experience.

OBJECTIVE: To determine the predominant histopathological patterns seen in the testicular biopsies taken during the investigation of male infertility and to compare the obtained histopathological findings with those seen in other similar studies. METHODS: This is a retrospective study performed on 230 testicular biopsies which were examined in the Department of Pathology at King Khalid University Hospital in Riyadh over a period of 10 years. The histopathological findings were grouped into 8 different morphologic categories. We have utilized a classification that is principally morphologic but that uses known or suspected clinical associations in the case of karyotypic abnormalities and excurrent duct obstruction. RESULTS: Of the total of 230 testicular biopsies studied, 72 cases showed normal spermatogenesis, of which 50 cases were suspected to be associated with excurrent duct obstruction. Germinal cell aplasia with and without focal spermatogenesis was found in about 90 cases. Thirty cases showed hypospermatogenesis, 25 cases showed maturation arrest and 12 cases showed end stage tubular sclerosis with interstitial fibrosis. Only one case was noted to show features associated with karyotypic abnormalities. CONCLUSIONS: A higher percentage of germinal cell aplasia was noted in this study when compared with other similar investigations including one previous local study. Possible causes of these discrepancies may be related to several factors including environmental effects. The design of the different studies and the criteria used for patient selection or both could also explain the cause of these observed differences.

Morphologic patterns of male infertility in Saudi patients.

OBJECTIVE: To determine the predominant histopathological patterns seen in the testicular biopsies taken during the investigation of male infertility and to compare the obtained histopathological findings with those seen in other similar studies. METHODS: This is a retrospective study performed on 230 testicular biopsies which were examined in the Department of Pathology at King Khalid University Hospital in Riyadh over a period of 10 years. The histopathological findings were grouped into 8 different morphologic categories. We have utilized a classification that is principally morphologic but that uses known or suspected clinical associations in the case of karyotypic abnormalities and excurrent duct obstruction. RESULTS: Of the total of 230 testicular biopsies studied, 72 cases showed normal spermatogenesis, of which 50 cases were suspected to be associated with excurrent duct obstruction. Germinal cell aplasia with and without focal spermatogenesis was found in about 90 cases. Thirty cases showed hypospermatogenesis, 25 cases showed maturation arrest and 12 cases showed end stage tubular sclerosis with interstitial fibrosis. Only one case was noted to show features associated with karyotypic abnormalities. CONCLUSION: A higher percentage of germinal cell aplasia was noted in this study when compared with other similar investigations including one previous local study. Possible causes of these discrepancies may be related to several factors including environmental effects. The design of the different studies and the criteria used for patient selection or both could also explain the cause of these observed differences.

Hepatic granulomas in an arab population: a retrospective study from a teaching hospital in Riyadh.

This is a retrospective analysis of the medical records of 116 patients who presented to the gastroenterology division, department of medicine at King Khalid University Hospital (KKUH) in Riyadh, Kingdom of Saudi Arabia and subsequently had a histopathologic diagnosis of hepatic granulomas. Infections contributed to 56% and were represented mainly by schistosomiasis and to a lesser extent by tuberculosis, brucellosis and hydatid disease. Lymphomas (8%) were the major representative of noninfectious causes. The etiology of 25% of granulomas remained undetermined. Weight loss, fever, anorexia and abdominal pain were the most frequent presenting symptoms in 53, 45, 43 and 42% of patients, respectively. Ten percent of the patients were asymptomatic. Hepatomegaly and splenomegaly were the predominant physical findings in 55% and 43% of patients respectively. Hepatic granulomas in this study are mainly caused by infections. Schistosomiasis, tuberculosis and brucellosis represented the most common etiologic factors.

Inhibition of benzo(a)pyrene-induced forestomach carcinogenesis in mice by thymoquinone.

The modulating effect of thymoquinone (TQ) on benzo(a)pyrene (BP)-induced forestomach tumours was investigated in female Swiss albino mice, receiving oral administration of BP at a dose of 1 mg twice weekly for 4 weeks. Administration of 0.01% of TQ in drinking water 1 week before, during and after BP treatment until the end of the experiment resulted in significant suppression of BP-induced tumourigenesis when compared with the group receiving BP alone. TQ inhibited both BP-induced forestomach tumour incidence and multiplicity by 70% and 67%, respectively. Lipid peroxide accumulation and decreased glutathione (GSH) content and glutathione-S-transferase (GST) and DT diaphorase activities were observed in the liver of BP-treated tumour-bearing mice. TQ alone showed a significant induction in the enzyme activities of hepatic GST and DT diaphorase. Mice treated with TQ along with BP showed almost normal hepatic lipid peroxides and GSH levels, and normal enzyme activities compared to the control group. The present data may indicate the potential of TQ, the main constituent of the volatile oil of Nigella sativa seed, as a powerful chemopreventive agent against BP-induced forestomach tumours in mice. The possible modes of action of TQ may be through its antioxidant and anti-inflammatory activities, coupled with enhancement of detoxification processes.

The protective action of thymol against carbon tetrachloride hepatotoxicity in mice.

The protective action of thymol (paramethyl-isopropyl-phenol) was investigated against carbon tetrachloride (CCl(4))-induced hepatotoxicity in male Swiss albino mice. The CCl(4)at a dose of 20 microl kg(-1)produced damage to liver cells and was followed by the significant increase (P<0.001) in serum alanine aminotransferase (ALT) activity and hepatic lipid peroxidation after 24 h. The hepatocellular necrosis was further confirmed by histopathological examination of liver section. Oral administration of thymol in a single dose (300 mg kg(-1)) resulted in significant (P<0.05) amelioration of CCl(4)-induced hepatotoxicity. Thymol also inhibited lipid peroxidation induced by CCl(4)in vivo. The protection offered by thymol was also evident from histopathology photomicrograph. In a separate in vitro assay, thymol inhibited the non-enzymatic lipid peroxidation of normal mice liver homogenate induced by Fe(3+)-ascorbate. The present study suggests that thymol protects the liver against CCl(4)-induced toxicity and the protection may be mediated through its ability to inhibit lipid peroxidation. However, other interactions between thymol and CCl(4)remains to be elucidated. 1999 Academic Press.

Protective effect of aminoguanidine against cardiovascular toxicity of chronic doxorubicin treatment in rats.

The cardiotoxicity-induced by chronic treatment of doxorubicin have recently be attributed to free radical formation and/or release of nitric oxide. In the present study, an already established rat model of doxorubicin -induced cardiotoxicity was used. Doxorubicin in a total cumulative dose of 15 mgkg(-1) I.P. given in six equal injections over two week period was administered. After three weeks of doxorubicin administration, the blood pressure, serum lactate dehydrogenase, lipid peroxides, asites fluid and mortality rate were significantly increased. Doxorubicin-induced cardiotoxicity was further confirmed by examining the histopathology of heart sections. Myocardial fibres necrosis with prominent acute inflammatory cells were observed in rats hearts treated with doxorubicin. Aminoguanidine, an inhibitor of nitric oxide synthase, 100 mgkg(-1) injected every other day for two week was given concurrently with doxorubicin. Aminoguanidine given concurrently with doxorubicin return blood pressure, lactate dehydrogenase and lipid peroxides to normal control values. Furthermore, aminoguanidine reduces the mortality rate, ascites fluid formation- induced by doxorubicin and improved the histopathology of rats hearts treated with doxorubicin. In conclusion, inhibition of nitric oxide formation may be beneficial in protecting rat hearts against doxorubicin- induced cardiotoxicity.

Primary synovial sarcoma of the penis--case report and literature review.

Urogenital synovial sarcoma is an exceedingly rare lesion that can be clinically confused with chronic inflammatory masses and granulomas, squamous cell carcinoma, malignant melanoma or metastatic tumours. We present a case of primary synovial sarcoma of the penis in a 29-year-old Egyptian male. This case report is, to the best of our knowledge, the first report in the medical literature. A review of other penile sarcomas is included with a description and discussion of their pathological and clinical manifestations.