A historical overview of laryngeal carcinoma and the first total laryngectomies.

Laryngeal cancer was a well known entity since antiquity and its treatment evolved through several phases. The lack of knowledge in anatomy and pathology as well as the absence of anesthesia and proper instrumentation made the treatment almost impossible. Ancient physicians were performing laryngotomy or tracheotomy in an attempt to prevent the suffocation symptoms produced by tumoral masses. In 19th century the invention of laryngoscope and the advent of pathology and anesthesiology encouraged surgeons to operate on man. In 1873 Theodor Billroth (1829-1894) performed the first laryngectomy followed by several other colleagues among which Enrico Bottini (1837-1903) and Themistocles Gluck (1853-1942). Thanks to their contribution a new era came in laryngeal cancer treatment: the conservation laryngeal surgery.

Uterine cancer in the writings of Byzantine physicians.

Byzantine physicians recognized uterine cancer as a distinct disease and tried to suggest a therapeutic approach. The work of Oribasius, Aetius of Amida, Paul of Aegina, Cleopatra Metrodora and Theophanes Nonnus reflects the Hippocratic-Galenic scientific ideas as well as their own concept on this malignancy. According to their writings uterine cancer was considered an incurable disease and its treatment was based mainly on palliative herbal drugs.

Undiagnosed primary cardiac liposarcoma in an adult: a case report and review of the literature.

Well-differentiated liposarcomas are locally aggressive malignant mesenchymal neoplasms, which rarely metastasize to the heart and pericardium. Primary cardiac liposarcomas are extremely rare as well, and in both instances, symptoms are difficult to recognize. Therefore, accurate antemortem diagnosis seldom happens. A rare case of an undiagnosed, primary, well-differentiated cardiac liposarcoma is presented, in a 67-year-old man who suffered a sudden cardiac death. The tumor seemed to arise from the epicardium of the left ventricle and expand into the myocardium of the left ventricle and intraventricular septum. Macroscopic and histopathological findings are presented, as well as a short review of current literature.

Correlations between CCN1 immunoexpression and myocardial histologic lesions in sudden cardiac death.

CCN1 (CYR61) is a member of the CCN family of secreted matricellular proteins; it can regulate the expression of genes involved in angiogenesis and matrix remodeling. The latter mechanisms seem to be of vital importance in the pathophysiology of sudden cardiac death. We performed an immunohistochemical analysis on 62 cardiac tissue specimens derived from individuals of young and middle age who had died of sudden cardiac death. CCN1 immunopositivity was detected in 80.6% of all specimens. Semiquantitative statistical analysis of the staining results revealed that CCN1 immunoreactivity was significantly associated with ischemic morphology and hypertrophy of myocardial fibers, interstitial edema, and atheromatosis of coronary arteries in more than 10% of the myocardial fibers. Taking the previously mentioned correlations into account, ischemia seems to induce myocardial expression of CCN1; therefore, CCN1 immunostaining could be evaluated as a complementary tool in the assessment of ischemic areas when no tissue evidence of necrosis is available.

Effect of Saffron on Metabolic Profile and Retina in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet.

Saffron is a spice that has been traditionally used as a regimen for a variety of diseases due to its potent antioxidant attributes. It is well documented that impaired systemic oxidative status is firmly associated with diverse adverse effects including retinal damage. The aim of this study was to investigate the role of saffron administration against the retinal damage in apoE -/- mice fed a high-fat diet, since they constitute a designated experimental model susceptible to oxidative stress. Twenty-one mice were allocated into three groups: Group A (control, n = 7 c57bl/6 mice) received standard chow diet; Group B (high-fat, n = 7 apoE -/- mice) received a high-fat diet; and Group C (high-fat and saffron, n = 7 apoE -/- mice) received a high-fat diet and saffron (25 mg/kg/d) through their drinking water. The duration of the study was 20 weeks. Lipidemic profile, glucose, C-reactive protein (CRP), and total oxidative capacity (PerOX) were measured in blood serum. Histological analysis of retina was also conducted. Administration of saffron resulted in enhanced glycemic control and preservation of retinal thickness when compared with apoE -/- mice fed a high-fat diet. The outcomes of the study suggest the potential protective role of saffron against retinal damage induced by oxidative stress. Nevertheless, verification of these results in humans is required before any definite conclusions can be drawn.

Ontogeny of intrinsic innervation in the human thymus and spleen.

The ontogeny of the innervation of human lymphoid organs has not been studied in detail. Our aim was to assess the nature and distribution of parenchymal nerves in human fetal thymus and spleen. We used the peroxidase immunohistochemical technique with antibodies specific to neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100 protein, and tyrosine hydroxylase (TH) and evaluated our results with image analysis. In human fetal thymus, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerves were identified associated with large blood vessels from 18 gestational weeks (gw) onwards, increasing in density during development. Their branches penetrated the septal areas at 20 gw, reaching the cortex and the corticomedullary junction between 20 and 23 gw. Few nerve fibers were seen in the medulla in close association with Hassall's corpuscles. In human fetal spleen, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were localized in the connective tissue surrounding the splenic artery at 18 gw. Perivascular NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were seen extending into the white pulp, mainly in association with the central artery and its branches, increasing in density during gestation. Scattered NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers and endings were localized in the red pulp from 18 gw onward. The predominant perivascular distribution of most parenchymal nerves implies that thymic and splenic innervation may play an important functional role during intrauterine life.

Metabolic effects of Crocus sativus and protective action against non-alcoholic fatty liver disease in diabetic rats.

Non-alcoholic fatty liver disease (NAFLD) is the result of the accumulation of adipose tissue deposits in the liver and it is associated with type 2 diabetes. Crocus sativus (saffron) is known for its antioxidant and its potential hypoglycemic effects. We investigated the role of saffron on NAFLD in diabetic rats. Thirty adult male rats were allocated into three groups; control (n=10), which received normal diet; streptozotocin (STZ) group (n=10), which received normal chow diet, 10% fructose in their drinking water and STZ (40 mg/kg body weight; STZ-saffron group (n=10), which followed the same dietary and pharmacological pattern as STZ group and were additionally supplemented with saffron (100 mg/kg/day). Metabolic profile was measured and histopathological examination of the liver was evaluated. STZ group exhibited the highest glucose levels at the end of the experiment (P<0.05), while there was no difference between control and STZ-saffron group (584 vs. 213 mg/dl vs. 209 mg/dl, respectively). STZ group revealed higher percentage of steatosis (5-33%) when compared to the other two groups (P<0.005). Saffron exhibits both hypoglycemic and hepatoprotective actions. Yet, further studies enlightening the exact mechanisms of saffron's mode of actions are required.

Age-related fibromuscular dysplasia in the human left ventricle papillary muscles arteries.

We describe histologically cases of patients between 31 and 60 years of age who had fibromuscular dysplasia (FMD) in the tunica media (TM) of the left ventricle papillary muscles (PM) arteries. We also compared them with our previous findings in subjects younger than 30 years of age. We examined histologically samples taken from the tip of the anterior PM of the left ventricle in 200 healthy male hearts. In 33 cases (16.5 %), FMD was in the TM. We divided these cases into three subgroups (A, B, C) based on the degree of replacement of smooth muscle cells by fibrous tissue, and thus identified 17, 11 and 5 cases, respectively. Until the age of 41, the typical lesions were often localized within the TM. Beyond that age, the fibrous tissue increased in the TM wall and in the surrounding area of the vessels, causing dysfunction of the PM. Degenerative lesions, as well as inflammatory infiltration, were found after the age of 53. The findings of this study will be useful to cardiologists and cardiac surgeons, in pointing out that, after the age of 44 years old, some PM and their supporting valves may present a degree of dysfunction.

Primary melanoma of the gallbladder: does it exist? Report of a case and review of the literature.

With the occasion of a case of malignant melanoma of the gallbladder, which appeared to be primary, we have reviewed the literature and the result of this research was that primary melanoma of the gallbladder remains a questionable medical entity. Only few cases of both primary and metastatic gallbladder melanoma have been reported so far, and the only agreement is that surgery is the mainstay treatment. The role of adjuvant chemotherapy, hormonotherapy or immunotherapy for both primary and metastatic disease remains undefined.

Abruptio placentae and idiopathic arterial calcification in a stillborn.

We report a case of idiopathic arterial calcification in a stillborn of 22 weeks gestational age. The pregnancy was complicated by abruptio placentae and the postmortem examination showed widespread arterial calcification in the placenta, as well as in the pulmonary, renal, cerebellar, and brain arteries.

Ontogeny of intrinsic innervation in the human kidney.

We aimed to define, for the first time, the ontogeny of intrarenal innervation and to assess the distribution and nature of parenchymal nerves in the human fetal kidney. Our material consisted of routinely-processed renal tissue sections from 17 human fetuses, six of 20-24 gestational weeks (gw) and 11 of 25-40 gw, and three adults. We used immunohistochemistry with antibodies to the pan-neural markers neuron-specific enolase (NSE), neurofilaments (NF), PGP9.5, S100, and the adrenergic marker tyrosine hydroxylase (TH). NSE-, NF-, S100-, and PGP9.5-positive nerves, associated with arterial and venous vasculature, were identified in the renal cortex from 20 gw onwards, and their density appeared to increase with gestation, reaching adult levels at 28 gw. Most of the intrarenal nerves were TH-positive. Nerve fibers extended from the corticomedullary region to the outer cortex, reaching the renal capsule in the 3rd trimester. In detail, NSE-, NF-, S100-, PGP9.5-, and TH-immunoreactive fibers were observed in close apposition to the renal artery and its branches, occasionally reaching the afferent and efferent arteriole (3rd trimester). Nerve fibers were detected in close apposition to the juxtaglomerular apparatus in the 2nd and 3rd trimesters. In the renal medulla, NSE-, PGP9.5-, S100-, and TH-positive nerve fibers were detected close to tubular cells as early as 20 gw. However, their density gradually decreased during the 3rd trimester, and they were not observed in the medulla of the adult kidney. In conclusion, the human fetal kidney appears richly innervated during the 2nd and 3rd trimesters. There is a progressive increase in the density of parenchymal nerve fibers towards term from the corticomedullary region to the cortex. Most intrarenal nerves are adrenergic and have a predominant perivascular distribution, implying that renal innervation plays an important functional role during intrauterine life.

Kugel's artery: an anatomical and angiographic study using a new technique.

In this study, we tried to resolve the confusion in the literature regarding the existence and course of Kugel's artery. With the aid of a new technique, we studied 100 human hearts ex vivo by radiography and by direct observation through dissection, to demonstrate anatomical and postmortem angiographic findings of Kugel's artery. Kugel's artery was found in only 6 hearts out of 100 (6%). It originated from the proximal left circumflex artery and ended in the right coronary artery in 2 cases; from the right coronary artery and ended in the same artery in 2 cases; from the left circumflex artery and ended in the same artery in 1 case; and from the right coronary artery through the sinus node artery, ending in the left circumflex artery, in 1 case. In all 100 hearts, an anastomotic network of small atrial branches was found in the same area (lower portion of the interatrial septum), connecting the large vessels indirectly. Branches of the sinus node artery in all hearts, and of the atrioventricular node artery in 66 hearts, participated in this network. Our procedure showed the detailed course of Kugel's artery and its course independent from the atrioventricular node artery and from the anastomotic network. In conclusion, in all cases an anastomotic network of small atrial branches courses through the lower interatrial septum and connects indirectly the proximal and distal ends of the larger coronary arteries. Kugel's artery provides an additional direct arterial anastomosis in the same area in 6% of the hearts.

Retinal toxicity of intravitreal trastuzumab in a rabbit model: preliminary results of an experimental study.

PURPOSE: To evaluate the retinal toxicity of intravitreal trastuzumab in a rabbit model. METHODS: Fourteen New Zealand albino rabbits, weighing between 2.5 and 3 kg were used for this study. In the first group (n=6), 0.1 mL trastuzumab 10 mg/mL was injected into the vitreous. In the second group (n=6), the same volume of sterile balanced saline solution was injected intravitreally (sham injection). Additionally, 0.1 mL of 2 other concentrations of trastuzumab (7.5 and 5 mg/mL, respectively), was injected into the vitreous of 2 rabbits. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of inflammation, infection, and toxicity. An electroretinogram (ERG) was performed at baseline and 14 days after the injection. The animals were killed on day 14 and a histological examination was performed in the enucleated eyes. RESULTS: The clinical examination was unremarkable on either sham or intravitreal injection of trastuzumab. Conversely, the ERG was greatly affected and in 2 cases extinguished 14 days after trastuzumab injection. Consistent with electrophysiological abnormalities of the retina, signs of retinal edema in experimented eyes, suggesting morphologic retinal damage, were observed. In contrast, in the sham injected eyes, the ERG was normal without histopathologic retinal changes. CONCLUSIONS: Intravitreal trastuzumab seems to be toxic to the retina in albino rabbits even at a concentration of 5 mg/mL. Further studies are needed to evaluate the safety of intravitreal trastuzumab in models of choroidal neovascularization, as well as to obtain experience concerning the intravitreal toxicity of trastuzumab in primates too and not only in rabbits.

Potential role of apoptosis and apoptotic regulatory proteins in colorectal neoplasia: correlations with clinico-pathological parameters and survival.

An imbalance between apoptotic and proliferative processes is believed to underlie colorectal neoplasia. We evaluated the expression of bcl-2, p53, mdm2 proteins, and apoptosis in colorectal neoplasms, as well as their correlation with clinico-pathological parameters, using image analysis. Biopsies from 46 colorectal cancers, 121 adenomas, and 25 controls were studied using monoclonal antibodies against p53, bcl-2, mdm2 and the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL) method for apoptosis. P53 and bcl2 protein expression was higher in adenomas >or=1 cm (P < 0.03) and tubulovillous-villous adenomas (P < 0.03), and correlated with dysplasia (P < 0.03). In Cox regression analysis, Dukes' stage was the most significant independent prognostic indicator of a worse survival (P < 0.019), whereas when stage was eliminated, bcl-2 expression was also a powerful predictor for bad prognosis (P = 0.02). In conclusion, both bcl-2 and p53 immunohistochemical profiles may be useful adjuncts in detecting adenomas with a malignant potential, whereas bcl-2 could be used in combination with Dukes' stage as a predictor of prognosis in colorectal cancer.

Isolated colonic leukocytoclastic vasculitis causing segmental megacolon: report of a rare case.

We report the case of a 44-year-old white man who presented with progressively worsening crampy abdominal pain and distention. Deterioration of his clinical picture along with leukocytosis and radiographic evidence of severe colonic dilation rendered exploratory laparotomy necessary. Greatly distended and inflamed transverse and descending colon were evident and an extended left colectomy was performed. Characteristic changes of leukocytoclastic vasculitis in the serosal and muscular layers of the resected colon were demonstrated at histopathologic examination. Systemic leukocytoclastic vasculitis, usually coexisting with Henoch-Schonlein purpura, commonly affects the small bowel with clinical evidence of ischemia or bleeding. Colon involvement is infrequently reported in the context of systemic disease. Isolated colonic leukocytoclastic vasculitis without extraintestinal manifestations is rare. A previously unreported case of localized leukocytoclastic vasculitis of the left colon resulting in the impressive presentation of megacolon, without the presence of any precipitating factor or associated systemic disease is presented here, with an overview of the related literature.

Rosacea: a clinicopathological approach.

BACKGROUND: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. METHODS: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. RESULTS: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. CONCLUSION: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.