Multifocal sclerosing angiomatoid nodular transformation of the spleen in a patient with simultaneous metachronous liver metastasis after colon cancer surgery: a first case report.

Sclerosing angiomatoid nodular transformation of the spleen (SANT) is a benign, extremely rare vascular lesion of the spleen with unknown pathogenesis. SANT is often discovered incidentally, and can sometimes be found in patients with a history of cancer. Based on absent definitive radiological signs and varying growth patterns, distinction from malignant processes such as metastasis can be very difficult. Therefore, surgical resection of the spleen is indicated in most cases of patients with history of cancer. We report a case of a bifocal manifestation of SANT in the spleen in a patient with history of colon cancer and newly-diagnosed metachronous liver metastases.

Multicenter phase II trial to investigate safety and efficacy of gemcitabine combined with cetuximab as adjuvant therapy in pancreatic cancer (ATIP).

BACKGROUND: To investigate whether addition of cetuximab to standard adjuvant chemotherapy with gemcitabine improves outcome in pancreatic cancer, specifically whether the rate of disease-free survival (DFS) at 18 months (primary end point) exceeds the previously reported 35% of gemcitabine alone. PATIENTS AND METHODS: Prospective, open-label, multicenter, nonrandomized phase II study in 76 patients with R0- or R1-resected ductal adenocarcinoma of the pancreas included between October 2006 and November 2008. Gemcitabine and cetuximab were administered for 24 weeks. Secondary end points included overall survival (OS) and toxic effect. RESULTS: Seventy-three patients received cetuximab. Median DFS was 10.0 [95% confidence interval (CI) 8.9-13.6] months and the DFS rate at month 18 of 27.1% (16.7%-37.6%) was inferior to 35%. Median OS was 22.4 (18.2-27.9) months. Subgroup analyses revealed a nonsignificant increase in DFS for patients with versus without skin toxic effect ≥ grade 2 (median 14.7 versus 8.3 months, P = 0.073) and wild-type versus mutated K-Ras (median 11.5 versus 9.3 months, P = 0.57). Grade 3/4 toxic effects included neutropenia (11.0%), thrombopenia (7%), skin toxic effect (7%) and allergic reactions (7%). CONCLUSION: Addition of cetuximab to adjuvant gemcitabine does not seem to improve DFS or OS of unstratified pancreatic cancer patients. Trends for improved DFS in patients with wild-type K-Ras and skin toxic effect remain to be confirmed.

[Significance of autopsy in patients with head and neck cancer]. / Stellenwert der Autopsie bei Patienten mit Kopf-Halstumoren.

BACKGROUND: Nowadays, the morphological assessment of samples obtained from living patients has a greater importance than the scientific knowledge which is gained by autopsy. Therefore, the aim of the study was a retrospective analysis of causes of death in patients with head and neck cancer. MATERIAL AND METHODS: The autopsy rate, clinical parameters of oncologic patients as well as autopsy findings like lethal complications, distant metastases and second primary tumors were retrospectively analyzed. RESULTS: From 1968 to 2007 in 91 patients with malignant tumors of the head and neck an autopsy was performed. In these 39 years an autopsy was performed in 45.9% of dead oncologic patients. Autopsy findings revealed distant metastases in 46.2% and second primary tumors in 17.6% of the patients. 49.5% of the patients died from pneumonia, 20.9% from tumor bleeding and 10% from progressive cachexia. CONCLUSION: The study confirms the global trend of a decline in autopsy numbers in the last 3 decades. However, as an important instrument of quality assurance autopsies continue to play an essential and indispensable role in medical research.

Analysis of clinically suspected orbital cavernomas.

BACKGROUND: Orbital cavernomas are low-flow vascular malformations that are the most common benign neoplasms of the orbit in adults, typically becoming symptomatic in the middle age. METHODS: The medical records of six patients with clinically suspected orbital cavernomas receiving elective surgical excision were analysed concerning symptoms, physical findings, treatment results and visual outcome. The pathologic slides were evaluated, and additional immunohistochemical stains were done if necessary to obtain diagnosis. RESULTS: Histologic evaluation revealed three of six cases not being cavernomas, although the clinical and macroscopic findings were consistent with orbital cavernomas. Two of them were haemorrhagic lymphangiomas, and one was a solitary fibrous tumour. CONCLUSIONS: Haemorrhagic lymphangiomas and other vascular tumours may mimic orbital cavernomas regarding anamnesis, radiologic and intraoperative findings and gross examination. Therefore, exact histologic evaluation is necessary to get the correct diagnosis.

Clear cell follicular adenoma of the thyroid--a challenge in intra-operative diagnostics.

Pure clear cell lesions of the thyroid gland are rare and prone to pose severe diagnostic challenges. We report the case of a 61-year-old man with a clear cell adenoma of the thyroid. The patient presented with a hypoechoic thyroid nodule. Fine needle aspiration cytology rendered the primary diagnosis of a follicular neoplasia, and right thyroid lobectomy was performed. By intra-operative frozen section, the diagnosis given was clear cell lesion of unknown malignant potential. Based on the light microscopic findings and the immunohistochemical profile, the lesion was diagnosed as clear cell follicular adenoma of the thyroid. A follicular thyroid lesion presenting with clear cell changes in fine needle aspiration cytology or intra-operative frozen section consultation constitutes a diagnostic challenge to every surgical pathologist. As immunohistochemistry of cytologic specimens is hampered by several methodological problems, any thyroid lesion with clear cell features warrants further histologic assessment to render the correct diagnosis.

Prospective study on neck dissection after primary chemoradiation therapy in stage IV pharyngeal cancer.

BACKGROUND: Definitive chemoradiation is a well-established option in the treatment of locally advanced squamous cell carcinoma of the head and neck. The intention of this study was to evaluate its efficacy on cervical lymph node metastases in a prospective study after a standardized protocol for chemoradiation (CRT) and histopathological evaluation, respectively. PATIENTS AND METHODS: The data of 25 patients (10 oropharynx, 15 hypopharynx) who received planned neck dissection after definitive chemoradiation for UICC stage IV carcinomas of the pharynx were analyzed. All patients were sonomorphologically staged positive for lymph nodes (3 patients: N1; 2 patients N2a; 7 patients N2b; 9 patients N2c and 4 patients N3). A neck dissection was carried out 8.9+/-1.5 weeks (range 6-13) post treatment. The specimens obtained from the different neck levels were histologically examined for viable tumour cells. RESULTS: Local control was achieved in 100% of all patients on endoscopy 9 weeks after the chemoradiation. In 14/25 patients (56%), still viable tumour tissue was found in the neck dissection (ND) specimen. Only one of these 14 patients (7%) was deemed suspicious for residual lymphadenopathy from clinical and diagnostic findings at re-staging after chemoradiation, the others were staged yN0. Postsurgical complications occurred in six patients (24%) such as bleeding and prolonged wound healing in one patient each and functional deficits in an additional four patients. One patient developed a scar recurrence seven months after surgery. CONCLUSION: Based on these findings, the ultimate efficacy of primary CRT should not be judged 8-10 weeks after the treatment. Therefore planned neck dissection should be performed no earlier than 12 weeks after primary CRT.

Graft-dependent renal hyperparathyroidism despite successful kidney transplantation.

INTRODUCTION: Only a few reports can be found on the recurrence or persistence of hyperparathyroidism after total parathyroidectomy and autotransplantation (PTX + AT) following kidney transplantation (KTX). The objective of the present study was to assess the frequency and pathophysiological mechanisms responsible for the development of graft-dependent renal hyperparathyroidism (rHPT) after KTX. PATIENTS AND METHODS: Between 1986 and 2006, 69 patients underwent surgery for rHPT after KTX at our institution. Patients with reoperations at the parathyroid autograft (AT) were identified. Kidney graft function (KGF) was assessed by the glomerular filtration rate (GFR). Representative parts of the parathyroid gland chosen for autotransplantation during the initial parathyroidectomy and of the excised AT at reoperation were reanalyzed according to the morphologic pattern and the proliferative index. RESULTS: Eight of the 69 patients underwent reoperation of the AT. All patients had undergone initial PTX + AT before KTX. The GFR before parathyroid reoperation was 66.6 +/- 9.6 ml/min per1.73 m(2) (mean +/- SEM). Histopathological re-examination revealed nodular hyperplasia in the parathyroid tissue for autotransplantation and in the excised parathyroid autografts. The Ki67 index was increased in the glands chosen for autotransplantation prior to KTX, but was overall low in the excised autografts. DISCUSSION: Although not reported in the literature to date, tertiary hyperparathyroidism (tHPT) may arise from parathyroid autografts even in patients with a good KGF. In these cases, graft-dependent tHPT represents the inability of autonomous, nodular parathyroid tissue to regress despite the recovery of renal function. Non-nodular tissue should be selected for parathyroid autotransplantation to decrease the incidence of graft-dependent recurrent rHPT.

The status of neck node metastases in breast cancer--loco-regional or distant?

Metastases to cervical lymph nodes do not exclusively derive from malignancies of the head and neck area. In the literature the region where distant metastases of breast carcinomas to the neck occur is exclusively named "supraclavicular". The system established by head and neck surgeons regarding neck node topography allows interdisciplinary management of patients with cervical lymph node metastases from breast cancer. Twelve patients suffering from breast cancer who presented with cervical masses have been examined. Most lymph node metastases were found in the posterior triangle of the neck and at the caudo-jugular level, but some metastases were even found in the upper jugular levels. The results presented show that neck node metastases of breast cancer are located superiorly to the supraclavicular region in more than 50% of the cases. According to the AJCC Staging System for Breast Cancer metastases located in the supraclavicular fossa are assessed as loco-regional metastases (N3c). Lymph node metastases situated above the supraclavicular region are not mentioned, but should be considered as distant metastases. This important question remains unanswered and deserves clarification in the current classification of the AJCC Staging System for Breast Cancer.

The effect of enterocystoplasty on bone strength assessed at four different skeletal sites in a rat model.

The objective of the study was to investigate bone strength at four different skeletal sites in a chronic animal model of urinary diversion. Young male Wistar rats (120) were allocated randomly to four groups undergoing ileocystoplasty; ileocystoplasty and resection of the ileocecal segment; colocystoplasty; or sham operation (controls). After 8 months the lumbar vertebrae, femora, and tibiae were harvested at necropsy. Bone strength was assessed biomechanically at four different skeletal sites: vertebra L3, femoral middiaphysis, femoral neck, and distal femoral metaphysis. Bone mass and architecture were assessed using standard static histomorphometry of the proximal tibial metaphysis (trabecular bone volume [BV/TV]; trabecular number [Tb.N]) and ash weight. Statistically significant differences of biomechanical parameters between groups were observed at three skeletal sites with corresponding changes in tibial histomorphometry. Isolated ileocystoplasty resulted in decreased maximum load values of L3 (-16.4%; p < 0.0035) and a substantial reduction in tibial BV/TV (-34.7%; p < 0.05). Ileocystoplasty combined with resection of the ileocecal segment led to a significant loss of bone strength of L3 (-32.4%; p < 0.0015) and a dramatic reduction of tibial BV/TV (-45.9%; p < 0.01). Loss of tibial metaphyseal bone mass was predominantly caused by a decrease in Tb.N. (p < 0.01). Colonic augmentation had no significant effect on bone strength or histomorphometric values. In conclusion, this is the first experimental study to demonstrate the relevance of histomorphometrically proven bone loss after enterocystoplasty in terms of biomechanical variables.

Skeletal growth and long-term bone turnover after enterocystoplasty in a chronic rat model.

OBJECTIVE: To investigate skeletal growth and bone metabolism in a chronic animal model of urinary diversion. MATERIALS AND METHODS: Young male Wistar rats (120) were allocated randomly to four groups undergoing: ileocystoplasty, ileocystoplasty and resection of the ileocaecal segment, colocystoplasty, and controls. All animals received antibiotics for 1 week after surgery; half of each group remained on oral antibiotics. Bone-related biochemistry was measured in serum and urine. Dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT) were used to determine bone mass ex vivo. RESULTS: Most (90%) of the rats survived the study period (8 months); six rats died from bowel obstruction at the level of the entero-anastomosis and four had to be killed because of persistent severe diarrhoea. Vital intestinal mucosa was found in all augmented bladders. There were no differences in bone length and volume. Loss of bone mass was almost exclusively in rats with ileocystoplasty and resection of the ileocaecal segment (-37.5%, pQCT, P < 0.01). There was no hyperchloraemic metabolic acidosis or gross impairment of renal function. Hypomagnesaemia, hypocalcaemia and decreased insulin-like growth factor-binding protein 3 were the only significant findings on blood analysis. Deoxypyridinoline crosslinks in urine were higher in rats with an enterocystoplasty than in controls. CONCLUSIONS: Enterocystoplasty in rats neither impairs skeletal growth nor bone quantity, but leads to significant loss of bone mass when combined with resection of the ileocaecal segment. Rarefaction of the trabecular network is confined to the metabolically highly active cancellous compartment, most likely as a consequence of intestinal malabsorption.

Effect of N-acetylcysteine treatment on NO2-impaired type II pneumocyte surfactant metabolism.

Inhalation of nitrogen dioxide (NO2) is known to alter the composition of the bronchoalveolar lavage (BAL) and to impair the surfactant metabolism of type II pneumocytes. However, information is sparse as to whether application of the widely used antioxidant N-acetylcysteine (NAC) is capable of preventing or reducing these alterations. The aim of the study was to investigate if in vivo administration of NAC to NO2-inhaling rats protected BAL parameters and physiology of type II pneumocytes from impairment. For this purpose, rats were exposed to 720 p.p.m. h-1 NO2, that was applied continuously, intermittently or repeatedly. During inhalation one group of rats received saline and the other group received NAC antioxidant (200 mg kg-1, intraperitoneally) once a day. The BAL protein and phospholipid content increased most in the continuously and repeatedly NO2-exposed rats when compared to the controls, while the intermittent exposure did not change these parameters. Application of NAC led to a marked decrease of the protein elevation for the continuously and intermittently exposed groups, but exhibited no influence on the BAL phospholipid. Surprisingly, all NO2 exposure modes elevated the glutathione content (reduced and oxidized) in the BAL. Application of NAC clearly decreased the content of both forms of glutathione in the continuously and the repeatedly NO2-exposed groups. Phospholipid synthesis, measured by choline uptake into type II cells, was increased most after continuous NO2 inhalation. The NAC reduced this increase moderately. Whereas choline uptake by type II cells was obviously stimulated by NO2, the stimulated secretion of phosphatidylcholine from these cells was decreased by this oxidant. Only continuous exposure reduced this activity markedly. The NAC clearly restored the impaired secretion activity in the cells from the continuously NO2-exposed animals. Since the efficacy of NAC in the prevention of NO2-induced impairments in the surfactant system is striking mainly in the continuously exposed group, we suggest that administration of NAC to NO2-induced lung injury partially restores altered BAL components and the impaired physiology of type II pneumocytes.

alpha-tocopherol improves impaired physiology of rat type II pneumocytes isolated from experimentally injured lungs.

BACKGROUND: Oxidant stress delivered by nitrogen dioxide (NO2) inhalation impairs the function of extracellular surfactant as well as surfactant phospholipid metabolism in type II pneumocytes. Because protection against oxidant stress is important to normal lung function, the lung contains a variety of antioxidants, including vitamin E. Whether administration of this antioxidant during NO2 inhalation attenuates NO2-induced alterations in phospholipid metabolism in type II pneumocytes has not been studied. METHODS: We exposed rats to identical NO2 body doses (720 p.p.m. x h) using continuous, intermittent, or repetitive protocols. During exposure periods, the animals received daily intramuscular injections of vitamin E (25 mg kg-1). We isolated type II pneumocytes from NO2-exposed rats and evaluated them for cell yield and viability, as well as for synthesis and secretion of phosphatidylcholine (PC) as measures of surfactant metabolism. RESULTS: The yield of type II pneumocytes was significantly elevated from animals that had been exposed continuously to NO2 whereas in intermittently and repeatedly exposed rats, cell yield was similar to yield from control animals. Viability of the isolated cells was similar in controls and all NO2 exposure protocols. Vitamin E treatment of the NO2-exposed rats neither changed cell yield nor cell viability. Phospholipid de novo synthesis, as estimated by choline incorporation into PC, was increased most after continuous NO2 inhalation whereas in the other conditions there was only a slight increase. Vitamin E administration further increased phospholipid synthesis; this difference reached statistical significance only in the case of intermittent NO2 exposure. Secretion of phosphatidylcholine from type II cells was only reduced after continuous NO2 inhalation and administration of the antioxidant reduced the impairment. CONCLUSION: Because vitamin E appears to preserve the ability of type II pneumocytes isolated from NO2-exposed rats to synthesize and secrete surfactant lipid, we conclude that administration of vitamin E may mitigate NO2-induced lung injury.

The role of bone scintigraphy in patients with Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare disorder that has been reported fewer than 60 times in the literature. Although clinical findings seem to be specific at first sight, histologic classification remains unclear. It has not been decided whether ECD is part of the spectrum of histiocytoses or whether it may be a lipid storage disorder or even a primary macrophage cell disorder, although it does show a distinct histologic pattern. However, the clinical appearance alone shows several typical features, rendering the diagnosis very probable if present. This article illustrates the importance of bone scanning in ECD, because the scintigraphic pattern of involved skeletal sites may in themselves lead to the diagnosis. Several differential diagnoses are considered. The importance of bone scintigraphy as an imaging method in patients with an unclear diagnosis is discussed, as exemplary in ECD, as is its role for the detection of sites of skeletal involvement in other diseases.

Pulmonary aspergillosis in an unselected autopsy series.

The present study was performed to analyze the relationship between underlying diseases and the morphologic form of aspergillosis. This retrospective analysis of 3284 autopsies yielded 18 cases of aspergillosis. The specific diagnosis of aspergillosis was rendered by a monoclonal antibody versus Aspergillus spp. Patients with hematological disorders, such as acute leukemia and aplastic anemia, made up about 35% of all patients dying of invasive aspergillosis. Diseases of the airways and the pulmonary parenchyma constituted the second most pathogenetic factor for the development of aspergillosis. The morphologic form of aspergillosis was closely related to the underlying diseases. Non- and semi-invasive forms of aspergillosis--saprophytic infection and chronic necrotizing aspergillosis--were observed only in patients with an isolated underlying pulmonary disease devoid of any other precipitating factor. In contrast, seven patients, five of whom suffered from hematological diseases, had no underlying lung disease and developed aspergillus pneumonia. The remaining 5 patients with aspergillus pneumonia showed a combination of underlying extrapulmonary disease and pulmonary alterations that preceded aspergillosis. The local distribution of fungal infection showed a characteristic distribution pattern with a predominance of the upper lung lobes. Hematogeneous spread beyond the lungs occurred exclusively in cases with aspergillus pneumonia. We conclude that the different forms of aspergillosis are closely related to the nature of the underlying disease.

Proliferation and number of Clara cell 10-kDa protein (CC10)-reactive epithelial cells and basal cells in normal, hyperplastic and metaplastic bronchial mucosa.

Clara cell 10-kDa protein (CC10) is an inhibitor of phospholipase A2 and binds to phosphatidylinositol. It may therefore interfere with intracellular signal transduction. Bronchial CC10-reactive cells have been described by several authors. In contrast to the bronchiolar CC10-containing Clara cell, which is a progenitor cell of terminally differentiated airway epithelium, the role of bronchial CC10-reactive cells remains to be elucidated. We assessed the number of bronchial CC10-reactive cells in relation to cytokeratin (CK) expression and proliferative activity in normal, hyperplastic and squamous metaplastic epithelium. Sixty-five human bronchial mucosal specimens were investigated immunohistochemically for CK expression (CK7, CK13 and CK5/6), proliferative activity (MIB-1) and number of CC10-reactive epithelia. The proliferation fraction of CC10-reactive cells was assessed with double staining for MIB-1 and CC10. The proliferation index of the epithelium differed significantly between normal, hyperplastic and metaplastic epithelium. The number of CC10-reactive cells was inversely related to the epithelial proliferation. Bronchial CC10-reactive cells showed no proliferative activity as assessed using immunohistochemical double staining for CC10 and MIB-1. In contrast to normal and hyperplastic epithelium, squamous metaplasia disclosed CK5/6 in all epithelial layers, a loss of CK7 and a gain of CK13. We conclude that CC10-reactive cells have no progenitor role in the bronchial mucosa. However, because the proliferative activity is inversely related to the number of CC10-reactive cells, the CC10 protein may play a role in the regulation of epithelial repair. Squamous metaplasia most likely originates from basal cells.

The influence of lymph node counts on the detection of pelvic lymph node metastasis in prostate cancer.

The present study was done to determine the influence of tumor stage and the patients' age on the number of pelvic lymph nodes obtained during standard pelvic lymphadenectomy before radical retropubic prostatectomy. Furthermore, we assessed whether the number of pelvic lymph nodes examined affects the sensitivity of pN-classification. The data of 283 consecutive patients who had undergone standardized open pelvic lymphadenectomy and radical retropubic prostatectomy for clinically organ-confined prostate cancer were reviewed retrospectively. There were striking interindividual differences in the number of lymph nodes (5-40; median: 16). The quantity was independent of pathologic tumor stage (pT) and the patients' age. In cases with 13 or more lymph nodes examined, the rate of metastatic involvement was twice as high as in lower lymph node counts. The detection of lymph node metastases--and consequently the prognostic accuracy of pN-classification--is mainly influenced by the total number of lymph nodes examined. These data suggest that at least 13 lymph nodes should be investigated to achieve optimum information.

Thrombotic pulmonary arteriopathy in polycythemia vera.

Pulmonary infarction and hemorrhage are important differential diagnoses in pulmonary coin lesions, especially in patients with underlying hematologic malignancies. We report a 58-year-old female patient suffering from polycythemia vera presenting with multiple pulmonary coin lesions. Open lung biopsy and subsequent histologic investigations showed organized pulmonary infarction and primary pulmonary thrombotic arteriopathy. Although histologic features are non-contributory in distinguishing organized thrombosis from organized thromboembolism, the clinical setting and localization of the lesions suggest that in the present case the vascular lesions are due to organized thrombosis.

Effects of nitrogen dioxide exposure on Clara cell proliferation and morphology.

The present study was performed to relate Clara cell proliferation and Clara cell morphology to duration and intensity of nitrogen dioxide (NO2) exposure as a model of lung injury in rats. Male Sprague-Dawley rats were exposed to 5, 10 and 20 ppm NO2 for three (short term exposure) and 25 days (long term exposure). Epithelial proliferation was immunohistochemically assessed by BrdU-incorporation into the bronchial and bronchiolar epithelium. Clara cell specific 10 kD protein was detected using an antibody versus recombinant protein. Following short term exposure Clara cells showed a significant alteration of their morphology: the cells lost the apical intraluminal projections, and the damaged epithelium was covered by a layer of CC10 reactive material. After long term exposure the Clara cell morphology was indistinguishable from that of unexposed controls. In all short term exposure groups cellular proliferation was higher in the bronchiolar epithelium than in the bronchial epithelium. Whereas short term exposure to 5 ppm NO2 sufficed to induce a maximum epithelial proliferation of the bronchiolar epithelium, long term exposure to 5 ppm NO2 yielded no significant increase in the epithelial proliferation, a finding reflecting the adaptation of the airway epithelium to oxidative stress. Long term exposure to 10 and 20 ppm NO2 resulted in a dosilinear increase of cell proliferation in the bronchial and bronchiolar epithelium. Double labelling of CC10 and BrdU showed that BrdU uptake and hence proliferation were restricted to Clara cells. We conclude that changes of the Clara cell morphology are closely related to the extent of inhalative stress and functional status of the Clara cell. The results are in keeping with the assumption that the Clara cell exerts progenitor cell functions in the airway epithelium.