Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis.

BACKGROUND: Association studies have implicated the glycosaminoglycan hyaluronan (hyaluronic acid, HA) and its degrading enzymes the hyaluronidases in tumour progression and metastasis. Oligosaccharides of degraded HA have been ascribed a number of biological functions that are not exerted by high-molecular-weight HA (HMW-HA). However, whether these small HA oligosaccharides (sHA) have a role in tumour progression currently remains uncertain due to an inability to analyse their concentration in tumours. METHODS: We report a novel method to determine the concentration of sHA ranging from 6 to 25 disaccharides in tumour interstitial fluid (TIF). Levels of sHA were measured in TIF from experimental rat tumours and human colorectal tumours. RESULTS: While the majority of HA in TIF is HMW-HA, concentrations of sHA up to 6 µg ml(-1) were detected in a subset of tumours, but not in interstitial fluid from healthy tissues. In a cohort of 72 colorectal cancer patients we found that increased sHA concentrations in TIF are associated with lymphatic vessel invasion by tumour cells and the formation of lymph node metastasis. CONCLUSIONS: These data document for the first time the pathophysiological concentration of sHA in tumours, and provide evidence of a role for sHA in tumour progression.

COX-2, TFF1, and Src define better prognosis in young patients with gastric cancer.

BACKGROUND AND OBJECTIVES: Despite its dwindling occurrence, gastric cancer remains a leading cause of cancer related mortality worldwide. Molecular determinants of prognosis that impact survival are being sought out as a means to facilitate rational clinical decision-making and enhance patient management. In this study, we evaluated three molecules implicated in gastric carcinogenesis and demonstrated that the differential expression of cyclooxygenase-2 (COX-2) and the viral oncogene homolog Src proteins could explain the differences in survival observed in patients older and younger than 50 years of age. METHODS: We evaluated 5-year survival in a cohort of 423 gastric cancer patients using chronological age as a variable. Additionally, we assessed the protein expression of three molecules (COX-2, TFF1, Src) implicated in the pathogenesis of gastric cancer using immunohistochemistry. RESULTS: We found that patients younger than 50 years of age had a better 5-year survival rate in all tumor stages. We found that the expression of COX-2 and Src correlated significantly with survival in this group without any significant impact attributable to TFF1. CONCLUSIONS: Our study demonstrates that young gastric cancer patients have a better prognostic outlook that could in part be explained by the differential expression of COX-2 and Src.

[Maxillary ameloblastoma extending into the sinonasal tract]. / Expansion eines Ameloblastoms in den sinunasalen Trakt.

Maxillary ameloblastomas can extensively expand into the paranasal sinuses or even the nasal cavity due to a slow growth pattern. Sinusitis is rarely the first tumor-related complaint. Due to the various growth forms of ameloblastomas the challenging histological differential diagnosis includes several other odontogenic as well as benign and malignant non-odontogenic tumors, e.g. tumors from the mucosa of the paranasal sinuses, salivary glands and Rathke's pouch. Despite the radical surgical approach a complete resection with wide margins cannot always be achieved. Maxillary ameloblastomas show the highest recurrence rates.

Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis.

The gastric hormone ghrelin is known as an important factor for energy homeostasis, appetite regulation and control of body weight. So far, ghrelin has mainly been examined as a serological marker for gastrointestinal diseases, and only a few publications have highlighted its role in local effects like mucus secretion. Ghrelin can be regarded as a gastroprotective factor, but little is known about the distribution and activity of ghrelin cells in pathologically modified tissues. We aimed to examine the morphological changes in ghrelin expression under several inflammatory, metaplastic and carcinogenic conditions of the upper gastrointestinal tract. In particular, autoimmune gastritis showed interesting remodeling effects in terms of ghrelin expression within neuroendocrine cell hyperplasia by immunohistochemistry. Using confocal laser microscopy, the gastrin/cholecystokinin receptor (CCKB) could be detected on normal ghrelin cells as well as in autoimmune gastritis. Functionally, we found evidence for a physiological interaction between gastrin and ghrelin in a primary rodent cell culture model. Additionally, we gathered serological data from patients with different basic gastrin levels due to long-term autoimmune gastritis or short-term proton pump inhibitor treatment with slightly reactive plasma gastrin elevations. Total ghrelin plasma levels showed a significantly inverse correlation with gastrin under long-term conditions. Autoimmune gastritis as a relevant condition within gastric carcinogenesis therefore has two effects on ghrelin-positive cells due to hypergastrinemia. On the one hand, gastrin stimulates the proliferation of ghrelinpositive cells as integral part of neuroendocrine cell hyperplasia, while on the other hand, plasma ghrelin is reduced by gastrin and lost in pseudopyloric and intestinal metaplastic areas. Ghrelin is necessary for the maintenance of the mucosal barrier and might play a role in gastric carcinogenesis, if altered under these pre neoplastic conditions.

[Dual-source CT: in vitro characterization of gallstones using dual energy analysis]. / Dual-Source-CT: In-vitro-Charakterisierung von Gallensteinen mittels Dual-Energy-Analyse.

PURPOSE: Despite clinically available high-resolution CT, the detection and classification of gallstones remains a challenge in some cases. This pilot study examines whether noninvasive characterization of gallstones in vitro is possible using dual-energy analysis (DECT) of dual source CT datasets. MATERIALS AND METHODS: A total of 43 gallstones (0.4 - 1.5 cm) were examined at 80 kV, 140 kV and in the dual-energy mode. The monoenergetic datasets were examined by two independent examiners and classified as calcium, cholesterol or pigment stones. The results were compared with the pathological classification as the clinical gold standard. After creating reference images for each group via dual-energy analysis, the classification was repeated and compared with the gold standard again. RESULTS: Using the monoenergetic analysis at 80 kV, the sensitivity and specificity were 100 / 84 % and 100 / 88 % for calcium stones. For cholesterol stones the values were 54 / 89 % and 54 / 85 % and for pigment stones 70 / 80 % for both examiners. At 140 kV, the sensitivity and specificity for calcium stones were 100 / 84 % for both examiners, 46 / 92 % for cholesterol stones for both examiners and the sensitivity and specificity were 80 / 75 % and 80 / 80 % for pigment stones. Using the reference images established by DECT, both examiners were able to correctly classify all gallstones. CONCLUSION: The present data indicates that DECT is able to correctly classify Gallstones according to the clinical gold standard in vitro. Clinical studies have to demonstrate whether these results lead to optimized clinical decision making.

[Recurrent and metastasizing atypical fibroxanthoma]. / Rezidivierendes und metastasierendes atypisches Fibroxanthom.

Atypical fibroxanthoma is a rare skin tumor that arises particularly on sun-exposed skin. Although it is considered to be a benign tumor, rarely, metastases arise. The accurate classification of aggressive processes of atypical fibroxanthoma is currently still the subject of discussion. The case of an 81-year-old patient with relapsing atypical fibroxanthoma of the right auricle is presented. With the second relapse, a single metastasis in the right parotid gland was detected. A complete tumor excision was performed, and the patient declined the recommended postoperative radiotherapy. The patient has not show any signs of relapse for 60 months now. Atypical fibroxanthoma and the appropriate therapy for it are described, and the newest discoveries regarding this disease are discussed on the basis of the current literature.

[Hepaticolithiasis. Rare benign disease of the intrahepatic bile ducts]. / Hepatikolithiasis. Seltene benigne Erkrankung der intrahepatischen Gallenwege.

Hepaticolithiasis is a rare disease of the intrahepatic bile ducts endemic to east Asia which also is known as oriental cholangiohepatitis. Beside strictures and metabolic disturbance, the main cause of intrahepatic stones is acquired or congenital malformation of the intrahepatic biliary ducts. In the following we show a case of hepaticolithiasis and concurrent pancreatic metaplasia.

[Pasqualini's syndrome]. / Pasqualini-Syndrom.

INTRODUCTION: Pasqualini's syndrome is an isolated, incretory functional disorder of the testes with a secondary Leydig cell insufficiency but, unlike Klinefelder's syndrome, with normal spermiogenesis and fertility. This unusual form of hypogonadism is caused by an inherent LH secretion disorder of the pituitary gland. The result of this is the secondary Leydig cell insufficiency and a corresponding peripheral androgen deficiency. In this communication we present the case of a 67-year-old man with Pasqualini's syndrome and a histologically confirmed left seminoma. In view of the current lack of data and our experience, we describe the properties of this uncommon syndrome; therapy, prognosis and possible relationship with seminoma are discussed in more detail. CASE REPORT: The 67-year-old male presented in our outpatient department with the urgent suspicion of a left testicular tumour as a painless swelling of the testis since about three months. In the case history we found a previously diagnosed hypogonadotropic hypogonadism, which is described in the literature as the so-called Pasqualini syndrome. On palpation, the left testis was about fist-size, scirrhous, mildly pressure sensitive and highly suspicious. Sonography of the testes revealed the enlarged left testis to be completely inhomogeneous with hypo- and hyperdense areas and large spatial requirements with unremarkable perfusion. On the basis of the clinically and sonographically supported diagnosis of a tumour of the left testis and inguinal exposure of the testes was performed. Intraoperative histology of a sample confirmed the diagnosis of a testicular tumour in the sense of a seminoma. A high left ablatio testis was carried out. DISCUSSION: The occurrence of testicular tumours of the seminoma type in association with Pasqualini's syndrome has not previously been described in the literature. Thus, we assume that the seminoma had occurred at this age independently of the Pasqualini syndrome. For the treatment of Pasqualini's syndrome not only hCG but also testosterone have been employed with success. The patient must continue therapy for his whole life. The results of interruption tests confirm that it is not a passing ailment but rather a persisting, endogenous disease. PRACTICAL CONCLUSIONS: Since the molecular genetics and genesis of this disease have not been clarified unambiguously, further clinical and experimental studies are necessary in order to better understand the disease. An increased risk of testicular tumours has not yet been observed on account of the small number of cases of Pasqualini's syndrome.

Localised massive tumourous xanthomatosis of the small intestine.

INTRODUCTION: There are various disorders of the intestine described with accumulations of vacuolated macrophages including single or multiple xanthelasmata, Wolman's disease, cholesteryl ester storage disease (CESD), xanthomatogranulomatotic disease and xantheloma disseminatum. CLINICAL CASE: In this paper, we report on an exceptional case of a 68-year-old male patient with a localised, massive accumulation of vacuolated, most likely lipid-loaded macrophages with an infiltrative pattern in the muscularis mucosa and propria of the small intestine leading to a tumourous mass requiring surgical removal due to impaired gut function. No enlargement of the liver or the spleen and no evidence of general abnormal lipid storage were detected elsewhere. No evidence of Wolman's or CESD was present. Also, on the ultra-structural level, the macrophages contained no cholesterol clefts typical for either Wolman's and CESD. Instead, largely empty, partly large vacuoles were seen, which most likely contained fatty acids removed during processing. DISCUSSION: The pathogenetic mechanism of the massive local accumulation of histiocytic cells in this part of the intestine in our case remains un-clear. In summary, this case demonstrates that on rare occasions histiocytic proliferations can mimic tumourous masses with severe functional impairment of the intestine and thus should be in the differential diagnosis of gastrointestinal motility disorders.

Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model.

BACKGROUND AND AIMS: There is controversy about the effect of the influence of hyperthermia and chemotherapeutic agents on the healing of intestinal anastomosis. The effects of hyperthermic intraperitoneal chemoperfusion (HIPEC) of wound healing after colonic anastomosis were investigated in a rat model. MATERIALS AND METHODS: Thirty-six Wag/Rija rats were randomized into three groups of 12 animals each: group I: control (only colonic anastomosis was performed) (n = 12); group II: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed before HIPEC; group III: HIPEC (mitomycin C in a concentration of 20 mg/m(2) (n = 12) colonic anastomosis was performed after HIPEC. Bursting pressure and bursting sites were recorded 4 and 10 days after intervention. Collagen deposits, inflammation and foreign body reactions were evaluated. RESULTS: Lower bursting pressure and lost of collagen were found in both HIPEC groups and compared with the control group. There was almost no difference between both HIPEC groups. They were noted overwhelmingly at the anastomosis in the HIPEC group. The degree of collagen accumulation was well-correlated with bursting pressure. CONCLUSION: These results have shown that hyperthermic intraperitoneal chemoperfusion (HIPEC) impairs wound healing in colonic anastomosis in rats.

[Congenital cystic juvenile granulosa cell tumor of the testes. Scrotal space-occupying lesion in a male neonate]. / Kongenitaler zystischer juveniler Granulosazelltumor des Hodens. Skrotale Raumforderung beim männlichen Neugeborenen.

This article reports on a newborn with a scrotal space-occupying lesion and histologically proven granulosa cell tumor of the testes. A massive scrotal space-occupying lesion was diagnosed in a full-term male neonate with a birth weight of 2,260 g and body length of 45 cm. Sonography of the right testicle revealed a mass 6x6x4 cm in size which was multiply septate and cystic. The testicular parenchyma was poorly defined with a Swiss cheese appearance. Chemical analysis of blood serum evidenced normal levels of testosterone, beta-HCG, and inhibin B as well as physiologically a clearly elevated alpha-fetoprotein level at 35,350 ng/ml. Based on the clinical and sonographic findings of the right testicle, inguinal surgical exposure of the testes was undertaken. Since there was hardly any testicular parenchyma, we decided to perform high inguinal ablation of the right testicle. This case report confirms that congenital granulosa cell tumors usually exhibit benign behavior during the neonatal period.

Histological response of peritoneal carcinomatosis after hyperthermic intraperitoneal chemoperfusion (HIPEC) in experimental investigations.

BACKGROUND: In selected patients with peritoneal carcinomatosis from colorectal cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. The aim of this study was to evaluate the tumor response of peritoneal carcinomatosis in tumor-bearing rats treated with HIPEC. METHODS: CC531 colon carcinoma (2,5 x 106 cells), implanted intraperitoneally in Wag/Rija rats, was treated by hyperthermic intraperitoneal chemotherapy. After 10 days of tumor growth the animals were randomized into five groups of six animals each: group I: control (n = 6), group II: sham operated animals (n = 6), group III: hyperthermic intraperitoneal perfusion (HIP) without cytostatic drugs, group IV: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group V: mitomycin C i.p. alone in a concentration of 10 mg/m2 (n = 6). After 10 days the extent of tumor spread and histological outcome were analysed by autopsy. RESULTS: All control animals developed extensive intraperitoneal tumor growth. Histological tumor load was significantly reduced in group III and group V and was lowest in group IV. In group II tumor load was significantly higher than in group I. Implanted metastases were significantly decreased in group IV compared with group I and group II. CONCLUSION: These findings indicate that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread.

Successful uterus cryopreservation in an animal model.

Cryopreservation of whole organs would not only be advantageous for experimental biology but also for transplantation surgery. The objective of this study was to evaluate the feasibility of cryopreserving swine uterus as an experimental model of cryopreservation affecting a whole visceral muscle organ. Organs were frozen slowly (0.2 degrees C/min) after arterial perfusion with 10% dimethyl sulfoxide solution for 10 min and equilibration in this solution for 30 min. Viability of the organs was tested by biochemical parameters, LIVE/DEAD fluorescent staining and capability for contraction in a perfusion system. Ten fresh and ten cryopreserved uteri showed living cells in the LIVE/DEAD assay, and were viable for at least 7 h as shown by their ability to produce rhythmic contractions after oxytocin administration. This is the first report known to us on successful cryopreservation of a whole swine uterus to demonstrate that perfusion with a cryoprotectant and slow freezing provides a promising method for cryopreserving whole organs, and may encourage further studies with other cryoprotective agents and freezing protocols as well as other organs.

[Long-term experiences in the therapy of esthesioneuroblastoma]. / Langzeit-Erfahrungen in der Therapie des Asthesioneuroblastoms.

BACKGROUND: Esthesioneuroblastoma is a rare and clinically variable tumor of nasal sinus and skull base and challenging for modern multidisciplinary therapy. There are no generally known prognostic factors or generally accepted standard therapy regimens. PATIENTS AND METHODS: Between 1975 and 2001 26 patients were treated after the diagnosis of esthesioneuroblastoma was established. The cases were evaluated retrospectively. According to the classification of Kadish 1 patient (4 %) had stage A, 16 patients (53 %) stage B and 11 cases (43 %) had stage C tumors. Hyams grading could be obtained in 22 cases (81 %). Tumors were in 12 patients (52 %) graded I or II and in 10 cases tumors had grade III or IV (48 %). Operative therapy was performed in 23 patients (88.5 %), being in 5 patients a single mode therapy. In 18 cases combined therapy was performed (surgery and radiotherapy or radiotherapy and chemotherapy). RESULTS: Actuarial survival was 61.5 % (16/26). Disease specific 10- and 15-year-survival according to the estimation of Kaplan-Meier was 76.2 %. Patients with small tumors (Kadish A/B) had a 15-year-survival of 86.7 % compared to 63.6 % in cases with advanced tumors (Kadish C). In 7 cases (26.9 %) recurrences developed. Salvage therapy was performed in 5 cases (71.4 %) with a success rate and a 15-year survival each of 60 %. CONCLUSIONS: Therapy of esthesioneuroblastoma is challenging because of rarity and biologic variability of the tumor and and because of lack of a standard therapy. An interdisciplinary multimodal therapeutic approach is necessary especially in case of advanced tumors with promising results. Histopathological grading according to Hyams and tumor stage are important factors for survival and prognosis. Although recurrence can occur with high frequency even after prolonged time interval, long time survival can be improved after aggressive salvage therapy. Therefore longterm follow up is mandatory.

The use of an open-freezing system with self-seeding for cryopreservation of mouse ovarian tissue.

Chemoradiotherapy in young women with cancer has substantially improved life expectancy in these patients, but these treatments often cause infertility. One method of preserving fertility is to cryopreserve ovarian tissue. In this study, an automatic open-vessel freezing system with self-seeding was tested for cryopreservation of murine ovarian tissue; the mouse is a species widely used in human and veterinary medical research. The freezing system concerned, is used for cryopreservation of oocytes and embryos in Europe. Twenty severe combined immunodeficiency (SCID) mice were ovariectomized. The ovarian tissue was either directly transplanted heterotopically into the neck muscle (group 1, n = 6) or cryopreserved after equilibration with 1.5 M dimethylsulphoxide and propanediol. After thawing, the tissue was transplanted in SCID mice (group 2, n = 6). Before and after thawing, a part of the ovarian tissue was examined with the LIVE/DEAD fluorescent viability staining. The count of follicles revealed intact (fresh 24.1%/thawed 21.7%), impaired (fresh 35.1%/thawed 35.4%), and dead follicles (fresh 40.8%/thawed 42.9%). The healthy follicular loss because of the cryopreservation was 10.0%. All recipient mice were killed after 3 weeks. Transplanted ovarian tissue was found macroscopically in all mice. Histological examination showed several growing follicles in all developmental phases in both groups of SCID mice [group 1 (fresh grafts): 315 +/- 76.3 (mean +/- SD); group 2 (cryopreserved grafts): 237 +/- 63.4]. These results demonstrate that the use of an open-freezing system allows the survival of cryopreserved mouse ovarian tissue.

The impact of immunological parameters on the development of phantom pain after major amputation.

OBJECTIVES: To investigate the relationship between local and systemic inflammatory markers and phantom limb pain. METHODS: In 39 consecutive patients undergoing major amputations nerve biopsies, serum and clinical data was collected. Patients were followed up for 12 months to report on the incidence and severity of phantom limb pain. RESULTS: After 12 months, 78% of the surviving patients had phantom pain, the symptom usually commencing within 14 days of operation. The severity of macrophage infiltration within the nerve biopsy was negatively correlated to the inception of phantom pain ( P = 0.026). While serum TNF-alpha concentration was positively correlated to mortality ( P = 0.021). CONCLUSIONS: The immune status existing before the amputation and the local immunological milieu influence the onset of phantom pain.

Neoadjuvant chemotherapy does not increase postoperative complication rate after resection of colorectal liver metastases.

BACKGROUND: This paper discusses, whether neoadjuvant chemotherapy has an impact on the rate of postoperative complications after primary resection of liver metastases from colorectal carcinoma. METHODS: Of 183 patients 64 were studied. The patients were subdivided into two matched groups of 32 patients each-prior neoadjuvant chemotherapy (CT-group) vs. (control-group, primary resection). RESULTS: There were no postoperative complications in 24 patients of the control group (75%) and 26 patients of the CT-group (81%). Following prior chemotherapy, no major complications such as liver failure were observed, even after extended resections. CONCLUSION: Neoadjuvant chemotherapy prior to surgical resection of colorectal liver metastases does not result in an increase of postoperative morbidity and mortality.

[Angiomyolipoma of the colon - case report and review of the literature]. / Das Angiomyolipom des Kolons - Fallbericht und Literaturübersicht.

Angiomyolipoma is one of the benign hamartomas that is found sporadically or associated with tuberous sclerosis. It is a rare soft tissue tumor involving mostly the kidneys, sometimes other visceral organs. The tumor is composed of smooth muscle cells, adipocytes and small sized hyalinized vessels. We present the case of a 74-year-old man with a bifocal angiomyolipoma of the colon. This diagnosis was confirmed at surgery, where a partial colectomy was performed. Histologic examination disclosed the tumor. The patient had no signs of family history of tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of bifocal colonic angiomyolipoma.

Late pulmonary metastasis in uterine PEComa.

Perivascular epithelioid cell tumours (PEComas) other than angiomyolipoma, clear cell "sugar" tumour of the lung, and lymphangioleiomyomatosis are very rare mesenchymal tumours. The uterus seems to be the most prevalent site of involvement, but only 13 cases of uterine PEComa have been described. Three of these cases exhibited local aggressive behaviour and only one showed metastasis. Because of the extremely small number of cases, PEComas are considered tumours of uncertain malignant potential. This report describes a 68 year old woman, who presented with multiple pulmonary lesions seven years after the initial diagnosis of well differentiated endometrial stromal sarcoma. Histological and immunohistochemical analysis of the pulmonary lesions, in addition to re-evaluation of the primary uterine tumour, led to the final diagnosis of metastatic uterine PEComa. The findings indicate that any PEComa might have malignant potential. Spreading of this tumour to other organs might become evident even several years after primary manifestation.