First presentation of a frameshift mutation in the SETD2 gene of a juvenile psammomatoid ossifying fibroma (JPOF) associated with an aneurysmal bone cyst.

BACKGROUND: The rarity of juvenile psammomatoid ossifying fibroma (JPOF) and lack of cytogenetic studies prompted us to report a novel SETD2 gene mutation in a benign odontogenic tumour. CASE PRESENTATION: A 21-year-old man presented with a hard, expanded mandibular cortex. Computed tomography revealed multilocular radiopacity in the mandible; this was reconstructed via segmental mandibulectomy using a vascularised iliac crest flap. Based on the clinical and histological findings, we diagnosed JPOF associated with an aneurysmal bone cyst. Microscopically, the solid area was characterised by many rounded or angular ossicles in a cellular fibrous stroma. The stromal cells were spindle-like or stellate. Next-generation sequencing detected a frame shift mutation of the SETD2 gene, while the copy number was normal. CONCLUSIONS: Our findings suggest further genetic studies should be performed to assess whether this mutation is related to tumour genesis. .

Relevance of surgery in patients with non-variceal upper gastrointestinal bleeding.

INTRODUCTION: Upper GI bleeding remains one of the most common emergencies with a substantial overall mortality rate of up to 30%. In severe ill patients, death does not occur due to failure of hemostasis, either medical or surgical, but mainly from comorbidities, treatment complications, and decreased tolerated blood loss. Management strategies have changed dramatically over the last two decades and include primarily endoscopic intervention in combination with acid-suppressive therapy and decrease in surgical intervention. Herein, we present one of the largest patient-based analysis assessing clinical parameters and outcome in patients undergoing endoscopy with an upper GI bleeding. Data were further analyzed to identify potential new risk factors and to investigate the role of surgery. PATIENTS AND METHODS: In this retrospective study, we aimed to analyze outcome of patients with an UGIB and data were analyzed to identify potential new risk factors and the role of surgery. Data collection included demographic data, laboratory results, endoscopy reports, and details of management including blood administration, and surgery was carried out. Patient events were grouped and defined as "overall" events and "operated," "non-operated," and "operated and death" as well as "non-operated and death" where appropriate. Blatchford, clinical as well as complete Rockall-score analysis, risk stratification, and disease-related mortality rate were calculated for each group for comparison. RESULTS: Overall, 253 patients were eligible for analysis: endoscopy was carried out in 96% of all patients, 17% needed surgical intervention after endoscopic failure of bleeding control due to persistent bleeding, and the remaining 4% of patients were subjected directly to surgery. The median length of stay to discharge was 26 days. Overall mortality was 22%; out of them, almost 5% were operated and died. Anticoagulation was associated with a high in-hospital mortality risk (23%) and was increased once patients were taken to surgery (43%). Patients taking steroids presented with a risk of death of 26%, once taken to surgery the risk increased to 80%. Patients with liver cirrhosis had a risk of death of 42%; we observed a better outcome for these patients once taken to theater. Clinically, once scored with Blatchford score, statistical correlation was found for initial need for blood transfusion and surgical intervention. Clinical as well as complete Rockall score revealed a correlation between need for blood transfusion as well as surgical intervention in addition with a decreased outcome with increasing Rockall scores. Risk factor analysis including comorbidity, drug administration, and anticoagulation therapy introduced the combination of tumor and non-steroidal antirheumatic medication as independent risk factors for increased disease-related mortality. CONCLUSION: UGIB remains challenging and endoscopy is the first choice of intervention. Care must be taken once a patient is taking antirheumatic non-steroidal pain medication and suffers from cancer. In patients with presence of liver cirrhosis, an earlier surgical intervention may be considered, in particular for patients with recurrent bleeding. Embolization is not widely available and carries the risk of necrosis of the affected organ and should be restricted to a subgroup of patients not primarily eligible for surgery once endoscopy has failed. Taken together, an interdisciplinary approach including gastroenterologists as well as surgeons should be used once the patient is admitted to the hospital to define the best treatment option.

[Implementation of Robot-Assisted Surgery]. / Aufbau eines Roboterprogramms.

The implementation of robot-assisted surgery requires a multi disciplinary approach with appropriate training and cooperation of surgical, anesthetic and technical staff. Besides acquiring the technical skills and getting used to complex technique, patient selection and an appropriate frequency of procedures are required to avoid complications.

[Management of delayed complications after esophagectomy]. / Management von Spätkomplikationen nach Ösophagusresektion.

Esophagectomy and subsequent reconstruction represent major physiological insults to the upper gastrointestinal (GI) tract, which as a consequence can lead to malnutrition, dysphagia and reflux. From a technical perspective, operative reconstruction involving gastric pull-up with a 2-3 cm wide tube and an anastomosis cranial to the azygos vein may minimize the symptoms. Overall, the problems tend to improve approximately 6 months after the operation. Newly occurring delayed physical functional impairments with previously known underlying malignant disease may be indicative of cancer relapse. Interventional techniques, such as stent placement or brachytherapy may be better suited for treatment of recurrent disease.

[Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and medical therapy. Developed during the 10th German GIST-meeting, Göttingen]. / Gastrointestinale Stromatumoren (GIST)--Neues zu Pathologie, Chirurgie und medikamentöser Therapie. Erarbeitet im Rahmen des 10. Deutschen GIST-Treffens, Göttingen.

The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.

Neuroendocrine adenoma of the middle ear (NAME) mimicking as chronic otitis media with an episode of facial nerve palsy.

OBJECTIVES: To increase awareness of neuroendocrine adenomas of the middle ear (NAME), rare lesions often mistaken for other entities or chronic otitis media. Histogenesis remains controversial, although the consensus tends toward a pluripotent stem cell of the middle ear mucosa as the origin of the lesion. The tumour is characterised by dual differentiation with exocrine and endocrine components. The most common symptoms are conductive hearing loss, tinnitus and vertigo. The treatment of choice is complete surgical removal of the tumour with no adjuvant radiotherapy being required. CASE REPORT: We report the case of a 23-year-old man presenting with chronic otitis media, conductive hearing loss, vertigo and tinnitus who, some years previously, had suffered from an episode of facial nerve palsy. Conservative therapy failed and so surgery was performed. Tumour-like masses were encountered and histological and immunohistochemical examination revealed a neuroendocrine adenoma of the middle ear. CONCLUSION: This rare entity should be considered as differential diagnosis when treating chronic inflammatory disease not responding to conservative therapy or dealing with unclear expansive processes of the middle ear. MRI scans should be performed since CT scans are inconclusive.

Post-mortem histopathological investigations of the bone marrow in forensic medicine: an important issue for both the forensic and clinical pathologist.

In the forensic literature only a few scientific reports are dealing with series of histopathological bone marrow (BM) investigations, mainly concerning changes after drug abuse and alcoholic consumption. In a period of 13 years (1995-2008) we routinely investigated 225 BM specimens from anterior iliac crests taken at forensic autopsies if the cause of death was unclear or vague, septicaemia was suspected or known, in cases of presumed haemorrhagic diathesis or bleeding tendencies, spleens were found to be enlarged or intoxications were suspected or proofed. In 78 cases (34.66%) abnormal histopathologic changes were found. Forty of those revealed neoplastic, mainly haematological diseases, which were unknown during lifetime. Referring to our findings, extraction of post-mortem BM specimens for histopathological investigations should become an essential issue for both the forensic and clinical pathologist.

[Cerebrotendinous xanthomatosis. Hereditary lipid storage disease leading to bilateral swelling of Achilles tendon]. / Zerebrotendinöse Xanthomatose. Bilaterale Achillessehnenschwellung durch angeborene Stoffwechselstörung.

Cerebrotendinous xanthomatosis is a rare hereditary lipid storage disease characterised by deposits of cholestanol. In a female patient with bilateral swelling of the Achilles tendon who underwent biopsy, cerebrotendinous xanthomatosis was confirmed by combining disease patterns. She suffered from ataxia, depression, epilepsy, reduced intelligence, bilateral cataracts, gallstones, and atherosclerosis. Concentration of serum cholestanol was 10 times higher than normal. As causal therapy, ursodeoxycholic acid and statin drugs were prescribed to halt progression.

Hyperplastic epithelial lesions of the vocal folds: combined use of exfoliative cytology and laryngostroboscopy in differential diagnosis.

The mainstay of successful tumor therapy is early detection of neoplastic tissue. Although exfoliative cytology has proven to be a reliable tool, its importance is still underestimated. Laryngostroboscopy is the most important tool for functional investigation in laryngological and phoniatric diagnosis. Stroboscopic evaluation allows early detection of infiltrative processes of the vocal folds. Aim of our study was to demonstrate that combination of both, exfoliative cytology and stroboscopy, provides a highly sensitive and easy to perform method in differential diagnosis of epithelial hyperplastic lesions of the vocal folds. In 130 patients with varying degrees of vocal fold keratosis up to glottic cancer, preoperative layngostroboscopy was performed. Stroboscopy was classified pathological in case of reduced or abolished amplitude of vocal fold vibration and/or reduced or abolished mucosal wave propagation. Under general anaesthesia histology with corresponding cytological specimens were obtained. The latter were classified in three groups reaching from normal (I), dysplastic (II), up to malignant (III) cytology. Invasive carcinoma was diagnosed in 32 cases by histology, corresponding malignant cytology was found in 21 specimens (sensitivity: 74%). By certain combination of cytology with pathological stroboscopy, a sensitivity of more than 97% can be achieved. Combination of cytology and stroboscopy allows detection of glottic cancer with a sensitivity of 97%, in contrast to 74% as found by cytology alone. This combination can be used as preliminary or sorting procedure and gives the opportunity of early detection, as well as for follow-up examinations. For repeated biopsies can cause scars with consecutive voice impairment, this procedure is very smooth but nevertheless reliable method.

Expression of platelet-derived growth factor receptor in low-grade endometrial stromal sarcomas in the absence of activating mutations.

AIMS: To investigate platelet-derived growth factor receptor (PDGFR)alpha and PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS). Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors, which act through an inhibitory effect on class 3 receptor tyrosine kinase members such as PDGFRalpha, PDGFRbeta and c-kit. METHODS AND RESULTS: The immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37 archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour cells) and positive (weakly positive 11-50% positive cells; strongly positive > 50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by 19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for PDGFRbeta, but endothelial cells stained positive. A mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen metastatic ESS from three patients detected no mutations leading to amino acid changes in the mature protein. CONCLUSIONS: Patients with PDGFRalpha+ ESS may benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and paracrine stimulation loops, blocking neovascularization and enhancing the effects of chemotherapy.

Immunohistochemical and mutational analysis of PDGF and PDGFR in desmoid tumours: is there a role for tyrosine kinase inhibitors in c-kit-negative desmoid tumours?

AIM: To determine the platelet-derived growth factor (PDGF) alpha and beta status of desmoid tumours. Desmoid tumours are rare monoclonal neoplasms that appear to have no metastatic potential. Surgical resection and radiotherapy in the event of a positive surgical margin is the first-line treatment. Recurrences are frequent. Treatment results using non-steroidal anti-inflammatory agents, anti-oestrogen compounds and other agents such as Imatinib mesylate have been published. Therapy with Imatinib has been proposed as a therapeutic option, although in most reports desmoid tumours are reported to be c-kit-. METHODS AND RESULTS: We performed immunohistochemical analysis on 124 archived samples (85 patients) of desmoid tumours using antibodies to PDGFalpha, PDGFbeta, PDGFRalpha and PDGFRbeta. All desmoid tumours showed immunoreactivity with antibodies to PDGFalpha and PDGFRalpha, whereas with antibodies to PDGFbeta and PDGFRbeta no specific reaction could be detected. Mutational analysis of PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) on frozen material from 14 patients was performed, but no mutations leading to amino acid changes in the mature protein were identified. CONCLUSION: The absence of an activating mutation in a protooncogene does not exclude the efficacy of tyrosine kinase inhibitors through other possible mechanisms, and these might be a therapeutic option for patients with desmoid tumours in whom established local and systemic approaches fail to control the disease.

Survival benefit in patients after palliative resection vs non-resection colon cancer surgery.

AIM: To evaluate survival in patients undergoing palliative resection versus non-resection surgery for primary colorectal cancer in a retrospective analysis. METHODS: Demographics, TNM status, operating details and survival were reviewed for 67 patients undergoing surgery for incurable colorectal cancer. Palliative resection of the primary tumor was performed in 46 cases in contrast to 21 patients with non-resection of the primary tumor and bypass surgery. Risk factors for postoperative mortality and poor survival were analyzed with univariate and multivariate analyses. RESULTS: The two groups were comparable in terms of age, gender, preoperative presence of ileus and tumor stage. Multivariate analysis showed that median survival was significantly higher in patients with palliative resection surgery (544 vs 233 d). Differentiation of the tumor and tumor size were additional independent factors that were associated with a significantly poorer survival rate. CONCLUSION: Palliative resection surgery for primary colorectal cancer is associated with a higher median survival rate. Also, the presence of liver metastasis and tumor size are associated with poor survival. Therefore, resection of the primary tumor should be considered in patients with non-curable colon cancer.

["Fast-Track" for laparoscopic-assisted rectum resection--what can be achieved? First results of a feasibility study]. / "Fast-Track" bei laparoskopisch assistierter Rektumresektion--was kann erreicht werden? Erste Ergebnisse einer Machbarkeitsstudie.

AIM: "Fast-track" multimodal rehabilitation is increasingly entering the perioperative management strategies in colon surgery aiming at minimized perioperative morbidity and accelerated recovery. So far little is known about the complementary effects of minimally invasive surgery along with "fast-track" rehabilitation in the treatment of rectal cancer. The aim of this pilot study was to investigate the influence of "fast-track" perioperative management on morbidity, recovery and length of hospital stay in laparoscopically-assisted rectum resections and to compare those data to earlier results. METHODS: An interdiciplinary "fast-track" multimodal rehabilitation strategy with avoidance of mechanical bowel cleansing, with a restrictive intravenous intra- and postoperative fluid regimen, forced mobilisation, and early enteral nutrition was introduced into clinical practice and applied in 16 laparoscopically-assisted rectum resections. Data were collected in the course af a prospective analysis. The mean patient age was 62 (42-79) years. RESULTS: Mean time of surgery was 245 (SD 46) min, and the mean intraoperative infusion rate was 11.2 (SD 2.6) ml/kg/BW. On day 2, 14 of the 16 patients tolerated solid food and 12 patients had had bowel movements. All patients returned to their initial body weight by day 4. The median postoperative hospital stay was 7.5 days (6-20), 12 patients were discharged between day 6 and 8. Two patients were readmitted for intestinal atony, one patient developed an anastomotic leakage. CONCLUSIONS: "Fast-track" rehabilitation is feasible in rectum surgery and seems to complement the beneficial effects of minimally invasive surgery without increasing the complication rate.

Crohn's disease activity index and Vienna classification--is it worthwhile to calculate before surgery?

BACKGROUND: Crohn's disease (CD) patients with increased disease activity may reveal an increased risk for perioperative complications. The "Crohn's disease activity index" (CDAI) and the "Vienna classification" (VC) were developed for standardized disease activity estimations. The significance of these scores to predict extent, type and early outcome of surgery in CD patients was analyzed. METHODS: In 179 surgically treated CD patients, the CDAI and VC were assessed from a prospective database. Relations of the scores with CD risk factors, type, number, location and complications of surgery were analyzed. RESULTS: VC behavior and location subtypes were associated with distinct types of surgery (i.e. "strictureplasty" in "stricturing disease", "colon surgery" in "colon involvement"), but not with surgery type and extent or outcome. Surgery extent (i.e. with 5 vs. 3 "surgical sites" 425 +/- 25 vs. 223.3 +/- 25) and complications (357.1 +/- 36.9 (with) vs. 244.4 +/- 13 (without)) were associated with elevated CDAI levels; however, nicotine abuse remained the only significant risk factor for perioperative complications after multiple logistic regression. CONCLUSION: The significance of VC or CDAI for predicting the extent of surgery or complications is limited. None of the tested variables except preoperative nicotine abuse influenced the likelihood for perioperative complications.

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial.

Oral capecitabine (Xeloda) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings pound3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Immunohistochemical analysis of desmoid tumours.

BACKGROUND/AIMS: Although the standard treatment for desmoid tumours is complete surgical resection with wide margins, the optimal adjuvant treatment for recurrent or inoperable disease is unclear, often being based on sporadic immunohistochemical reports with a low number of cases. Therefore, a large immunohistochemical study was performed, to provide a theoretical basis for adjuvant treatment regimens. METHODS: One hundred and sixteen tissue samples from 80 patients (49 female, 31 male; mean age, 34 years; range, 0-83) with desmoid tumours (46 extra-abdominal, 21 abdominal, 13 intra-abdominal) were tested for oestrogen receptors alpha and beta, progesterone and androgen receptors, and somatostatin, in addition to HER2, cathepsin D, Ki-67, and c-KIT by immunohistochemistry. RESULTS: All samples were negative for oestrogen receptor alpha, HER2, and the progesterone receptor. Positive staining for the androgen receptor was found in six extra-abdominal cases. Staining for oestrogen receptor beta was positive in four extra-abdominal, two abdominal, and one intra-abdominal case. Staining for somatostatin was positive in six extra-abdominal, two abdominal, and one intra-abdominal case, and staining for cathepsin D was positive in all cases. Positive staining for Ki-67 was found in 14 extra-abdominal, three abdominal, and three intra-abdominal cases. C-KIT was detectable in one abdominal case only. CONCLUSIONS: The data from this immunohistochemical study show that the published effects of antioestrogens and imatinib mesylate in the treatment of aggressive fibromatoses may not be attributable to oestrogen receptor alpha or c-KIT expression.

Expression of BCL-2 in liver grafts after adenoviral transfer improves survival following prolonged ischemia and reperfusion in rat liver transplantation.

UNLABELLED: Apoptosis represents a crucial mechanism of ischemia-reperfusion injury after liver transplantation. Bcl-2 may inhibit apoptosis. This study investigates the effect on ischemia/reperfusion injury and survival after rat liver transplantation of adenoviral bcl-2 transfer into donor livers. METHODS: A nonreplicative adenovirus, expressing bcl-2 under control of a tetracyclin-inducible promoter (adv TetOn bcl-2) was used to treat male Lewis rats in combination with a second adenovirus transferring the TetOn repressor protein under control of a cytomegalovirus promoter (advCMVRep). Virus induction was achieved by addition of doxycyclin to the drinking water. Controls were pretreated with a control adenovirus (advCMV GFP) or with doxycycline. Liver transplantations were performed after 16-hour graft storage. Bcl-2 expression was evaluated by Western blot and immunohistology. Survival was monitored for 7 days, and tissue specimens were collected at 24 hours and 7 days post reperfusion. RESULTS: After pretreatment with advTetOn bcl-2/adv CMVRep, intrahepatic bcl-2 expression was evident at 24 hours and 7 days but was absent among controls. Bcl-2 expression was detected in hepatocytes and, to a high degree, in sinusoidal lining cells. TUNEL-positive sinusoidal lining cells were strikingly reduced after bcl-2 transfer (0.1 +/- 0.3 cells/hpf, mean +/- SD) compared to control virus (4.8 +/- 2.3) or doxycyclin-treated grafts (1.3 +/- 0.2); P < .05. After bcl-2 treatment, survival after transplantation was 100%, whereas it was 50% in both control groups (P = .035). CONCLUSION: The study shows the feasibility of transient, doxycyclin-controlled adenoviral gene transfer in a transplantation model. Bcl-2 expression increased survival after ischemia/reperfusion in rat liver transplantation, potentially through protection of sinusoidal lining cells.

Giant hamartoma of the retro- and parapharyngeal region. Case report and review of literature.

Hamartoma designates a tumor-like, non-neoplastic malformation, or in-born error of tissue development, often with an abnormal mixture of tissue indigenous to the region. In the head and neck, epithelial and mesenchymal hamartomas are uncommon. We present the case of a 9-year-old boy with a huge hamartoma of 800ml (cm(3)) volume of the right retro- and parapharyngeal region. It had fully occluded the nasopharynx, indented the base of the tongue and left a minimal airway passage transorally. Food uptake was severely hampered by the lesion. The patient underwent a combined transoral and external approach for complete resection of the tumor. This is the first reported case of a retro- and parapharyngeal hamartoma with metaplastic bone formation in the literature and further more, the largest hamartoma in head and neck ever reported in this age group.