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.

[Robotic Rectal Cancer Surgery]. / Roboterassistierte Rektumkarzinomchirurgie.

BACKGROUND: The oncological outcome of patients with rectal cancer has improved considerably over the past few decades. This is mainly due to the introduction of the surgical concept of total mesorectal excision (TME) and the implementation of multimodal treatment strategies. Additionally, it has recently been demonstrated that the oncological results of open and laparoscopic TME are comparable. For some time there has been an ongoing debate on the potential relevance of robotic assistance systems in visceral surgery. The aim of this study was to evaluate the operative and perioperative outcomes of patients with rectal or rectosigmoid cancer, who were operated on using the Da Vinci Surgical System. PATIENTS AND RESULTS: We retrospectively analysed the outcomes of 202 consecutive patients, who were operated between September 2010 and November 2015 in three Surgical Centers. The cohort consisted of 136 men and 66 women with a mean BMI of 28. We performed the following procedures: 49 anterior rectal resections, 119 low anterior rectal resections, and 34 abdominoperineal excisions. Conversion to an open procedure was required in 13 patients. Non-surgical complications (n = 27) occurred in 24 patients (12%) and surgical complications (n = 67) in 62 patients (31%). Most complications were due to abdominal or sacral wound infections (n = 25) and anastomotic leaks (n = 18). The mortality rate within 30 days was 2%. The rate of R0 resections was 95%, with circumferential resection margins being negative in 98% of the patients. The quality of the mesorectal resection was scored as good in 91% of the patients. CONCLUSIONS: The Da Vinci Surgical System can be used safely and with a low complication rate for surgical treatment of rectal cancer. While primary evidence suggests that the outcome of robotic-assisted surgery is comparable with open and laparoscopic surgery, its definitive value has to be determined upon publication of the prospective randomized ROLARR trial. The main advantages of the Da Vinci system are its endowristed instruments with multiple degrees of freedom and its optimised visualisation (3D, stable camera platform controlled by the surgeon). Another positive feature is the significant ergonomic advantage for the surgeon.

Metastatic recurrence after complete resection of colorectal liver metastases: impact of surgery and chemotherapy on survival.

PURPOSE: Surgery is the standard of care for resectable colorectal liver metastases (CRC-LM). Unfortunately, 60% of patients develop secondary metastatic recurrence (SMR) after R0-resection of CRC-LM. We investigated the impact of surgical re-intervention and chemotherapy (Ctx) on survival in a consecutive series of patients with SMR. METHODS: From 01/2001 to 11/2011, 104 out of 178 consecutive patients with R0-resection of CRC-LM developed SMR and were evaluated. The impact of surgical and Ctx re-interventions on recurrence free (RFS) and cancer-specific survival (CSS) was analyzed. Median follow-up was 28.0 (95%CI: 19.4-37.4) months. RESULTS: SMR occurred in 81 patients at a single site (49× liver, 18× lung, 14× other) and in 23 patients at multiple sites. Forty-two patients were scheduled for primary surgery. Fifty-three patients were classified as non-resectable and treated with median 5.0 [IQR, 3.0-10.0] cycles of Ctx, combined with an EGFR/VEGF-antibody in 27 patients. Nine patients received best supportive care only. R0/R1 resection could be achieved in 35 patients primarily and even in 8 patients secondarily after Ctx. Surgical morbidity and mortality were 16 and 0%, respectively. The 5-year RFS rates for patients with R0 versus R1-resection were 22 and 24% (p = 0.948). The 5-year CSS rate for R0/R1-resected patients was 38% versus 10% for those patients treated by Ctx alone (p < 0.001). CONCLUSION: In SMR, surgical re-intervention is feasible and safe in a remarkable number of patients and offers significantly longer CSS compared to patients without resection.

Bilobar spreading of colorectal liver metastases does not significantly affect survival after R0 resection in the era of interdisciplinary multimodal treatment.

PURPOSE: Bilobar colorectal liver metastases (CRLM) are often considered incurable or associated with poor prognosis even after R0 resection. In this single-center study, we evaluate the impact of CRLM spreading on recurrence-free survival (RFS) and cancer-specific overall survival (CSS) after R0 resection of CRLM with respect to multimodal treatment strategies including perioperative chemotherapy and multistep resections. METHODS: Between January 2001 and December 2010, R0 resection could be achieved in 70 patients with bilobar and 100 with unilobar CRLM. Extent of disease, perioperative chemotherapy, surgical procedures, adjuvant treatment, histopathological workup, RFS, and CSS were compared between both cohorts. RESULTS: Forty-six (66 %) patients with bilobar and 26 (26 %) patients with unilobar CRLM received preoperative chemotherapy (p < 0.001). For bilobar CRLM, more extended and multistep resection including portal vein occlusion were performed (29 % versus 3 %; p < 0.001). Morbidity (39 % versus 28 %, p = 0.183) and mortality (1 % versus 3 %, p = 0.644) rates were comparable in both patients' cohorts. Postoperative therapy was applied in adjuvant intent to 42 (60 %) versus 51 (51 %) patients (p = 0.275). The 5-year RFS and CSS rates were 24 % versus 31 % (p = 0.169) and 42 % versus 55 % (p = 0.131), respectively. CONCLUSIONS: To our single-center experience, there is no significant effect of CRLM spreading (bilobar versus unilobar) on RFS and CSS rates. Bilobar CRLM are more likely to require extended multimodal efforts to achieve R0 resection.

[Rectal cancer: current status of multimodal therapy--when and how?]. / Rektumkarzinom: Aktueller Stand der multimodalen Therapie--wann und wie?

Preoperative 5-fluorouracil-based radiochemotherapy (RCT) followed by quality assessed total mesorectal excision (TME surgery) are the two most important elements of multimodal treatment for patients with locally advanced rectal cancer (UICC stages II and III). The optimum sequence of these neoadjuvant modalities complemented by adjuvant (postoperative) chemotherapy, has been addressed in several randomised trials. Especially within the trials of the German Rectal Cancer Study Group (GRCSG), preoperative RCT has been shown to be superior to postoperative treatment for a variety of endpoints (pathologically confirmed complete tumour remission (pCR), RCT-induced tumour regression, R0 resection rates (including circumferential resection margins) and long-term locoregional control). This neoadjuvant multimodal strategy has decreased the 5-year and 10-year local recurrence rates below 10%, and the development of distant metastases (e.g., 35% to 45% liver metastases) remains the predominant reason for failure. Furthermore, approximately 25% of patients do not receive adjuvant chemotherapy, mainly due to surgical complications, patients' refusal or the investigator's discretion. Thus, today, integrating more effective systemic therapy into (preoperative) multimodal regimens is the most accepted challenge! But from the clinical point of view this demand is also a dilemma. The question to be addressed is how and when to apply intensified systemic therapy with adequate dosage and intensity as well as acceptable treatment-associated toxicity. The increase of therapeutic options requires valid predictive biomarkers that may help to stratify patients into regimens associated with low toxicity (5-FU monotherapy alone) or into more intensified treatment for better long-term outcome. In summary, the use of biomarkers for individualised risk-adapted treatment is one of the most promising areas of clinical investigations, not only in rectal cancer. The assessment of individual tumour response, toxicity, and prognosis during multimodal treatment of rectal cancer as a model of a very common solid tumour offers radiooncologists, surgeons, pathologists, gastroenterologists as well as oncologists immense insights into the under-standing of tumour biology.

The mesopancreas is the primary site for R1 resection in pancreatic head cancer: relevance for clinical trials.

PURPOSE: The prognosis of patients with pancreatic cancer remains poor, even after potentially curative R0 resection. This discrepancy may be due to the histopathological misclassification of R1 cases as curative resections (R0) in the past. MATERIALS AND METHODS: To test this hypothesis, color coding of all resection margins and organ surfaces as part of a standardized histopathological workup was implemented and prospectively tested on 100 pancreatic head specimens. RESULTS: Thirty-five patients were excluded from the analysis owing to the pathohistological diagnosis; only pancreatic ductal adenocarcinoma, distal bile duct adenocarcinoma, and periampullary adenocarcinoma were included. Applying the International Union Against Cancer criteria, 32 cancer resections were classified R0 (49.2%), while 33 cases turned out to be R1 resections (50.8%). The mesopancreas was infiltrated in 22 of the 33 R1 resection specimens (66.6%). It proved to be the only site of tumor infiltration in 17 specimens (51.5%). Applying the Royal College of Pathologists' criteria, 46 resections were classified R1 (70.8%). As expected, the mesopancreas again was the most frequent site of noncurative resection (n = 27; 58.7%). CONCLUSION: Using the intensified histopathological workup for pancreatic head cancer specimens resulted in an increased rate of R1 resections and the mesopancreas represents the primary site for positive resection margins. Such results are of relevance for patients' stratification in clinical trials.

Papular exanthem discloses acute myeloid leukaemia: interphase fluorescence in situ hybridization revealed deletion of p53 and gain at 8q22/8q24/Tel8q without trisomy 8.

We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.

[Extramural Gastral GIST Manifested by Spontaneous Perforation with Acute Intraabdominal Bleeding and Haemoperitoneum]. / Extramuraler GIST des Magens mit Manifestation durch Spontanruptur und akuter intraabdomineller Blutung mit Hämatoperitoneum.

We report on the case of a 38-year-old male patient with a huge extramural gastrointestinal stromal tumour (GIST) of the stomach, located in the left upper and middle abdominal cavity that was diagnosed on the basis of a spontaneous -rupture and consecutive haemoperitoneum. The lesion was resected completely in an emergency operation. The tumour was classified as a high-risk lesion for aggressive biological behaviour and with regard to tumour rupture with perforation of the serosa, an adjuvant systemic therapy was indicated.

Two-stage hepatectomy (R0) with portal vein ligation--towards curing patients with extended bilobular colorectal liver metastases.

BACKGROUND AND AIMS: Patients with bilobular colorectal liver metastases (CRLM) experience poor prognosis, especially when curative resection cannot be achieved. However, resectability in these patients is often limited by low future remnant liver volume (FRLV). The latter can be enhanced by a two-stage liver resection, using portal vein ligation to induce liver hypertrophy. The aim of this prospective pilot study was to evaluate safety, secondary resectability, and time to recurrence of two-stage hepatectomy with portal vein ligation (PVL) and complete surgical clearance of the FRLV in patients with bilobular CRLM. MATERIALS AND METHODS: Out of 24 patients (63+/-8.26 years) with extended bilobular CRLM (metachronous n=10, synchronous n=14), 18 received preoperative 5-FU-based chemotherapy combined with oxaliplatin or irinotecan. Staging included thoracoabdominal computed tomography and (18)F-fluorodeoxyglucose-positron emission tomography scans. First-stage procedure consisted of PVL, resection of all CRLM in the FRLV, and radiofrequency ablation (RFA) of CRLM situated near the future resection plane. RESULTS: During first-stage procedure, 7x RFA, 4x non-anatomical resections, and 4x bisegmentectomies were performed additionally to PVL. FRLV/body-weight ratio increased from 0.4% to 0.6% within 55 days (median) after PVL. Second-stage hepatectomy was performed in 19 patients without tumor progression. R0 resection was possible in 14 patients. During a median follow-up of 17 months, intrahepatic recurrence occurred in two, and extrahepatic recurrence in nine out of 14 patients. CONCLUSION: Two-stage hepatectomy with PVL and complete surgical clearance of FRLV is safe even after intensified systemic chemotherapy resulting in a curative resection rate of 58.3% (73.7% of re-explored cases).

[Evidence-based surgery of rectal cancer]. / Evidenzbasierte Chirurgie des Rektumkarzinoms.

Over the past four decades, the treatment algorithms for rectal cancer have fundamentally changed, which resulted in a considerable improvement of oncological outcomes. In this context, the surgical concept of total mesorectal excision and the implementation of multimodal treatment strategies represent key milestones. These improvements were complemented by a standardized histopathological work-up of the surgical specimen and the introduction of high-resolution magnetic resonance imaging (MRI) diagnostics. In addition, novel surgical techniques have been introduced, such as laparoscopic and robotic rectal resection. Other technological innovations include intraoperative pelvic neuromonitoring and fluorescence imaging. This review highlights the current evidence for selected, sometimes controversially discussed principles of surgical treatment strategies in rectal cancer.

[Is acute appendicitis a surgical emergency?] / Ist die akute Appendizitis ein chirurgischer Notfall?

Acute appendicitis is one of the most common causes of acute abdomen. Whereas patients with a complicated form of appendicitis need prompt surgery, short preoperative delays are tolerable for patients with uncomplicated appendicitis. Delays of up to 8 h between hospital admission and beginning of surgery are not associated with increased rates of perforation or postoperative complications.

Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping.

We revisited the cytogenetic alterations of the cervical adenocarcinoma cell line HeLa through the use of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH). SKY analysis unequivocally characterized all abnormal chromosomes. Chromosomal breakpoints were primarily assigned by simultaneous assessment of SKY painted chromosomes and inverted 4,6-diamidino2-phenylindole banding from the same cell. Twenty clonally abnormal chromosomes were found. Comparison with previously reported HeLa G-banding karyotypes revealed a remarkably stable cytogenetic constitution because 18 of 20 markers that were found were present before. The classification of 12 markers was refined in this study. Our assignment of the remaining six markers was consistent with those described in the literature. The CGH map of chromosomal copy number gains and losses strikingly matched the SKY results and was, in a few instances, decisive for assigning breakpoints. The combined use of molecular cytogenetic methods SKY, CGH, and FISH with site-specific probes, in addition to inverted 4,6-diamidino-2-phenylindole or conventional G-banding analysis, provides the means to fully assess the genomic abnormalities in cancer cells. Human papillomaviruses (HPVs) are frequently integrated into the cellular DNA in cervical cancers. We mapped by FISH five HPV18 integration sites: three on normal chromosomes 8 at 8q24 and two on derivative chromosomes, der(5)t(5;22;8)(qll;q11q13;q24) and der(22)t(8; 22)(q24;q13), which have chromosome 8q24 material. An 8q24 copy number increase was detected by CGH. Dual-color FISH with a c-MYC probe mapping to 8q24 revealed colocalization with HPV18 at all integration sites, indicating that dispersion and amplification of the c-MYC gene sequences occurred after and was most likely triggered by the viral insertion at a single integration site. Numerical and structural chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as well as FISH localization of HPV18 integration at the c-MYC locus in HeLa cells are common and representative for advanced stage cervical cell carcinomas. The HeLa genome has been remarkably stable after years of continuous cultivation; therefore, the genetic alterations detected may have been present in the primary tumor and reflect events that are relevant to the development of cervical cancer.

The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis.

Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, approximately 3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by > or =1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth.

[Intraoperative multidimensional visualization]. / Intraoperative mehrdimensionale Visualisierung.

Modern intraoperative techniques of visualization are increasingly being applied in general and visceral surgery. The combination of diverse techniques provides the possibility of multidimensional intraoperative visualization of specific anatomical structures. Thus, it is possible to differentiate between normal tissue and tumor tissue and therefore exactly define tumor margins. The aim of intraoperative visualization of tissue that is to be resected and tissue that should be spared is to lead to a rational balance between oncological and functional results. Moreover, these techniques help to analyze the physiology and integrity of tissues. Using these methods surgeons are able to analyze tissue perfusion and oxygenation. However, to date it is not clear to what extent these imaging techniques are relevant in the clinical routine. The present manuscript reviews the relevant modern visualization techniques focusing on intraoperative computed tomography and magnetic resonance imaging as well as augmented reality, fluorescence imaging and optoacoustic imaging.

[Present treatment strategies for rectal carcinoma]. / Aktuelle Behandlungsstrategien beim Rektumkarzinom.

In the last ten years, considerable progress has been achieved in the treatment of rectal cancer. According to improved interdisciplinary staging, rectal carcinomas can be treated based on a stage-dependent concept: "low-risk" pT1 (G1/G2) carcinomas can be cured by local full wall excision, while "high-risk" pT1 (G3/G4) and pT2 carcinomas require transabdominal resection. In contrast, locally advanced rectal cancers in cUICC-II/-III stages (T3/T4 or N(+)) should receive long-term, 5-FU-based, neoadjuvant chemoradiotherapy according to the excellent results of the CAO/AIO/ARO-94 trial of the German Rectal Cancer Study Group. High-quality resection must be based on radical oncologic principles such as "no-touch" technique, radicular dissection of vessels, and total mesorectal excision. Multimodal treatment is completed with adjuvant 5-FU-based chemotherapy. This therapeutic approach led to a reduction in the 5-year local recurrence rate to 6% and disease-free survival of approximately 68% in advanced rectal cancer (overall survival: 76%).

[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.

Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling.

Intercellular adhesion mediated by the E-cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation. In carcinomas, E-cadherin function is frequently disturbed, and has been suggested to increase invasion and metastasis of tumour cells. beta-catenin has also been implicated in signaling pathways essential for tumour formation. We analysed the E-cadherin/catenin adhesion system of colorectal tumours at different clinical stages. In primary carcinomas (n = 91), there was a frequent reduction in E-cadherin (44%) and alpha-catenin expression (36%). In contrast, beta-catenin and gamma-catenin expression were seldom reduced (4% and 15%, respectively). Similar expression patterns were observed in liver metastases from unrelated colorectal tumours (n = 27). There was a significant relationship between loss of E-cadherin and alpha-catenin expression and poorly differentiated (G3-4) tumours. Our results suggest that reduction of E-cadherin/alpha-catenin expression is a frequent event in primary and metastatic colorectal carcinomas. Furthermore, beta-catenin expression remains normal in colorectal cancer, suggesting the essential role of beta-catenin in signaling pathways.

Mucins (MUC1 and MUC3) of gastrointestinal and breast epithelia reveal different and heterogeneous tumor-associated aberrations in glycosylation.

In a comprehensive study, we examined the expression of the membrane and secretory mucins MUC1 and MUC3, respectively, in normal and neoplastic gastrointestinal and breast epithelia before and after specific alterations of their glycan structures by neuraminidase, alpha-fucosidase, or carbohydrate-specific periodate oxidation. MUC1 mRNA was also identified in normal colorectal tissues by in situ hybridization. The data revealed that normal colorectal epithelia express both MUC1 mRNA and protein, which were detectable after periodate oxidation with all tested MUC1-specific antibodies. During tumorigenesis in the colon, MUC1 became recognizable without periodate treatment concomitantly with highly dysplastic lesions and the malignant state. In the breast, in which MUC1 is detectable with most antibodies in normal epithelium as well as in carcinomas, staining could be enhanced by pretreatment with periodate and casually by enzyme treatments. MUC3 was detectable in normal and neoplastic colorectal tissues and was more intensely stained after periodate oxidation. It was absent in normal breast even after pretreatment but was expressed in seven of 20 breast carcinomas. Therefore, incomplete glycosylation, abnormal distribution, and ectopic expression of mucins are characteristics of malignancy. Periodate oxidation may be widely applicable to immunohistochemistry for examining changes in glycosylation and for detecting antigens masked by glycans.

Transesophageal biopsy of mediastinal and pulmonary tumors by means of endoscopic ultrasound guidance.

OBJECTIVE: The aim of this study was to investigate the value of endoscopic ultrasound-guided biopsy for the diagnosis of thoracic lesions. METHODS: Transesophageal ultrasound-guided biopsy was performed in 29 patients with mediastinal (n = 25) or pulmonary tumors (n = 4). A flexible echoendoscope with a 7.5 MHz curved array transducer (Pentax FG 32 UA, Hamburg, Germany) and a biopsy device with a fine needle (diameter 0.8 mm) were used for all examinations. Three patients were excluded from the analysis of the data because a definite diagnosis based on surgery or follow-up was not available. RESULTS: Real-time visualization of the biopsy procedure with endoscopic ultrasound enabled accurate tissue sampling even of small mediastinal lesions with a diameter of less than 1 cm. Diagnostic material was obtained in 23 of the 26 patients (88%). In 3 cases (12%) non-representative biopsy material was found in the specimen. The sensitivity and specificity of transesophageal biopsy in the diagnosis of malignancy were 89% and 83%, respectively. Histologic analysis of the biopsy specimens established malignancy in 17 of 23 patients, whereas benign lesions were diagnosed in 6 patients. Endoscopic ultrasound-guided biopsy confirmed the diagnosis suggested by conventional diagnostic methods in 15 of 23 patients (65%), whereas an unsuspected diagnosis was disclosed in 8 patients (35%). The results of the biopsy had considerable impact on the therapeutic strategy. None of the patients had complications related to the procedure. CONCLUSIONS: Endoscopic ultrasound-guided biopsy provides a new minimally invasive approach to the biopsy of lesions in the posterior mediastinum and may complement surgical staging procedures.

Effects of serotonin on hilar neurons and granule cell inhibition in the guinea pig hippocampal slice.

Intracellular recordings in guinea pig hippocampal slices were used to study the effects of serotonin (5-HT) on presumed inhibitory hilar neurons and on postsynaptic inhibition of granule cells. 5-HT applied by the bath hyperpolarized only 50% of the hilar neurons tested but all CA3 neurons and granule cells, presumably by activating a K-conductance. The bath application of 4-aminopyridine (4-AP, 50 microM) induced burst discharge activity in hilar neurons and giant inhibitory postsynaptic potentials (IPSPs) in granule cells consisting of a Cl- and K-component. 5-HT (5-10 microM) reversibly blocked the K-component of giant IPSPs in granule cells, but not their Cl-component. In the majority of hilar neurons 5-HT increased the frequency of 4-AP induced burst discharges even when hilar neurons were hyperpolarized. Only in a few hilar neurons 5-HT blocked 4-AP induced burst discharges. We conclude that the changes in burst discharge pattern of hilar neurons correspond with the differential effect of 5-HT on Cl- and K-mediated inhibition of granule cells.