The effect of TGF-ß1 polymorphisms on pulmonary disease progression in patients with cystic fibrosis.

BACKGROUND: Transforming Growth Factor-ß1 (TGF-ß1) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-ß1 are associated with neutrophilic inflammation, lung fibrosis and loss of pulmonary function. AIM: The aim of this study was to assess the relationship between genetic TGF-ß1 polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-ß1 polymorphisms on inflammatory cytokines in sputum was investigated. METHODS: 56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-ß1 sequence using the SNaPshot® technique. Individual "slopes" in forced expiratory volume in 1 s (FEV1) for all patients were calculated by using documented lung function values of the previous five years. The status of Pseudomonas aeruginosa (Pa) infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1ß, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing. RESULTS: The homozygous TT genotype at codon 10 was associated with a lower rate of chronic Pa infection (p < 0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (p < 0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (p < 0,05). Higher levels of TGF-ß1 in plasma were associated with a more rapid FEV1 decline over five years (p < 0.05). CONCLUSIONS: Our results suggest that polymorphisms in the TGF-ß1 gene have an effect on lung function decline, Pa infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-ß1 inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus minimally invasive esophagectomy for resectable esophageal adenocarcinoma, a randomized controlled trial (ROBOT-2 trial).

BACKGROUND: For patients with esophageal adenocarcinoma or cancer of the gastroesophageal junction, radical esophagectomy with 2-field lymphadenectomy is the cornerstone of the multimodality treatment with curative intent. Both conventional minimally invasive esophagectomy (MIE) and robot assisted minimally invasive esophagectomy (RAMIE) were shown to be superior compared to open transthoracic esophagectomy considering postoperative complications. However, no randomized comparison exists between MIE and RAMIE in the Western World for patients with esophageal adenocarcinoma. METHODS: This is an investigator-initiated and investigator-driven multicenter randomized controlled parallel-group superiority trial. All adult patients (age ≥ 18 and ≤ 90 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 218) with resectable esophageal adenocarcinoma of the intrathoracic esophagus or adenocarcinoma of the gastroesophageal junction are randomized to either RAMIE (n = 109) or MIE (n = 109). The primary outcome of this study is the total number of resected abdominal and mediastinal lymph nodes specified per lymph node station. CONCLUSION: This is the first randomized controlled trial designed to compare RAMIE to MIE as surgical treatment for resectable esophageal adenocarcinoma or adenocarcinoma of the gastroesophageal junction in the Western World. The hypothesis of the proposed study is that RAMIE will result in a higher abdominal and mediastinal lymph node yield specified per station compared to conventional MIE. Short-term results and the primary endpoint (total number of resected abdominal and mediastinal lymph nodes per lymph node station) will be analyzed and published after discharge of the last randomized patient within this trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04306458 . Registered 13th March 2020, https://clinicaltrials.gov/ct2/show/NCT04306458; Date of first enrolment 18.01.2021; Target sample size 218; Recruitment status: Recruiting; Protocol version 2; Issue date 10.03.2020; Rev. 02.02.2021; Authors ET, PCvdS, PPG.

Diagnostic criteria and symptom grading for delayed gastric conduit emptying after esophagectomy for cancer: international expert consensus based on a modified Delphi process.

Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air-fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process.

A structured training program for minimally invasive esophagectomy for esophageal cancer- a Delphi consensus study in Europe.

Evidence suggests that structured training programs for laparoscopic procedures can ensure a safe standard of skill acquisition prior to independent practice. Although minimally invasive esophagectomy (MIO) is technically demanding, no consensus on requirements for training for the MIO procedure exists. The aim of this study is to determine essential steps required for a structured training program in MIO using the Delphi consensus methodology. Eighteen MIO experts from 13 European hospitals were asked to participate in this study. The consensus process consisted of two structured meetings with the expert panel, and two Delphi questionnaire rounds. A list of items required for training MIO were constructed for three key domains of MIO, including (1) requisite criteria for units wishing to be trained and (2) to proctor MIO, and (3) a framework of a MIO training program. Items were rated by the experts on a scale 1-5, where 1 signified 'not important' and 5 represented 'very important.' Consensus for each domain was defined as achieving Cronbach alpha ≥0.70. Items were considered as fundamental when ≥75% of experts rated it important (4) or very important (5). Both Delphi rounds were completed by 16 (89%) of the 18 invited experts, with a median experience of 18 years with minimally invasive surgery. Consensus was achieved for all three key domains. Following two rounds of a 107-item questionnaire, 50 items were rated as essential for training MIO. A consensus among European MIO experts on essential items required for training MIO is presented. The identified items can serve as directive principles and core standards for creating a comprehensive training program for MIO.

18FDG-PET-CT improves specificity of preoperative lymph-node staging in patients with intestinal but not diffuse-type esophagogastric adenocarcinoma.

INTRODUCTION: The accuracy of preoperative lymph-node staging in patients with adenocarcinoma of the esophagogastric junction (AEG) or gastric cancer (GC) is low. The aim of this study was to assess the accuracy of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) for lymph-node staging in patients with AEG or GC, with or without neoadjuvant treatment. PATIENTS AND METHODS: 221 consecutive patients with GC (n = 88) or AEG (n = 133) were evaluated. Initial staging included endoscopic ultrasound (EUS), multidetector spiral CT (MDCT) and PET-CT. PET-CT was performed for restaging in patients after neoadjuvant treatment (n = 94). Systematic lymphadenectomy was routinely performed with histopathological assessment of individual mediastinal and abdominal lymph-node stations. Preoperative staging from EUS, MDCT, and PET-CT was correlated with histopathological results. RESULTS: PET-CT showed a high specificity (91%) and positive predictive value (89%) for the preoperative detection of lymph-node metastases. In comparison, EUS was more sensitive (73% versus 50%, P < 0.01) but less specific (60%, P < 0.01). In patients with intestinal/mixed-type tumors, PET-CT improved the detection of extra-regional lymph-node metastases (P = 0.01) and distant metastases (P = 0.01) compared to CT alone. In contrast, lymph-node assessment by PET/CT after neoadjuvant treatment (32%, P < 0.01) and in diffuse-type cancers (24%, P < 0.01) is futile because of low sensitivities. CONCLUSION: PET-CT does not improve the overall accuracy of N staging, but does improve specificity compared to EUS and MDCT in AEG and GC. We do not recommend routine PET-CT for the initial staging in patients with diffuse-type cancer or for restaging of lymph nodes after neoadjuvant treatment.

Skeletal stability of maxillary advancement with and without a mandibular reduction in the cleft lip and palate patient.

The stability of surgical maxillary advancement in a consecutive series of patients with cleft lip and palate who underwent Le Fort I osteotomy with and without simultaneous mandibular setback surgery was evaluated. Preoperative, postoperative, and follow-up lateral cephalograms of 21 patients were assessed to compare differences in surgical movement and postoperative relapse between two groups: those who underwent maxillary surgery alone and those who underwent bimaxillary surgery. Differences in the number of patients who experienced relapse of <2mm, 2-4mm, and >4mm between the groups were also compared. Mean advancement of the cleft maxilla was 5.5mm in the maxilla only group and 3.6mm in the bimaxillary group, with a mean horizontal relapse of 0.8mm and 0.2mm, respectively. Mean surgical movement in the vertical dimension was comparable in the two groups and the magnitude of vertical relapse was less than 0.4mm overall. Approximately 80% of patients in both groups experienced horizontal relapse of less than 2mm. There was no significant difference in the degree of postoperative relapse between those who had single-jaw surgery and those who had two-jaw surgery.

An undigested cherry tomato as a rare cause of small bowel obstruction.

Small bowel obstruction due to undigested fibre from fruits and vegetables is a rare but known medical condition. We report a case of small bowel obstruction caused by a whole cherry tomato in a patient without a past medical history of abdominal surgery. A 66-year-old man presented to the emergency department complaining of lower abdominal pain with nausea and vomiting. His last bowel movement had occurred on the morning of presentation. He underwent abdominal computed tomography (CT), which showed a sudden change of diameter in the distal ileum with complete collapse of the proximal small bowel segment. Laparoscopy confirmed a small bowel obstruction with a transition point close to the ileocaecal valve. An enterotomy was performed and a completely undigested cherry tomato was retrieved. To our knowledge, this is the first reported case of a small bowel obstruction caused by a whole cherry tomato.

Nonmyeloablative allogeneic stem cell transplantation for chronic lymphocytic leukaemia offers the possibility of disease control with minimal morbidity and mortality--a single institution experience.

Allogeneic stem cell transplantation is a treatment option for patients with poor risk CLL. We conducted a retrospective analysis of all CLL patients allografted at our institution, the University Hospital of Cologne, Germany. Data was collected on 40 patients from 2004 to 2012. The mean age was 54, and the majority were male (75 %). On average, the patients were diagnosed 6 years (range 2-12) prior to transplant with an average of 4 years (range 1-8) from time of first-line therapy to transplant. The remission states at the time of transplant were complete remission (CR) (n = 4), stable disease (n = 10), partial remission (n = 20) and progressive disease (n = 6). Only reduced intensity conditioning regimens were employed. The average CD34(+) cell dose was 4.16 × 10(6)/kg. Neutrophil engraftment was seen by day +17 (range 10-23) post-transplant, and 88 % achieved 95-100 % donor chimerism by day 100. Overall survival, progression-free survival and non-relapse mortality at 2 years post-transplant were 65, 52.5 and 27.5 %, respectively. A total of 51 % of patients were found to be minimal residual disease (MRD)-negative at 1 year post-transplant. Our single-centre experience confirms the valuable role of allogeneic stem cell transplantation (allo-SCT) in the treatment of poor risk CLL patients with promising long-term survival and acceptable transplant-related mortality. The advent of newer therapeutic agents should not hinder the consideration of allo-SCT for this patient cohort as it remains the only curative option for these patients.

Histopathological evidence of invasive gastric mucormycosis after transarterial chemoembolization and liver transplantation.

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8 months earlier and 40 days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5 weeks, followed by 7 weeks of posaconazole. Follow-up biopsies after 1 and 5 months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication.

RNA/DNA co-analysis from human saliva and semen stains--results of a third collaborative EDNAP exercise.

A third collaborative exercise on RNA/DNA co-analysis for body fluid identification and STR profiling was organized by the European DNA Profiling Group (EDNAP). Twenty saliva and semen stains, four dilution series (10-0.01 µl saliva, 5-0.01 µl semen) and, optionally, bona fide or mock casework samples of human or non-human origin were analyzed by 20 participating laboratories using an RNA extraction or RNA/DNA co-extraction method. Two novel mRNA multiplexes were used: a saliva triplex (HTN3, STATH and MUC7) and a semen pentaplex (PRM1, PRM2, PSA, SEMG1 and TGM4). The laboratories used different chemistries and instrumentation and a majority (16/20) were able to successfully isolate and detect mRNA in dried stains. The simultaneous extraction of RNA and DNA from individual stains not only permitted a confirmation of the presence of saliva/semen (i.e. tissue/fluid source of origin), but allowed an STR profile of the stain donor to be obtained as well. The method proved to be reproducible and sensitive, with as little as 0.05 µl saliva or semen, using different analysis strategies. Additionally, we demonstrated the ability to positively identify the presence of saliva and semen, as well as obtain high quality DNA profiles, from old and compromised casework samples. The results of this collaborative exercise involving an RNA/DNA co-extraction strategy support the potential use of an mRNA based system for the identification of saliva and semen in forensic casework that is compatible with current DNA analysis methodologies.

Complex anastomotic leaks following esophageal resections: the new stent over sponge (SOS) approach.

A new approach for the treatment of complicated anastomotic leaks following esophageal resections by combining vacuum-assisted therapy with covered self-expanding stents is reported. This is not an approach for a simple leak but a rescue maneuver for complex uncontained leaks. It is known that anastomotic leakages particularly situated in the chest can be successfully treated with endoscopically placed self-expanding stents with/without additional drainage. If this approach fails, reoperation with substantial morbidity is frequently necessary. Two complicated anastomotic leakages refractory to stenting alone were successfully treated with the combination of an endo-sponge-assisted device covered by a self-expanding metallic stent. If stent therapy fails or the perianastomotic abscess cavity is large and complex to drain from outside, the endoscopic two-modality approach can be considered.

[18F]-fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemotherapy in gastric cancer.

BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy is applied to improve the prognosis of patients with advanced gastric cancer. However, only a major histopathological response will provide a benefit. Recent studies suggest that [(18)F]-fluorodeoxyglucose-positron-emission-tomography (FDG-PET) correlates with response and survival in patients with gastroesophageal adenocarcinomas undergoing neoadjuvant chemotherapy. We evaluated the potential of FDG-PET for the assessment of response and prognosis in the multimodality treatment of gastric cancer. METHODS: Study patients were recruited from a prospective observation trial. Forty two patients with advanced gastric cancer received neoadjuvant chemotherapy and subsequently 40 patients underwent standardized gastrectomy (2 patients with tumor progression had therapy limited to palliative chemotherapy without surgery). Histomorphologic regression was defined as major response when resected specimens contained <10% vital tumor cells. FDG-PET was performed before and 2 weeks after the end of neoadjuvant chemotherapy with assessment of the intratumoral FDG-uptake [pre-treatment standardized uptake value (SUV1); post-treatment SUV (SUV2); percentage change (SUVDelta%)]. RESULTS: Histomorphological tumor regression was confirmed as a prognostic factor (P = 0.039). No significant correlations between SUV1, SUV2, or SUVDelta% and response or prognosis were found. CONCLUSION: FDG-PET seems not to be an imaging system that effectively characterizes major/minor response and survival in patients with gastric cancer following multimodality treatment.

Lack of prognostic significance of serum DNA methylation of DAPK, MGMT, and GSTPI in patients with non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: To further improve the screening, diagnosis and therapy of patients with non-small cell lung cancer (NSCLC) additional diagnostic tools are desperately warranted. Aim of this study was to investigate the potential of the DNA methylation of DAPK, MGMT, and GSTPI in serum of patients with NSCLC as a prognostic molecular marker in this disease. METHODS: Seventy-six patients with NSCLC were included in this study. The analysis of DNA methylation in serum of patients was performed on pre-operative samples. Following DNA isolation and bisulfite-treatment, DNA methylation was analyzed by quantitative-methylation-specific real-time PCR with beta-actin as the internal reference gene. RESULTS: DNA methylation was detectable with following frequencies: DAPK 68.4%, MGMT 7.9%, GSTPI 0%. There were no associations between DNA methylation status and histology, tumor stage, grading or gender detectable. With a mean follow-up of 19.7 months the median survival was 26.3 months. There were no associations between the status of DNA methylation in patient's serum and prognosis detectable. CONCLUSION: The analysis of DNA methylation in serum of patients with NSCLC by quantitative-methylation-specific real-time PCR is technically feasible. Although our results suggest quantification of DNA methylation in serum not of prognostic significance in this disease, further studies are warranted to determine the future potential of this molecular approach.

Survivin expression in gastric cancer: Association with histomorphological response to neoadjuvant therapy and prognosis.

BACKGROUND AND OBJECTIVES: Neoadjuvant therapy is applied to improve the prognosis associated with advanced gastric cancer. Only patients with a major response seem to have a survival benefit. Predictive markers to allow individualisation of treatment could be helpful. We examined the association of survivin protein expression with histopathologic response to neoadjuvant chemotherapy and prognosis in patients with gastric cancer. METHODS: Forty patients with gastric cancer received neoadjuvant chemotherapy. Afterwards, 38 patients underwent total gastrectomy, while 2 patients received definitive chemotherapy because of tumour progression. Histomorphologic regression was defined as major response when resected specimens contained <10% tumour cells. Intratumoural survivin expression was determined by immunohistochemistry in pre- and post-therapeutic specimens and correlated with clinicopathologic parameters. RESULTS: The pre- and post-therapeutic intratumoural survivin protein expression was not associated with histomorphologic regression. Post-therapeutic survivin expression did not have prognostic impact. A significant association was detected between pre-therapeutic survivin levels and prognosis: patients with a higher survivin protein expression showed a significant survival benefit. In multivariate analysis pre-therapeutic survivin expression was characterised as an independent prognostic marker, besides pN-status and histopathologic regression. CONCLUSIONS: The pre-therapeutic survivin protein expression seems to be an independent prognostic marker in the multimodality treatment of advanced gastric cancer.

[Symptomatic cardiac metastasis. Isolated visceral manifestation of a cutaneous malignant melanoma]. / Symptomatische Herzmetastase. Solitäre viszerale Manifestation eines kutanen malignen Melanoms.

Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was admitted because of dyspnea and intrathoracic pain 8 years after surgery of a superficial spreading melanoma and 4 years after resection of in-transit metastases. MRI and echocardiography disclosed an intracavitary right atrial mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac symptoms in a patient with elevated risk for distant metastases of melanoma should be further investigated to discover cardiac metastasis early.

HIF-1alpha protein expression is associated with the environmental inflammatory reaction in Barrett's metaplasia.

The oxygen-regulated transcription factor subunit hypoxia inducible factor-1alpha (HIF-1alpha) is involved in angiogenesis, energy metabolism, cell survival, and inflammation. We examined the protein expression of HIF-1alpha within the progression of Barrett's sequence as well as the type and degree of the environmental inflammatory reaction. Squamous epithelium (SE), metaplastic, low- and high-grade dysplastic lesions, and tumor tissue of 57 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analyzed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. HIF-1alpha protein expression increased significantly from SE to Barrett's metaplasia (BM) (P < 0.0001). From metaplasia through low- and high-grade dysplasia to cancer, no further increase could be detected. Active and chronic inflammation were also significantly different between SE and BM (P < 0.0001) but not during further progression in the sequence. HIF-1alpha protein expression did not correlate with histopathologic parameters or survival. HIF-1alpha protein expression pattern resembles the active and chronic environmental inflammatory reaction. All were significantly increased in metaplasia compared to SE without further change in tumor development. HIF-1alpha protein expression appears to be associated with inflammatory processes in the development of BM.

Serosal penetration is an important prognostic factor for gastrointestinal stromal tumors.

Predicting the malignant potential of gastrointestinal stromal tumors (GISTs) remains difficult. We assessed the value of serosal penetration, an established prognostic factor in solid tumors, to determine the clinical outcome in patients with GISTs. From 1996-2002, 25 consecutive patients with GIST underwent surgical resection at our Department. The histopathological presence of serosal penetration was assessed to predict clinical outcome. In addition, the established histopathological classification system by Franquemont (modified by using the Ki-67 proliferation index), was applied to each study patient. A Ki-67 index > or =5% (p<0.001) and a mitotic rate > or =5/50 high-power fields (p<0.047) significantly correlated with a shorter survival, whereas a tumor size >5 cm (p=0.07) tended towards a worse prognosis. The survival of patient groups defined by Franquemont (p=0.03) were of prognostic relevance. The presence of serosal penetration significantly correlated (p<0.01) with a shorter survival. Our data suggest that the presence of serosal penetration is a negative prognostic factor for GISTs. Serosal penetration may become a useful additional parameter for the classification of the malignant potential of GISTs. Since our data are merely hypothesis-generating, serosal penetration should be evaluated in large prospective databases.

Comparative analysis of four histopathological classification systems to discriminate benign and malignant behaviour in gastrointestinal stromal tumors.

UNLABELLED: The prognostic value of the four most common histopathological classification systems in gastrointestinal stromal tumors (GISTs) was evaluated retrospectively. PATIENTS AND METHODS: Twenty-five consecutive patients with resected GIST and a follow-up of five years or more for surviving patients were included in this analysis. All the tumors were c-KIT (CD117) positive and were additionally re-evaluated for the number of mitoses per 50 high-power fields (HPF) and Ki-67 proliferation index. The four most commonly applied histopathological classification systems of the WHO, Franquemont (modified by using the Ki-67 proliferation index), Fletcher and Miettinen were applied to each patient. RESULTS: The survival of patient groups classified by Franquemont (p = 0.03) and the WHO (p = 0.031) were of prognostic relevance, while the grouping of patients by classifications according to both, Fletcher and Miettinen did not show a significant prognostic value. CONCLUSION: The classification systems of Franquemont (modified) or WHO appear to be advantageous for the evaluation of malignant potential and clinical outcome in patients with GISTs. Our data are merely hypothesis generating and should be validated in larger clinical studies.

Adenocarcinoma developing in de novo Barrett's mucosa in the remnant esophagus after esophagectomy: clinical and molecular assessment.

For many patients after subtotal esophagectomy and gastric pull-up, reflux of gastric contents to the esophageal stump is the leading clinical problem. Besides symptoms such as heartburn and regurgitation, de novo formation of columnar mucosa in the esophageal remnant is a well-known and frequent phenomenon. In this context, the remnant supra-anastomotic esophagus serves as an in vivo model for the study of Barrett's carcinogenesis. We present a retrospective case analysis of a patient who developed de novo Barrett's metaplasia followed by de novo invasive carcinoma 28 months after gastric pull-up by assessing clinical and molecular parameters.

Association of COX-2 expression with corresponding active and chronic inflammatory reactions in Barrett's metaplasia and progression to cancer.

AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The aim of this study was to examine a possible association between COX-2 protein expression and the development and progression of the Barrett's metaplasia-dysplasia-carcinoma sequence and the type and degree of associated inflammatory reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high-grade dysplastic lesions and tumour tissue of 49 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analysed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. Within the Barrett's sequence, a significant progressive increase in COX-2 expression was identified (P < 0.0001). The most significant differences were detected between squamous epithelium and Barrett's metaplasia (P < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic inflammation were significantly different between squamous epithelium and Barrett's metaplasia (P < 0.0001), but not during further progression in the sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is significantly associated with a change in the local inflammatory reaction, but not during further progression through dysplasia to cancer. This supports the potential of a chemoprevention strategy using COX-2 inhibitors independent of the extent and type of the inflammatory reaction in Barrett's oesophagus.