Chondrosarcoma of the Chest Wall: A Review of 53 Cases from Two Institutions.

BACKGROUND/AIM: Chondrosarcomas (CS) of the chest wall are rare, but present an aggressive biological behavior compared to CS of the extremities. The aims of the present study were to determine factors associated with oncological outcomes as well as complications. PATIENTS AND METHODS: We retrospectively analyzed 53 patients (42 primary, 11 recurrent tumors). In total, 39 central CS, 10 peripheral CS, 3 dedifferentiated CS and 1 mesenchymal CS were included. The ribs were most commonly affected (68%). Overall survival and disease-free survival were estimated with Kaplan-Meier analyses and compared with log-rank test. RESULTS: Mean follow-up was 7 years. Negative margins were achieved in 87% of patients. Thirty patients (57%) remained continuously disease-free (NED), three (5%) NED after treatment of relapse, seven (13%) were alive with disease, twelve (23%) were dead with disease and one of other cause. The 10-year survival rate was 81% and 45% in primary and recurrent tumors, respectively. Survival was significantly affected by tumor stage (p<0.001), local recurrence (p=0.025) and metastases (p=0.002). Six complications (16%) were observed. CONCLUSION: The outcome is rather poor, especially in patients with local recurrence. Presumably due to a high biological aggressiveness, a stricter definition of surgical margins should be considered for this location.

The simultaneous expression of both ephrin B3 receptor and E-cadherin in Barrett`s adenocarcinoma is associated with favorable clinical staging.

BACKGROUND: In intestinal epithelium, tyrosine kinase receptor Ephrin B3 (Eph B3) maintains the architecture of the crypt-villus axis by repulsive interaction with its ligand ephrin-B1. While loss of Eph B3 is linked to colorectal cancer initiation, overexpression of Eph B3 in cancer cell lines inhibits growth and induces functional changes with decreased mesenchymal and increased epithelial markers. In order to study this tumor suppressor activity of Eph B3 in esophageal adenocarcinoma we analyzed the simultaneous expression of Eph B3 and E-cadherin in both the healthy esophagus and in Barrett's carcinoma. METHODS: Simultaneous expression of Eph B3 and E-cadherin was investigated in samples from 141 patients with Barrett's carcinoma and from 20 healthy esophagi using immunhistology and quantitative PCR. Results from healthy squamous epithelium, Barrett's metaplasia and staging-specific esophageal adenocarcinoma were correlated. RESULTS: A significantly reduced E-cadherin mRNA expression could be detected in adenocarcinoma compared to dysplasia. The immunhistological activity of E-cadherin and Eph B3 was reduced in adenocarcinoma compared to dysplasia or healthy esophageal mucosa. The intracellular E-cadherin distribution changed significantly from the cytoplasm to the membrane, when the Eph receptor was simultaneously expressed. Simultaneous expression of E-cadherin and Eph B3 showed a significant inverse correlation to tumor stage. CONCLUSIONS: We present novel evidence of the tumor suppressor activity of Eph B3 in esophageal adenocarcinoma possibly due to the impact on redistribution of cellular E-cadherin to the membrane. Our results suggest that this effect might play a role in the dysplasia-adenocarcinoma sequence, the infiltrative growth pattern and the development of lymph node metastases.

The amount of neoadjuvant chemotherapy for Barrett's carcinoma does not correlate with long-term survival.

INTRODUCTION: Several studies have proven an ameliorated prognosis after a neoadjuvant therapy for locally advanced Barrett's carcinoma in case of response. The necessary amount of neoadjuvant chemotherapy within a multimodal therapy concept with following oesophageal resection has never been evaluated so far. METHODS: The clinical course of 122 patients with Barrett's carcinoma, who all underwent a neoadjuvant chemotherapy with cisplatin, five fluorouracil and leucovorin and following oesophagectomy, was reviewed. The pretherapeutic clinical and postoperative histopathological staging, histopathological response, clinical course, recurrence rates and long-term survival were retrospectively analysed and compared to the data of 30 patients, who were included in the same multimodal therapy concept, but who had to cease the chemotherapy early because of toxicity. RESULTS: Postoperative pathological staging showed that the response rate correlates with the N and R status. The responding patients benefit from longer survival. Comparing the two subgroups, we could not find a significant difference in response rate, tumour staging, resection rate, long-term survival or pattern of recurrent disease. However, postoperative morbidity and mortality did not correlate with severe chemotherapy-induced toxicity. CONCLUSIONS: This is the first study on the necessary number of chemotherapy cycles in terms of a neoadjuvant therapy for Barrett's carcinoma. We could show a similar downstaging effect, a good histopathological response and a comparable ameliorated long-term survival of patients with one compared to patients with three chemotherapy cycles. A biological selection seems to determine the course of the disease already at this early stage.

Interleukin-10 and -12 predict chemotherapy-associated toxicity in esophageal adenocarcinoma.

INTRODUCTION: Chemotherapy-associated mucositis often prevents completion of an entire chemotherapy cycle. The underlying pathophysiology of chemotherapy-associated mucositis has not been well established. The individual immunologic predisposition of patients seems to play an important role. METHODS: One hundred fifty-six patients with locally advanced or metastatic esophageal adenocarcinoma received neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin followed by resection. Before the neoadjuvant therapy, monocytes were isolated from blood samples and were stimulated with lipopolysaccharide and interferon. An enzyme-linked immunosorbent assay was used to measure interleukin (IL)-10 and -12 levels and correlated with patients' clinical course. RESULTS: Twenty-two patients (14,1%) developed grade III to IV mucositis (according to the NCI-Common toxicity criteria scales) within the neoadjuvant chemotherapy. Pretherapeutic low IL-10 (<24.1 pg/ml) and high IL-12 (>5500 pg/ml) levels were significantly associated with mucositis causing a therapy interruption or even cessation. Patients with high IL-10 (>43.6 pg/ml) and low IL-12 (<4408.5 pg/ml) levels had an uneventful neoadjuvant chemotherapy. CONCLUSIONS: Pretherapeutic individual monocyte function is correlated with the development and the grade of chemotherapy induced mucositis. This knowledge might help us in predicting the grade of mucositis and in understanding the genesis regarding the association to pro- and anti-inflammatory effects of monocyte cytokines.

The diagnostic challenge of mediastinal sarcoidosis accompanying esophageal cancer.

The primary staging of an oesophageal cancer can be difficult, if accompanied by sarcoidosis. In these patients endosonography, CT and PET may not be sufficient for staging purposes concerning lymph node and distant metastases. In these special cases operative biopsies of enlarged lymph nodes and unclear pulmonary nodules have to be obtained. In connection with the radiographic examinations the histopathological results of the biopsies contribute to further precise staging and help to decide on a curative versus a palliative therapy concept.

Microarray-based response prediction in esophageal adenocarcinoma.

PURPOSE: In locally advanced (uT(3), N(+)) adenocarcinomas of the esophagus, neoadjuvant chemotherapy improves patient outcome. However, only a subgroup of patients responds. Therefore, in the present study, we evaluated whether the response to neoadjuvant chemotherapy can be predicted by a pretreatment tumor biopsy analysis. EXPERIMENTAL DESIGN: Biopsies of 47 patients with locally advanced (uT(3), N(+)) adenocarcinoma of the esophagus were obtained during primary staging. All patients underwent neoadjuvant chemotherapy with cisplatin, 5-fluorouracil, and leucovorin and subsequent resection of the esophagus. Biopsies were used for microarray analysis. The predominance of tumor cells within the specimens was >70%. Affymetrix U133 plus 2.0 gene chips with 54675 probe sets were used. A statistical comparison of patients responding to chemotherapy versus nonresponding patients was done. All patients were examined with immunohistology against Ephrin B3 receptor and Ki-67. RESULTS: A total of 86 genes were at least 2-fold differentially regulated comparing responding with nonresponding adenocarcinomas of the esophagus. The predominant genes encoded for the regulation of the cell cycle, transduction, translation, cell-cell interaction, cytoskeleton, and the signal transduction. The strongest difference was seen for the Ephrin B3 receptor. This result could be confirmed by immunhistology. A statistical significant correlation between the Ephrin B3 receptor, chemotherapy response, pathologic staging, and grading could be shown. CONCLUSIONS: There were significant differences in the gene profile between patients with adenocarcinoma of the esophagus responding to neoadjuvant chemotherapy compared with nonresponding patients. This suggests that it could be possible to characterize patients responding to chemotherapy even before starting the treatment using customized microarray analysis.

Early response evaluation and prediction in neoadjuvant-treated patients with esophageal cancer.

Since the introduction of multimodal therapy regimens, the prognosis of esophageal cancer has improved. There is undoubtedly true for patients with surgically resected tumors in the case of a response to neoadjuvant chemotherapy or chemoradiation. Important conclusions can be drawn from this regarding the indication for perioperative therapies, the radicality of surgery, or the surgical indications. Thus, most of the current research in this field is aimed at the early identification of this subset of patients, at the beginning of, or even before, neoadjuvant treatment. Conventional staging tools have failed to predict responses to neoadjuvant therapy. However, molecular imaging methods, e.g. positron emission tomography (PET)-scans, have shown promising results in the early selection of responders and non-responders during the course of neoadjuvant therapy, allowing physicians to alter the treatment plan accordingly. Even more desirable is the identification of potential responders before the start of neoadjuvant therapy. Preliminary molecular data on biopsy specimens demonstrate the possibility of early response prediction in these patients. We present the current knowledge on response evaluation and prediction in esophageal cancer and draw conclusions for future clinical practice and studies in this review.

Results of a multimodal therapy in patients with stage IV Barrett's adenocarcinoma.

BACKGROUND: Locally advanced and metastatic Barrett's carcinomas account for the majority of this tumor entity at the time of diagnosis. Many studies have shown that a multimodal therapy concept consisting of neoadjuvant chemotherapy followed by resection can result in improved long-term survival in patients responding to chemotherapy. The benefit of a multimodal therapy concept in patients with stage IV disease remains unclear. METHODS: A total of 178 patients with Barrett's carcinoma who underwent multimodal therapy with resection of the tumor were reviewed. The pathological staging and the clinical course of patients with metastatic disease, who were treated equally, were compared to patients with locally advanced tumors. RESULTS: As expected, postoperative pathological staging showed that patients with metastatic disease have a more advanced T- and N-status. Moreover, the histopathological response according to Becker showed a chemoresistence in 84% of cases with metastatic disease, whereas 54% of patients with locally advanced carcinomas had a good response rate. Overall survival was poor, with 9 months in the metastatic group. CONCLUSIONS: This is the first study to compare the outcome of a modern multimodal therapy concept in patients with metastatic Barrett's carcinoma in comparison to patients with the locally advanced form of the disease. There are profound differences in the two groups with regard to survival time and response rates. Because of the poor outcome to date, multimodal therapy with resection of the tumor in stage IV disease cannot be recommended.

Multicentric Adenocarcinomas in a Long-Segment of Barrett's Esophagus.

This report describes a complicated course of a 58-year-old patient with multicentric Barrett's carcinoma within a long-segment of Barrett metaplasia. After abdominal-thoracic resection of the cancer, with incomplete removal of the long-segment metaplastic lesion, invasive carcinoma was diagnosed in the remnant Barrett's segment. Endoscopic mucosal resection was done, but Barrett's mucosa was left in situ again. Recurrent tumor growth was diagnosed only few months later. Finally, transthoracic complete resection on the remnant Barrett's segment was performed. Thus, our case demonstrates impressively the appearance of multicentric adenocarcinomas in Barrett's esophagus and underlines the necessity of resection of the complete Barrett mucosa.

Response of the lower esophageal sphincter to gastric distention by carbonated beverages.

Gastroesophageal reflux disease often occurs in patients with normal resting pressure and length of the lower esophageal sphincter. Such patients often have postprandial reflux. The mechanism of postprandial reflux remains controversial. To further clarify this, we studied the effect of carbonated beverages on the resting parameters of the lower esophageal sphincter. Nine asymptomatic healthy volunteers underwent lower esophageal sphincter manometry using a slow motorized pull through technique after ingestion of tap water and carbonated beverages. Resting pressure, overall length, and abdominal length of the lower esophageal sphincter were measured. All carbonated beverages produced sustained (20 minutes) reduction of 30-50% in all three parameters of the lower esophageal sphincter. In 62%, the reduction was of sufficient magnitude to cause the lower esophageal sphincter to reach a level normally diagnostic of incompetence. Tap water caused no reduction in sphincter parameters. Carbonated beverages, but not tap water, reduce the strength of the lower esophageal sphincter. This may be relevant to the pathogenesis of gastroesophageal reflux disease, especially in Western society.

Increased risk of ischemic bowel complications during treatment with bevacizumab after pelvic irradiation: report of three cases.

PURPOSE: To assess the rate of severe bowel complications during treatment with the anti-vascular endothelial growth factor monoclonal antibody bevacizumab. METHODS AND MATERIALS: We performed a retrospective evaluation of bevacizumab-associated severe intestinal adverse events from our institutional database. RESULTS: A total of 33 patients started treatment with bevacizumab at our institution during the first 6 months after its approval in Germany. Three patients (9%) presented with severe bowel complications: two with acute ischemic colitis and one with gastrointestinal perforation with a fatal outcome. All 3 patients had undergone radiotherapy directed to the pelvis before treatment with bevacizumab. None of the 30 patients without bowel complications had been pretreated with infradiaphragmatic irradiation. Histologic evaluation of bowel biopsies and resection specimens revealed severe ischemic bowel damage as the pathophysiologic background of the clinical findings. CONCLUSION: This report contributes to the pathophysiologic clarification of bevacizumab-induced bowel complications and points to a potentially increased risk of severe ischemic damage during treatment with bevacizumab in patients who have undergone previous radiotherapy.

Current concepts of percutaneous abscess drainage in postoperative retention.

In recent years, percutaneous abscess drainage (PAD) of intraabdominal abscesses has become an important tool with regard to the treatment of intraabdominal sepsis. The aim of this study is to assess the value of PAD in the treatment of postoperative retentions. Between 1995 and 1999, the postoperative course of 3346 patients undergoing major abdominal surgery was analyzed. Mortality, morbidity, and comparison of different locations of intraabdominal abscesses were assessed. PAD was considered successful when the patient improved clinically within 24 hours, a decrease in the size of the abscess formation was noted, and complete recovery without further surgical intervention occurred. Out of 3346 operated patients, 174 (5.2%) were diagnosed as having an intraabdominal abscess formation and were treated by PAD. In 63 patients the abscess developed within the upper quadrants, in 66 patients the abscess developed within the lower quadrants, and in the remaining 45 patients the abscess developed within the retroperitoneal cavity or pelvis. The success rate of PAD was 85.6% with a morbidity rate of 4.6%. The least successful location for PAD was the left upper quadrant. Patients with abscess drainage in the right upper and lower quadrant experienced a high success rate. One patient died due to the PAD procedure. Unsuccessful PAD was closely related to an increase in mortality. In the case of intraabdominal abscess formation after visceral surgery, PAD should be the primary procedure. Attention should be paid to abscess formations in the left upper quadrant because there is an increased likelihood of complications caused by PAD.

Experimental evidence for mutagenic potential of duodenogastric juice on Barrett's esophagus.

The aim of this article is to review the current experimental knowledge of mutagenesis in Barrett's esophagus (BE) with special emphasis on the effect of bile salts and acid. Human evidence of direct mutagenicity is rare. Only the correlation of increased quantities and a change in the quality of bile salts with the complications of duodenogastric reflux such as BE and esophageal adenocarcinoma as an indirect marker of mutagenicity has been shown in several studies. Further evidence comes from p53 studies demonstrating an increased number of mutated p53 genes in patients with BE, esophageal adenocarcinoma, or both. Most animal and cellular experiments are carried out in a neutral pH environment, not reflecting the true nature of a reflux episode. The few studies using moderate low acid reflux conditions in combination with bile salts demonstrated a combined effect on mutagenicity. Our current knowledge of bile salt mutagenicity is predominantly based on experiments with hepatocytes and colon cancer cell lines. Future studies must be aimed at esophageal cell lines, cultured Barrett's tissue, and esophageal adenocarcinoma cell lines.