Multi-Parametric MRI-Directed Focal Salvage Permanent Interstitial Brachytherapy for Locally Recurrent Adenocarcinoma of the Prostate: A Novel Approach.

Even with the technological advances of dose-escalated IMRT with the addition of the latest image guidance technologies, local failures still occur. The combination of MRI-based imaging techniques can yield quantitative information that reflects on the biological properties of prostatic tissues. These techniques provide unique information that can be used for tumor detection in the treated gland. With the advent of these improved imaging modalities, it has become possible to more effectively image local recurrences within the prostate gland. With better imaging, these focal recurrences can be differentially targeted with salvage brachytherapy minimizing rectal and bladder toxicity. Here we report a novel use of MRI-directed focal brachytherapy after local recurrence. This technique offers a unique opportunity to safely and successfully treat recurrent prostate cancer, previously treated with definitive radiation therapy. The use of multi-parametric MRI-directed focal salvage permanent interstitial brachytherapy for locally recurrent adenocarcinoma of the prostate is a promising strategy to avoid more aggressive and expensive treatments that are associated with increased morbidity, potentially improving survival at potentially lower costs.

Effort, safety, and findings of routine preoperative endoscopic evaluation of morbidly obese patients undergoing bariatric surgery.

BACKGROUND: Obesity is becoming an epidemic health problem and is associated with concomitant diseases, such as sleep apnea syndrome and gastroesophageal reflux disease (GERD). There is no standardized diagnostic workup for the upper gastrointestinal tract in obese patients; many patients have no upper gastrointestinal symptoms, and few data are available on safety of endoscopy in morbidly obese patients. METHODS: Sixty-nine consecutive diagnostic upper gastrointestinal endoscopies in morbidly obese patients (26 men, 43 women; mean age 43.4 +/- 10.9 years) were prospectively evaluated from January to December 2008 in an outpatient setting before bariatric procedures. Sedation was administered with propofol. Data on sedation, critical events, and examination times were recorded, as well as pathological findings. RESULTS: The patients' mean body mass index was 47.6 +/- 7.9 (range, 35.1-73.3) kg/m(2); 17.4% reported GERD symptoms. The mean duration of the endoscopy procedure (including sedation) was 20.3 +/- 9.3 (range, 5-50) min, and the whole procedure (including preparation and postprocessing) took 58.2 +/- 19 (range, 20-120) min. The mean propofol dosage was 380 +/- 150 (range, 80-900) mg. Two patients had critical events that required bronchoscopic intratracheal O(2) insufflation due to severe hypoxemia (<60% SaO: (2)). Nearly 80% of patients had pathological findings in the upper gastrointestinal tract. Only 20% reported upper gastrointestinal symptoms. Pathologic conditions were found in the esophagus in 23.2% of the patients, in the stomach in 78.2%, and in the duodenum in 11.6%. The prevalence of Helicobacter pylori infection was 8.7%. CONCLUSIONS: Upper gastrointestinal endoscopy can be performed safely. However, careful monitoring and anesthesiological support are required for patients with concomitant diseases and those receiving sedation. Because 80% of the patients with pathological findings were asymptomatic, every morbidly obese patient should undergo endoscopy before bariatric surgery because there may be findings that might change the surgical strategy.

[Esophageal squamous cell carcinoma: pre-operative combined radiochemotherapy from a surgical oncological viewpoint]. / Plattenepithelkarzinom des Osophagus : Präoperative kombinierte Radiochemotherapie aus chirurgisch-onkologischer Sicht.

Esophageal squamous cell carcinomas (ESCCs) are an interdisciplinary challenge in terms of diagnosis, multimodal and/or surgical treatment procedures and also postoperative management as they are often associated with multiple comorbidities. The gold standard for a curative treatment approach is radical surgery, which is standardized and can be carried out with acceptable morbidity and mortality rates. ESCCs are usually diagnosed at locally advanced tumor stages and neoadjuvant treatment procedures are therefore used. Patients who respond to neoadjuvant therapy (responders) have a significantly better survival rate. The neoadjuvant studies that are currently available need to be critically assessed as they do not include response as an end point. In this context the WHO clinical response evaluation that has been used up to now is questionable. The histopathological findings with percentage proportions of residual tumor cells represent the gold standard for evaluating the response. Positron-emission tomography as a response criterion is predictive for the histopathological response and survival. ESCC patients who are classified as non-responders do not appear to benefit from surgical resection. In the future the results of a response evaluation and of pretreatment molecular biological tests could have a place in the process of pretherapeutic and peritherapeutic oncological decision-making in patients with ESCCs.

[Selection criteria for peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) in peritoneal carcinomatosis]. / Selektion zur Peritonektomie mit hyperthermer intraoperativer Chemotherapie (HIPEC) bei Peritonealkarzinose.

BACKGROUND: Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours. METHODS: On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed. RESULTS: Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy. CONCLUSION: The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus.

Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P=0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P=0.0061) and p53-phospho (P=0.0064). Expression of p53 correlated with expression of p53-phospho (P<0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma.

Squamous cell carcinoma and Zenker diverticulum.

Squamous cell carcinoma in a Zenker diverticulum is a very rare condition. We report a case of a patient with a Zenker carcinoma, who was primarily functionally inoperable and therefore received neoadjuvant radiochemotherapy before cardiac bypass surgery. After a complicated course with cardiogenic shock and myocardial infarction, a re-evaluation of functional risk analysis and the tumor situation revealed operability. Subsequently, partial hypopharyngectomy and partial cervical esophageal resection with lymphadenectomy was performed. Reconstruction of the gastrointestinal continuity was made by interposition of a free small bowel graft and microvascular anastomosis. The postoperative course showed a small anastomotic leakage of the hypopharyngeal-small bowel anastomosis, which was successfully treated conservatively.

Expression of cyclo-oxygenase 1 and 2, prostaglandin E synthase and transforming growth factor beta1, and their relationship with vascular endothelial growth factors A and C, in primary adenocarcinoma of the small intestine.

BACKGROUND: Primary adenocarcinomas of the small intestine are rare. The prostaglandin biosynthetic pathway plays a major role in carcinogenesis and is linked with angiogenesis in various tumours. Promotion of tumour growth by transforming growth factor (TGF) beta may be mediated through the prostaglandin pathway. METHODS: Expression of cyclo-oxygenase (COX) 1 and 2, prostaglandin E synthase (PGES), TGF-beta1 and vascular endothelial growth factor (VEGF) A and C genes was analysed in 54 primary adenocarcinomas of the small intestine and corresponding normal intestinal mucosa. All patients had undergone surgical resection without previous antineoplastic therapy. Target gene expression was analysed at the mRNA level by reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters as well as survival. COX-2 protein expression was examined by immunohistochemistry. RESULTS: Expression of COX-2 protein was detected immunohistochemically in 98 per cent of the carcinomas. COX-1, COX-2, VEGF-A, VEGF-C, PGES and TGF-beta1 mRNA expression varied markedly in different tumours, but all were overexpressed compared with levels in normal intestinal mucosa. There were significant associations between levels of COX-1, COX-2, TGF-beta1 and PGES mRNAs and those of VEGF-A and VEGF-C. CONCLUSION: Correlations between levels of mRNA for COX-1, COX-2, TGF-beta1 and PGES and those for proangiogenic factors VEGF-A and VEGF-C suggest a role for these factors in the propagation of primary adenocarcinomas of the small intestine.

[Curative vs palliative strategies in locoregional recurrence of gastrointestinal malignancies]. / Therapeutische Strategien bei lokoregionalen Rezidiven gastrointestinaler. Tumoren Palliation oder Kuration?

Locoregional recurrence is a relevant problem in surgical oncology. Intraluminal local relapse only occurs when the primary resection is carried through with inappropriate safety margins. If possible, a second surgical resection with wider margins is the treatment of choice. When the primary resection was appropriately done, extraluminal relapse in the original tumor bed indicates the primary tumor was already in an advanced stage. The indication for a second resection must be considered carefully. A realistic prospect of long-term tumor control exists only when the second resection yields tumor-free margins and is combined with chemo- and radiotherapy. There is usually no curative treatment option for recurrences in the draining lymph node region, the so-called fourth dimension.

Responders benefit from neoadjuvant radiochemotherapy in esophageal squamous cell carcinoma: results of a prospective phase-II trial.

BACKGROUND: We present the results of a prospective phase-II-study of neoadjuvant combined radiochemotherapy followed by surgical resection in patients with histological proven locally advanced squamous cell carcinoma of the esophagus located at or above the level of the tracheal bifurcation. METHODOLOGY: Between February 1995 and March 2000 a total of 76 patients with esophageal squamous cell carcinoma (uT3/4N0/+-categories) received simultaneous combined neoadjuvant radiochemotherapy consisting of a continuous intravenous infusion of 5-fluorouracil (300 mg/m2/day) 7 day per week concurrently with conventional fractioned external beam radiation therapy (2 Gy/day), five fractions per week up to a total dose of 30 Gy. RESULTS: Radiochemotherapy related acute severe toxicity rate (CTC-grade-III) occurred in 34 patients, two patients died. Sixty-four patients underwent surgery with a complete resection in 48 patients. Three patients died during a 90-day post-operative course. The histopathological workup revealed no viable residual tumour cells in eight patients (ypCR) and according to the modified criteria of Mandard in 26 patients a histopathological response. Twenty-two of these patients underwent a R0-resection. The median follow-up time was 5.4 years with an overall median survival time of 20.6 months. The median survival in the 26 responders was 32.3 months versus 19.5 months in 38 non-responders (p=0.03). CONCLUSIONS: Patients with locally advanced squamous cell carcinoma of the esophagus, who respond to preoperative neoadjuvant combined radiochemotherapy, seem to have more benefit from subsequent resection than non-responding patients.