[Coronoid reconstruction with autologous iliac crest bone graft in chronic elbow instability through a medial approach]. / Coronoidaufbau mittels Beckenkammspan über einen medialen Zugang zur Therapie von chronischen Coronoiddefekten mit posteromedialer Rotationsinstabilität.

OBJECTIVE: Neutralizing a posteromedial rotatory instability (PMRI) caused by coronoid deficiency by restoration of the humeroulnar joint surface with an autologous iliac crest bone graft. INDICATIONS: Surgery is indicated in patients with chronic deficiency of the anteromedial facet of the coronoid with subsequent PMRI. CONTRAINDICATIONS: Coronoid reconstruction is not recommended in patients with advanced osteoarthritis of the elbow caused by subluxation of the humeroulnar joint. General contraindications like acute infection, pregnancy and lack of operability should also be taken into account. SURGICAL TECHNIQUE: First, a medial approach is established and the base of the coronoid is prepared. Afterwards an autologous iliac crest bone graft is placed onto the defect and secured by screws or a plate. In addition, a reconstruction of the anterior bundle of the medial collateral ligament with an autologous tendon graft is performed. POSTOPERATIVE MANAGEMENT: An elbow orthesis is worn for 6 weeks after surgery to avoid valgus or varus stress. There is no restriction in range of motion. A continuous passive motion elbow chair supports the patient in regaining elbow mobility. RESULTS: Between 2015 and 2017, we treated 10 patients suffering from chronic coronoid defects with coronoid reconstruction. Eight of the patients were available for follow-up 86 weeks after surgery. The mean age was 41.4 years. In all patients, elbow range of motion and patient-related outcome measures were improved after surgery. Plain radiographs illustrated correct centering of the elbow joint. One patient had to undergo elbow arthroplasty and was excluded. Coronoid reconstruction with an autologous iliac crest bone graft restored humeroulnar joint congruency and improved satisfaction in patients suffering from chronic coronoid deficiency.

Quality assurance of radiotherapy in the ongoing EORTC 1420 "Best of" trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure.

INTRODUCTION: The current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS). MATERIALS AND METHODS: Submitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV). RESULTS: 65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD). CONCLUSIONS: This is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients' clinical outcome.

Is pre-operative heart rate variability a prognostic indicator for overall survival and cancer recurrence in patients with primary colorectal cancer?

BACKGROUND: Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer. METHODS: Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival. RESULTS: A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607-1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802-2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599-1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706-2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications. CONCLUSIONS: Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.

Deepening trochleoplasty and medial patellofemoral ligament reconstruction normalize patellotrochlear congruence in severe trochlear dysplasia.

AIMS: The aim of this study was to evaluate cartilaginous patellotrochlear congruence and patellofemoral alignment parameters after deepening trochleoplasty in severe trochlear dysplasia. PATIENTS AND METHODS: The study group comprised 20 patients (two male, 18 female; mean age 24 years (16 to 39)) who underwent deepening trochleoplasty and medial patellofemoral ligament (MPFL) reconstruction for the treatment of recurrent lateral patellar dislocation due to severe trochlear dysplasia (Dejour type B to D). Pre- and postoperative MRI investigations of the study group were compared with MRI data of 20 age- and gender-matched control patients (two male, 18 female; mean age 27 years (18 to 44)) regarding the patellotrochlear contact ratio, patellotrochlear contact area, posterior patellar edge-trochlear groove ratio, and patellar tilt. RESULTS: Preoperatively, all parameters in the study group indicated significant patellar malalignment, including a reduced patellotrochlear contact ratio (mean 0.38 (0.13 to 0.59) vs mean 0.67 (0.48 to 0.88); p < 0.001), reduced contact area (mean 128 mm2 (87 to 190) vs mean 183 mm2 (155 to 227); p < 0.001), increased patellar lateralization (mean 0.82 (0.55 to 1.0) vs mean 0.99 (0.93 to 1.1); p < 0.001) and increased patellar tilt (mean 25.8° (8.1° to 43.0°) vs mean 9.1° (0.5° to 16.8°); p < 0.001). Postoperatively, all parameters in the study group improved significantly and reached normal values compared with the control group. The patellotrochlear contact ratio increased to a mean of 0.63 (0.38 to 0.85) (p < 0.001), the contact area increased to a mean of 187 mm2 (101 to 255) (p < 0.001), the posterior patellar edge-trochlear groove ratio improved to a mean of 0.96 (0.83 to 0.91) (p < 0.001), and the patellar tilt decreased to a mean of 13.9° (8.1° to 22.1°) (p < 0.001) postoperatively. CONCLUSION: Deepening trochleoplasty and MPFL reconstruction normalized the patellotrochlear congruence and patellofemoral alignment parameters. Modifying the dysplastic trochlea involves approximating the trochlear morphology to the shape of the patella rather than inducing a patella and trochlea mismatch. Cite this article: Bone Joint J 2019;101-B:325-330.

[Performance control after arthroscopic arthrolysis with capsulectomy in fresh-frozen elbow joints]. / Erfolgskontrolle nach arthroskopischer Arthrolyse mit Kapsulektomie am Ellenbogengelenk im Fresh-frozen-Präparat.

BACKGROUND AND OBJECTIVE: Posttraumatic or postoperative movement restrictions in elbow joints can often occur (including capsular contracture) and can generate everyday limitations. In persistent elbow stiffness, arthroscopic arthrolysis with removal of the dorsal and ventral capsule portions can be carried out. The purpose of this study was to assess the efficacy of arthroscopic capsulectomy by means of an in vitro anatomical study. METHODS: A standardized elbow arthroscopy with ventral and dorsal capsulectomy was performed and image-documented in five fresh-frozen elbow specimens. Subsequently, open dissection of the elbow joint was performed to analyze the amount of residual capsule by means of photodocumentation of the specimens. RESULTS: Regardless of the surgeon and surgical experience, anterior and posterior remnants of the capsule remained in all specimens. Dorsal capsule strands around the standard arthroscopy portals were noticed particularly more often in the area of the high dorsolateral camera portal. An incomplete capsulectomy was seen on the ulnar side at the level of the posterior medial ligament (PML) in the immediate vicinity of the ulnar nerve. Ventrally, a capsulectomy was performed from the radial side and also the ulnar side until the brachialis muscle and additionally a complete capsulectomy as far as the anterior medial ligament (AML) and radial collateral ligament (RCL) was achieved. The capsule was completely resected in a proximal direction. Distally, irrelevant capsular remnants were found in the region of the annular ligament and distal of the tip of the coronoid process. CONCLUSION: Arthroscopic arthrolysis can be performed with a high degree of radicality. The radicality must be self-critically taken into account in one's own action. The radicality of the portal change may even be higher ventrally than with an isolated column procedure. On the other hand, it must be critically considered that posteriorly, the PML cannot be adequately addressed by means of arthroscopy due to the risk of ulnar nerve injury. Portal changes might help to enable a more complete visualization of the joint capsule and may avoid leaving possibly relevant remnants of the capsule. If a release of the PML is required, this may have to be carried out in combination with an ulnar nerve release in a mini-open technique.

Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

Assessment of elevated compartment pressures by pressure-related ultrasound: a cadaveric model.

PURPOSE: There is a risk of misinterpreting the clinical signs of acute compartment syndrome of the lower limb resulting in delayed fasciotomy. Up to date, the diagnosis of compartment syndrome is based on clinical assessment and of invasive needle pressure measurement in uncertain cases. Close monitoring is necessary for early recognition of raising compartment pressures. Clinical assessment of muscle firmness by the physician's palpation alone is unreliable. Thus, a device objectifying this assessment would be beneficial. The purpose of this study was to determine the feasibility of muscle compartment elasticity measurements by a novel and non-invasive device using pressure-related ultrasound. METHODS: In a cadaveric model, the anterior tibial compartment was prepared to simulate raising intra-compartmental pressures (0-80 mmHg) by saline infusion. Standard invasive pressure monitoring was compared with a novel method to determine tissue elasticity. Changing cross-sectional view in B-mode ultrasound was exerted to measure the compartment depth before and after physician's probe compression of 100 mmHg. Compartment displacement (∆d) was measured and related to the corresponding compartmental pressure (Spearman correlation coefficient). Delta (mm) of the control group at 10 mmHg compartment pressure was compared with measured data at rising compartmental pressures of 30, 50, and 70 mmHg using the Wilcoxon rank-sum test. The intra-observer reliability (κ) was additionally calculated. RESULTS: Fresh and never frozen lower human limbs (n = 6) were used. The average displacement measured in the anterior tibial compartment was 2.7 mm (0.3-6.7 mm). A concordant consistent correlation between the compartmental displacement and the intra-compartmental pressure occurred. The Spearman coefficient (r s = 0.979) showed a significant correlation between the rising pressure and the decreasing tissue displacement visualized by ultrasound. The intra-observer value kappa showed reliable values (κ 10 = 0.73, κ 30 = 0.80, and κ 70 = 0.79). CONCLUSIONS: We introduce a new method of ultrasound imaging enhanced with probe pressure measurement to determine changes of the visco-elastic behavior of isolated muscle compartments. Pressure-related ultrasound could be a reliable tool to determine the correlation between the measured compartmental displacement and the increasing intra-compartmental pressure. Its accuracy revealed promising results. This technique may help the physician to objectify the clinical assessment of compartment elasticity, mainly indicated in cases of unconscious patients and imminent pathology. Further clinical studies and improvements of this technique are required to prove its accuracy and reliability in cases of compartment syndrome.

Aggressive Breast Cancer during Pregnancy with a Rare Form of Metastasis in the Maternal Placenta.

Breast cancer is the second most common cancer diagnosed during pregnancy. Here we describe a 29-year-old patient with a recurrence of breast cancer with simultaneous brain, pulmonary and placenta metastasis. An overview of the literature on placenta metastases is provided together with a report on the interdisciplinary medical management.

Contrast enhanced ultrasound (CEUS) reliably detects critical perfusion changes in compartmental muscle: a model in healthy volunteers.

PURPOSE: The purpose of this study was to assess the utility of contrast enhanced ultrasound (CEUS) in the differentiation between physiological and simulated pathophysiological lower limb muscle perfusion pressures in healthy volunteers. METHODS: The lower limb muscle perfusion pressures in eight healthy volunteers were assessed in the supine position (as a control) and then subsequently in an elevated position with a thigh tourniquet applied to induce venous stasis. An intravenous bolus injection of 2.5 ml contrast agent was given to create a perfusion signal, which was measured with a multiple-frequency probe. Semiquantitative analysis was performed using specific software to create a perfusion curve which allowed measurement of six parameters: the time to arrival (TTA) starting from bolus application (s); peak of signal intensity (%); time to peak (TTP) maximum (seconds); regional blood volume (RBV), regional blood flow (RBF), and mean transit time (MTT) in seconds. Statistical analysis was performed using the Mann-Whitney U test as a non-parametric test (IBM SPSS statistics, version 21, USA). RESULTS: The group of simulated hypoperfusion showed significant higher values for TTA (39.8 ± 5.1 s) (p = 0.028), TTP (43.8 ± 13.6 s) (p = 0.003), RBV (8,424 ± 5,405) (p = 0.028), and MTT (262 ± 90.6 s) (p = 0.005). In contrast, the parameter of regional blood flow (32.1 ± 10.9) was significantly lower (p = 0.038). The peak signal intensity (25.8 ± 8.2 %) was lower, but this was not significant (p = 0.083). CONCLUSIONS: CEUS provides a reliable non-invasive imaging modality for the assessment of lower limb muscle perfusion pressures. This may be of clinical use in the assessment of a developing compartment syndrome. Further clinical studies are required to further define its accuracy and reproducibility.

Prediction of residential radon exposure of the whole Swiss population: comparison of model-based predictions with measurement-based predictions.

Radon plays an important role for human exposure to natural sources of ionizing radiation. The aim of this article is to compare two approaches to estimate mean radon exposure in the Swiss population: model-based predictions at individual level and measurement-based predictions based on measurements aggregated at municipality level. A nationwide model was used to predict radon levels in each household and for each individual based on the corresponding tectonic unit, building age, building type, soil texture, degree of urbanization, and floor. Measurement-based predictions were carried out within a health impact assessment on residential radon and lung cancer. Mean measured radon levels were corrected for the average floor distribution and weighted with population size of each municipality. Model-based predictions yielded a mean radon exposure of the Swiss population of 84.1 Bq/m(3) . Measurement-based predictions yielded an average exposure of 78 Bq/m(3) . This study demonstrates that the model- and the measurement-based predictions provided similar results. The advantage of the measurement-based approach is its simplicity, which is sufficient for assessing exposure distribution in a population. The model-based approach allows predicting radon levels at specific sites, which is needed in an epidemiological study, and the results do not depend on how the measurement sites have been selected.

[Modern radiotherapeutic concept - stereotactic, adjuvant, palliative]. / Moderne strahlentherapeutische Konzepte - stereotaktisch, adjuvant, palliativ.

Radiotherapy is an important and well integrated part in modern treatment concepts for cancer of the lung and pleura. Thanks to technical progress in the last years radiotherapy has managed to prove its role in all stages of lung cancers and has opened a spectrum of new treatment options. Stereotactic radiotherapy of the early NSCLC has become the standard treatment for radically inoperable patients. It provides better local control rates than traditional conventionally fractionated radiotherapy. In stage III NSCLC, simultaneous radiochemotherapy is an effective option with equal results compared to surgery. The standard treatment for limited disease SCLC is primary simultaneous radiochemotherapy. All patients with good response after primary treatment profit from prophylactic cranial irradiation. Adjuvant radiotherapy is a component of the trimodal treatment for curative approaches in patients with pleura mesothelioma. Palliative radiotherapy is the standard treatment for brain metastases, bone metastases and compression or obstruction from thoracal tumour mass.

Postoperative radiotherapy after radical prostatectomy: indications and open questions.

Biochemical relapse after radical prostatectomy occurs in approximately 15-40% of patients within 5 years. Postoperative radiotherapy is the only curative treatment for these patients. After radical prostatectomy, two different strategies can be offered, adjuvant or salvage radiotherapy. Adjuvant radiotherapy is defined as treatment given directly after surgery in the presence of risk factors (R1 resection, pT3) before biochemical relapse occurs. It consists of 60-64 Gy and was shown to increase biochemical relapse-free survival in three randomized controlled trials and to increase overall survival after a median followup of 12.7 years in one of these trials. Salvage radiotherapy, on the other hand, is given upon biochemical relapse and is the preferred option, by many centers as it does not include patients who might be cured by surgery alone. As described in only retrospective studies the dose for salvage radiotherapy ranges from 64 to 72 Gy and is usually dependent on the absence or presence of macroscopic recurrence. Randomized trials are currently investigating the role of adjuvant and salvage radiotherapy. Patients with biochemical relapse after prostatectomy should at the earliest sign of relapse be referred to salvage radiotherapy and should preferably be treated within a clinical trial.

[Digital necrosis in a patient with atherosclerosis: also a paraneoplasia?]. / Fingernekrose bei einem Patienten mit Atherosklerose - auch paraneoplastisch bedingt?

HISTORY AND ADMISSION FINDINGS: A 59-year-old man was admitted with an acral necrosis of the left 3rd finger, which had developed during several weeks. Furthermore, the patient complained of diarrhoea. INVESTIGATIONS: Acral light plethysmography showed critical ischemia of digitus II and V, and impaired distal perfusion of digitus I and IV. Duplex sonography revealed atherosclerotic plaques in the supraaortal vessels with stenosis of the left axillary artery which was confirmed by ultrasound. However, no differences in the pressure of ulnar and radial arteries existed. Colonoscopy and abdominal computed tomography revealed two colon neoplasms, including hepatic metastasis. TREATMENT AND COURSE: The stenosis of the left axillary artery was considered as the source of distal embolisation. However, after morphologically successful angioplasty distal necrosis worsened with involvement of additional fingers. Later in the course, diagnostic work-up of diarrhoa established the diagnosis of metastatic colorectal cancer. Finally, the patient died because of intercurrent pneumonia. CONCLUSION: Spontaneous acral necrosis may develop due to embolisation or local thrombotic vessel occlusion. Progression despite successful treatment of a potential source of embolism points to a significant coagulopathy, as in metastatic cancer.

Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer. Treatment outcome outside clinical trials.

BACKGROUND: Phase II trials of neoadjuvant treatment in UICC-TNM stage II and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity. PATIENTS AND METHODS: Retrospective evaluation of 34 patients treated from 2005-2008 outside clinical trials (CTR) with neoadjuvant irradiation (45-50.4 Gy) and simultaneous capecitabine 825 mg/m(2) b.i.d. on days 1-14 and 22-35 and oxaliplatin 50 mg/m(2) on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000 mg/m(2) b.i.d. on days 1-14 and oxaliplatin 130 mg/m(2) on day 1 (XELOX) prior to simultaneous chemoradiotherapy. RESULTS: UICC-TNM stage regression was observed in 60% (n = 20). Dworak's regression grades 3 and 4 were achieved in 18.2% (n = 6) and 15.1% (n = 5) of the patients. Sphincter-preserving surgery was performed in 53% (n = 8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1 patient had progressive disease and 5 patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n = 6) and perianal pain 9% (n = 3). Nevertheless, severe cardiac events (n = 2), severe electrolyte disturbances (n = 2), and syncopes (n = 2) were observed as well. CONCLUSION: Treatment efficacy and common toxicity are similar to the reports of phase I/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CTR.

Clinical, molecular- and cytogenetic analysis of a case of severe radio-sensitivity.

In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.

Lack of complex I is associated with oncocytic thyroid tumours.

Oncocytic tumours are characterised by hyperproliferation of mitochondria. We immunohistochemically analysed all enzymes of the oxidative phosphorylation system in 19 oncocytic thyroid tumours. A specific lack of complex I was detected, which was expressed at <5% of the level determined in surrounding non-cancerous tissue.

Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial.

Oxaliplatin and 5-fluorouracil have a significant activity in locally advanced oesophageal squamous cell cancer (OSCC). However, their optimal dosage and efficacy when combined with concurrent radiotherapy as neoadjuvant treatment are unknown. This non-randomised, phase I/II study aimed to define the maximum tolerated dose (MTD) and assessed the histopathological tumour response rate to neoadjuvant oxaliplatin in weekly escalating doses (40, 45, 50 mg m(-2)) and continuous infusional 5-fluorouracil (CI-5FU; 225 mg m(-2)) plus concurrent radiotherapy. Patients had resectable OSCC. Resection was scheduled for 4-6 weeks after chemoradiotherapy. During phase I (dose escalation; n=19), weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) was established as the MTD and was the recommended dosage for phase II. Oesophageal mucositis was the dose-limiting toxicity at higher doses. During phase II, histopathological responses (<10% residual tumour cells within the specimen) were observed in 10 of 16 patients (63%; 95% confidence interval: 39-82%). Overall, 16 of the 25 patients (64%) who underwent resection had a histopathological response; tumour-free resection (R0) was achieved in 80%. Neoadjuvant weekly oxaliplatin 45 mg m(-2) plus CI-5FU 225 mg m(-2) with concurrent radiotherapy provides promising histological response rates and R0 resection rates in locally advanced OSCC.

Histopathological response after preoperative radiochemotherapy in rectal carcinoma is associated with improved overall survival.

BACKGROUND: Recent studies showed improved local control after preoperative radiochemotherapy (RCTX) in patients with locally advanced rectal carcinoma, but failed to demonstrate a survival benefit. Our aims were to determine outcome and impact of histopathological response after preoperative RCTX. METHODS: One hundred four patients with uT3 rectal carcinoma were treated with preoperative RCTX of 45 Gy and continuous 5-FU infusion between 1997 and 2001 (group I). Histopathological response was evaluated in all specimens after tumor resection. Group II consisted of 114 patients with uT3 rectal carcinoma treated with postoperative RCTX between 1988 and 1997. RESULTS: Group I showed a 6.1% 5-year local recurrence rate compared to 15.3% in group II (P = 0.023). Overall survival rates did not differ significantly between both groups (P = 0.225). Histopathological responders had a significantly improved 5-year overall survival with 89.1 (7.8)% compared to 68.7 (6.7)% of the non-responders (P = 0.008) and were identified as an independent prognostic factor. CONCLUSIONS: Significant improvement of overall survival was observed for histopathological tumor responders after neoadjuvant radiochemotherapy. Our protocol of preoperative radiochemotherapy confirms the results of the multi-center studies in regard to local control and overall survival.