Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08).

Background: This open-label, phase III trial compared chemoradiation followed by surgery with or without neoadjuvant and adjuvant cetuximab in patients with resectable esophageal carcinoma. Patients and methods: Patients were randomly assigned (1 : 1) to two cycles of chemotherapy (docetaxel 75 mg/m2, cisplatin 75 mg/m2) followed by chemoradiation (45 Gy, docetaxel 20 mg/m2 and cisplatin 25 mg/m2, weekly for 5 weeks) and surgery, with or without neoadjuvant cetuximab 250 mg/m2 weekly and adjuvant cetuximab 500 mg/m2 fortnightly for 3 months. The primary end point was progression-free survival (PFS). Results: In total, 300 patients (median age, 61 years; 88% male; 63% adenocarcinoma; 85% cT3/4a, 90% cN+) were assigned to cetuximab (n = 149) or control (n = 151). The R0-resection rate was 95% for cetuximab versus 97% for control. Postoperative treatment-related mortality was 6% in both arms. Median PFS was 2.9 years [95% confidence interval (CI), 2.0 to not reached] with cetuximab and 2.0 years (95% CI, 1.5-2.8) with control [hazard ratio (HR), 0.79; 95% CI, 0.58-1.07; P = 0.13]. Median overall survival (OS) time was 5.1 years (95% CI, 3.7 to not reached) versus 3.0 years (95% CI, 2.2-4.2) for cetuximab and control, respectively (HR, 0.73; 95% CI, 0.52-1.01; P = 0.055). Time to loco-regional failure after R0-resection was significantly longer for cetuximab (HR 0.53; 95% CI, 0.31-0.90; P = 0.017); time to distant failure did not differ between arms (HR, 1.01; 95% CI, 0.64-1.59, P = 0.97). Cetuximab did not increase adverse events in neoadjuvant or postoperative settings. Conclusion: Adding cetuximab to multimodal therapy significantly improved loco-regional control, and led to clinically relevant, but not-significant improvements in PFS and OS in resectable esophageal carcinoma. Clinical trial information: NCT01107639.

Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02).

BACKGROUND: This multicenter phase II study investigated the efficacy and feasibility of preoperative induction chemotherapy followed by chemoradiation and surgery in patients with esophageal carcinoma. PATIENTS AND METHODS: Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the esophagus received induction chemotherapy with cisplatin 75 mg/m(2) and docetaxel (Taxotere) 75 mg/m(2) on days 1 and 22, followed by radiotherapy of 45 Gy (25 x 1.8 Gy) and concurrent chemotherapy comprising cisplatin 25 mg/m(2) and docetaxel 20 mg/m(2) weekly for 5 weeks, followed by surgery. RESULTS: Sixty-six patients were enrolled at eleven centers and 57 underwent surgery. R0 resection was achieved in 52 patients. Fifteen patients showed complete, 16 patients nearly complete and 26 patients poor pathological remission. Median overall survival was 36.5 months and median event-free survival was 22.8 months. Squamous cell carcinoma and good pathologically documented response were associated with longer survival. Eighty-two percent of all included patients completed neoadjuvant therapy and survived for 30 days after surgery. Dysphagia and mucositis grade 3/4 were infrequent (<9%) during chemoradiation. Five patients (9%) died due to surgical complications. CONCLUSIONS: This neoadjuvant, taxane-containing regimen was efficacious and feasible in patients with locally advanced esophageal cancer in a multicenter, community-based setting and represents a suitable backbone for further investigation.

[17 year old patient with acute abdominal pain, hematochezia and exanthema]. / 17-jähriger Mann mit akuten Bauchschmerzen, Hämatochezie und Exanthem.

A 17-year old adolescent presented with abdominal pain, petechial lesions, arthralgia, and hematochezia. Abdominal ultrasound showed a suspicious ileocecal region and a lower endoscopy revealed the picture of an ileitis terminalis. The diagnosis of Purpura Henoch Schoenlein was made and confirmed by skin-biopsy showing a leucocytoclastic vasculitis. This case report demonstrates the various clinical symptoms of Purpura Henoch Schoenlein and its clinical course.

Neurological improvement and rehabilitation potential following toxic myelopathy due to intrathecal injection of doxorubicin.

STUDY DESIGN: Case report of a 31-year-old woman who presented with toxic myelopathy due to intrathecal administration of doxorubicin. OBJECTIVE: To describe the pathology and the rehabilitation of an uncommon complication of intrathecal drug administration during the oncologic treatment of acute lymphoma. SETTING: Spinal cord rehabilitation center, University Hospital. METHOD: Clinical and radiological observations during a rehabilitation program. RESULTS: Evidence of neurological improvement and rehabilitation potential after severe myelopathy due to intrathecal injection of doxorubicin. CONCLUSION: This is, to our knowledge, the first report of severe myelopathy following accidental intrathecal administration of doxorubicin. Despite early complete paraplegia, some neurological and functional recovery was observed.

Subdural catheter migration may lead to baclofen pump dysfunction.

OBJECTIVES: To report an unusual cause of intrathecal drug delivery failure in baclofen pump device. STUDY DESIGN: A case report of an SCI patient treated with intrathecal baclofen, presenting a drug withdrawal. SETTING: Regional spinal cord injuries centre in Geneva (Switzerland). METHODS: We present a case of a 38-year-old male with complete T9 spastic paraplegia for 15 years, treated with intrathecal baclofen for 11 years. He recently presented to our centre with a spastic hypertonic episode, associated with rhabdomyolysis. RESULTS: Standard investigations were unrevealing. However, a CT scan performed after injecting a radio-opaque solution by the side port of the pump, showed an unexpected catheter migration into the subdural space. Surgical revision reversed withdrawal symptoms. CONCLUSIONS: Subdural catheter migration must be considered in the differential diagnosis of intrathecal drug delivery system failures. We recommend the use of the CT scan after contrast injection, to detect the localization of the distal catheter tip and confirm the normal diffusion into the subarachnoid space.

Perioperative detection of disseminated tumour cells is an independent prognostic factor in patients with colorectal cancer.

BACKGROUND: The objective of the present investigation was to assess the prognostic significance of disseminated tumour cells in peritoneal lavage, and peripheral and mesenteric venous blood in patients undergoing curative resection of colorectal cancer. METHODS: The prognostic impact of perioperative cytological and immunocytochemical detection of disseminated colorectal cancer cells was evaluated prospectively. Peritoneal lavage fluid, and peripheral and mesenteric venous blood from 53 consecutive patients undergoing curative surgery for colorectal cancer were analysed. The dichotomous results (positive versus negative) from the cytological and immunocytochemical analysis were used as a predictor along with other co-variates in proportional hazard regression models of disease-free and overall survival. RESULTS: Disseminated colorectal cancer cells were found in 13 of 53 patients (25 per cent) using cytology (CYT) and/or immunocytochemistry (ICC). The median follow-up at the time of the analysis was 37 months. In multivariate proportional hazard regression models CYT/ICC status was a significant predictor for disease-free (P = 0.002) and overall (P = 0.006) survival. CONCLUSION: Disseminated tumour cells detected by CYT and ICC represent an independent prognostic factor in patients undergoing surgery for colorectal cancer and may identify patients at high risk of recurrence.

Hypothalamic amnesia with spontaneous confabulations: a clinicopathologic study.

Previous studies demonstrated that patients producing spontaneous confabulations fail to suppress currently irrelevant memory traces and have anterior limbic lesions, particularly involving the orbitofrontal cortex or the basal forebrain. Here, a woman is described who had sarcoidosis damaging the medial hypothalamus and endocrine dysfunction, and a severe memory failure characterized by spontaneous confabulation, disorientation, and severely impaired free recall with preserved recognition. Isolated hypothalamic damage may produce the same type of memory disorder as orbitofrontal damage.

[Minimal invasive surgery. Aspects of surgical oncology of the gastrointestinal tract]. / Minimal-invasive Chirurgie. Aspekte der chirurgischen Onkologie des Gastrointestinaltrakts.

The general potential and current position of minimally invasive surgery for the surgical treatment of malignant tumours of the gastrointestinal tract are discussed. A reliable validation of these procedures for tumour surgery is still impossible due to the lack of long-term results, the selective experience, and the ongoing process of learning and development. However, it seems clear that minimally invasive procedures will have an important position within surgical oncology. This is especially true with respect to improved staging of gastrointestinal tumours by laparoscopy and various palliative procedures that may be performed laparoscopically. Minimally invasive procedures may suffice for the treatment of certain, highly selected cases of preneoplastic and early cancerous lesions. The definitive acceptance of minimally invasive procedures in the future will require further clinical, preferably randomised trials, comparing the advantages of the minimally invasive access route to possible long-term disadvantages with regard to recurrence-free and overall survival.

Prophylactic surgery in families with familial adenomatous polyposis (FAP) and in colitis.

Colorectal cancer is the second most common cause of death from malignant tumors in western countries with approximately 3800 new cases/year in Switzerland. For individuals known to be at high risk for the development of colorectal cancer, screening, chemoprevention and/or prophylactic surgery are the only tools to avoid unnecessary premature death from this disease. With modern molecular and/or genetic testing the risk of developing colorectal cancer can be more precisely estimated on an individualized basis. These individuals need to be enrolled in strong surveillance programs and are clear candidates for prophylactic surgery. The risk of prophylactic surgery (morbidity, mortality, quality of life following surgery) must be clearly weighted against the increasing risk of cancer. These patients should be treated in experienced centers for colorectal surgery in close connection with a genetic testing and counseling team, a molecular laboratory and a psychological support group.

Visual agnosia and optic aphasia: are they anatomically distinct?

A patient with left infero-medial occipital-temporal infarct suffered a visual agnosia that, by a minor change of the task, could be manipulated to optic aphasia. Tools in actual use and pantomimes of tool use were better named than stationary tools, a dissociation that suggests differences in the ability of stimuli to evoke associations over multiple modalities. Based on this case and analysis of previous reports we suggest that optic aphasia differs from visual agnosia primarily in the degree of callosal disconnection and that the preserved demonstration of tools use and semantic classification of optic aphasia reflect right hemisphere contribution to visual processing.

[Neglect--the frequently neglected syndrome of neglect]. / Neglekt--das oft vernachlässigte Syndrom der Vernachlässigung.

In daily clinical practice "neglect" is the term for a syndrome following a right parietal lesion with inability of the patient to concentrate on events on the left side. A patient is described who was admitted for headaches and in whom neurologic investigation revealed left sided neglect as the only sign. A glioma of the right hemisphere was found. The clinical search for neglect is described and possible mechanisms are discussed. Neglect is regarded as a disturbance of directed attention. The arguments in favour of attributing dominance for this function to the right hemisphere are presented.