Boerhaave's syndrome: successful conservative treatment in two patients.

The Boerhaave syndrome is a spontaneous, post-emetic rupture of the esophagus and a rare but potentially fatal cause of upper gastrointestinal bleeding. There are currently no guidelines on the optimal treatment of these patients, although there is a strong tendency towards a surgical approach. We present 2 cases of male patients, 66- and 77-year old respectively, both admitted to the emergency department with hematemesis. Unexpectedly, these turned out to be caused by the Boerhaave syndrome. Based on the severity of presentation, either a conservative or endoscopic treatment was adopted, both with good outcome.

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.

BACKGROUND: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. METHODS: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. RESULTS: Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect ≥grade 2 was associated with increased PFS (P = 0.05). CONCLUSION(S): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. ClinicalTrials.gov Identifier: NCT00747097.

A phase II randomized study of combined infusional leucovorin sodium and 5- FU versus the leucovorin calcium followed by 5-FU both in combination with irinotecan or oxaliplatin in patients with metastatic colorectal cancer.

BACKGROUND: Leucovorin Sodium (LV/Na) has a high solubility, and is stable when given with continuous infusion of 5-FU. It could maintain significant plasma concentration of 5, 10-meTHF during the whole 5-FU perfusion with the potential of increasing 5-FU cytotoxicity. We conducted a randomized phase II clinical trial on leucovorin calcium (LV/Ca) and LV/Na in metastatic colorectal cancer patients (mCRC). Main objectives were to assess efficacy and safety. PATIENTS AND METHODS: Fifty seven patients with mCRC and no previous chemotherapy for metastatic disease were randomized to receive LV/Na or LV/Ca with irinotecan or oxaliplatine combined with infusional 5-FU. LV/Na was defined as warranting further evaluation in phase III if true overall response rate (ORR) > 35% (α=5%, ß=10% in case of true ORR >55%, 51 evaluable patients planned/arm). RESULTS: Results for LV/Ca and LV/Na arm respectively were: observed ORR, 55% (significantly higher than 35%, p = 0.02) and 61% (p = 0.004). Median overall survival durations were 11.9 months and 22.9 months (p = 0.02) and PFS 8.0 vs. 11.5 months (ns). Grade 3 events were 64% and 46% (p = 0.28). CONCLUSION: Both LV/Na and LV/Ca disclosed an ORR > 35% with comparable safety.

Clinical trial: Preliminary efficacy and safety study of a new Budesonide-MMX® 9 mg extended-release tablets in patients with active left-sided ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with relapses. Many patients need systemic corticosteroids to induce clinical remission. AIM: Efficacy and safety of Budesonide-MMX® 9 mg tablets, a new oral, extended-release formulation, were evaluated in patients suffering from active, left-sided UC with colitis activity index (CAI) <14. METHODS: 36 patients were treated once daily for 4 weeks with Budesonide-MMX® 9 mg tablets or placebo. In an additional 4-week period, all patients received Budesonide-MMX®. CAI, endoscopic index and histology were assessed after 4 and 8 weeks. Primary end-point was remission, and/or CAI reduction by 50% after 4 weeks. Morning cortisol was assayed after 4 and 8 weeks, and a short ACTH-test was performed at week 8. RESULTS: 32 patients were analysed. After 4 weeks, 47.1% of the patients in the Budesonide-MMX® 9 mg tablets group achieved the primary end-point vs. 33.3% of patients on placebo. In addition, 47.1% of budesonide patients and another 33.3% of placebo recipients improved without remission by 4 weeks. The CAI reduction was significant with Budesonide (p<0.0001) tablets and not with placebo (p=0.1). Neither morning cortisol nor pituitary-adrenal axis was more frequently suppressed with Budesonide tablets than with placebo. CONCLUSIONS: Budesonide-MMX® 9 mg tablets induced a fast and significant clinical improvement of active left-sided UC without suppression of adrenocortical functions and without important toxicity EudraCT number 2004-000896-33.

Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015.

BACKGROUND: The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI: irinotecan (180 mg/m(2) i.v. on days 1, 15 and 22); FA (200 mg/m(2) i.v. on days 1, 2, 15, 16, 29 and 30); 5-FU (400 mg/m(2) i.v. bolus, then 22-h, 600 mg/m(2) infusion) or CAPIRI: irinotecan (250 mg/m(2) i.v. infusion on days 1 and 22); capecitabine p.o. (1000 mg/m(2) b.i.d. on days 1-15 and 22-36). Patients were additionally randomly assigned to receive either placebo or celecoxib (800 mg: 2 x 200 mg b.i.d.). RESULTS: The trial was closed following eight deaths unrelated to disease progression in the 85 enrolled (629 planned) patients. Response rates were 22% for CAPIRI + C, 48% for CAPIRI + P, 32% for FOLFIRI + C and 46% for FOLFIRI + P. Median PFS and overall survival (OS) times were shorter for CAPIRI versus FOLFIRI (PFS 5.9 versus 9.6 months and OS 14.8 versus 19.9 months) and celecoxib versus placebo (PFS 6.9 versus 7.8 months and OS 18.3 versus 19.9 months). CONCLUSION: Due to the small sample size following early termination, no definitive conclusions can be drawn in relation to the noninferiority of CAPIRI compared with FOLFIRI.

Azathioprine induced colitis: a case report and review of the literature.

We report a case of an allergic hypersensitivity reaction on azathioprine presenting with colitis. Allergic reactions on azathioprine are common in patient with inflammatory bowel disease. The clinic of the allergic reaction on azathioprine in our patient was atypical in the way it mimicked an acute exacerbation of inflammatory bowel disease. The pathogenesis of the allergic reaction is still unclear. Although re-challenge can be life-threatening and should always be done with precautions, it may definitively proof the causal association with the drug and decide for definitive cessation In allergic reactions there is no link with TPMT activity but other genetically predispositions are proposed.

Internal jugular vein thrombosis after ovarian stimulation.

Thromboembolic events are serious, but fortunately rare, complications following ovarian stimulation for IVF. Here, we report a case of internal jugular vein thrombosis after ovarian stimulation with gonadotrophins. Most of the cases of thrombosis are late complications of ovarian hyperstimulation syndrome (OHSS) or hereditary hypercoagulability. Screening for these risk factors in our patient was negative. The patient was successfully treated with low molecular weight heparin and a twin pregnancy is ongoing.

Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation.

The authors describe a case of severe sensory-motor polyneuropathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weaning from the ventilator was possible. Further intensive physical rehabilitation required an additional 6 months hospital stay, and 18 months later, neurological recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of thallotoxicosis and the present treatment is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery.

The impact of routine admission abdominal sonography on patient care.

In a prospective study of 1000 consecutive patients, abdominal sonography added diagnostic information to that available by history and physical examination in 8.9%. The yield ranged from a high of 27.4% in patients with acute abdominal symptoms to a low of 2.7% in screening sonograms of patients without abdominal symptoms. Sonographically guided biopsy-proven diagnoses were obtained in 6.6% of the patients and were clinically not suspected in 4.4%. The percentage of false-positive and false-negative sonographic studies was 0.5% and 1.1%, respectively. Sonography shortened the duration of hospitalization in 15.3%.

The role of desferrioxamine in dialysis-associated mucormycosis: report of three cases and review of the literature.

We report 3 patients on maintenance hemodialysis who developed a fulminant, disseminated and fatal form of mucormycosis. The diagnosis was made by microscopy and culture in 1 case, yielding Rhizopus rhizopodiformis, and by post-mortem microscopy in the two other cases. These patients were receiving desferrioxamine (DFO) for aluminum overload and had no iron-overload. Ten similar patients, all (with only one possible exception) receiving DFO, have been reported from American centers. The mechanism by which DFO could precipitate mucormycosis is unsettled. The explanation might be that DFO acts as a siderophore to the Mucorales fungi. High serum levels of DFO in renal failure could enhance this mechanism. Epidemiological data, provided from an inquiry in 25 Flemish dialysis centers, support the association between DFO treatment and dialysis-associated mucormycosis.