The detection of early micrometastasis or disseminated single tumor cells poses a problem for conventional diagnosis procedures. Using a panel of monoclonal antibodies against cytokeratin and the 17-lA epithelial antigen we identified immunocytochemically tumor cells in bone marrow of patients with breast cancer (n = 155) and colorectal cancer (n = 57) at the time of surgery of the primary tumor. Monoclonal antibody CK2, recognizing the human cytokeratin component 18 in simple epithelia, appeared to be the most suitable reagent because of its negative reaction with bone marrow samples of the noncarcinoma patients (n = 75). Its specificity was further demonstrated in a double-marker staining procedure using an anti-leukocyte common antigen monoclonal antibody (T200) as counterstain. A comparative analysis showed that immunocytology was clearly superior to conventional cytology (n = 212) and histology (n = 39). In 9.5-20.5% of patients without distant metastasis, tumor cells could be detected in bone marrow. We found a significant correlation between tumor cells in bone marrow and conventional risk factors, such as distant metastasis or lymph node involvement. In a first approach toward immunotherapy we demonstrated in 3 patients that infused monoclonal antibody 17-lA can label single tumor cells in bone marrow in vivo. We then used this approach to follow up 7 patients undergoing 17-4A therapy in an adjuvant clinical trial.

IntroductionVomiting is a common sign in dogs presenting to emergency services. It can be self-limiting, a sign of a life-threatening extraintestinal, or intestinal disorder. Reasonable diagnostics should be performed to determine the underlying cause. This study aimed to assess the utility of diagnostic tests in vomiting dogs, and its correlation with patient history, and physical examination results. Additionally, parameters to differentiate uncomplicated vomiting from complicated vomiting were investigated.MethodsIn this prospective, observational, clinical study, data from 99 client-owned dogs with vomiting, presenting as first opinion cases, were evaluated. History, physical examination, duration of clinical signs, overall number of episodes of vomiting, appetite, and additional clinical signs were recorded. The standardized diagnostic evaluation of all patients included venous blood gas analysis, complete blood count, serum biochemistry profile, canine pancreatic lipase, abdominal radiographs, ultrasound, and urinalysis. Follow-up was performed 4–5 days later. Based on severity of disease and clinical course, dogs were categorized to “uncomplicated vomiting” (UN), or “complicated vomiting” (COM). The utility of each test for diagnosing the cause of vomiting was evaluated. Spearman correlation coefficient, Chi-squared-, unpaired t-, and Mann–Whitney U-test were used. Statistical significance was defined as p ≤ 0.05.ResultsOut of the 99 dogs, 34 had uncomplicated courses of disease (UN). In 60/99 cases, a diagnosis was obtained, and in 39/99 cases, the cause for vomiting remained unknown. Longer duration of clinical signs, and reduced appetite were associated with higher utility of abdominal ultrasound. A poor mentation was associated with a higher utility of blood examinations and abdominal radiographs. Dogs presenting with an impaired mentation or with additional clinical signs other than diarrhea, were more likely to be in the COM group.DiscussionBased on this investigation, general recommendations concerning the diagnostic approach for patients with vomiting could not be provided. For dogs who have exclusively vomiting as a clinical sign, and present in good mentation, further investigations might not be beneficial, and these dogs may recover with symptomatic treatment alone. Additional diagnostics could be indicated in dogs with additional clinical signs other than diarrhea.