A 45-year-old female with hypokalemic rhabdomyolysis due to VIP-producing composite pheochromocytoma.

The watery diarrhea, hypokalemia and achlorhydria (WHDA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing extra-pancreatic tumors is rare. We report on a 45-year-old woman who suffered from persistent secretory diarrhea for six years and who was admitted to hospital with complaints of muscular weakness and myalgia. Biochemical testing revealed pronounced rhabdomyolysis due to severe hypokalemia. Gastrointestinal evaluation of long-standing diarrhea including endoscopy of the upper and lower gastrointestinal tract and the small intestine did not show any pathologies. An abdominal computed tomography scan revealed a mass of 4 × 5 cm in the left adrenal gland demonstrating a strong uptake in the 123I-labelled metaiodobenzylguanidine scintigraphy. Plasma levels of chromogranin A, calcitonin, parathormone, basal renin and most prominently VIP were increased in line with a increased 24 hour urinary secretion of noradrenaline, dopamine, normetanephrine and vanillymandelic acid. A WDHA (watery diarrhea, hypokalaemia, achlorhydria) syndrome with hypokalemic rhabdomyolysis due to a VIP-producing adrenal tumor was diagnosed that was removed surgically. The histological evaluation demonstrated a composite pheochromocytoma. Diarrhea stopped immediately after surgery together with a normalization of laboratory parameters. In conclusion, this case report focuses on the rare clinical presentation of secretory diarrhea and electrolyte disturbances in combination with hypokalemic rhabdomyolysis which was caused by a VIP-producing composite pheochromocytoma.

Phase I trial of recombinant human gamma-interferon and recombinant human tumor necrosis factor in patients with advanced gastrointestinal cancer.

Recombinant human gamma-interferon and recombinant human tumor necrosis factor are two representatives of a new class of antineoplastic agents. In vitro studies have suggested synergistic cytotoxic activities when the agents are combined. We report a phase I study of these two agents when administered daily for 5 consecutive days every 2 weeks in patients with advanced gastrointestinal cancers. Toxicity resulting from these agents was significant with hyperbilirubinemia representing the dose-limiting toxicity. Significant, although transient, myelosuppression was also observed. The maximal tolerated doses were 150 micrograms/m2/day for 5 days for each agent. Suggestive antineoplastic activity in biliary and pancreatic cancer was observed. Phase II trials of this combination are currently in progress.

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

BACKGROUND: Vedolizumab, a monoclonal antibody targeting the α4ß7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. AIM: To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. METHODS: This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. RESULTS: Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. CONCLUSION: Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks.

Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix.

PURPOSE: A phase II study was performed to evaluate the antitumor activity and toxicity of irinotecan (CPT-11), a water-soluble derivative of camptothecin, in patients with prior chemotherapy-treated squamous cell cancer of the cervix. PATIENTS AND METHODS: Forty-two patients were included in the study. The median age was 44 years (range, 24 to 59 years). The median Zubrod performance status was 1. All patients were refractory to first-line chemotherapy and 88% had received prior radiotherapy. The initial dose of CPT-11 was 125 mg/m2 given as a weekly 90-minute intravenous infusion for 4 weeks, every 6 weeks. Subsequent doses were unchanged, reduced, or omitted according to toxicity grade. RESULTS: Forty-two patients were assessable for response. The overall response rate was 21%. The median time to response was 6 weeks and the median duration of response was 12 weeks. The overall median duration of survival was 6.4 months. A statistically significant survival advantage (median of 12.6 v 5.1 months) was found in patients whose disease responded to the treatment (P < .015). The major dose-limiting toxic effects (grade > or = 3) were nausea and vomiting (45%), diarrhea (24%), and granulocytopenia (36%). Grade > or = 3 anemia was encountered in 62% of patients and the incidence of thrombocytopenia was negligible. Less severe side effects were alopecia (48%), drug fever (43%), anorexia (33%), fatigue (33%), skin rash (21%), stomatitis (14%), and allergic reaction (9%). The gastrointestinal intolerance was dose-related. The incidence of bone marrow depression did not decrease with dose reduction, possibly because of a cumulative effect or hematologic intolerance by a subset of patients. CONCLUSIONS: CPT-11 has significant activity in refractory cervical carcinoma. Gastrointestinal intolerance and hematologic toxicity must be monitored carefully. Further studies of alternative schedules may improve the tolerance and response rate.

Advanced practice issues: results of the ONS Advanced Practice Nursing survey.

PURPOSE/OBJECTIVES: To ascertain the critical issues in current advanced practice nurse (APN) roles in oncology. DESIGN: Descriptive. SETTING: National. SAMPLE: 368 Oncology Nursing Society (ONS) APNs in oncology practice. METHODS: Subjects completed an 11-page self-administered questionnaire comprised of 62 multiple-choice and open-ended questions. Subjects were asked to identify level of importance for ONS to address selected issues in each section. MAIN RESEARCH VARIABLES: Demographic information and APN issues regarding practice, outcomes, prescriptive authority, reimbursement, education, continuing education, licensure and certification, legislation, and challenges facing oncology APNs. FINDINGS: The majority of APNs were nurse practitioners working in a hematology/oncology practice in an urban setting providing direct patient care. Priority practice issues were lack of agreement among state boards of nursing related to privileges, lack of understanding of the role by patients and healthcare professionals, and lack of an APN definition. Important APN outcomes were symptom management, quality of life, patient/family satisfaction, and cost of care. Priority educational topics were oncology disease management, pharmacology, advanced physical assessment, and reimbursement. Challenges facing oncology APNs were lack of an APN definition, reimbursement issues, documentation of outcomes, prescriptive authority, variance in education, merging of current roles, certification, loss of cancer specialty, and second licensure. CONCLUSIONS: Numerous APN issues continue to be unresolved. APN outcomes research is needed to validate the oncology APN role in cancer care. IMPLICATIONS FOR NURSING PRACTICE: Survey results and specific recommendations have been forwarded to the ONS Steering Council and Board of Directors for implementation decisions.

Palliation of gastrointestinal obstructive disorders.

Gastrointestinal and biliary obstructive disorders are complications encountered in advanced cancer nursing that are associated with significant morbidity and mortality. Patients with bowel gastric, or hepatobiliary obstruction require prompt and accurate diagnosis, so that appropriate care is initiated to treat the obstruction and related symptoms. Intensive nursing care aimed at comfort, psychological support, and patient/family education is essential for the well-being of patients suffering from a gastrointestinal obstructive disorder.

Barriers to palliative and supportive care.

The goal of palliative care is to provide comprehensive and intense symptom management and psychological, educational, social, and spiritual support. Barriers to palliative care that nurses encounter may be conceptualized into three main levels: the patient/family, professional, and system barriers. Recommendations for nurses, health care policy makers, and other health professionals to address the barriers are discussed. Future research and work needs to be implemented at all three levels to optimize the quality end-of-life care.

[Food allergies/prevention and diagnosis]. / Nahrungsmittelallergien/Prävention und Diagnostik.

Both immunological (antibody-mediated) and non-immunological mechanisms can trigger allergic reactions and intolerance phenomena to food. A decisive contribution to the genesis of a food allergy is the interaction of "external" factors such as early ingestion of antigens, no breast-feeding, enteritis, and "internal" ones such as genetic influences, a family history of allergies. Correct diagnosis is guided and determined by anamnestic information, identification of characteristic signs and symptoms after ingestion of a particular foodstuff (allergen elimination or provocation), skin test, release of histamine from leucocytes, exclusion or confirmation of other causes and the detection of an immunological equivalent for the patient's disease. The article also includes recommendations on allergen avoidance and for avoiding influences that could provoke a food allergy.

[Fenoterol in chronic obstructive bronchitis--comparison of the efficacy of various application forms. Advantages and disadvantages of metered dose inhalers with a small or large expander and a mechanical atomizer]. / Fenoterol bei chronisch-obstruktiver Bronchitis--Wirkungsvergleich verschiedener Applikationsformen. Vor- und Nachteile der Dosieraerosole mit kleinem oder grossem Expander und eines mechanischen Verneblers.

After an initial inhalation of 1,25 mg fenoterol in 2 ml 0,9% NaCl by means of Pari Privat randomized on the following two days, two groups of ten respectively eleven patients with relatively stable respiratory tract obstruction were tested for the reversibility of the obstruction with a metered dose inhaler as follows: Group 1 (10 patients) received the metered dose inhaler with a small expander alternatively on even days and on the odd days without the expander. Group 2 (11 patients) received the metered dose inhaler with the large expander (130 mm X 35 mm) alternatively on the even days and with the small expander (100 mm X 30 mm) on the odd days. All patients showed a significant improvement of the bronchial obstruction regardless of the type of inhalation. Auxiliary appliances (inhalation appliances, expanders for the metered dose inhaler) are therefore only necessary, when the patients cannot cope at all or cannot cope optimally with the simple metered dose aerosol.

Preoperative nutritional status and outcome of elective total hip replacement.

Preoperative malnutrition increases the morbidity rate and length of hospitalization for various types of surgical patients. However, among patients who undergo elective total hip replacement, it is unclear how preoperative nutritional data can be used to detect a high risk subgroup. The purpose of this study was to identify preoperative nutritional factors that could be used to define a subgroup of patients who have undergone elective total hip replacement who are at high risk for poor post-operative outcome. Preoperative nutritional factors were evaluated in 89 consecutive patients who underwent elective total hip replacement. An inverse relationship was found between serum albumin and length of stay. Patients with an albumin level less than 3.9 were twice as likely to require prolonged hospitalization ( > 15 days) when compared with those in whom the albumin level was 3.9 or greater. Complications were related to the preoperative orthopaedic diagnosis of avascular necrosis of the hip. A subgroup of the patients undergoing elective total hip replacement who are at risk for prolonged recovery can be identified preoperatively by using a serum albumin level of less than 3.9 g/dL. The traditional normal range for albumin may be inappropriate for these patients.

Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments.

Preliminary report of the activity of docetaxel in advanced or recurrent squamous cell cancer of the cervix.

Eighteen patients with squamous cell cancer of the cervix were treated with i.v. docetaxel 100 mg/m2 over 1 h every 21 days. No patient received prior chemotherapy, except as a radiation sensitizer. Median age was 42 years (range 30-58) and Zubrod performance status was 1 (0-2). Ten (59%) patients had prior surgery and 11 (65%) had prior radiation therapy. Sixteen patients were evaluable for response. Two patients had a partial response (13%; 95% CI 0-32%) and eight (50%; 95% CI 23-77%) had stable disease. Dose reduction to 75 mg/m2 was required in 10 patients and to 55 mg/m2 in one patient. Granulocytopenia was the major hematopoietic toxicity (31% grade 3 and 44% grade 4). Docetaxel is active in patients with squamous cell cancer of the cervix and may be tolerable at this dose schedule.

A phase I clinical and pharmacological study of oral 9-nitrocamptothecin, a novel water-insoluble topoisomerase I inhibitor.

9-Nitrocamptothecin (9NC) is a water-insoluble topoisomerase I inhibitor with a broad antitumor activity in animal models. To determine the maximum tolerated oral dose (MTD), a phase I study was performed in patients with advanced cancer refractory to conventional chemotherapy. 9NC was administered orally with escalating doses to cohorts of five patients beginning at 1 mg/m2/day for five consecutive days every week for 4 weeks. Increments were 0.5 mg/m2/day for each cohort. Toxicity was evaluated in 28 patients diagnosed with various malignancies. Seven patients received 1 mg/m2/day for 28 weeks; 10 patients, 1.5 mg/m2/day for 68 weeks; and 26 patients, 2 mg/m2/day for 159 weeks. At 1.5 mg/m2/day or higher, the dose-limiting toxicity was hematologic, with grade 4 anemia in eight (29%); neutropenia in seven (25%) and thrombocytopenia in five (18%). Grade 2 or higher toxic effects occurred at each dose level: nausea and vomiting in 15 (54%), diarrhea in nine (32%), chemical cystitis in seven (25%), neutropenic sepsis in six (21%) and weight loss in five (18%) (N=28). Responses were observed after 2-8 weeks of therapy in five patients with pancreatic, breast, ovarian and hematologic tumors. Fourteen patients had a disease stabilization and one patient received treatment up to 18 months. The MTD of 9NC given orally has been estimated at 1.5 mg/m2/day for five consecutive days weekly. 9NC may be tolerated for sustained periods of time, but has the potential for significant hematologic, gastrointestinal and urinary bladder toxicity. Significant antitumor activity was observed, warranting further clinical investigations.