Total parenteral nutrition during acute pancreatitis: Clinical experience with 156 Patients

Over a 3-year period, 156 of 815 patients admitted to a single institution with acute pancreatitis received total parenteral nutrition (TPN) for 2,572 patient days. Seventy had simple acute pancreatitis (group I) and 86 (group II) developed local complex disease (pseudocyst, abscess, or necrotic gland). In groups I and II, respectively, days without oral intake (NPO) were 13.6±1.5 (SEM) and 24.0±2.1 (p<0.005), hospital days were 19.8±1.7 and 35.8±3.2 (p<0.005), and duration of TPN was 10.9 ±1.0 and 21.0±2.3 days (p<0.005). Thirty-three patients in group I and 53 in group II required exogenous insulin. Alteration of standard formulas was necessary in 87 patients, but cessation of therapy was necessary in only one instance. Twenty catheters were removed for suspected sepsis with only 3 confirmed cases. Fat-based formulas were well tolerated in 15% of patients. During TPN, body weight rose from 95.0±2.4% to 97.4±4.3% of ideal in group I and remained at 90.5±1.8% in group II. Albumin rose from 3.36±0.10 to 3.50±0.08 g/dl in group I and from 3.01±0.07 to 3.35±0.07 g/dl in group II. The entire cohort differed from 10 randomly chosen patients who did not receive TPN in terms of days NPO (2.8±0.3) and hospital days (5.5±0.6). Variables associated with prolongation of hospital stay and time NPO were number of prognostic criteria, local complex disease, and underlying chronic pancreatitis only in select groups. We conclude that during acute pancreatitis, TPN can be administered safely but with careful monitoring and we recommend early aggressive therapy in the subgroups noted above and when underlying malnutrition exists. In the borderline patient, TPN may be administered by peripheral vein until the severity of disease is manifest.

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Resumen En el curso de un período de 3 años, 156 de 815 pacientes hospitalizados en una sola institución por pancreatitis aguda recibieron nutrición parenteral total (NPT) durante 2,572 paciente-días. Setenta presentaban pancreatitis aguda simple (grupo I) y 86 (grupo II) desarrollaron enfermedad local complicada (pseudoquiste, absceso, o necrosis de la glándula). Las siguientes fueron las características de los grupos I y II, respectivamente: días sin ingesta oral (NPO) 13.6±1.5 (SEM) y 24.0±2.1 (p<0.005), días de hospitalización: 19.8±1.7 y 35.8±3.2 (p<0.005), y duración de la NPT: 10.9±1.0 y 21.0 ±2.3 días (p<0.005). Trienta y tres pacientes en el grupo I y 53 en el grupo II requirieron insulina exógena. Se requirió alterar la fórmula estándar en 87 pacientes, pero sólo fue necesario cesar la terapia en un caso. Veinte catéteres fueron retirados por sospecha de sepsis, pero sólo en 3 se confirmó. Las fórmulas a base de grasa fueron bien toleradas en 15% de los pacientes. En el curso de la NPT el peso corporal ascendió de 95.0±2.4% a 97.4±4.3% del peso ideal en el grupo I y se mantuvo a un 90.5±1.8% en el grupo II. La albúmina ascendió de 3.36±0.10 a 3.50±0.8 g/dl en el grupo I y de 3.01±0.07 a 3.35±0.07 g/dl en el grupo II. Toda la cohorte se diferenció de un grupo de 10 pacientes escogidos al azar que no recibieron NPT en términos del número de días NPO (2.8±0.3) y de días de hospitalización (5.5±0.6). Las variables que aparecieron asociadas con prolongación de la hospitalización y el tiempo NPO fueron el número de criterios de pronóstico, la enfermedad complicada, y la presencia de pancreatitis crónica subyacente sólo en grupos seleccionados. Nuestra conclusión es que en el curso de la pancreatitis aguda, la NPT puede ser administrada con seguridad pero bajo monitoría cuidadosa, y recomendamos terapia agresiva precoz en los subgrupos anotados anteriormente y cuando exista mal nutrición concomitante. En el paciente limitrofe se puede administrar la NPT por vía periférica hasta cuando la gravedad de la enfermedad se haga manifiesta.

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Résumé Pendant une période de 3 ans, 156 des 815 patients admis pour pancréatite aiguë ont reçu une alimentation parentérale totale (APT), soit en tout 2,572 jours patient. Soixante dix patients (groupe I) avaient une pancréatite simple et 86 (groupe II) avaient aussi une maladie locale complexe (pseudokyste, abcès ou nécrose du pancréas). La durée du jeûne était respectivement de 13.6±1.5 (ET) et de 24.0±2.1 (p<0.005), la durée moyenne de séjour était respectivement de 19.8±1.7 et de 35.8 ±3.2 (p<0.005) alors que la durée d'APT était respectivement de 10.9±1.0 et de 21.0±2.3 jours (p<0.005). Trente-trois patients dans le groupe I et 53 dans le groupe II avaient besoin d'insuline exogène. Un changement dans la formule standard a été nécessaire chez 87 patients mais l'APT n'a du être arrêté complètement que chez un patient seul. Vingt cathéters ont été enlevés avec suspicion de sepsis, confirmée cependant dans 3 cas seulement. Les compositions à base de lipides ont été bien tolérées chez 15% des patients. Pendant l'APT, le poids du corps s'est élevé de 95.0±2.4% à 97.4±4.3% du poids idéal chez les patients du groupe I et est resté à 90.5±1.8% chez ceux du groupe II. L'albumine s'est élevée de 3.36±0.10 à 3.50 ±0.08 g/dl dans le groupe I et de 3.01±0.07 à 3.35±0.07 g/dl dans le groupe II. La durée du jeûne (2.8±0.3) et la durée moyenne de séjour (5.5±0.6) de l'ensemble des patients différaient de ces mêmes données chez 10 autres patients choisis au hasard. Les facteurs associés avec un séjour hospitalier prolongé et sans alimentation orale étaient le nombre de critères pronostiques, l'existence de complications locales, et de pancréatite chronique sous-jacente chez certains patients. Nous concluons que pendant la pancréatite aiguë, l'APT peut être administrée sans danger sous contrôle permanent et nous conseillons un traitement agressif et précoce dans le sous groupe mentionné plus haut ou quand existe un état de nutrition déficient. Chez le patient limite, on peut se contenter d'APT par une veine périphérique tant que des signes de gravité ne se manifestent pas.

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Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Breast Biopsies with ABBI(R): Experience with 183 Attempted Biopsies

When first introduced, the advanced breast biopsy instrumentation (ABBI^®) system seemed to have many advantages as a diagnostic procedure. Problems have arisen, however, both in terms of patient unsuitability and mechanical failure. In addition, there has been uncertainty as to whether the complete lesion removal it afforded could be considered definitive treatment in malignant cases. Incision margins were looked at to investigate that possibility. Of the 183 patients we saw in our first year of experience with ABBI, 48 (26%) were rejected for being poor candidates for it. In the remaining 132 biopsies there were 31 (23%) technical difficulties. All told, 14 malignancies were discovered, all of which appeared to have pathology-free incision margins radiologically. However, 13 of these 14 (93%) proved on pathologic examination to have residual malignancy. ▪     

Double β-lactam regimen compared to an aminoglycoside/β-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C±T), both agents being administered only if the initial granulocyte count was below 200/l, or ceftazidime plus piperacillin (C+P). The overall response rate was 71% (39 of 60 for C±T and 45 of 58 for C+P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C+P regimen (P=0.06), there was no difference in response for patients with bacteremia and profound (<100/gml) sustained granulocytopenia. The double -lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced execllent serum bactericidal levels (C±T geometric mean peak 1:170; C+P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C+P and in 6 of 89 trials in the C±T group (P=0.19). The incidence of secondary infections in patients with profound (<100/l) sustained granulocytopenia was lower in the C±T group (P=0.04). Alimentary canal anaerobic flora preservation with C±T, and suppression with C+P, was demonstrated. These results suggest that these regimens are of similar effectiveness and neigher is associated with major toxicity.     

Confocal microscopy for real-time detection of oral cavity neoplasia.

PURPOSE: The goal of this study was to characterize features of normal and neoplastic oral mucosa using reflectance confocal microscopy. EXPERIMENTAL DESIGN: Oral cavity biopsies were acquired from 17 patients at the Head and Neck Clinic of The University of Texas M. D. Anderson Cancer Center who were undergoing surgery for squamous cell carcinoma within the oral cavity. Reflectance confocal images were obtained at multiple image plane depths from biopsies within 6 h of excision. After imaging, biopsies were fixed in 10% formalin and submitted for routine histological examination. Reflectance confocal images were compared with histological images from the same sample to determine which tissue features contribute to image contrast and can be potentially imaged using in vivo confocal microscopy. RESULTS: Confocal images were successfully acquired from 15 biopsy pairs from 17 patients. Depth-related changes in cell diameter and nuclear density were observed at multiple anatomical sites within the oral cavity. In squamous cell carcinomas, densely packed, pleomorphic tumor nuclei could be visualized with distinct differences in nuclear density and morphology distinguishable between confocal images of neoplastic and nonneoplastic oral cavity. Other features of noncancerous and cancerous oral tissue that could be identified in the confocal images included areas of inflammation, fibrosis, muscle fibers, and salivary glands. CONCLUSIONS: Our results support the potential for this tool to play a significant role in the clinical evaluation of oral lesions, real-time identification of tumor margins, and monitoring of response to therapeutic treatment.     

Overly Literal Interpretations of Speech in Autism: Understanding That Messages Arise from Minds

Children with autism and children with Down's syndrome watched the following enactment. A protagonist put one item in location A and another in location B and then left the scene. Subsequently, the items were swapped the other way round. Finally, the protagonist (who remained ignorant of the swap) requested the item in A. The observing child participant was asked to judge (1) which item the protagonist wanted and (2) which item the protagonist put in A. Unlike children with Down's syndrome, those with autism made more errors in judging that the speaker wanted the item in B than in judging that the item the speaker put in A is now in B; children with autism wrongly tended to interpret utterances literally, and they did this significantly more frequently than children with Down's syndrome. We conclude that children with autism have a difficulty making non literal interpretations that cannot be explained as (1) a realist bias, (2) an inability to inhibit a prepotent response, and (3) a failure to keep track of the exchange of items.     

An Investigation of Adolescents' Substance Use Behaviors, Depressed Affect, and Suicidal Behaviors

Data from a four-wave panel design of 975 adolescents were used to study inter-relationships among suicidal behaviors, depressive symptoms, and substance use behaviors. Persistently high levels of problem drinking and depressive symptoms were associated with higher levels of suicidal thoughts and attempts. Higher levels of depressive symptoms and greater cigarette and illicit drug use distinguished suicidal ideators from attempters. Adolescents attempting suicide reported lower levels of family social support, a greater use of substances to cope with stressors, and a higher density of substance-using peers. Implications of the findings for preventive interventions with high-risk teens are discussed.     

PBPK model for radioactive iodide and perchlorate kinetics and perchlorate-induced inhibition of iodide uptake in humans.

Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)-iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I- and cold ClO4- in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the measured levels of serum and urinary ClO4- from drinking water exposures, ranging from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid 131I- uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I- in serum from various tracer studies, are also successfully simulated. This model's parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I- provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to I- incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins.     

Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer.