Transplantation and Debulking Procedures for Neuroendocrine Tumors.

An array of treatment modalities is currently available in the management of patients with neuroendocrine tumors (NETs). Complete resection of the primary tumor and all metastatic lesions represents the only approach possessing intent to cure. However, due to patients' disease frequently being at an advanced stage on initial diagnosis only a minority of individuals are candidates for radical procedures. Cytoreductive surgery (debulking) may potentially confer improvements in quality of life and prolong overall survival. In light of the recent introduction of effective nonsurgical treatment options, the indication for cytoreductive surgery needs to be carefully assessed. The presence of nonresectable liver metastases is not a contraindication for resection of the primary tumor including locoregional disease in small bowel NETs. Resection of primary pancreatic NETs in the setting of unresectable metastatic liver disease may have a beneficial effect on the prognosis of selected patients with a tumor requiring less aggressive local surgery. Liver transplantation presents a generally accepted approach in meticulously selected patients with unresectable liver metastases. Stringent and validated selection criteria are not available. While overall survival is satisfactory, high recurrence rates hinder outcomes and call for the development and implementation of neoadjuvant and adjuvant concepts. Advances in intestinal transplantation over time may justify consideration of an individual with advanced neuroendocrine tumor disease unresponsive to standard medical or surgical treatment.

Modified liver-free multivisceral transplantation for a metastatic small bowel neuroendocrine tumor: a case report.

Neuroendocrine tumors originating from the small bowel frequently metastasize to the lymph nodes and/or liver. Although surgical extirpation of the primary tumor and locoregional metastases epitomizes the management of patients with such tumors, this is not always possible with conventional surgical techniques. Nonresectable, slow-growing tumors involving the mesenteric root represent a generally accepted indication for deceased donor intestinal and multivisceral transplantation. Furthermore, vascularized sentinel forearm flaps offer opportunities for monitoring graft rejection and tailoring immunosuppression regimens. Here, we report the first documented case of modified liver-free multivisceral transplantation preceded by neoadjuvant 177-lutetium peptide receptor radionuclide therapy in a patient with a small bowel neuroendocrine tumor and extensive lymph node metastases in the mesenterium. At a follow-up of 21 months the patient is biochemically and radiologically disease-free.

Emotion-modulated startle in anxiety disorders is blunted by co-morbid depressive episodes.

BACKGROUND: While anxiety has been associated with exaggerated emotional reactivity, depression has been associated with blunted, or context insensitive, emotional responding. Although anxiety and depressive disorders are frequently co-morbid, surprisingly little is known about emotional reactivity when the two disorders co-occur. METHOD: We utilized the emotion-modulated startle (EMS) paradigm to examine the effects of a concurrent depressive episode on emotional reactivity in young adults with anxiety disorders. Using an archival dataset from a multi-disciplinary project on risk factors in childhood-onset depression, we examined eye-blink startle reactions to late-onset auditory startle probes while participants viewed pictures with affectively pleasant, unpleasant and neutral content. EMS response patterns were analyzed in 33 individuals with a current anxiety (but no depressive) disorder, 24 individuals with a current anxiety disorder and co-morbid depressive episode and 96 healthy controls. RESULTS: Control participants and those with a current anxiety disorder (but no depression) displayed normative linearity in startle responses, including potentiation by unpleasant pictures. By contrast, individuals with concurrent anxiety and depression displayed blunted EMS. CONCLUSIONS: An anxiety disorder concurrent with a depressive episode is associated with reactivity that more closely resembles the pattern of emotional responding that is typical of depression (i.e. context insensitive) rather than the pattern that is typical for anxiety (i.e. exaggerated).

A study of telephone screening and direct observation of surgical wound infections after discharge from hospital.

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.

Clinicoanatomic studies in dysarthria: review, critique, and directions for research.

More than 30 years ago, Darley, Aronson, and Brown (1969) proposed clinicoanatomic correlations for seven perceptual types of dysarthria. These correlations have not been systematically re-examined even though imaging technologies developed in recent years provide the means to do so. This review considers data from published imaging studies as well as data from selected medical interventions to evaluate the current state of knowledge that relates lesion site to the nature of a speech disturbance. Although the extant data are not sufficient to allow a complete evaluation of the seven types of dysarthria described by Darley et al., relevant information has been reported on lesions of the pyramidal pathway, extrapyramidal pathway, and cerebellum. In general, the results are best explained by an equivalence mode of brain-behavior relationship in which a type of dysarthria is associated with a lesion in one of two or more brain structures. Criteria also are proposed for future studies of clinicoanatomic relationships in neurogenic communication disorders.

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma.

BACKGROUND: The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukaemia. OBJECTIVES: To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). METHODS: Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3-6 months. RESULTS: Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. CONCLUSIONS: These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.

The role of carbohydrate in the assembly and function of polymeric IgG.

The carbohydrate present on glycoprotein can influence their biologic and functional properties. In the present paper we have assessed the role of oligosaccharides in the polymerization and effector functions of IgG with the 18 amino acid extension of IgM added to its carboxy terminus (IgGmutp). We found that IgG1mutp and IgG3mutp lacking the carbohydrate addition site in C(H)2, in the tail-piece or both assembled into polymers as well as the glycosylated versions. Aglycosylated polymers retained the ability to activate complement as assayed by C1q binding and hemolysis, although they were not as effective as their wild type polymer counterparts. Although IgGmutp lacking the carbohydrate in the tail-piece was able to bind to FcgammaRII, completely aglycosylated polymers lost the ability to bind to both FcgammaRI and FcgammaRII, suggesting a critical role for the C(H)2 sugar in FcR binding. Absence of the mutp carbohydrate increased the half life of polymeric IgG1, whereas absence of the carbohydrate in C(H)2 accelerated the clearance rate.

Synergistic effects of tumour necrosis factor and morphine on gut barrier function.

OBJECTIVE: To study the effects of tumour necrosis factor (TNF) and morphine on intestinal permeability, intestinal transit and bacterial translocation in the rat. DESIGN: A randomized interventional controlled experiment. SETTING: University surgery and microbiology research laboratory. PARTICIPANTS: Forty-four rats in five groups as follows: control (n = 9); treated with morphine every 2 hours for 8 hours (n = 9); treated with TNF for 5 minutes (n = 10); treated with TNF plus morphine every 2 hours for 8 hours (n = 6); and treated with TNF plus morphine every 3 hours for 24 hours (n = 10). MAIN OUTCOME MEASURES: Intestinal permeability as measured by the uptake of chromium-51 ethylenediaminetetraacetate (51Cr-EDTA) over 8 hours, intestinal transit as measured by the amount of 51Cr-EDTA remaining in the gastrointestinal tract at the time of animal sacrifice, intestinal bacteria counts and translocation of bacteria as measured from bacterial counts of mesenteric lymph nodes, spleen and liver at the time of sacrifice. RESULTS: Morphine increased intestinal transit time and ileal bacteria counts (p < 0.05). TNF alone did not increase intestinal permeability or bacterial translocation. TNF plus morphine increased intestinal transit time, intestinal permeability, bacterial counts and bacterial translocation (p < 0.05). CONCLUSIONS: Morphine or increased intestinal transit time, or both, increases the concentration of intestinal bacteria. Morphine plus TNF increases intestinal bacteria counts, intestinal permeability and bacterial translocation. Morphine alone does not increase intestinal permeability or bacterial translocation.

Sleep without drugs.

Disturbed sleep is a common problem, particularly among elderly people, and is usually treated with hypnotics. The side effects of longterm administration of hypnotic drugs are well known, but despite this there remains a substantial population of chronic users. These people can be helped to reduce their dependence on hypnotics through psychological techniques. A group of longterm users treated in this manner were shown to reduce their intake of hypnotics significantly more than a group of users who did not receive any psychological treatment. Furthermore, the treated patients did not experience any deterioration in their sleep patterns, and their subjective refreshment from sleep improved significantly.For the patient with sleep problems, psychological techniques are preferable to the longterm use of hypnotics both as a weaning-off agent and as an alternative to drugs.

Hypnotics and hangovers: a pilot study of chlormezanone in general practice.

Ten patients were included in this pilot study of chlormezanone, assessing its effects on duration and quantity of sleep and daytime performance using a pursuit rotor and a digit symbol test. Comparisons of the sleep assessments favoured chlormezanone, although the differences were not statistically significant. There was no evidence of any reduction in daytime performance after chlormezanone. The comparison of chlormezanone and placebo on the pursuit rotor test and the visual analogue assessment of hangover both slightly favoured the drug, but there were no significant differences. The study has demonstrated that it is feasible to evaluate hypnotic drugs more exactly in general practice.

Long-term therapy with sodium cromoglycate (intal, lomudal or aarane): effects and side effects.

Review of 72 atopic asthmatic children from the age of three years demonstrated that the long-term use of sodium cromoglycate (Intal, Lomudal or Aarane) produced no serious side effects clinically or on pathological testing. Almost all the children improved, especially in their heights and weights. There is some evidence that girls showed a better response than boys. A possible explanation of growth improvement is discussed and it is concluded that SCG not only prevents asthmatic symptoms but it gives asthmatic children the best chance of maturing normally.