Thrombocytopenia After Isolated Limb or Hepatic Perfusions with Melphalan: The Risk of Heparin-Induced Thrombocytopenia

Background: Three cases of heparin-induced thrombocytopenia (HIT) were observed in patients undergoing isolated limb perfusion (ILP) with melphalan. This occurrence prompted the discontinuation of prophylactic postoperative heparin in ILP patients and its avoidance in patients undergoing isolated hepatic perfusion (IHP). The need to reassess these decisions led to a review of thrombocytopenia in both patient populations.Methods: Records of all patients treated with ILP or IHP at our institution from July 1992 through November 1996, were reviewed. Nine IHP patients were tested prospectively for heparinrelated antibodies using serum samples obtained perioperatively and during the second postoperative week.Results: Thrombocytopenia (<100,000 platelets/L) developed postoperatively in 30% of 131 ILP patients and in 77% of 56 IHP patients. No cases of HIT were identified other than the three who had been previously diagnosed. The prevalence of HIT in heparinized ILP patients was 2.8% (3/108). All nine IHP patients developed heparin-related antibodies postoperatively.Conclusions: Because the prevalence of HIT following ILP is in the range observed in other clinical settings, postoperative heparin prophylaxis is an option. However, it probably should be limited to the first week, and daily platelet counts should be reviewed for a pattern of thrombocytopenia consistent with HIT. The prevalence of heparin-related antibodies after IHP is so high that prophylactic heparin should be avoided in this setting.     

p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

MRI and MRS in HMG-CoA lyase deficiency

3-Hydroxy-3-Methylglutaryl coenzyme A lyase (HMG-CoA) deficiency is a rare inborn error of leucine catabolism. The disease is characterized by recurrent episodes of metabolic acidosis, hyperammonemia without ketosis, hypoglycemia, lethargy, hepatomegaly, and seizures. This study has evaluated the magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) findings of three patients with HMG-CoA deficiency. The common findings on all of the MRI scans were multiple, coalescent, marked lesions in periventricular white matter and arcuate fibers, most prominently in frontal or periatrial regions that were superimposed on diffuse, slightly hyperintense subcortical white matter signal. Involvement of the caudate nucleus and the dentate nucleus were observed in the reported patients. MRS studies by both STEAM and PRESS spectra of all patients revealed a decrease in N-acetylaspartate and elevation in both myoinositol and choline. A pathologic peak at 1.33 ppm, which is compatible with lactate, and a particular peak at 2.42 ppm in all patients were also found. The combination of both MRI and MRS findings could be considered as being specific in patients with HMG-CoA lyase deficiency.     

Health impact of head and neck cancer

A multidimensional Head and Neck Quality of Life (HNQOL) instrument and a general health status measure were administered to 397 patients with head and neck cancer. Scores for the 4 domains of the HNQOL (communication, eating, pain, and emotional well-being) were calculated. Patient demographics, comorbidities, clinical characteristics, treatment data, disability status, and a global "overall bother" score were assessed. When compared with the US population aged 55 to 64 years, the group had significantly worse scores in the 8 health domains of the SF-36. Patients' overall bother scores from the head and neck cancer treatment correlated best with the HNQOL emotion domain (r = 0.71) and the HNQOL pain domain (r = 0.63), and least with the patients' perception of their response to treatment (r = 0.39). Pain, eating, emotion, physical component summary score, age, and an interaction term between eating and emotion were significant predictors for overall bother. Of the 217 patients who were working before the diagnosis of cancer, 74 (34. 1%) reported that they had become disabled. Patients who had more than 1 type of treatment were 5.9 times more likely to report themselves as disabled (odds ratio [OR] = 5.94, P < 0.01), even after adjusting for age, emotion score, and physical component summary score, which were other factors that predicted disability.     

Laparoscopic management of suspicious adnexal masses

OBJECTIVE: Our aim was to evaluate the feasibility and applicability of operative laparoscopy in the management of adnexal masses that do not meet the standard serum CA 125 and ultrasonographic criteria for benignity. STUDY DESIGN: One hundred thirty-eight patients underwent operative laparoscopy for removal of suspicious adnexal masses. The CA 125 level was >35 mIU/ml in 39 of 138 (28%) patients; ultrasonographic findings were abnormal in 127 of 138 (92%); masses were >10 cm in 43 of 138 (32%) of patients. RESULTS: Malignancies were discovered in 14% (19/138) of patients. Eight percent (11/138) of the procedures were converted to laparotomy, six because of inability to dissect the mass laparoscopically and five for staging or debulking of carcinoma. Operative times ranged from 25 to 210 minutes, with a mean of 86. Three major complications were encountered-an enterotomy and a lacerated vena cava, both of which were repaired laparoscopically, and a small bowel herniation through a lateral port site that required reoperation. Hospital stays ranged from 0 to 11 days, with a mean of 1.5. In two patients with "apparent" stage I adnexal carcinomas recurrence was diagnosed 6 and 38 months after surgery. CONCLUSIONS: Laparoscopic management of suspicious adnexal masses is technically feasible, with a low rate of morbidity and a short hospital stay. Adnexal carcinomas can be identified and managed appropriately with staging and complete resection as indicated. (Am J Obstet Gynecol 1996;175:1451-9.)     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

The use of the iSTAT portable analyzer in patients undergoing cardiopulmonary bypass

Objective. To evaluate the utility of the iSTAT blood analyzer, a bedside device for hematocrit, sodium, potassium, and glucose measurement during cardiopulmonary bypass (CPB).Methods. Forty patients scheduled for elective CPB were evaluated prospectively. In addition to using the iSTAT analyzer, blood samples were analyzed at four time points: following induction of anesthetic, 10 min. after initiation of CPB, 60 min. after initiation of CPB, and following heparin neutralization by protamine. Blood glucose concentration was measured by the hospital laboratory using a Kodak Analyzer and by a glucose meter, electrolytes were evaluated by the Kodak Analyzer and BGE (a device which is commonly used for satellite laboratory determinations of electrolyte and blood gas results), and hematocrit samples were measured by the hospital laboratory using an NE 8,000 and a centrifuge. The means and standard deviations of the differences between the methods were calculated.Results. The hematocrit values determined by the iSTAT machine, when adjusted for the level of total protein (according to manufacturer's directions), differed from the laboratory values by 0.53 = 1.46 percentage points. An alternative to measuring total protein and making the adjustment is simply adding 1 % to the hematocrit in the pre-CPB period and 3% on-CPB or post-CPB, which we found to yield values that differed from the laboratory by 0.52 ± 1.42 percentage points. For all four tests (hematocrit, sodium, potassium, and glucose) the iSTAT had a similar relationship to the laboratory values as did the other commonly used means (centrifuge, BGE, and glucose meter) of clinical evaluation.Conclusion. In summary, we found that in patients undergoing CPB, the iSTAT values agreed sufficiently well with standard laboratory values and that the iSTAT instrument can be relied upon for bedside measurements.Presented in part at the Annual Meeting of the Society of Cardiovascular Anesthesiologists, Philadelphia, PA, May 1995, and at the 70th meeting of the IARS, Washington DC, March 1996. Supported in part by a grant by iSTAT Corporation.     

Metabolic base production and mucosal vulnerability during acid inhibition in a mammalian stomachin vitro

Acid inhibition increases gastric mucosal susceptibility to damage by luminal acid. This might be due to reduced metabolic CO₂ and bicarbonate whereas, during normal acid, secretion cytoprotective CO₂/HCO₃- production parallels acid production. Metabolic activity and mucosal damage caused by luminal acid perfusion was determined in anin vitro mouse stomach, with and without acid inhibition, and at 0%, 1%, or 5% serosal CO₂ supply. Without acid inhibition there was no mucosal damage at any level of serosal CO₂/HCO₃- supply. Acid inhibition reduced metabolic CO₂ production by 29% (P<0.004) and resulted in microscopic damage to 55% of the mucosal area and perforation in four of five stomachs (P<0.05). Although, 1% CO₂ supply completely replaced the reduction in metabolic CO₂, it did not protect against mucosal damage. Overreplacement by 5% serosal CO₂/HCO₃- was required to prevent damage. There was no correlation between luminal CO₂/HCO₃- output and mucosal damage. The protection by endogenous or exogenous CO₂/HCO₃- appears to act intracellularly rather than by intragastric or intercellular neutralization.This study was supported by Swiss National Foundation grants 32-26369.89 and 32-33626.92. The morphometry equipment was supported by a grant from the Osterreichische Nationalbank.     

Octreotide as first-line treatment for women with metastatic breast cancer

Summary Octreotide is a synthetic somatostatin analogue which has shown inhibitory activity against human breast cancer cells in culture. Ten patients with metastatic breast cancer and no prior hormonal therapy exposure received octreotide at 150 g subcutaneously thrice daily. No objective responses were observed and the median time to treatment failure was short at 57 days.     

Significance of wet autoclave pretreatment in immunohistochemistry

Until recently the only way to rescue masked epitopes in routinely processed surgical pathological material was enzymatic digestion. The use of heat for antigen retrieval, first by microwave irradiation, represents an important breakthrough in immunohistochemistry. With the acceptance of microwave oven pretreatment, various modified techniques and alternative heating methods have also been proposed. Wet autoclave pretreatment for tissue proteolysis is a highly reliable alternative to the microwave antigen retrieval technique. It provides uniform heating of the slides, hence an even enhancement of staining intensity in a variety of formalin-sensitive antigens, and it also offers consistent interlaboratory results. The method has been introduced in routine diagnostic immunohistochemistry for the detection of estrogen-and progesterone receptors, L26-, Ki-67- and bcl-2 antigens and variable types of cytokeratins (1/5/10/11, 8, 13, 19). Experimentally, wet autoclaving can be used very successfully for the immunophenotyping of p53 and mdm2 expression, for the detection of adhesion molecules (CD44, integrins) and some anti-inflammatory molecules (annexins), among others. It has produced a substantial improvement in the visualisation of silver-stained nucleolar organizer regionsassociated proteins (AgNORs) in routine paraffin sections and along with modified silver staining and standardized AgNOR parameters assessed by image analysis. Wet autoclaving-based AgNOR staining has been proposed by a European multicentric study group as the standardized method for AgNOR analysis in archival material.