Ross C. Smith

Immunohistochemistry for SDHB divides gastrointestinal stromal tumors (GISTs) into 2 distinct types.

The Carney triad (CT) is gastrointestinal stromal tumor (GIST), paraganglioma, and pulmonary chondroma. The GISTs of CT show different clinical, molecular, and morphologic features to usual adult GISTs but are similar to the majority of pediatric GISTs. We postulated that these GISTs would show negative staining for succinate dehydrogenase B (SDHB). We performed SDHB immunohistochemistry on GISTs arising in 5 individuals with CT, 1 child, 7 individuals with GIST in young adulthood including 2 with germline KIT mutations, 3 individuals with neurofibromatosis 1, one 63-year-old female with multifocal gastric epithelioid GIST with lymph node metastases, and 104 consecutive unselected individuals with apparently sporadic GIST. The GISTs and paragangliomas arising in CT, the pediatric GIST, and the multifocal gastric GIST from the 63-year-old showed negative SDHB staining. GISTs from the 7 young adults and 3 with neurofibromatosis were SDHB positive. Of the unselected GISTs, 101 (97%) were positive. One of the negative GISTs arose in a 48-year-old female with previous recurrent multifocal gastric GISTs and the other 2 arose in females also in their 40s with gastric GISTs with epithelioid morphology. We conclude that negative staining for SDHB is characteristic of the GISTs of CT and the subgroup of pediatric GISTs which it resembles. Furthermore, when negative staining occurs in apparently sporadic GISTs in adults, the GISTs show morphologic and clinical features similar to pediatric and CT type GISTs. GISTs may therefore be divided into type 1 (SDHB positive) and type 2 (SDHB negative) subtypes.

Non-covalent cross-linking of lipid bilayers by myelin basic protein: a possible role in myelin formation.

Myelin basic protein associates with bilayer vesicles of pure egg phosphatidylcholine, L-alpha-dimyristoyl phosphatidylcholine and DL-alpha-dipalmitoyl phosphatidylcholine. Under optimum conditions the vesicles contain 15-18% of protein by weight. The binding to dipalmitoyl phosphatidylcholine is facilitated above its gel-to-liquid crystalline transition temperature. At low ionic strength the protein provokes a large increase in vesicle size and aggregation of these enlarged vesicles. Above a sodium chloride concentration of 0.07 M vesicle fusion is far less marked but aggregation persists. The pH- and ionic strength-dependence of this aggregation follows that of the protein alone; in both cases it occurs despite appreciable electrostatic repulsion between the associated species. A similar interaction was observed with diacyl phosphatidylserine vesicles. These observations, which contrast with earlier reports in the literature of a lack of binding of basic protein to phosphatidylcholine-containing lipids, demonstrate the ability of this protein to interact non-ionically with lipid bilayers. The strong cross-linking of lipid bilayers suggests a role for basic protein in myelin, raising the possibility that the protein is instrumental in collapsing the oligodendrocyte cell membrane and thus initiating myelin formation.

The predictive value of body protein for chemotherapy-induced toxicity.

The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy‐induced neutropenia was examined in the current study.

Changes in body composition during breast cancer chemotherapy with the CMF-regimen.

Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1–3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4].The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF‐based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out‐patients (median age 47, range 26–70 years) receiving adjuvant CMF‐based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2–6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal.There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p<0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p=0.003) and mean fat mass of 1.49 kg (p=0.008).We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.

Circular dichroic analysis of the secondary structure of myelin basic protein and derived peptides bound to detergents and to lipid vesicles

In aqueous solution bovine myelin basic protein exhibits no significant alpha-helical or beta-pleated sheet structure. However, in vivo this protein is associated largely with the myelin membrane: experiments have therefore been performed to determine the structure of the protein when bound to lipid bilayers. Circular dichroism spectra show that this protein undergoes a major conformational change on binding to lipid bilayer vesicles formed from diacylphosphatidylserine or diacylphosphatidic acid, and on binding to micelles of several detergents. Association with diacylphosphatidylcholine failed to induce a structural change: this observation is interpreted in terms of an earlier report that lysophosphatidylcholine does increase the alpha-helical content of basic protein. These circular dichroism measurements and studies of the binding to the bilayer-forming lipids appear to provide support for significant hydrophobic lipid-protein interactions. Similar studies using two peptides produced by cleavf basic protein indicate that a major structure-forming region in the middle of the protein has been disrupted by this scission.

MUC1 expression in primary and metastatic pancreatic cancer cells for in vitro treatment by 213 Bi-C595 radioimmunoconjugate

Control of micrometastatic pancreatic cancer remains a major objective in pancreatic cancer treatment. The overexpression of MUC1 mucin plays an important role in cancer metastasis. The aim of this study was to detect the expression of MUC1 in human primary tumour tissues and three pancreatic cancer cell lines (CAPAN-1, CFPAC-1 and PANC-1), and target MUC1-positive cancer cells in vitro using 213Bi-C595 alpha-immunoconjugate (AIC). The expression of MUC1 on pancreatic tumour tissues and cancer cell lines was performed by immunohistochemistry and further confirmed by confocal microscope and flow cytometry analysis on the cell surface. Cytotoxicity of 213Bi-C595 was tested by MTS assay. Apoptosis was documented using TUNEL assay. Overexpression of MUC1 was found in ∼90% of tested tumour samples and the three pancreatic cancer cell lines. 213Bi-C595 is specifically cytotoxic to pancreatic cancer cells in a concentration-dependent fashion. These results suggest that overexpression of MUC1 in pancreatic cancer is a useful target, and that the novel 213Bi-C595 AIC selectively targets pancreatic cancer cells in vitro. 213Bi-C595 may be a useful agent for the treatment of micrometastases or minimal residual disease (MRD) in pancreatic cancer patients with overexpression of MUC1 antigen.

Synoptic reporting improves histopathological assessment of pancreatic resection specimens

Aim: We examined whether introduction of a standardised pancreatic cancer minimum data set improved the reporting of key pathological features across multiple institutions. Methods: From seven different pathology departments that are members of the New South Wales Pancreatic Cancer Network, 109 free text reports and 68 synoptic reports were compared. Results: AJCC stage could not be inferred from 44% of free text reports, whereas stage was reported in all 68 synoptic reports. In the free text reports 28 different names were used to designate margins. All margins were reported in only 12 (11%) of the free text reports compared with 64 (94%) of the synoptic reports (p = 0.0011). The presence or absence of lymphovascular or perineural invasion was reported in 72 (66%) and 92 (84%) of free text reports, respectively. In contrast, lymphovascular space and perineural invasion were reported in all synoptic reports (p = 0.0011 and p = 0.0058). Conclusion: We conclude that synoptic reporting of pancreatic resections without any other intervention increases the information contained within histopathology reports. Therefore, the introduction of minimal data set synoptic reports is a simple and feasible mechanism to immediately improve reporting for pancreatectomy specimens.

The role of psychosocial factors in the development of breast carcinoma: Part II†

The authors conducted the current study to determine whether personality predisposes some individuals to develop cancer.

Effect of an elemental diet on body composition: A comparison with intravenous nutrition

Measurements of changes in body fat, protein, and water were carried out on two comparable groups of 14 ill surgical patients each over 2-wk period during which one group received an elemental diet (nonprotein energy source was 67% carbohydrate and 33% fat) and the other a course of intravenous nutrition (nonprotein energy source was 100% carbohydrate). The patients fed with the elemental diet had no significant changes in body weight, fat, protein, water, or plasma proteins over the study period, and although the patients fed intravenously also had no changes in body protein or plasma proteins, there was an average gain of 3.2 kg of body weight. This weight gain was mainly extracellular water. It is concluded that the administration of the elemental diet by continuous infusion was comparable to intravenous nutrition in maintaining body protein in these very ill patients and had the advantage of being cheaper and easier to manage. The problem of extracellular water accumulation seen in the patients fed intravenously was not present in the patients who received the elemental diet.

Comparison of Outcomes following Transhiatal or Ivor Lewis Esophagectomy for Esophageal Carcinoma

p= 0.05); if two surgeons operated concurrently, THO could be performed 40 minutes quicker than THO or ILO performed by a single surgeon (p= 0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7 days for THO (p= 0.014). The 30-day mortality was 5.1%; total in-hospital mortality was 7.1% with no difference for operation type. There were similar morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no significant effect of surgical technique; there were no apparent advantages for either operation when patients were compared by tumor type or matched for stage. Hence THO is a valid alternative to ILO, particularly for stage II and III cancer.