Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data

A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.     

The increase in the intracellular Ca2+ concentration induced by mechanical stimulation is propagated via release of pyrophosphorylated nucleotides in mammary epithelial cells

Mechanical stimulation of one mammary tumor cell in culture induced an increase in its intracellular calcium concentration which spread to surrounding cells. The increase in calcium can also be induced by addition of a solution in which cultured mammary tumor cells were stimulated by repeated pipetting (solution after pipetting cells, SAPC). The activity of the SAPC was completely abolished by treatment with snake venom phosphodiesterase or pyrophosphatase. Uridine triphosphate (UTP), uridine diphosphate (UDP) and ATP (1 M each) were detected in the SAPC, whereas 5-UMP and 5-AMP were produced by phosphodiesterase digestion. A mixture of UTP, UDP and ATP (1 M each) elicited a calcium response which was comparable to that induced by SAPC, while UTP, UDP or ATP alone at 1 M elicited a small increase in calcium concentration in mammary tumor cells. Suramin, a competitive antagonist of P₂ purinoceptors, diminished the spreading of the calcium wave induced by mechanical stimulation. It also blocked the responses to SAPC, UTP, UDP and ATP. These findings suggest that the mechanical stimulation results in the release of UTP, UDP and ATP into the extracellular space which mediates induction of the spreading calcium response via P_2U-type purinoceptors.     

99mTc-MIBI scan in mammary Pagets disease: a case report

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.     

Antitumor effect of trimelamol against human breast carcinoma xenografts in nude mice

The antitumor effect of N-2, N-4, N-6-trihydroxymethyl-N-2, N-4, N-6-trimethylmelamine (trimelamol), a synthetic analogue of hexamethylmelamine, was investigated using human breast carcinoma xenografts in nude mice. Four tumor models, T-61, Br-10, R-27 and MCF-7 were estrogen receptor (ER)-positive and their growth was estradiol-dependent. The MX-1 model was ER-negative and grew estradiol-independently. Sixty mg of trimelamol per kg dissolved in 5% dimethylsulphoxide (DMSO) with 5% glucose was administered intraperitoneally for 5 days weekly for three weeks. Trimelamol showed potent antitumor activity on T-61 and MX-1 in a dose-responsive manner with a marginal effect on Br-10, whilst R-27 and MCF-7 were insensitive to this agent. This antitumor spectrum on human breast carcinoma xenografts was similar to that of hexamethylmelamine previously reported using the same xenograft models. Trimelamol is water-soluble and does not require metabolic activation which is needed for hexamethylmelamine. These advantages allow the paraenteral administration of trimelamol, and warrant the further investigation of this drug for breast carcinomas.     

Catecholamine Release caused by Carbon Dioxide Insufflation during Laparoscopic Surgery

Purpose

We evaluated plasma catecholamine levels during pneumoperitoneum in laparoscopic surgery.

Materials and Methods

Plasma epinephrine and norepinephrine were evaluated in 29 patients who underwent laparoscopic retroperitoneal surgery in a half lateral decubitus position (group 1) or laparoscopic varicocelectomy in a Trendelenburg position (group 2).

Results

The levels of epinephrine and norepinephrine increased significantly 5 minutes after carbon dioxide insufflation compared to levels after Veress needle insertion and just before insufflation. The elevation of catecholamine levels during laparoscopic procedures was greater in group 1.

Conclusions

Our results indicate that carbon dioxide insufflation may cause catecholamine release during laparoscopic surgery. Careful monitoring of hemodynamics is mandatory at the beginning of the procedure.     

Radon daughter plateout--II. Prediction model

By a linear programming procedure, we have optimized the Jacobi room model to fit our data on the partitioning of radon daughters between air and wall surfaces (plateout), obtained at high radon concentrations in a small chamber. Subsequently, the optimized model yielded estimates that compared well with plateout data obtained at lower concentrations in a room-sized chamber. (The experimental work is described separately.) The major change made in the Jacobi model was to reduce the deposition velocity of free airborne radon daughters from 1 to 0.05 cm/sec. This value was obtained by using a fast algorithm to solve the linear programming to arrive at the "best fit". Lesser changes were made in other parameters.     

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole.

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.     

Characterization of clones of tumorigenic feline cells transformed by a chemical carcinogen

Tumorigenic clonal lines derived from soft agar colonies induced by DMBA-transformed feline embryo cells were isolated and characterized. The morphologically altered clonal cells formed large aggregates, growing in this aggregate form when suspended in liquid growth medium above an agar base and forming colonies in soft agar with high efficiency. When inoculated into athymic nude mice, chemically altered clonal cells produced progressively growing sarcomas. Cells established from the tumors morphologically resembled the DMBA-transformed feline embryo cells and were characterized as cat cells by karyological analysis. The tumorigenic lines were negative for feline oncornavirus-associated cell membrane antigen (FOCMA), and for "gag-X" the transformation-related polyprotein which is encoded by the replication defective feline sarcoma virus.