Radiation damage to the rectum and anus: pathophysiology, clinical features and surgical implications.

Radiation kills cancer cells by inducing various degrees of deoxyribonucleic acid fragmentation and disruption of intracellular membranes that lead to either immediate or delayed cell death. Although radiation can be effective in destroying cancer, its usefulness is limited by damage to normal tissues that surround the target tumour or those in the path of the radiation beam. The rectum and anus are damaged frequently during radiotherapy for abdominopelvic malignancy, including preresection therapy for rectal cancer. Such damage is often associated with lesions in the perineal skin, genitourinary tract, colon, and small intestine. Surgical intervention often is required for the most severe forms of these complications.

The temperature dependence of cardioplegic distribution in the canine heart.

BACKGROUND: Cold cardioplegic arrest can produce cooling contracture and suboptimal myocardial protection. This study examines whether cooling contracture is associated with maldistribution of cardioplegic solution, particularly subendocardial hypoperfusion, which may impair recovery. METHODS: Canine hearts were arrested by antegrade cold and warm blood cardioplegia in random order. Cardioplegic distribution was measured using radiolabeled microspheres before and just after induction of each period of arrest. RESULTS: With cold cardioplegia, perfusion of left ventricular subepicardial and midwall regions decreased. Subendocardial to subepicardial perfusion ratios increased significantly in the left ventricle as a whole, the anterior and posterior regions of the left ventricular free wall, and the interventricular septum. With warm arrest, transmural flow distribution was not significantly altered from preceding prearrest values. At constant coronary flow, coronary perfusion pressure was initially similar after induction of arrest at both temperatures, but it rose subsequently during warm cardioplegia. CONCLUSIONS: The data suggest that during normothermic arrest, vasomotor tone regulates cardioplegic distribution, and hyperkalemic vasoconstriction is of slow onset. In the absence of beating and with vasomotion inhibited by hypothermia, cardioplegic distribution during cold arrest appears to be primarily dependent on vascular anatomy. There was no evidence of subendocardial underperfusion during cooling contracture.

Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance spectroscopy.

BACKGROUND: Warm continuous blood cardioplegia provides excellent protection, but must be interrupted by ischemic intervals to aid visualization. We hypothesized that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia mitigates the deleterious effects of normothermic ischemia. METHODS: Isolated cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes of global ischemia at 10 degrees C or 37 degrees C, or 45 minutes of normothermic ischemia without prior cardioplegia. Left ventricular function was measured at baseline and during 2 hours of recovery. Metabolism was continuously evaluated by phosphorus-31 magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate was 71% +/- 4%, 71% +/- 7%, and 38% +/- 5% of baseline at 30 minutes, and 71% +/- 4%, 48% +/- 5%, and 39% +/- 6% at 42 minutes of ischemia in the cold ischemia, warm ischemia, and normothermic ischemia without prior cardioplegia groups, respectively. Left ventricular systolic function, left ventricular relaxation, and high-energy phosphate levels recovered fully after cold cardioplegia and ischemia. Prior cardioplegia delayed the decline in intracellular pH during normothermic ischemia initially by 9 minutes, and better preserved left ventricular relaxation during recovery, but did not ameliorate the severe postischemic impairment of left ventricular systolic function, marked adenosine triphosphate depletion, and creatine phosphate increase. Left ventricular distensibility decreased in all groups. CONCLUSIONS: When cardioplegia is followed by prolonged ischemia, better protection is provided by hypothermia than by normothermia. Prior cardioplegia confers little advantage on recovery after prolonged normothermic ischemia but delays initial ischemic metabolic deterioration, which would contribute to the safety of brief interruptions of warm cardioplegia.

Adenocarcinoma of the urachus masquerading as a right lower quadrant mass: a case report.

We report a patient who presented initially with a right lower quadrant mass which was attached to the anterior abdominal wall. The final pathological diagnosis was adenocarcinoma of the urachus, an exceedingly rare bladder tumor.

The role of laparoscopy in the management of intussusception in the Peutz-Jeghers syndrome: case report and review of the literature.

A 15-year-old girl with known Peutz-Jeghers syndrome and with nausea and vomiting of all ingested food was transferred from an outside institution. Physical examination revealed a palpable upper abdominal mobile mass. Upper gastrointestinal series revealed a stacked coin appearance consistent with small bowel intussusception. An abdominal computed tomographic scan showed a left upper quadrant sausage-shaped mass with invagination of bowel into bowel suggestive of small bowel intussusception. The patient was taken to the operating room for a combined upper endoscopy and laparoscopy. Laparoscopy confirmed the radiologic findings and a jejuno-jejunal intussusception was identified and reduced laparoscopically. The endoscope could not be passed to the level of the polyp, thus, this loop of small bowel was resected laparoscopically. The final pathologic diagnosis was multiple hamartomas. We conclude that laparoscopy is a safe and effective method of managing intussusception in the Peutz-Jegher syndrome because the pathologic lead point is a benign hamartoma. A combined endoscopic and laparoscopic approach can be used to treat proximal small bowel intussusception and this could possibly eliminate the need for laparotomy and reduce the post-operative complications associated with multiple reoperations in this patient population.

Warm and cold blood cardioplegia. Comparison of myocardial function and metabolism using 31p magnetic resonance spectroscopy.

BACKGROUND: Standard myocardial protection during cardiac surgery uses hypothermic arrest, but warm heart surgery, recently introduced, is now used in many centers. We hypothesized that warm continuous blood cardioplegia (WCBC) would provide better myocardial preservation than cold continuous blood cardioplegia (CCBC). METHODS AND RESULTS: In isolated cross-perfused canine hearts, left ventricular (LV) function and myocardial O2 consumption (MVO2) were measured at constant LV volume, coronary perfusion pressure, and heart rate before and after 75 minutes of arrest at 37 degrees C or 10 degrees C. Metabolism was evaluated by 31P nuclear magnetic resonance spectroscopy. LV resting tone increased transiently after arrest by CCBC but not WCBC (38 +/- 3.9 versus 2.9 +/- 0.5 mm Hg, P < .0005). Myocardial ATP changed over time differently in the groups (P < .001), declining at the outset of CCBC and returning to control levels during the recovery period after CCBC or WCBC. Intracellular pH rose from 7.17 +/- 0.03 to 7.85 +/- 0.05 during CCBC (P < .0005 versus WCBC). MVO2 declined dramatically during arrest at either temperature but to a lower value during CCBC (P < .0005). LV pressure recovered to 86.1 +/- 5.1% of its prearrest value after CCBC and to 97.2 +/- 7.8% following WCBC (P = NS). After CCBC but not WCBC, there were small but significant increases in LV end-diastolic pressure (by 1.3 mm Hg, P < .05) and in the LV relaxation constant, tau (from 37.3 +/- 1.5 to 42.3 +/- 2.4 milliseconds, P < .05). CONCLUSIONS: The increase in intracellular pH during CCBC is largely accounted for by physicochemical factors. Group differences in ATP over time may be related to rapid cooling contracture during CCBC. The data suggest that CCBC mildly impairs LV function but that WCBC preserves function and metabolism at or near prearrest levels.

Activation of the particulate low Km phosphodiesterase of adipocytes by addition of cAMP-dependent protein kinase.

The purified catalytic subunit (C) of cAMP-dependent protein kinase produced a 2-fold activation of the low Km phosphodiesterase in crude microsomes (P-2 pellet) of rat adipocytes. This activation was C subunit concentration-dependent, ATP-dependent, blocked by a specific peptide inhibitor, and lost if the C subunit was first heat denatured. The concentration of ATP necessary for half-maximal activation of the low Km phosphodiesterase was 4.50 +/- 1.1 microM, which was nearly the same as the known Km of C subunit for ATP (3.1 microM) using other substrates. The concentration of C subunit producing half-maximal activation of phosphodiesterase was 0.22 +/- 0.04 microM, slightly less than the measured concentration of total C subunit in adipocytes (0.45 microM). The activation of the low Km phosphodiesterase by C subunit was specific, since on an equimolar basis, myosin light chain kinase, cGMP-dependent protein kinase, or Ca2+/calmodulin-dependent protein kinase II did not activate the enzyme. The percent stimulation of phosphodiesterase by C subunit was about the same as that produced by incubation of adipocytes with a cAMP analog, and the enzyme first activated in vivo with the analog was not activated to the same extent (on a percentage basis) by in vitro treatment with C subunit. Treatment of the crude microsomes with trypsin resulted in transfer of phosphodiesterase catalytic activity from the particulate to the supernatant fraction, but the enzyme in the supernatant was minimally activated by C subunit, suggesting either loss or dislocation of the regulatory component. The C subunit-mediated activation of phosphodiesterase was preserved after either transfer of phosphodiesterase activity to the supernatant fraction by nonionic detergents or partial purification of the transferred enzyme. The present findings are consistent with the suggestion that protein kinase regulates the concentration of cAMP through phosphodiesterase activation and provide direct evidence that the mechanism of activation involves phosphorylation.