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PubMed1999

The surgical management of chronic pancreatitis: duodenum-preserving pancreatectomy.

Duodenum-preserving pancreas resection for chronic pancreatitis results in a subtotal resection of the pancreatic head. Of 488 patients suffering from chronic pancreatitis with an inflammatory mass in the head, 48% had a common bile duct stenosis in the ERCP, 63% had a pancreatic main duct stenosis, 25% had a duodenum stenosis, and 17% showed vascular obstruction--mainly compression or occlusion of the portal vein. Hospital mortality after duodenum-preserving head resection was 0.9%. In the late follow-up, 88% of patients were free of pain and 60% were professionally rehabilitated. The incidence of diabetes mellitus in the late follow-up was 14%; however, 6% of the patients had a lasting improvement of endocrine function. Late mortality after a median follow-up of 6 years (1-22 years after surgical treatment) was 9%. Only 10% of the patients needed further hospitalization due to recurrent attacks of acute pancreatitis. Duodenum-preserving head resection should be the surgical procedure of choice in chronic pancreatitis with an inflammatory mass in the head of the pancreas and in cases with pancreas divisum after failure of medical and interventional treatment. Duodenum-preserving total pancreatectomy is a last-resort surgical treatment after failure of left resection for pain in chronic pancreatitis.

Chronic Disease↗
PubMed1987

Observations on the anatomy of the stomach and duodenum of the bowhead whale, Balaena mysticetus.

Gastric and cranial duodenal structure of the bowhead whale (Balaena mysticetus) was examined grossly and microscopically. The stomach was arranged in a series of four compartments. The first chamber, or forestomach, was a large nonglandular sac lined by a keratinized stratified squamous epithelium. It was followed by the fundic chamber, a large, somewhat globular and entirely glandular compartment. At the entrance of the fundic chamber, a narrow cardiac gland region could be defined. The remaining mucosa of the chamber contained the proper gastric glands. A narrow, tubular connecting channel, the third distinct gastric division, was lined by mucous glands and joined the fundic chamber with the final stomach compartment, or pyloric chamber. This fourth chamber was also tubular and lined by mucous glands but was of a diameter considerably larger than the connecting channel. The stomach terminated at the pyloric sphincter which consisted of a well-developed band of circular smooth-muscle bundles effecting a division between the pyloric chamber and small intestine. The small intestine began with the duodenal ampulla, a dilated sac considerably smaller than the fundic chamber of the stomach. The mucosa of this sac contained mucous glands throughout. The ampulla led without a separating sphincter into the duodenum proper which continued the intestine in a much more narrow tubular fashion. The mucosal lining of the duodenum was composed of villi and intestinal crypts. Although their occurrence varied among whales, enteroendocrine cells were identified within the mucous glands of the cardiac region, connecting channel, pyloric chamber, and cranial duodenum. The hepatopancreatic duct entered the wall of the duodenum shortly after the termination of the duodenal ampulla and continued intramurally along the intestine before finally joining the duodenal lumen.

Animals↗
PubMed1991

Sensory innervation of the canine esophagus, stomach, and duodenum.

The sensory innervation of the postpharyngeal foregut was investigated by injecting the enzyme horseradish peroxidase (HRP) into the walls of the esophagus, stomach, or duodenum. The transported HRP was identified histochemically, labeled neurons in the spinal and vagal ganglia were counted, and the results were plotted using an SAS statistical program. The spinal sensory fields of each viscus were defined using three determinations: craniocaudal extent, principal innervation field, and peak innervation field. The data revealed that innervation fields are craniocaudally extensive, the sensory field of each viscus overlaps significantly with its neighbor, yet each viscus can be characterized by a field of peak innervation density. Craniocaudal innervation of the esophagus spans as many as 22-23 paired spinal ganglia (C1-L2). There are two peak innervation fields for the cervical (C2-C6 and T2-T4) and for the thoracic (T2-T4 and T8-T12) sectors of the esophagus. The sensory innervation of the stomach extends craniocaudally over as many as 25 paired spinal ganglia (C2-L5). The peak innervation field of the stomach spans a large area comprising the cranial, middle, and the immediately adjoining caudal thoracic ganglia (T2-T10). The duodenum is innervated craniocaudally by as many as 15 paired thoracolumbar ganglia (T2-L3). Peak innervation originates in the middle and caudal thoracic ganglia and cranial lumbar (T6-L1) ganglia. There is a recognizable viscerotopic organization in the sensory innervation of the postpharyngeal foregut; successively more caudal sectors of this region of the alimentary canal are supplied with sensory fibers from successively more caudal spinal dorsal root ganglia. Vagal afferent innervation of the esophagus, stomach, and duodenum is bilateral and originates predominantly, but not exclusively, from vast numbers of neurons in the nodose (distal) ganglia. The esophagus is innervated bilaterally and more abundantly by jugular (proximal) ganglia neurons than is either the stomach or duodenum. The physiological significance of the findings are discussed in relation to the phenomena of visceral pain and referred pain.

Afferent Pathways↗
PubMed1987

Duodenum-preserving total pancreatectomy for end stage chronic pancreatitis.

The classical Whipple procedure for chronic pancreatitis has been associated with significant long term postoperative morbidity. The pylorus-preserving procedure of Longmire has reduced but not eliminated the long-term morbidity. Preservation of the whole duodenum with total pancreatectomy has been introduced for the treatment of patients with end-stage chronic pancreatitis after favourable experience with this procedure in infants for nesidioblastosis. Fourteen patients with chronic pancreatitis have had a total pancreatectomy with preservation of the duodenum and the bile duct. All patients are still alive (median follow-up 9.5 months) and none suffered major complications in the perioperative period. One patient developed a biliary stricture at 3 months, requiring biliary reconstruction. Six of the patients have returned to full-time work; nine require no analgesia. All patients require pancreatic enzyme replacement, and all patients have gained weight postoperatively. Diabetic control is satisfactory with a twice daily insulin regime. Duodenum-preserving total pancreatectomy is feasible in the adult without mortality or high morbidity; early experience suggests that preserving the duodenum improves gastrointestinal function with easier control of the diabetes.

Adult↗
PubMed1994

Complications of adjacent organs in chronic pancreatitis managed by duodenum-preserving resection of the head of the pancreas.

Chronic pancreatitis frequently generates complications through involvement of adjacent organs. Distal common bile duct stenosis and segmental duodenal stenosis, the most frequent complications, are usually treated by resection or bypass procedures. This study presents experience with duodenum-preserving resection of the head of the pancreas in the treatment of patients with chronic pancreatitis with predominant involvement of the pancreatic head and coexisting complications involving adjacent organs. This procedure preserves the structure and function of the bile duct and duodenum. Sixty-six patients with severe chronic pancreatitis underwent duodenum-preserving resection of the head of the pancreas. Thirty-eight had associated complications of neighbouring organs: 37 had distal common bile duct stenosis, seven had duodenal stenosis, ten had evidence of segmental portal hypertension and one suffered from a pancreatopleural fistula. Details of all patients were documented prospectively; mean follow-up was 4.2 years. The complications of adjacent organs were permanently eradicated in 36 of 38 patients. Two patients required endoscopic stenting for persisting bile duct obstruction. There was substantial or complete relief of all symptoms in 35 patients. Duodenum-preserving resection of the head of the pancreas is effective in the treatment of severe chronic pancreatitis with predominant involvement of the pancreatic head and provides definitive management of associated complications of adjacent organs.

Adult↗
PubMed2002

Differential induction of CYP1A1 in duodenum, liver and kidney of rats after oral intake of soil containing polycyclic aromatic hydrocarbons.

We have analyzed the induction of the cytochrome P450 enzyme CYP1A1 as a biomarker of effect in duodenum, liver and kidney of rats after oral intake of contaminated soil particles. The soil samples originated from industrial sites and were contaminated with polycyclic aromatic hydrocarbons (PAH) to variable extents, ranging from 60 to 4700 mg PAH/kg soil. Soil samples were administered for one week as a mixture with commercial rodent diets. After exposure, microsomes of several organs were prepared and analyzed for CYP1A1, enzymatically and by Western blots. All contaminated soils led to induction of CYP1A1 in duodenal mucosa cells, regardless of their extent of contamination, showing that relevant doses were mobilized in the gastrointestinal tract and adsorbed. Subsequent distribution of non-metabolized compounds is indicated by induction of CYP1A1 in the liver. However, some samples did not lead to a response in the liver, due to their quantitative and qualitative contaminant composition. In accordance with previous results, there is a sigmoidal dose-response relationship between induction of hepatic CYP1A1 levels and the soil contamination with higher condensates of PAH. In contrast, the response in the duodenum appeared to be hyperbolic and correlated well with the amounts of total PAH. Highly contaminated soil, being nearly devoid of higher condensates of PAH, led to pronounced induction in the duodenum but failed to induce CYP1A1 in the liver. Successful passage of contaminants through the intestinal barrier and the liver compartment is shown by increased CYP1A1 expression in the kidney. Compared with enzyme levels induced in the liver, those of the kidney are much lower and amount to only about 1/20 of the liver values for soils with high induction potential. Hence, oral PAH intake leads to differential induction patterns of CYP1A1 in duodenum, liver and kidney of rats. The observations raise questions concerning the role of the primary duodenal PAH metabolism in preventing contaminant-dependent hazardous effects, and of the significance of differential CYP1A1 expressions for carcinogenic processes in several tissues.

Animals↗
PubMed2000

Apoptosis in murine duodenum during embryonic development.

Duodenum is thought to go through a solid-core stage followed by recanalization during its development. This study investigates the role of apoptosis in normal duodenal development, especially during widening of the lumen, and hence, the possible role of apoptosis in duodenal atresia (DA). Twenty-four time-mated Sprague-Dawley rats were killed from day 13 to day 20 of gestation. Duodenums of 3 fetuses were chosen randomly from each rat and processed. Apoptosis was determined by the terminal deoxytransferase-mediated biotin dUTP nick-end labeling (TUNEL) technique (ApopTag). Apoptosis count and cross-sectional areas were measured with an image analyzer (MetaMorph). The number of apoptotic cells per unit area duodenum peaked on day 15 for the mucosal/submucosal layer and on day 14 for the muscular/mesenchymal layer. The maximal number of apoptotic cells per cross-section of duodenum was between 7 and 8. The cross-sectional areas of the duodenal wall and lumen increased exponentially between day 17 and day 19 while duodenal-wall thickness remained relatively constant throughout duodenal development. The localization, timing, and intensity of apoptosis do not suggest that apoptosis is responsible for the widening of the duodenal lumen; enlargement of the lumen is related to the increase in duodenal circumference. Apoptosis thus may not be involved in the pathogenesis of DA.

Animals↗
PubMed2000

Direct neuronal interactions between the duodenum and the sphincter of Oddi.

The sphincter of Oddi (SO) is a complex structure that must function in coordination with the motor activities of the gallbladder and the duodenum. It is now clear that a neural circuit exists between the duodenum and the SO, and it is likely that this network is largely responsible for the regulation of SO motility. Recent studies have demonstrated that this circuit provides excitatory cholinergic input to SO ganglia that can be activated by electrical stimulation of the duodenal mucosa, distention of the duodenum, and increased motor activity of the duodenum.

Autonomic Nervous System↗
PubMed1985

Effects of verapamil and dexamethasone on the 1,25-dihydroxyvitamin D3-mediated calcium absorptive mechanism in the organ-cultured embryonic chick duodenum.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to induce the biosynthesis of a specific, calcium-binding protein (CaBP) and to stimulate calcium transport in the organ-cultured embryonic chick duodenum. The biosynthesis of CaBP has been shown previously to exhibit an absolute dependence on the ambient calcium concentration of the culture medium. Verapamil, a calcium-channel blocker, decreased calcium influx into the organ-cultured duodenum and inhibited the induction of CaBP by 1,25(OH)2D3. Raising ambient calcium concentrations to as high as 10 mM did not prevent or reverse the inhibitory actions of verapamil. Dexamethasone, known to augment CaBP biosynthesis and calcium uptake in the organ-cultured duodenum in response to 1,25(OH)2D3, largely prevented inhibition of CaBP by verapamil. The actions of verapamil and dexamethasone were correlated with altered steady-state calcium concentrations of the organ-culture duodenum, strongly supporting a regulatory role of calcium in the 1,25(OH)2D3-mediated, intestinal calcium absorptive mechanism.

Animals↗
PubMed1985

Adrenocorticotropin and alpha-melanotropin in the myenteric plexus of the rat duodenum: an electron microscopic study.

Adrenocorticotropin (ACTH) immunoreactivity was localized at the ultrastructural level as positive 'cores' within large dense-cored vesicles (LDVs) of axons and dendrites of the rat duodenum. The immunostained vesicle 'cores' were 35-50 nm in mean diameter, corresponding to 'cores' of LDVs with a mean diameter of 80-90 nm. alpha-melanotropin (alpha-MSH) was detected also within LDVs, expressing the same mean diameter as ACTH-stained vesicles. alpha-MSH and ACTH were localized only within structures belonging to the enteric nervous system of the rat duodenum. alpha-MSH and ACTH, as detected by immunostaining, were absent in endocrine cells of the rat duodenum. These findings suggest the possibility that these peptides may have important physiological roles in the rat duodenum.

Adrenocorticotropic Hormone↗
PubMed1994

Developmental changes in the response of rat isolated duodenum to nicotine.

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.

Adenosine Triphosphate↗
PubMed1988

Motor activity of the gastric antrum, pylorus, and duodenum under fasted conditions and after a liquid meal.

Because the mechanisms that control the movement of food and digestive juices across the human pylorus are not completely understood, the aim of this study was to document the normal patterns of pressure activity in the antrum, pylorus, and duodenum and the associated pH changes in 9 healthy volunteers. Studies were carried out under fasting conditions and after ingestion of 300 ml of chocolate milk, using a unique 11-channel intraluminal probe that incorporated a sleeve sensor positioned across the pylorus and pH electrodes situated in the terminal antrum and proximal duodenum. The most common motor pattern recorded under fasting conditions consisted of regular coordinated contractions, most of which (a) involved the antrum and duodenum, (b) showed evidence of propagation through two or more adjacent channels, and (c) were associated with transient reductions in duodenal pH and transient elevations in antral pH. Ingestion of milk changed the motor pattern to one that was composed of pressure waves, which were confined to the pylorus with few or no pressure waves in the terminal antrum or proximal duodenum. Isolated pyloric pressure waves were gradually replaced by propagated antroduodenal contractions, which eventually occurred at a regular frequency that was higher than that observed under fasting conditions. After ingestion of milk, only the coordinated contractions were associated with transient reductions in duodenal pH. Isolated pyloric pressure waves were also observed under fasting conditions just before or just after phase III of the migrating motor complex, and 17% of these were accompanied by episodes of duodenal acidification.

Adult↗
PubMed1991

Role of capsaicin-sensitive afferent neurons in alkaline secretory response to luminal acid in the rat duodenum.

The role of capsaicin-sensitive afferent neurons in acid-induced HCO3- secretion was investigated in the duodenum of anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential differences were continuously monitored, and HCO3- output was determined by pH change. Under these conditions, duodenal pH, potential difference, and HCO3- output were significantly increased in response to IV injection of prostaglandin E2 (300 micrograms/kg) and luminal acidification (10 mmol/L HCl, 10 minutes). These responses induced by luminal acid were significantly attenuated by SC pretreatment with indomethacin (5 mg/kg), preexposure of the mucosa to lidocaine (4%, 15 minutes), functional ablation of capsaicin-sensitive afferent neurons, or even prior application of capsaicin (6 mg/mL, 30 minutes) to the duodenum. Although capsaicin application by itself (0.3-6 mg/mL) produced a concentration-dependent increase of HCO3- output, this effect was significantly reduced by lidocaine, indomethacin, or chemical deafferentation and exhibited a tachyphylaxis after repeated application at a high concentration (6 mg/mL). Neither of these treatments significantly affected the HCO3- response induced by prostaglandin E2. It was concluded that stimulation of capsaicin-sensitive afferent neurons increased duodenal HCO3- secretion and that these neurons may be involved in the mechanism of HCO3- response induced by luminal acid in the duodenum.

Animals↗
PubMed1994

Role of B1 and B2 receptors and of nitric oxide in bradykinin-induced relaxation and contraction of isolated rat duodenum.

Bradykinin (BK) and its analogues induce a typical biphasic response (relaxation followed by contraction) in the isolated rat duodenum. We studied the role of B1 and B2 BK receptors and nitric oxide (NO) in relaxation and contraction of the isolated rat duodenum. Both effects are concentration-dependent: BK has shown an EC50 (contraction) of 3.8 +/- 1.9 x 10(-7) M and an IC50 (relaxation) of 3.0 +/- 0.7 x 10(-9). Similar results were obtained with the selective B2 receptor agonists [Hyp3,Tyr(Me)8]-BK and [Phe8 psi (CH2-NH)Arg9]-BK, showing an EC50 of 9.6 +/- 1.9 x 10(-7) M and 5.6 +/- 2.9 x 10(-7) M and an IC50 of 3.5 +/- 0.6 x 10(-10) M and 6.8 +/- 1.7 x 10(-10) M, respectively. Furthermore, the effects induced by these three agonists were not altered when tissues were treated with 42.1 microM Mergetpa, a carboxypeptidase N inhibitor. While the relaxant and contractile effects elicited by BK were significantly inhibited in the presence of Hoe 140 (0.7 microM), a selective B2 receptor antagonist, those induced by the selective B1 receptor agonist desArg9-BK were not. Furthermore, [Leu8]-desArg9-BK (2.6 microM), which is both a pure and selective B1 receptor antagonist, acted as an agonist on the rat duodenum, inducing a biphasic relaxant and contractile effect. These relaxant and contractile effects were not altered by drugs that inhibit or stimulate NO production, such as L-NAME (200 microM), a combination of L-NAME (200 microM) and indomethacin (2.5 microM), L-arginine (1 mM), or superoxide dismutase (20 U/ml). However, the contractile effect was significantly reduced when tissues were preincubated with methylene blue (100 microM), which inhibits activation of guanylate cyclase. We conclude that 1) BK and its analogues selectively activate a B2 receptor, producing a biphasic effect (relaxation and contraction); 2) DesArg9-BK may either acts via a different receptor which might be another B1 receptor subtype or a typical B1 receptor where [Leu8]-desArg9-BK acts as a partial agonist; and 3) neither NO nor the prostaglandin pathway mediates BK-induced relaxation in the isolated rat duodenum.

Amino Acid Oxidoreductases↗
PubMed1991

Central and peripheral type benzodiazepine ligands displace [3H][3-ME-HIS2]TRH from its binding sites in the brain and the anterior pituitary and antagonize the effect of TRH in the rat duodenum.

The effects of central (clonazepam, an agonist, and FG 7142, an inverse agonist), mixed (diazepam) or peripheral type (Ro 5-4864) benzodiazepine receptor ligands on the action of TRH on the transmurally stimulated rat duodenum and binding of [3H][3-Me-His2] TRH in the rat anterior pituitary, hypothalamus, cortex and brainstem have been studied. TRH dose-dependently inhibited the contractions of transmurally stimulated rate duodenum. Clonazepam (5 x 10(-6) M), diazepam (10(-5) M), Ro 5-4864 (10(-5) M) or FG 7142 (10(-5) M) attenuated the response of TRH in the rat duodenum. The action of these compounds was antagonized neither by the central type benzodiazepine antagonist flumazenil nor by peripheral type antagonist PK 11195 but instead PK 11195 itself counteracted TRH. TRH displaced [3H][3-Me-His2]TRH with Ki-values ranging 0.08 to 0.31 microM. Ki-values for clonazepam diazepam, Ro 5-4864, PK 11195 and FG 7142 ranged 6-117 microM, 3-23 microM, 20-67 microM, 20-40 microM and 260-420 microM, respectively, demonstrating fairly weak affinity to TRH-receptors. In saturation experiments, clonazepam and PK 11195 significantly increased KD but not Bmax of the labelled ligand while Ro 5-4864 increased both KD and Bmax. This indicates that all these compounds competitively inhibit the binding of [3H][3-Me-His2]TRH in the CNS which may also be the mechanism for their antagonism of the effect of TRH in the rat duodenum.

Animals↗
PubMed1981

Role of the duodenum in motilin release.

In order to study the regulatory mechanism of motilin release, plasma motilin was measured in healthy dogs during the fasting state and after the ingestion of ordinary nutrient. Fasting plasma motilin levels were found to fluctuate intermittently, but ingestion of a meal completely abolished the intermittent motilin release and resulted in low motilin levels lasting for 6-8 h. To clarify the role of the duodenum in this motilin release, an operation was performed in five dogs by which we excluded from the alimentary tract the upper half of the small intestine not including the duodenum from a point 2 cm below the larger pancreatic duct. After this operation meal ingestion still caused a decrease in plasma motilin levels. However, after a modified version of the operation was performed in 5 other dogs by which the upper half of the small intestine together with the duodenum was transected at the pyloric ring, plasma motilin was not suppressed by meal ingestion. The results suggest that motilin secretion is regulated by nutrieht ingestion and that the passage of nutrients through the duodenum plays an important role in its regulation.

Animals↗
PubMedDate not supplied

Bradykinin receptors in isolated rat duodenum.

Pharmacological properties of the bradykinin receptors in the isolated rat duodenum were investigated by examining the relaxant and contractile responses to bradykinin and [des-Arg9]-bradykinin, an agonist of B1 receptors. A specific desensitization and de novo formation for B1 receptors were observed. Changes in medium pH caused a decrease in the responses to bradykinin and [des-Arg9]-bradykinin of rat duodenum. Urea incubation in test tube inhibited the responses to bradykinin and [des-Arg9]-bradykinin of rat duodenum, while urea in bathing medium was ineffective. These findings strongly suggested that (a) ionic bonds are important in the interaction between bradykinin and its receptors, and (b) B2 receptors in rat duodenum are different from those in guinea pig ileum.

Animals↗
PubMed1988

Pathologic response of the pancreas and duodenum to experimental intraoperative irradiation.

The pancreas and duodenum of 24 beagle dogs were given intraoperative irradiation (IORT) with 6 MeV electrons. The dose range was 17.5 Gy to 40 Gy. Billroth II gastrojejunostomy was performed on all dogs prior to irradiation. Six control dogs received only Billroth II surgery. Starting 2 weeks after surgery, dogs in the irradiation groups were given 50 Gy 6 MV X rays external beam radiation therapy (EBRT) to the pancreas and duodenum. The total dose of 50 Gy was given in 2 Gy fractions over 5 weeks. Dogs were monitored for 135 days then necropsied. Gross and histopathologic changes in the pancreas and duodenum were evaluated and quantitative analysis of pancreatic lesions done. Duodenal ulcers were found following 32.5 Gy and 40 Gy IORT. The pancreases were atrophic in irradiated dogs and exocrine pancreatic insufficiency occurred in one dog given 25 Gy. Gross pancreatic atrophy correlated with IORT dose. Histopathologic evidence of radiation damage to the pancreas was observed in acinar cells. Islet cell lesions were not apparent. There was pancreatic fibrosis and damage to blood vessels and ducts. Dose-response relationships were observed for the index of damage to the pancreas as a whole, for pancreatic fibrosis and a decrease in normal acinar cells. Although 25 Gy IORT plus 50 Gy EBRT was tolerated by the duodenum to 135 days, these doses may cause later pancreatic injury as an expression of damage to blood vessels and ducts. Exocrine pancreatic insufficiency and diabetes mellitus may thus represent potential late complications of IORT following 25 Gy or higher doses.

Animals↗