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S T Eisenman,
S J Gibbons,
R D Singh,
C E Bernard,
J Wu, M G Sarr,
M L Kendrick,
D W Larson,
E J Dozois,
K R Shen,
G Farrugia
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ABSTRACT: Identification of markers of enteric neurons has contributed substantially to our understanding of the development, normal physiology, and pathology of the gut. Previously identified markers of the enteric nervous system can be used to label all or most neuronal structures or for examining individual cells by labeling just the nucleus or cell body. Most of these markers are excellent but have some limitations. TMEM100 is a gene at locus 17q32 encoding a 134-amino acid protein with two hypothetical transmembrane domains. TMEM100 expression has not been reported in adult mammalian tissues but does appear in the ventral neural tube of embryonic mice and plays a role in signaling pathways associated with development of the enteric nervous system. We showed that TMEM100 messenger RNA is expressed in the gastrointestinal tract and demonstrated that TMEM100 is a membrane associated protein. Furthermore TMEM100 immunoreactivity was restricted to enteric neurons and vascular tissue in the muscularis propria of all regions of the mouse and human gastrointestinal tract. TMEM100 immunoreactivity colocalized with labeling for the pan-neuronal marker protein gene product 9.5 (PGP9.5) but not with the glial marker S100ß or Kit, a marker of interstitial cells of Cajal. The signaling molecule, bone morphogenetic protein (BMP) 4, was also expressed in enteric neurons of the human colon and co-localized with TMEM100. TMEM100 is also expressed in neuronal cell bodies and fibers in the mouse brain and dorsal root ganglia. We conclude that TMEM100 is a novel, membrane-associated marker for enteric nerves and is as effective as PGP9.5 for identifying neuronal structures in the gastrointestinal tract. The expression of TMEM100 in the enteric nervous system may reflect a role in the development and differentiation of cells through a transforming growth factor β, BMP or related signaling pathway.
Neuroscience 02/2013; · 3.38 Impact Factor
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ABSTRACT: Symptomatic gastroesophageal reflux disease is common in our experience after vertical banded gastroplasty. Our aim was to determine the safety and efficacy of Roux-en-Y gastric bypass in the treatment of symptomatic gastroesophageal reflux disease complicating vertical banded gastroplasty. We evaluated prospectively collected data on 25 patients who underwent revisional bariatric surgery because of severe gastroesophageal reflux disease after vertical banded gastroplasty. Only 4 of 25 patients had gastroesophageal reflux disease symptoms prior to vertical banded gastroplasty. Endoscopic findings in 24 patients included esophagitis (58%), Barrett's esophagus (28%), pouchitis (29%), and gastritis (21%);7 (28%) of 25 patients had evidence of stenosis at the pouch outlet. Mean follow-up (complete in all 25) after Roux-en-Y gastric bypass was 37 +/- 7 months (range 3 to 102 months). There were no deaths. Postoperative complications occurred in six patients: pneumonia in two, wound infection in two, prolonged drainage of the defunctionalized stomach via gastrostomy in one, and fever in one. Median hospitalization was 7 days (range 5 to 43 days). At follow-up (37 +/- 7 months), 24 (96%) of 25 are completely or almost completely symptom free. Body mass index was 33 +/- 2 kg/m(2) before and 28 +/- 2 kg/m(2) after Roux-en-Y gastric bypass (P = 0. 001). Symptoms of gastroesophageal reflux disease are common after vertical banded gastroplasty. Conversion to Roux-en-Y gastric bypass is safe, relieves gastroesophageal reflux disease, and promotes further weight loss. Moreover, maladaptive eating (vomiting, and so forth) induced by vertical banded gastroplasty is relieved.
Journal of Gastrointestinal Surgery 04/2012; 4(3):276-81. · 2.83 Impact Factor
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ABSTRACT: Net absorption of water, electrolytes, and simple nutrients decreases early after jejunoileal autotransplantation (extrinsic denervation) in a canine model but recovers toward normal by 8 weeks. However, the ability of the extrinsically denervated ileum to adapt after total jejunectomy, which would be relevant as a model of segmental small bowel transplantation, remains unknown. Two groups of five dogs each were studied before and 2 weeks and 12 weeks after 50% proximal enterectomy. A control group remained neurally intact, whereas the other group underwent extrinsic denervation (Ext Den) of the remaining ileum. Using a perfusion technique, net absorption of water, electrolytes, and five simple nutrients (glucose, arginine, glutamine, and oleic and taurocholic acids) was measured at the three time points. Ileal morphometry was also evaluated. All dogs developed diarrhea, which resolved by 12 weeks in all but two of the Ext Den dogs. Weight in both groups was decreased at 2 weeks (P <0.05), returned to normal at 12 weeks in control dogs, but remained low in Ext Den dogs (P <0.05). Maximal weight loss was greater in the Ext Den group (P <0.05). No consistent or important differences in net absorptive fluxes of water, electrolytes, or simple nutrients were noted either within or between groups at any time point. Villous height, crypt depth, and longitudinal muscle width increased significantly at 12 weeks after jejunectomy in the Ext Den dogs, but not in the control dogs (P <0.05). Extrinsic denervation of the ileum results in persistent weight loss after proximal 50% enterectomy. Despite diarrhea, only minor changes in electrolyte absorption occur, and ileal net absorption of simple nutrients remains unaffected. The ileum of extrinsically denervated dogs undergoes a more prominent morphometric adaptation after jejunectomy. Extrinsic denervation necessitated by small bowel transplantation, independent of immune effects, does not appear to suppress the ileal adaptive response to maintain net absorption of water, electrolytes, and simple nutrients.
Journal of Gastrointestinal Surgery 04/2012; 5(5):517-24. · 2.83 Impact Factor
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ABSTRACT: Our aim was to determine the effects of small bowel transplantation on contractility of longitudinal muscle in the rat ileum. Full-thickness longitudinal muscle strips from four groups of rats (naive controls, sham-operated controls, and 1 week and 8 weeks after syngeneic orthotopic small bowel transplantation) were studied in vitro. Neither baseline contractility nor response to neural blockade (tetrodotoxin) or adrenergic/cholinergic blockade differed among the groups. Although the dose response to the cholinergic agonist bethanechol and to nitric oxide did not differ among groups, the ED50 (negative log of concentration giving half-maximal effect) for the adrenergic agonist norepinephrine was increased l week and 8 weeks after transplantation, indicating a hypersensitivity response not blocked by tetrodotoxin. Nonadrenergic, noncholinergic inhibitory responses to electrical field stimulation were of greater amplitude and occurred at lesser frequencies (>/=5 Hz) 1 week after small bowel transplantation, but returned to control values 8 weeks postoperatively. These inhibitory responses were blocked by the nitric oxide synthase inhibitor L-NMMA but not by methylene blue, a nonspecific inhibitor of guanylate cyclase. Small bowel transplantation induces a persistent adrenergic denervation hypersensitivity at the muscle and appears to upregulate, at least transiently, other inhibitory mechanisms mediated by neural release of nitric oxide. Small bowel transplantation does not alter muscle response to cholinergic pathways. These alterations in smooth muscle contractility may affect gut function early after clinical small bowel transplantation.
Journal of Gastrointestinal Surgery 04/2012; 4(1):77-85. · 2.83 Impact Factor
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ABSTRACT: Obscure gastrointestinal bleeding remains a significant diagnostic challenge. Our aims were (1) to determine the efficacy of intraoperative enteroscopy (IOE) in identifying lesions responsible for obscure gastrointestinal bleeding and (2) to determine the outcome of patients after treatment of these lesions. We retrospectively reviewed all patients who underwent IOE for obscure gastrointestinal bleeding from 1992 to 1998. Patients were divided into those with overt and those with occult gastrointestinal bleeding. Follow-up was complete in 67 patients (96%), with a median of 32 months (range 1 to 91 months). Seventy patients (52 overt and 18 occult) underwent IOE after extensive preoperative evaluation. Median duration of bleeding was 12 months, requiring a median of 14 blood transfusions. Risk factors for bleeding were identified in 46 patients (61%). A lesion was identified and treated in 52 patients (74%)-39 in the overt group and 13 in the occult group. Lesions identified were vascular (54%), ulcerations (31%), tumors (11%), and small bowel diverticula (4%). Overall, 35 patients (52%) were found to have one or more lesions at IOE that were treated surgically and had no further bleeding. IOE, through a mid-small bowel enterotomy, has low morbidity and is effective in that it identified a treatable lesion in 74% of patients, which led to cure of bleeding in 52%.
Journal of Gastrointestinal Surgery 04/2012; 5(2):162-7. · 2.83 Impact Factor
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ABSTRACT: Duodenal carcinoid tumors are uncommon. It is not known whether they behave more like carcinoid tumors in the appendix (indolent course) or those in the ileum (often virulent)-crucial information for determining the need for radical resection. A retrospective review at our tertiary referral center (from 1976 to 1999) identified 27 patients with primary duodenal carcinoid lesions, excluding functional islet cell tumors. Endoscopic biopsy provided the diagnosis in 78% of patients. Treatment was by endoscopic excision (n = 11), transduodenal excision (n = 8), pancreaticoduodenectomy (n = 3), segmental distal duodenectomy (n = 2), or palliative operation (n = 2). One patient did not undergo operation because of comorbidity. Eighteen of 19 patients with tumors smaller than 2 cm remained disease free after local (endoscopic or transduodenal) excision. The exception was a patient with a small periampullary carcinoid lesion. In contrast, all four patients with carcinoid tumors 2 cm or larger who were resected for cure developed a recurrence (2 to 9 years postoperatively). We conclude that duodenal carcinoid tumors smaller than 2 cm may be excised locally; to ensure complete resection we recommend open transduodenal excision for tumors between 1 and 2 cm. Endoscopic follow-up is indicated. It is unclear whether patients with larger tumors benefit from more aggressive locoregional resection. Ampullary/periampullary carcinoid tumors should be considered separately, as their behavior is unpredictable.
Journal of Gastrointestinal Surgery 04/2012; 5(6):588-93. · 2.83 Impact Factor
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ABSTRACT: Previous studies suggest that nitric oxide synthase is upregulated after small bowel transplantation which may have implications in enteric dysfunction after small bowel transplantation. The aim of this study was to determine the role of nitric oxide in nonadrenergic, noncholinergic inhibitory function after small bowel transplantation in rat jejunal circular muscle. The following four groups of rats (n = >/=8 rats per group) were studied: Neurally intact control animals; 1 week after anesthesia and sham celiotomy, and either 1 week or 8 weeks after isogeneic, orthotopic small bowel transplantation. Full-thickness jejunal circular muscle strips were evaluated under isometric conditions for spontaneous contractile activity, response to electrical field stimulation, and effects of exogenous nitric oxide and nitric oxide antagonists. Spontaneous activity did not differ among groups. Electrical field stimulation inhibited activity similarly in all groups. Exogenous nitric oxide, NG-monomethyl L-arginine monoacetate salt (a nitric oxide synthase inhibitor), and methylene blue (cGMP antagonist) had no effect on spontaneous activity. Neither nitric oxide antagonist altered the inhibitory response to neural excitation by electrical field stimulation in any group. Nitric oxide, a known inhibitory neurotransmitter in other gut smooth muscle, has no apparent role in rat jejunal circular muscle before or after small bowel transplantation.
Journal of Gastrointestinal Surgery 04/2012; 4(1):86-92. · 2.83 Impact Factor
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ABSTRACT: Long-term follow-up (>10 years) after vertical banded gastroplasty (VBG) is almost nonexistent. The aim of this study was to determine long-term outcome after VBG in a group of 71 patients studied prospectively. Seventy-one consecutive patients with morbid obesity (54 women and 17 men; mean age 40 years [range 22 to 71 years]) underwent VBG from 1985 to 1989 and were followed prospectively. Follow-up was obtained in 70 (99%) of the 71 patients. Weight (mean +/- standard error of the mean) preoperatively was 138 +/- 3 kg and decreased to 108 +/- 2 kg 10 or more years postoperatively. Body mass index decreased from 49 +/-1 to 39 +/- 1. Only 14 (20%) of 70 patients lost and maintained the loss of at least half of their excess body weight with the VBG anatomy. Vomiting one or more times per week continues to occur in 21% and heartburn in 16%. Fourteen patients have undergone conversion from VBG to Roux-en-Y gastric bypass (11 patients) or other procedures (3 patients) because of a combination of inadequate weight loss in 13 patients, gastroesophageal reflux in five, and frequent vomiting in four. Only 26% of patients after VBG have maintained a weight loss of at least 50% of their excess body weight; 17% underwent bariatric reoperation with good results. Thus VBG is not an effective, durable bariatric operation.
Journal of Gastrointestinal Surgery 04/2012; 4(6):598-605. · 2.83 Impact Factor
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ABSTRACT: Benign villous tumors of the duodenum are often managed by transduodenal local excision. Risk of local recurrence, coupled with improving safety of radical pancreaticoduodenectomy, has prompted reexamination of the roles of conservative and radical operations. The aim of this study was to determine long-term outcome after local and extended resection in order to identify factors to consider in planning operative strategy. Eighty-six patients (mean age 64 years) with villous tumors of the duodenum managed surgically from 1980 to 1997 were reviewed. Histologic findings, size, presence of polyposis syndromes, and extent of resection were correlated with outcome. Villous tumors were benign adenomas in 64 patients (74%), contained carcinoma in situ in three (4%), and invasive carcinoma in 19 (22%). The presence of cancer was not known preoperatively in 9 (47%) of the 19 with invasive carcinoma. Operative treatment included transduodenal local excision in 53 patients, pancreaticoduodenectomy in 20, pancreas-sparing duodenectomy in five, full-thickness excision in four, and other in six. Among the 50 patients with benign tumors managed by local excision, 17 had a recurrence with actuarial rates of 32% at 5 years and 43% at 10 years; four of the recurrences (24%) were adenocarcinomas. The recurrence rate was influenced by the presence of a polyposis syndrome but not by tumor size. Recurrence of benign villous tumors after local excision is common and may be malignant. Pancreaticoduodenectomy is appropriate for villous tumors containing cancer and may be considered an alternative for select patients with benign villous tumors of the duodenum. If local excision is performed, regular postoperative endoscopic surveillance is mandatory.
Journal of Gastrointestinal Surgery 04/2012; 4(1):13-21, discussion 22-3. · 2.83 Impact Factor
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P J Gomez-Pinilla,
S J Gibbons, M G Sarr,
M L Kendrick,
K Robert Shen,
R R Cima,
E J Dozois,
D W Larson,
T Ordog,
M J Pozo,
G Farrugia
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ABSTRACT: Aging produces inevitable changes in the function of most organs including the gastrointestinal tract. Together with enteric nerves and smooth muscle cells, interstitial cells of Cajal (ICC) play a key role in the control of gastrointestinal motility, yet little is known about the effect of aging on ICC. The aim of this study was to determine the effect of aging on ICC number and volume in the human stomach and colon.
Gastric and colonic tissues from patients aged 25-70 and 36-92 years old, respectively, and with no co-existent motility disorders were immunolabeled with an anti-Kit antibody and ICC were counted in the circular muscle and myenteric regions. Network volumes were measured using 3D reconstructions of confocal stacks. The effects of aging were determined by testing for linear trends using regression analysis.
In both stomach and colon, the number of ICC bodies and volume significantly decreased with age at a rate of 13% per decade. ICC size was only affected in the myenteric plexus in the colon. The changes associated with age were not differentially affected by sex or colonic region.
The number and volume of ICC networks in the normal human stomach and colon decline with age. This decrease in ICC likely reduces the functional capacity of the gastrointestinal motor apparatus, may contribute to changes in gastrointestinal motility with aging and may influence intestinal responses to insults such as disease, operative interventions and medications in older patients. Tissue specimens must be carefully age-matched when studying ICC in disease.
Neurogastroenterology and Motility 01/2011; 23(1):36-44. · 3.41 Impact Factor
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ABSTRACT: Extrinsic denervation contributes to enteric motor dysfunction after small bowel transplantation (SBT). Our aim was to determine changes in nonadrenergic, noncholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P (Sub P) in rat jejunal circular muscle after SBT. Muscle strips were studied in tissue chambers from six groups of rats (n > or = 6 per group): naïve controls (NC), animals 1 week after anaesthesia/sham celiotomy (SC-1), and 1 and 8 weeks after jejunal and ileal transection/reanastomosis (TA-1, TA-8) and after syngeneic, orthotopic SBT (SBT-1, SBT-8). Response to exogenous VIP and Sub P and their endogenous release during electrical field stimulation (EFS) were studied. Exogenous VIP and Sub P caused a dose-dependent inhibition and stimulation of mechanical activity in all groups respectively (P < 0.05). The responses to VIP and Sub P were decreased (compared to NC) in all groups at 1 and 8 weeks postoperatively. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) did not prevent the inhibition by exogenous VIP in any group, while the Sub P antagonist ([D-Pro(2),D-Trp(7,9)]-Sub P) prevented the effect of exogenous Sub P in NC, TA-8 and SBT-8 (P < 0.05). Responses to exogenous VIP were unaffected by the nitric oxide synthase inhibitor l-N(G)-nitro arginine and precontraction of muscle strips with Sub P. Endogenous release of VIP and Sub P during EFS was preserved after SBT. In circular muscle of rat jejunum, changes in neuromuscular transmission with VIP and Sub P during the first 8 weeks after SBT are not mediated by extrinsic denervation.
Neurogastroenterology and Motility 08/2008; 20(7):808-17. · 3.41 Impact Factor
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ABSTRACT: Factors regulating the conversion of the interdigestive migrating motor complex (MMC) to postprandial patterns of motility are not completely understood. This study assessed the effects of varying rates of nonnutrient duodenal flow on patterns of interdigestive motility before and after abdominal vagotomy. Six neurally intact dogs were prepared with serosal intestinal electrodes and a duodenal infusion catheter. After recovery, the dogs were studied by infusing an isosmolar, noncaloric, balanced electrolyte solution at rates of 0, 3, 6, 9, or 12 ml/min for 5 hours into the proximal duodenum. With increasing rates of duodenal infusion, the duration of phase I decreased progressively (P < 0.05), while the period of the MMC remained unchanged. The MMC was eventually inhibited at rates of 9 or 12 ml/min with establishment of a pattern of intermittent spike activity. These findings were similar in 3 of these dogs after transthoracic total abdominal vagotomy. Our findings suggest that increases in duodenal infusion rate, independent of caloric or nutrient content, modulate patterns of intestinal motility during the postprandial period; this effect does not appear to be vagally mediated.
Neurogastroenterology and Motility 06/2008; 4(1):71 - 76. · 3.41 Impact Factor
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ABSTRACT: Motilin is a putative hormone which induces a premature migrating motor complex when administered exogenously, but the target organ for this hormonal effect is undetermined. Our aim was to determine whether motilin and the motilin agonist, erythromycin, induce a premature migrating motor complex via an effect directly on the stomach. Six dogs underwent splenectomy and ligation of all branches of the splenic artery except the left gastroepiploic and short gastric arteries to the proximal stomach. An intra-arterial catheter was placed in the proximal splenic artery for close intra-arterial injection of motilin and erythromycin directly to the gastric corpus/proximal antrum. After recovery, the minimum effective dose required to induce a premature migrating motor complex was determined for motilin and for erythromycin given close intra-arterially or intravenously (systemically) by monitoring upper gut myoelectric activity. Minimum effective doses of motilin and erythromycin were the same whether given intra-arterially or intravenously. The latency interval or the time to onset of a premature Phase III was less than 2 minutes for intra-arterial or intravenous administration (P > 0.05). The characteristics of induced-Phase HI activity (appearance, duration, velocity) did not differ from spontaneous Phase HI activity (P > 0.05). Although plasma motilin concentrations increased after threshold doses of both motilin and erythromycin, increases in plasma motilin occurred later after erythromycin (lOmin) than after exogenous motilin (3 min). Our findings suggest that motilin initiation of the migrating motor complex does not occur by independent stimulation of putative receptors in the gastric corpus or proximal antrum.
Neurogastroenterology and Motility 06/2008; 5(4):253 - 263. · 3.41 Impact Factor
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ABSTRACT: Intestinal denervation contributes to enteric motor dysfunction after intestinal transplantation [small bowel transplantation (SBT)]. Our aim was to determine long-term effects of extrinsic denervation on functional non-adrenergic, non-cholinergic innervation with vasoactive intestinal polypeptide (VIP) and substance P. Contractile activity of jejunal longitudinal muscle from six age-matched, naïve control rats (NC) and eight rats 1 year after syngeneic SBT were studied in tissue chambers. Spontaneous contractile activity did not differ between groups. Exogenous VIP inhibited contractile activity dose-dependently in both groups, greater in NC than in SBT. The VIP antagonist ([D-p-Cl-Phe(6),Leu(17)]-VIP) and the nitric oxide synthase inhibitor l-N(G)-nitro arginine prevented inhibition by exogenous VIP and electrical field stimulation (EFS) in both groups. Exogenous substance P increased contractile activity dose-dependently, greater in NC than in SBT. The substance P antagonist ([D-Pro(2),D-Trp(7,9)]-substance P) inhibited effects of exogenous substance P and increased the EFS-induced inhibitory response. Immunohistofluorescence showed staining for tyrosine hydroxylase in the jejunoileum 1 year after SBT suggesting sympathetic reinnervation. In rat jejunal longitudinal muscle after chronic denervation, response to exogenous VIP and substance P is decreased, while endogenous release of both neurotransmitters is preserved. These alterations in excitatory and inhibitory pathways occur despite extrinsic reinnervation and might contribute to enteric motor dysfunction after SBT.
Neurogastroenterology and Motility 04/2008; 20(3):243-52. · 3.41 Impact Factor
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ABSTRACT: A mechanosensitive Na(+) current carried by Na(v)1.5 is present in human intestinal circular smooth muscle and contributes to regulation of intestinal motor function. Expression of this channel in different species is unknown. Our aim was to determine if Na(+) currents and message for the alpha subunit of the Na(+) channel (SCN5A) are found in circular smooth muscle cells of human, dog, pig, mouse and guinea pig jejunum. Currents were recorded using patch clamp techniques. Message for SCN5A was investigated using laser capture microdissection and reverse transcription polymerase chain reaction (RT-PCR). Na(+) currents were identified consistently in human and dog smooth muscle cells; however, Na(+) current was not found in pig (0/20) or guinea pig smooth muscle cells (0/21) and found only one mouse cell (1/21). SCN5A mRNA was found in circular muscle of human, dog, and mouse, but not in pig or guinea pig, and not in mouse longitudinal or mucosal layers. In summary, SCN5A message is expressed in, and Na(+) current recorded from, circular muscle layer of human and dog but not from pig and guinea pig. These data show that there are species differences in expression of the SCN5A-encoded Na(v)1.5 channel, suggesting species-specific differences in the electrophysiological response to mechanical and depolarizing stimuli.
Neurogastroenterology and Motility 03/2007; 19(2):135-43. · 3.41 Impact Factor
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ABSTRACT: The safety and efficacy of bariatric surgery in adolescents and especially in Medicare population have been challenged. Our aim was to determine short-term (30-day) and long-term outcomes of bariatric surgery in patients>or=60 years and <or=18 years old. Query of our 20-year bariatric surgery database identified 155 patients>or=60 years and 12 patients<or=18 years. We determined morbidity and mortality rates and sent a questionnaire to all surviving patients; 127 of 139 survivors>or=60 years and all 12 adolescents returned the questionnaire (92%) at a mean of 5 years (range 1-19 years). For patients>or=60 years, 30-day mortality was 0.7%, serious morbidity delaying discharge was 14%, and 5-year mortality was 5%. At a mean of 5 years, body mass index (BMI in kg/m2) decreased from a mean (+/-SEM) of 46+/-1 to 33+/-1 with a 51% resolution of weight-related comorbidities and an 89% subjective overall satisfaction rate. In patients<or=18 years, all with serious comorbidities, there were no deaths and no serious complications. BMI decreased from 55 (range 39-74) to 36 (range 27-53) at 4 years (range 1-8 years). Resolution of weight-related comorbidities was 82%, and satisfaction with outcome was 83%. Thirty-day hospital mortality (<1%) and 5-year mortality (5%) were much lower than reported previously in the senior population, with acceptable morbidity and importantly, with satisfactory outcomes. Bariatric surgery is safe and effective at high volume centers for patients with morbid obesity at both extremes of age.
Journal of Gastrointestinal Surgery 12/2006; 10(10):1392-6. · 2.83 Impact Factor
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ABSTRACT: Solid pseudopapillary neoplasms of the pancreas are rare malignant lesions of the pancreas that typically occur in young women. Large series from any one centre are notably absent in the literature. The aim of this study was to determine long-term outcomes of operative therapy.
The records of all 14 patients diagnosed with pseudopapillary neoplasms of the pancreas over 17 years were reviewed.
Thirteen of the 14 patients were female and the mean age at diagnosis was 30 years. Solid pseudopapillary neoplasm was suspected in only half of these patients before operation. On computed tomography, ultrasonography and/or magnetic resonance imaging, three lesions were solid, three were largely cystic, and five had solid and cystic components. All 14 patients underwent surgical exploration and curative resections were possible in 13, including distal pancreatectomy in nine, pancreaticoduodenectomy in three and resection of a local intraperitoneal recurrence in one patient. After follow-up ranging from 3 months to 20 years, 12 patients were alive, including one who had undergone re-exploration and resection of local and subcutaneous recurrences 9 years previously.
Solid pseudopapillary neoplasm of the pancreas should be considered in the differential diagnosis of any solid or partly cystic pancreatic mass in women aged less than 35 years. An attempt at en bloc resection without formal lymphadenectomy should be undertaken, including resection of synchronous or metachronous distant metastases.
British Journal of Surgery 07/2006; 93(6):733-7. · 4.61 Impact Factor
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ABSTRACT: Otilonium bromide (OB) is used as an intestinal antispasmodic. The mechanism of action of OB is not completely understood. As Ca(2+) entry into intestinal smooth muscle is required to trigger contractile activity, our hypothesis was that OB blocked Ca(2+) entry through L-type Ca(2+) channels. Our aim was to determine the effects of OB on Ca(2+), Na(+) and K(+) ion channels in human jejunal circular smooth muscle cells and on L-type Ca(2+) channels expressed heterologously in HEK293 cells. Whole cell currents were recorded using standard patch clamp techniques. Otilonium bromide (0.09-9 micromol L(-1)) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, OB inhibited L-type Ca(2+) current by 25% at 0.9 micromol L(-1) and 90% at 9 micromol L(-1). Otilonium bromide had no effect on Na(+) or K(+) currents. In HEK293 cells, 1 micromol L(-1) OB significantly inhibited the expressed L-type Ca(2+) channels. Truncation of the alpha(1C) subunit C and N termini did not block the inhibitory effects of OB. Otilonium bromide inhibited Ca(2+) entry through L-type Ca(2+) at concentrations similar to intestinal tissue levels. This effect may underlie the observed muscle relaxant effects of the drug.
Neurogastroenterology and Motility 05/2004; 16(2):167-73. · 3.41 Impact Factor
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ABSTRACT: Chronic pancreatitis is known to be a risk factor for pancreatic cancer.
To identify patients who were diagnosed with pancreatic cancer after undergoing surgery for histologically documented chronic pancreatitis.
Records of 484 consecutive patients who underwent surgery for chronic pancreatitis from 1976 to 1997 were reviewed.
Pancreatic cancer was diagnosed after a mean of 3.4 years (range: 2 months-1 years) in 14 patients (2.9%). In four patients, pancreatic cancer became evident within 12 months of surgery for chronic pancreatitis, suggesting cancer was present at the original surgery. Cancer presented with recurrent or persistent pain, jaundice, and/or weight loss. Pancreatic resection was possible in eight patients, but in the others, the cancer was inoperable. There was one long-term survivor (alive 14 years postoperatively), but for theothers mean survival was 10 months (16 months after resection vs. 4 months for inoperable cancer).
Pancreatic malignancy should be suspected in patients who have had surgery for chronic pancreatitis when symptoms (such as recurrent pain, jaundice, weight loss, or anorexia) recur. Attempts at curative pancreatic resection are indicated and can offer palliation and the potential for a cure.
Digestive and Liver Disease 08/2003; 35(7):482-5. · 3.05 Impact Factor
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ABSTRACT: Paget's disease of the breast is a rare disorder of the nipple-areola complex often associated with an underlying in situ or invasive carcinoma. Eczematoid changes of the nipple-areola complex and persistent soreness or itching should raise suspicion of this disease. The histogenesis of Paget's disease of the breast continues to be debated and is important when considering treatment options. The epidermotropic theory suggests that Paget's cells are ductal carcinoma cells that have migrated from an underlying carcinoma of the breast parenchyma to the epidermis of the nipple. The in situ transformation theory has been proposed to explain the development of this disorder in patients in whom an underlying mammary carcinoma is not found or when there is an underlying carcinoma anatomically remote from the nipple-areola complex. Paget's cells are believed to arise as malignant cells in the epidermis of the nipple independent from any other pathologic process within the breast parenchyma. The current standard treatment of biopsy-proven Paget's disease involves mastectomy, although some studies have proposed the use of breast conservation therapy for patients in whom an underlying breast cancer cannot be located. We propose a treatment algorithm for patients presenting with Paget's disease of the breast.
Langenbeck s Archives of Surgery 12/2001; 386(6):444-50. · 1.81 Impact Factor
