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Biomedical subjects

S J Lanspa

Publications and source records attributed to S J Lanspa.

At least 19 recordsLinked to original sources
PubMed2001

Mouth to pouch transit after restorative proctocolectomy: hydrogen breath analysis correlates with scintigraphy.

OBJECTIVES: Fast intestinal transit may be responsible for slow adaptation and unacceptable steady-state function after restorative proctocolectomy. Investigation of GI transit time may be valuable in such a setting. We hypothesized that postprandial hydrogen breath tests may yield transit data that correlate with technetium-labeled meal scintigrams. METHODS: This study compared intestinal transit after a lactulose and bean meal via the breath hydrogen and scintigraphy methods in 21 ileoanal pouch subjects. The meal consisted of baked beans (425 g), 30 ml (20 g) lactulose syrup, 1 mCi 99mtechnetium sulfur colloid in finely chopped liver and 170 ml tap water. The meal contained 120 Kcal (70% carbohydrate, 18% protein and 12% fat). RESULTS: Of 21 pouch subjects, 11 (53%) had breath tests and scintigraphy transit studies that differed by 5-21 min. Three of 21 (14%) scintigraphy mouth to pouch transit times were faster than breath test transits by 43-107 min. Seven of 21 (33%) subjects did not have breath test peaks >10 ppm. Mouth to pouch transit for breath hydrogen (104+/-16 min) and scintigraphy (98+/-7 min) tests had significant correlation (r = 0.96, p < 0.0001) among subjects with alveolar hydrogen peaks and accurate scintigrams (n = 11). Scintigrams were five times more expensive than breath tests. CONCLUSIONS: A peaking hydrogen breath test provides an alternative to scintigraphy for estimating intestinal transit after ileoanal pouch.

Adult↗
PubMed1998

Ileoanal pouch function and release of peptide YY.

PURPOSE: This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS: Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS: Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS: Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

Adolescent↗
PubMed1998

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.

PURPOSE: This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population. METHODS: Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P < 0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P = 0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P = 0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P = 0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P = 0.009 stage stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Heller myotomy is superior to dilatation for the treatment of early achalasia.

OBJECTIVES: To study the pretreatment characteristics that predispose a patient to rupture and to compare the outcome after dilatation with the outcome after surgical myotomy. DESIGN: A survey of all patients treated for achalasia at the Creighton University Medical Center, Omaha, Neb, during a 16-year period. Clinical examination and testing of consenting patients at 12 months and longer after treatment. SETTING: Tertiary referral center. PATIENTS: Of the 61 patients, 55 were treated with dilatation. Esophageal rupture developed in 8 patients (14.5%) with achalasia after pneumatic dilatation; these patients underwent surgery for the rupture. Dilatation failed in 8 other patients; these patients underwent a surgical myotomy. Six patients underwent a primary surgical myotomy. MAIN OUTCOME MEASURES: Duration of symptoms, weight loss, lower esophageal sphincter resting pressure and relaxation, amplitude and quality of distal esophageal contractions (assessed by manometry), 24-hour esophageal pH, and maximal esophageal diameter (assessed by barium swallow examination). RESULTS: Surgical myotomy at a mean (+/-SEM) of 44.9 +/- 18.6 months alleviated dysphagia in 13 (93%) of the 14 patients compared with only 12 (39%) of the 31 patients after dilatation at a mean (+/-SEM) of 55.0 +/- 11.7 months (P < .001). Of the 14 patients who underwent surgical myotomy, 13 (93%) were able to return to a normal diet compared with only 2 (7%) of the 31 patients who underwent dilatation (P < .001). Compared with patients without perforations, patients with perforations after pneumatic dilatation had pretreatment characteristics consistent with "early" disease: shorter symptom duration (20.1 +/- 5.4 vs 68.9 +/- 4.9 months, P < .001), less weight loss (4.7 +/- 1.2 vs 10.3 +/- 0.8 kg, P < .001), a less dilated esophagus (24.0 +/- 1.8 vs 45.6 +/- 3.0 mm, P < .005), lower lower esophageal sphincter resting pressures (19.3 +/- 2.6 vs 34.2 +/- 1.3 mm Hg, P < .001), a greater percentage of lower esophageal sphincter relaxation (47.6% +/- 4.9% vs 20.7% +/- 2.1%, P < .001), and a lower percentage of synchronous contractions in the distal esophageal body (66.2% +/- 4.9% vs 85.3% +/- 2.3%, P < .005). (All data given as the mean [+/-SEM].) All patients with pneumatic perforations were successfully treated by thoracotomy and surgical repair. CONCLUSIONS: Surgical myotomy provides a better long-term outcome. The early disease stage is associated with perforation after pneumatic dilatation. Surgical myotomy rather than balloon dilatation should be considered in patients with early achalasia.

Adult↗
PubMed1997

Effect of vitamin D receptor genotypes on calcium absorption, duodenal vitamin D receptor concentration, and serum 1,25 dihydroxyvitamin D levels in normal women.

It is well established that bone mineral density is under strong genetic control. Recently it was reported that the Bsm I restriction fragment length polymorphism of the vitamin D receptor (VDR) gene could account for up to 75% of the genetic variance in bone mineral density. However, the physiological basis for such an effect has not been established. The VDR gene codes for the vitamin D receptor protein which regulates intestinal calcium absorption. In order to assess the biochemical basis we studied the effect of common allelic variation of the VDR gene on intestinal VDR protein concentration, calcium absorption, and serum 1,25 dihydroxyvitamin D (1,25(OH)2D). Ninety-two Caucasian women were genotyped for Bsm I and Taq I polymorphism at the VDR gene locus. From these we compared 49 young women aged 25-35 years and 43 elderly women aged 65-83 years, who had all three measurements performed. There were no significant differences in intestinal VDR protein concentration, serum 1, 25(OH)2D, or radioactive calcium absorption among VDR genotype groups. Therefore, the small intestine does not seem to be a target for VDR gene polymorphism.

Absorption↗
PubMed1997

Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Decision Making↗
PubMed1997

Association between intestinal vitamin D receptor, calcium absorption, and serum 1,25 dihydroxyvitamin D in normal young and elderly women.

The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty-nine young women age 25-35 years were compared with 41 elderly women age 65-83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25-hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12-30% of the variance in the age-related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.

Adult↗
PubMed1995

An investigation of sources of variation in calcium absorption efficiency.

To examine putative sources of interindividual variation in calcium absorption efficiency, we studied 41 healthy premenopausal women (mean age, 36.4 yr). About half were randomized to pretreatment with supplemental 25-hydroxyvitamin D (25OHD; 20 micrograms/day [corrected] for approximately 34 days) before testing. We measured dietary factors, humoral regulators, intestinal motility, mucosal histology, mucosal vitamin D receptor levels, and calcium absorption efficiency. In winter tests, but not in summer tests, calcium absorption fraction was significantly higher in the pretreated group (mean, 0.465 vs. 0.387). Serum 25OHD, intestinal transit, and urinary calcium to creatinine ratio were all significantly and positively correlated to calcium absorption efficiency. However, neither the level of 1,25-dihydroxyvitamin D receptors in duodenal mucosa nor circulating 1,25-dihydroxyvitamin D was related to calcium absorption efficiency. These findings, which are consistent with other published human data, suggest that 25OHD plays a more prominent role in the regulation of calcium absorption than is generally believed. In a multiple regression model, serum 25OHD, mouth to cecum transit time, and fasting urinary calcium/creatinine ratio explained 44% of the observed variation in calcium absorption efficiency.

Absorption↗
PubMed1994

Surveillance in Lynch syndrome: how aggressive?

OBJECTIVE: To identify colorectal cancers occurring after colonoscopic screening in patients at risk for Lynch syndrome. METHODS: All cancers in Lynch syndrome families on file at the Creighton University Hereditary Cancer Institute were reviewed for history of prior colonoscopy. RESULTS: Of 225 individuals with 313 colon cancers, six patients from different families had colon cancers arising within 4 1/2 yr of colonoscopic surveillance. Another 17 patients had metachronous colon cancers within 5 yr of resection of their first colon cancer. CONCLUSION: Of 225 colorectal cancer patients from Lynch syndrome families, 10.2% of patients had colorectal cancer within 5 yr of colonoscopy or colon resection. In Lynch syndrome, the potential for interval neoplasms and the malignant potential of missed diminutive adenomas may differ from cases in the general population.

Adult↗
PubMed1993

Upper gastrointestinal manifestations in families with hereditary flat adenoma syndrome.

BACKGROUND: The hereditary flat adenoma syndrome (HFAS) is characterized by an autosomal dominantly inherited predisposition to multiple colonic adenomas (usually less than 100) with proximal predominance and flat as opposed to polypoid growth. Patients with the syndrome experience colorectal cancers in excess, and the lesions are distributed randomly in the colon. The polyps occur at a later age (median, 55 years) compared with age at onset of polyps in patients with familial adenomatous polyposis (FAP) and patients with the Lynch syndromes. FAP and HFAS are linked to the same locus on chromosome 5q21-q22. METHODS: Upper endoscopic examination was performed on 22 relatives from four families with HFAS. RESULTS: Fifteen patients from three of these families had multiple fundic gland polyps; four had duodenal or gastric adenomas. Periampullary carcinoma was present in two members from separate families. CONCLUSIONS: The authors conclude that the upper gastrointestinal tract pathologic characteristics of HFAS are similar to those described in FAP. Thus, those at risk for HFAS require upper endoscopic screening in addition to meticulous attention to the colon.

Adenocarcinoma↗
PubMed1993

Cancer control problems in the Lynch syndromes.

The Lynch syndromes account for about 4 to 6 percent of the total colorectal cancer (CRC) burden. Despite more than two decades of documentation in the literature, many physicians fail to recognize the clinical features of these syndromes. The lack of premonitory physical stigmata, coupled with the absence of a biomarker of cancer susceptibility, mandates full reliance on a well-orchestrated family history for diagnosis. These deficiencies impede cancer control. Even if the diagnosis is made, proper surveillance and management measures that are responsive to the Lynch syndromes' natural history may fail to be implemented. We describe CRC occurrences in patients from four extended Lynch syndrome kindreds. Failures in cancer control were attributable to poor patient compliance and/or to limited physician knowledge about the natural history and surveillance recommendations for the Lynch syndromes. Physicians need to more effectively educate their high-risk patients about the significance of genetic risk, the natural history of CRC, and the appropriate surveillance strategies in the Lynch syndromes.

Adolescent↗
PubMed1993

Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review.

Hereditary nonpolyposis colorectal cancer (HNPCC) dates to Warthin's description of family G, which he began studying in 1895. Warthin's observations were not fully appreciated until 1966 when two families with an autosomal dominant inheritance pattern of nonpolyposis colorectal cancer (CRC) and endometrial cancer were described. This condition was first termed the "cancer family syndrome" and was later renamed HNPCC. Some have proposed that HNPCC consists of at least two syndromes: Lynch syndrome I, with hereditary predisposition for CRC having early (approximately 44 years) age of onset, a proclivity (70%) for the proximal colon, and an excess of synchronous and metachronous colonic cancers and Lynch syndrome II, featuring a similar colonic phenotype accompanied by a high risk for carcinoma of the endometrium. Transitional cell carcinoma of the ureter and renal pelvis and carcinomas of the stomach, small bowel, ovary, and pancreas also afflict some families. Current estimates indicate that HNPCC may account for as much as 6% of the total CRC burden. There are no known premonitory phenotypic signs or biomarkers of cancer susceptibility in the Lynch syndromes. This report will summarize current knowledge, with emphasis on the manner in which this knowledge can be employed effectively for diagnosis and management of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1992

Measurement of T-kinin in rat plasma using a specific radioimmunoassay.

T-kinin (Ile-Ser-Bradykinin) has been isolated only from the plasma of the rat and it is unclear whether the peptide, or its biosynthetic precursor, T-kininogen, circulates in the human. An NH2-terminally directed antiserum to T-kinin was raised in rabbits using an immunogen prepared by coupling the free -SH group of T-kinin extended from its COOH-terminus by a cysteinyl residue to an -NH2 group on human serum albumin. A radioimmunoassay was developed using this antiserum and 125I-labelled [Tyr10]T-kinin as tracer that was sensitive (least-detectable concentration 3 fmol/tube) and relatively specific for T-kinin (cross-reactivity with bradykinin and kallidin less than 1%). Treatment of rat plasma with an excess of trypsin in the presence of a kininase inhibitor generated T-kinin immunoreactivity equivalent to 455 +/- 71 pmol/ml (mean +/- S.E.M.; n = 9) and this immunoreactivity was eluted from a reversed-phase HPLC column as a single peak with the same retention time as synthetic T-kinin. In contrast, treatment of plasma from healthy human subjects (n = 8) and from patients (n = 8) with inflammation due to acute or chronic gastrointestinal disease under the same conditions did not generate any detectable T-kinin immunoreactivity. It is concluded, therefore, that T-kininogen, the biosynthetic precursor of T-kinin in the rat, is either absent from the plasma of human subjects or is present in a concentration less than 30 fmol/ml. Similarly, T-kininogen is probably not an acute phase reactant in humans.

Adult↗
PubMed1992

Colon cancer genetics.

The terms "hereditary," "sporadic," and "familial" colorectal cancer (CRC) suggest a knowledge of causation; however, current understanding of CRC does not permit categorization of differing CRC risks in accord with their cause per se. Despite these serious shortcomings, these terms are defined operationally on the basis of a family history of cancer, and when available, additional phenotypic information. The sporadic type occurs in the absence of a family history of CRC in a first-degree relative. The familial type occurs when at least one first-degree relative has CRC. Both these categories require the exclusion of hereditary CRC. In the case of hereditary CRC, this type is defined as a family history of CRC occurring in a pattern that indicates autosomal-dominant inheritance, which also may involve certain phenotypic signs (depending on the specific disorder, i.e., florid adenomatous polyps, benign and malignant extracolonic lesions, cancer of unusually early onset, and multiple primary cancer, particularly synchronous and metachronous CRC). Although this operational classification does not produce etiologically homogeneous groups, it is believed to have pragmatic utility with respect to planning targeted surveillance and management strategies. Because of the distinctive natural history of CRC in hereditary syndromes, it is of paramount clinical importance to identify hereditary CRC when it does occur. Even in patients with no evidence of hereditary CRC syndrome, their family history may be second only to age in determining the best CRC screening program for those who are asymptomatic. In an attempt to provide a perspective on the clinical evaluation of CRC risk, research was reviewed on pathologic features and biomarkers that may be related to CRC causes, especially the genetic basis of CRC susceptibility. The long-term objective of studies on the genetic epidemiology of CRC is primary and secondary prevention through development of targeted management and surveillance recommendations (based on an understanding of CRC causation) that is relevant to hereditary, familial, and sporadic CRC.

Adult↗
PubMed1992

Hereditary flat adenoma syndrome: a variant of familial adenomatous polyposis?

We describe the clinical and pathologic features in four extended kindreds that are consistent with the hereditary flat adenoma syndrome (HFAS). This colon cancer susceptibility disorder is believed to be inherited as an autosomal dominant. The principal phenotypic marker is multiple colonic adenomas (usually less than 100), with a tendency for proximal location. The majority of these adenomas are flat or slightly raised and plaquelike, as opposed to polypoid. Colon cancers have typically developed in middle age and show no unusual histologic features. There are a variety of extracolonic manifestations, including adenomas and carcinomas of the small bowel and fundic gland polyps. The HFAS is contrasted with hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis (FAP) and shown to be distinct from both in the numbers and distribution of colonic adenomas and the typical age of cancer diagnosis. The clinical implications of these findings are discussed. Given its linkage to the FAP locus on 5q and the phenotypic parallels between HFAS and FAP, we conclude that HFAS is a variant of FAP.

Adenoma↗
PubMed1992

Epidemiologic characteristics of the flat adenoma of Muto. A prospective study.

UNLABELLED: The flat adenoma is an endoscopically visible lesion that histologically consists of adenomatous change near the luminal surface of colonic tubules. We have described three families with hereditary colon cancer with later age of onset than familial adenomatous polyposis (FAP) and with multiple proximal colonic flat adenomas. These families have been linked to the FAP locus on chromosome 5. Our aim was to determine whether the flat adenoma is pathognomonic of this hereditary flat adenoma syndrome (HFAS) or merely an atypical or early tubular adenoma with occurrence in patients other than those from colon cancer-prone families. METHODS: We prospectively examined a population referred for colonoscopy within a one-year period. During colonoscopy, flat adenomas were specifically sought and all lesions were removed endoscopically and evaluated histologically. Members of known hereditary colon cancer families were excluded. RESULTS: One hundred forty-eight patients underwent colonoscopy (64 men and 84 women). Median age was 61 years. Fifty-seven patients had 157 polyps. One hundred thirty-six polyps were reviewed histologically. Thirty-five (23.6 percent) of the referred patients had adenomas, of whom twelve patients had only flat adenomas while six had both flat and other adenomas (18 = 12 percent of 148). The associations between flat adenoma occurrence and various predictors (sex, race, prior colonic neoplasms, family history of cancer, synchronous adenomas) were similar to those seen with other adenomas. Flat adenomas were found in nearly equal proportions of patients under or over age 61 years (11 percent and 13 percent, respectively). Other adenomas were significantly more common in the older group (6 percent vs. 25 percent; P less than 0.002 by Fisher's exact test). CONCLUSION: In a referral practice, the flat adenoma has the same prevalence and associated risk factors as other adenomas, except for younger age of onset. Our data suggest that the flat adenoma represents an early stage of adenoma development that is manifested in a subset of patients from the general population and that, as an isolated event, does not provide a marker for a hereditary colon cancer-prone syndrome.

Adenoma↗
PubMed1992

Natural history of at-risk Lynch syndrome family members with respect to adenomas.

UNLABELLED: Our goal is to determine colon cancer surveillance strategy in patients at risk for Lynch's syndrome. Asymptomatic persons at 50% risk of having Lynch syndrome (age 25-70 years) were enrolled in colonoscopic screening. Those without adenomas were asked to return in one year. Those with adenomas were asked to return in six months because of concern for rapid malignant degeneration. RESULTS: Twenty-five males and thirty females participated. On initial exam, eight of fifty-five patients (14.5%) had adenomas. Logistic regression showed a significant effect of age on the probability of finding adenomas at initial examination (p < 0.02). Followup was available in 27 patients (mean 35.5 months). Kaplan-Meier estimation of time to finding new or previously missed adenomas was 58 months for patients clear on first colonoscopy and 16 months for patients who had adenomas on first exam (p < 0.01). One adenocarcinoma has been found arising in a tubulovillous adenoma. CONCLUSION: The short-term risk of colorectal cancer in Lynch syndrome relatives without adenomas is low, as is the risk in those who have had all visualized adenomas removed.

Adenoma↗