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Background Ulcerative colitis (UC) is an inflammatory bowel disease with an estimated prevalence of 181 cases per 100,000 adults in the USA. Hispanic or Latino individuals comprise 19% of the US population and 24% of individuals are races other than White; however, the efficacy and safety of advanced therapies for UC in these populations remains uncertain because of their underrepresentation in clinical trials. Underrepresentation has the potential to bias evidence towards therapies with understudied efficacy and safety in minority ethnic and racial groups. This post hoc analysis used pooled clinical trial data of advanced therapies in patients with UC stratified by ethnicity and race in order to identify differential efficacy and safety outcomes among the populations investigated. Methods GEMINI 1, VARSITY, and VISIBLE 1 were phase 3 or 3b clinical trials investigating vedolizumab (intravenous or subcutaneous) versus placebo or adalimumab in patients with moderately to severely active UC. Data from these trials were pooled to create three cohorts of patients who received adalimumab, vedolizumab, or placebo. The number and proportion of patients with each efficacy and safety outcome at week 52 were reported for each of the treatment cohorts, stratified by ethnicity and race. Ethnicity and race were self-reported in the three trials. Results Overall, 1,358 patients were included in the pooled treatment cohorts. Of the 465 patients with available ethnicity information, only 40 patients (8.6%) reported their ethnicity as Hispanic or Latino. Efficacy and safety outcomes were similar when stratified by ethnicity with some exceptions (Table 1). When stratified by race, efficacy and safety outcomes were similar among White and Asian patients (Table 2). In the vedolizumab cohort, 47.3% and 47.1% of White and Asian patients, respectively, had mucosal healing. Some differences were observed in the efficacy and safety outcomes of Black patients compared with White and Asian patients; however, the treatment cohorts included fewer than 10 Black patients. Conclusion In the GEMINI 1, VARSITY, and VISIBLE 1 trials, efficacy and safety outcomes were similar among racial and ethnic groups, with the exception of Black patients. However, this analysis was limited by the small sample size of patients of races other than White, as well as the limited availability of ethnicity information, which prevented robust comparisons of outcomes between patients of different ethnicities and races. Future clinical trials of advanced therapies should aim to recruit and report a diverse patient population with UC who are representative of the patients who will receive these treatments.

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Data from OCTAVE Induction 1&2 and OCTAVE Sustain demonstrated that a history of extraintestinal manifestations (EIMs) was shown not to influence the efficacy of tofacitinib 10 mg twice daily (BID).1 We explored the efficacy and safety of tofacitinib in patients (pts) with and without a history of EIMs in the open-label, long-term extension study, OCTAVE Open. Methods Efficacy and safety (treatment-emergent serious adverse events of interest) data from OCTAVE Open (NCT01470612) were analysed by history of EIMs. Tofacitinib dose in OCTAVE Open was based on baseline remission status; pts in remission received tofacitinib 5 mg BID; all others received 10 mg BID. The frequency of pre-defined prior and active EIMs at OCTAVE Open baseline (peripheral arthritis [PA]; sacroiliitis; ankylosing spondylitis [AS]; myopathy; pyoderma gangrenosum; erythema nodosum; scleritis, episcleritis; uveitis, iritis; oral ulcer/stomatitis; and thromboembolic disorder) and new occurrences of EIMs at Month (M)36, or at early termination, were evaluated in pts with non-missing data. Results In OCTAVE Open, 113/935 (12.1%) had EIMs at baseline (7/174 [4.0%] tofacitinib 5 mg BID; 106/761 [13.9%] tofacitinib 10 mg BID). Pts with EIMs were more likely to be female (61.1%), have a total Mayo score of ≥3 (93.8%) at OCTAVE Open baseline and have disease duration ≥6 years (60.2%), prior tumour necrosis factor inhibitor failure (61.9%), prior immunosuppressant treatment (86.7%) or corticosteroid use (54.0%) at induction study baseline, compared to those without EIMs (38.8%, 78.7%, 49.6%, 50.9%, 74.5% and 43.9%, respectively). There was no consistent trend in the proportions of pts with and without EIMs at baseline who met the OCTAVE Open efficacy endpoints (Table 1). Tofacitinib 5 and 10 mg BID had comparable safety in pts with or without EIMs at baseline (Table 2). In pts with EIMs at baseline, the most frequent active EIMs were PA (51/113 [45.1%]), sacroiliitis (6/113 [5.3%]), oral ulcer/stomatitis (5/113 [4.4%]), myopathy (4/113 [3.5%]) and AS (4/113 [3.5%]). At M36, 4/428 [0.9%] had new occurrences of PA and there were no new occurrences of sacroiliitis (0/468 [0%]), oral ulcer/stomatitis (0/460 [0%]), myopathy (0/469 [0%]) or AS (0/469 [0%]). Conclusion The presence or absence of a history of EIMs at baseline did not impact the long-term efficacy and safety of tofacitinib in pts with UC. New occurrences of EIMs were infrequent. Reference 1. Rubin DT et al. Therap Adv Gastroenterol 2021; 14: 1–12.

Postoperative recurrence of Crohn's disease in adults has been extensively studied; however, the course of Crohn's disease after surgery in children has not been well defined. The aim of this study was to examine the postoperative course of pediatric Crohn's disease and the factors that may predict early postoperative recurrence.We identified 100 resective surgeries in 79 children with Crohn's disease seen at the Children's Hospital of Philadelphia between 1978 and 1996. A retrospective, multivariable analysis of factors potentially influencing postoperative clinical recurrence was performed. Preoperative and postoperative height measurements were compared, and z scores were computed for height-for-age. Two-tailed t test was used for the analysis.Clinical recurrence rates were 17% at 1 yr, 38% at 3 yr, and 60% at 5 yr. Patients with colonic Crohn's disease had a significantly shorter postoperative recurrence-free interval (median 1.2 yr) than patients with ileocecal (median 4.4 yr) or diffuse disease (median 3.0 yr) (p = 0.01). On multivariable analysis, a high Pediatric Crohn's Disease Activity Index at the time of surgery (p = 0.01) and preoperative use of 6-mercaptopurine (6-MP) (p0.005) were also independently associated with higher postoperative recurrence rates. There was a significant improvement in z scores for height (p = 0.04) after surgery.In children undergoing resective surgery for Crohn's disease, high rates of postoperative Crohn's disease recurrence are associated with severe disease at the time of surgery, colonic Crohn's disease, and the preoperative use of 6-MP. Patients who require preoperative use of 6-MP are likely to suffer from a more aggressive disease and would benefit from postoperative 6-MP prophylaxis. Height growth was improved after intestinal resection for Crohn's disease.

Interleukin-8 (IL-8) is a chemotactic cytokine (chemokine), which both attracts and activates granulocytes. IL-8 could have a central function in the initiation and perpetuation of the inflammatory bowel diseases (IBD), due to its relative resistance to inactivation and long half-life in vivo. Using a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay, we have observed elevated levels of IL-8 mRNA in colonic mucosal sections obtained from surgically resected specimens from ulcerative colitis (UC) and Crohn's disease (CD) patients with actively inflamed mucosa. The level of IL-8 mRNA expression in the intestinal mucosal biopsies from UC and CD patients was much greater in involved as opposed to noninvolved mucosal sections. The highest expression of IL-8 mRNA detected by RT-PCR was in UC mucosa and in isolated intestinal epithelial cells from UC patients. Increased IL-8 production by cells in IBD intestinal mucosa as well as IBD epithelial cells may be involved in the continuous attraction and activation of granulocytes in the inflamed intestine in both UC and CD patients. Chemokines, such as IL-8, are potent chemoattractant molecules and may have a central role in the augmentation and perpetuation of inflammation in IBD.

Rapid resolution of symptoms and endoscopic inflammation in ulcerative colitis (UC) represent important treatment goals.To establish times to bleeding cessation and endoscopic healing for topical and oral mesalazine in active distal UC, a post hoc analysis of two published studies was performed.Study I (Sutherland 1987) compared mesalazine rectal suspension to placebo, while Study II (Safdi 1997) compared topical suspensions, either alone or in combination with oral mesalazine, and oral alone. Cessation of rectal bleeding (RB) was defined as absence of bleeding on four consecutive days. Endoscopic remission was defined as DAI mucosal healing (MH) subscore=0 and clinical remission as MH subscore =0-1 and ≥ 1-point improvement, plus RB subscore = 0.Study I: By Day 2, 31.4% of subjects using topical monotherapy reported no RB vs. 5.5% in the placebo arm (P0.0006); median time to RB cessation was 8 days. Significantly higher rates of endoscopic (25.0% vs. 7.8%, P0.005) and clinical remission (48.6% vs. 9.6%, P0.0001) were observed at Week 3. Study II: A significantly higher proportion of subjects achieved RB cessation with combination therapy vs. oral therapy, commencing by Day 8. By Week 3, a significantly higher proportion of subjects using combination therapy achieved clinical remission compared to oral therapy alone (57.9% vs. 18.2%, P0.05).Topical mesalazine suspension, either alone or in combination with oral mesalazine, led to earlier rectal bleeding cessation and mucosal healing. These data support use of topical therapy for more rapid treatment benefit in active distal ulcerative colitis.

The use of topical therapy in the treatment of ulcerative colitis has declined in recent years despite evidence of good efficacy.To review US prescription trends for 5-aminosalicylic acid (5-ASA) since the US approval of Asacol extended-release oral mesalazine (mesalamine) in 1992; to estimate the optimal level of 5-ASA exposure in the distal colon; to determine factors influencing distal colonic exposures; and to compare the effectiveness of different 5-ASA formulations (oral, topical suspension, foam, suppositories) in clinical trials.Review of clinical trials, physiologic studies and prescription trends of various mesalazine formulations for treatment of distal ulcerative colitis.Between 1992 and 2009, prescriptions for oral mesalazine increased sixfold, whereas topical suspensions declined by 10%. In clinical trials, topical therapy resulted in higher remission and clinical response rates than oral therapy, with trends to earlier improvement. The mucosal concentrations of 5-ASA achieved by topical agents in the distal colon were up to 200-fold higher than those achieved by oral administration alone. Despite active colitis, over 40% of a topically administered 4 g 5-ASA suspension (equal to 1.6 g) reached the sigmoid colon. This likely represents a therapeutic exposure of 5-ASA. Although topical therapies are less convenient than oral medications, treatment algorithms have failed to take into account quality of life improvements resulting from more rapid and complete treatment response.Topical mesalazine therapy is superior to oral therapy in distal ulcerative colitis for both therapeutic response and drug delivery. Practice patterns should be re-evaluated in light of this information.

Recent studies have focused on the importance of mucosal healing in ulcerative colitis (UC). However, it was still unclear whether higher doses of delayed-release mesalazine (mesalamine) could provide additional benefit.To examine how two doses of delayed-release mesalazine (4.8 g/day and 2.4 g/day) from ASCEND I and II compare in their relative ability to heal colonic mucosa over time.Primary data from two prospective 6-week, double-blind, randomised studies in patients with mildly to moderately active UC were pooled and analysed retrospectively. The mucosal healing analysis focuses on moderately active UC patients (n=391), comprising a majority of patients (84%). Additional analyses examined the relationship between mucosal healing and dose, clinical response to therapy and patient quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ).At week 3, mucosal healing (endoscopy subscore of 0 or 1) was achieved in 65% of moderately active UC patients on 4.8 g/day and 58% of patients on 2.4 g/day (P=0.219). At week 6, this increased to 80% for 4.8 g/day and 68% for 2.4 g/day (P=0.012). Healing rates with the higher dose were also greater across all extents of disease and in patients with prior steroid use. At 6 weeks, clinical response to therapy and mucosal healing were found to be well correlated (kappa=0.694). Likewise, the change in IBDQ at week 6 showed a significant relationship with mucosal healing (P0.0001).Mucosal healing rates in UC achieved at 6 weeks were statistically significantly higher with delayed-release mesalazine at 4.8 g/day vs. 2.4 g/day.

Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder.To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC.Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare.The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups.Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology associated with dysregulation of the gastrointestinal mucosal immune system. It is characterized by a waxing and waning course and approximately 15% of UC patients will experience a severe episode. The first line treatment for severe colitis includes IV corticosteroids, however, 40% of patients are non-responsive to corticosteroid therapy and may require either colectomy, intravenous infliximab or intravenous cyclosporine within 3-5 days of presentation. This review focuses on the management and treatment approaches to refractory UC.

Patients with Crohn's disease alternate between periods of active, symptomatic disease and periods of remission. The treatment goal for Crohn's disease is to induce and then maintain remission of symptoms.To review evidence from randomized, controlled, clinical trials on medical therapies for inducing and maintaining remission in patients with mild-to-moderate Crohn's disease, and to suggest the best evidence-based approaches for induction and maintenance therapies.PubMed search using the following terms: sulfasalazine or salicylazosulfapyridine or aminosalicylate or aminosalicylic acid or mesalamine or mesalazine or corticosteroid or prednisone or prednisolone or methylprednisolone or budesonide or antibiotic or metronidazole or ciprofloxacin or immunosuppressive or azathioprine or mercaptopurine or thiopurine or methotrexate and Crohn's disease.Randomized, controlled trials demonstrated that sulfasalazine, budesonide, and conventional corticosteroids are effective for inducing remission of mild-to-moderate Crohn's disease when administered for a period of 8-16 weeks. An ideal maintenance therapy does not currently exist.Selection of maintenance therapy is based on a combination of evidence from controlled trials and patient features including disease severity and location, co-morbidities, previous response to treatment, and previous surgical resection. The options for maintenance therapy include therapy cessation and patient observation following successful induction, budesonide, or immunosuppressive therapy.

Patient compliance with screening recommendations for colorectal cancer remains low, despite a 90% survival rate achieved with early detection. Bowel preparation is a major deterrent for patients undergoing screening colonoscopy. More than half of patients taking polyethylene glycol electrolyte lavage solution and sodium phosphate preparations experience adverse events, such as nausea and abdominal pain. Many adverse events may be associated with dehydration, including rare reports of renal toxicity in patients taking sodium phosphate products. Addressing dehydration-related safety issues through patient screening and education may improve acceptance of bowel preparations, promote compliance and increase the likelihood of a successful procedure.To evidence safety issues associated with bowel preparation are generally related to inadequate hydration.Dehydration-related complications may be avoided through proper patient screening, for example, renal function and comorbid conditions should be considered when choosing an appropriate bowel preparation. In addition, patient education regarding the importance of maintaining adequate hydration before, during and after bowel preparation may promote compliance with fluid volume recommendations and reduce the risk of dehydration-related adverse events.Proper patient screening and rigorous attention by patients and healthcare providers to hydration during bowel preparation may provide a safer, more effective screening colonoscopy.

A case of thoracic spine spasms secondary to a bleeding duodenal ulcer is presented. A 41-year-old male with 14-week history of thoracic spine spasm was treated with bed rest, spinal manipulation, physical therapy, medication, and a thoracolumbar brace. Subsequently, a provocative thoracic discogram performed at T9-T10 created periscapular pain and also reproduced the presenting thoracic spasms. Intradiscal electrothermal annuloplasty (IDET) was performed at the T9-T10 level, but without sustained relief. The patient presented to a spine center for evaluation. The diagnosis of thoracic discogenic disease was suspected. A second provocative thoracic discogram was performed and failed to reproduce his thoracic spasms. Three weeks after being referred to a chronic pain management physician, the patient presented to a local emergency room with hema-temesis. An endoscopic evaluation revealed a bleeding duodenal ulcer. Following medical treatment of the duodenal ulcer with a proton pump inhibitor the patient had complete resolution of his thoracic spasms. This represents the first reported case of thoracic spine spasms as an initial presenting symptom of a bleeding peptic ulcer.

Decreased bone mineral density, osteoporosis, is a common disorder in the United States and elsewhere in the world. This disorder is estimated to account for more than 1.5 million bone fractures each year and is estimated to cost over 13 billion dollars annually. Inflammatory Bowel Disease is a relatively common disorder with estimates suggesting that approximately one million Americans are afflicted by these conditions. Osteoporosis is a common extraintestinal complication of inflammatory bowel disease. The importance of the many possible mechanisms contributing to the loss of bone mass in IBD is uncertain. Several of these specific factors, including the use of corticosteroids, calcium deficiency, vitamin D deficiency, chronically active inflammatory bowel disease, and malnutrition. Assessment of the bone mineral density is an important exercise since new therapeutic options exist and new options are available to combat and even prevent this costly complication.

Various medications are used to control the symptoms of Crohn's disease. This article reviews the traditional medical therapies of Crohn's disease, including aminosalicylates and corticosteroids, and the broad armamentarium of immune modulators and biologic agents that are becoming increasingly important in the management of Crohn's disease.

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is currently the procedure of choice for ulcerative colitis patients who require colectomy. Despite its wide acceptance, a variety of long-term complications of the procedure exist that can be severe and even lead to pouch excision. Pouchitis occurs in up to one half of patients after IPAA, but is usually well controlled with medical therapy. A small percentage of patients develop chronic persistent pouchitis, which often requires long-term medical therapy and may result in pouch failure. Fistulas and strictures can also complicate the pouch procedure. In general, patients with Crohn's disease are not usually offered IPAA, because recurrence of disease, fistulas, abscesses, and strictures may lead to a higher incidence of pouch failure. Some ulcerative colitis patients develop complications after IPAA and are subsequently diagnosed with Crohn's disease. These patients may develop refractory fistulas, strictures, and extraintestinal manifestations of inflammatory bowel disease. Neoplastic transformation of the pelvic pouch has also been reported, particularly in patients with chronic pouchitis. Thorough follow-up and endoscopic surveillance with biopsies of the ileal pouch are therefore recommended.

Giant gastric ulcers are defined as ulcers with a diameter greater than 3 cm. Previously they have not been described in lung transplant recipients. We report a high incidence of symptomatic giant gastric ulcers and identify the risk factors for ulcer development in these patients. We examined the records of all 95 patients who had undergone lung transplantation at our institution from November 1991 to July 1995. Fourteen of the patients who underwent lung transplantation developed symptoms that required esophagogastroduodenoscopy. Three of these patients (21%) were found to have giant gastric ulcers. The relative risk of giant gastric ulcer in symptomatic patients undergoing endoscopy after lung transplantation is over 40 times that of population controls. The patients who developed giant gastric ulcers, despite H2 antagonist use, had all received bilateral lung transplantation and had received nonsteroidal antiinflammatory drugs, cyclosporine, and high-dose intravenous corticosteroids. The risk of developing giant gastric ulcers is significantly increased in patients who have undergone bilateral orthotopic lung transplantation. Clinicians should be made aware of this complication in order to avoid use of ulcerogenic medications in this population. Avoidance of these medications could potentially minimize the risk of this complication.

There are seven published cases of ileal carcinoid tumor misdiagnosed and treated as Crohn's disease. We evaluated 176 consecutive ileal carcinoid patients to determine the frequency with which this occurs. Clinical, hormonal, and radiographic data of those patients misdiagnosed were also analyzed to determine whether there were clinical lessons to be learned.Records of 176 patients with ileal carcinoid tumors were retrospectively reviewed. It was determined whether patients were diagnosed and treated for Crohn's before the diagnosis of carcinoid was established. Radiographic, hormonal, and clinical data were reviewed and comparison was made to those who were correctly diagnosed as having carcinoid.Of 176 ileal carcinoid patients, 4 were initially diagnosed and treated as having Crohn's; their mean age was 51.5 +/- 8.9 yr. The hormonal data of patients treated as Crohn's was indistinguishable from patients with known carcinoid. Two of four patients had colonoscopy performed, neither had terminal ileal intubation. None responded to medical therapy and all required surgery for diagnosis. The mean time from symptom onset to the establishment of the correct diagnosis was 24 +/- 6.9 months with a range of 6 to 45 months.Although rare, ileal carcinoid tumors may be misdiagnosed as Crohn's disease. In our study approximately 2.3% of patients with ileal carcinoid were initially diagnosed and treated as having Crohn's disease. The presence of disease refractory to medical therapy should alert clinicians to this possibility and urinary 5-HIAA levels should be obtained as a screening test.

Inflammatory bowel disease (IBD) is a painful and debilitating condition affecting the mucosal lining of the colon and other areas of the gastrointestinal tract. IBD generally falls into two major categories: ulcerative colitis (UC) and Crohn's disease. We have utilized dinitrobenzenesulfonic acid (DNBS) to induce experimental UC in rats. Histopathologic analysis indicates that DNBS induces a condition in animals similar to human UC. Biochemical results revealed 6- to 10-fold elevated levels of serine protease activity in colon tissue from animals with UC as compared with matched controls. We also observed elevated levels of protease activity in tissue samples obtained from human patients with UC. Hence, our results demonstrate that protease activity is increased in rodent and human UC. These proteases may play a significant role in destruction of colonic tissue in IBD. Protease inhibitors that target serine proteases may be useful pharmacological agents to limit tissue destruction in IBD.

The role of diet in the aetiology and pathogenesis of ulcerative colitis (UC) remains uncertain. Impaired utilization by colonocytes of butyrate, a product of bacterial fermentation of dietary carbohydrates escaping digestion, may be important. Sulphur-fermenting bacteria may be involved in this impaired utilization. Oxidative stress probably mediates tissue injury but is probably not of causative importance. Patients with UC are prone to malnutrition and its detrimental effects. However, there is no role for total parenteral nutrition and bowel rest as primary therapy for UC. The maintenance of adequate nutrition is very important, particularly in the peri-operative patient. In the absence of massive bleeding, perforation, toxic megacolon or obstruction, enteral rather than parenteral nutrition should be the mode of choice. Nutrients may be beneficial as adjuvant therapy. Butyrate enemas have improved patients with otherwise recalcitrant distal colitis in small studies. Non-cellulose fibre supplements are of benefit in rats with experimental colitis. Eicosapentaenoic acid in fish oil has a steroid-sparing effect which, although modest, is important, particularly in terms of reducing the risk of osteoporosis, but it seems to have no role in the patient with inactive disease. gamma-Linolenic acid and anti-oxidants also are showing promise. Nutrients may also modify the increased risk of colorectal carcinoma. Oxidative stress can damage tissue DNA but there are no data published at present on possible protection from oral anti-oxidants. Butyrate protects against experimental carcinogenesis in rats with experimental colitis. Folate supplementation is weakly associated with decreased incidence of cancer in UC patients when assessed retrospectively. Vigilance should be maintained for increased micronutrient requirements and supplements given as appropriate. Calcium and low-dose vitamin D should be given to patients on long-term steroids and folate to those on sulphasalazine.

Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue that is distinguished not only by the triad of skin hyperextensibility, articular hypermobility, and tissue fragility but also by its heterogeneity on clinical, genetic, and biochemical grounds. The phenotypical variance that characterizes this syndrome often makes its recognition difficult, and failure to recognize the disease despite a classic course is not uncommon. Diagnosis is paramount, however, so life-threatening associations can be searched for and unique principles of management can be instituted. Patients are prone to GI catastrophes such as perforation and massive bleeding, which can be compounded by grave surgical and vascular complications. A thorough knowledge of the GI manifestations of EDS and their management is mandatory to prevent unnecessary morbidity and mortality.

Recently, lung transplantation has been performed with increasing frequency and improved outcomes. GI complications have been observed and reported in patients undergoing cardiac and renal transplantations but only recently have been reported in patients after lung transplantation. No large cohort has been systematically analyzed for all GI complications after lung transplantation. The present study describes, categorizes, and assesses risk factors for the development of such GI complications.Records of 45 patients who underwent 47 single or bilateral orthotopic lung transplants between November 1991 and January 1994 were reviewed.Twenty-three patients (51%) had 64 GI complications requiring 13 operations on eight patients. The incidence of major abdominal procedures in the entire transplant cohort was 18% (8/45). Their operative mortality rate was 63% (5/8). Eighteen different types of nonoperative complications occurred and were subclassified into major and minor complications. Complications were defined as major if they required medical or surgical intervention and altered patient management. Most GI complications (73%) occurred within 1 month after transplantation. No risk factors were identified to ascertain who will develop GI complications.GI complications occur in more than one-half of lung transplant recipients early after transplantation and in the absence of identifiable risk factors. Because there are no precedent risk factors to suggest who will develop GI complications, clinicians must be alert to any warning signs and symptoms. The majority of complications are nonoperative, responding to conservative therapy, but there is a higher overall mortality rate for patients requiring operative intervention, necessitating an aggressive search for major, life-threatening complications in these immunosuppressed patients.

Barrett's esophagus is a medical condition in which the squamous mucosa that normally lines the distal esophagus is replaced by a columnar type of epithelium. Most definitions that have been used for inclusion of patients in studies have indicated that columnar mucosa must extend 3 cm or more above the gastroesophageal junction. The precise length refers to the distance above the manometrically defined lower esophageal sphincter. This measurement is somewhat cumbersome to make on a routine basis for all patients at the time of endoscopy and thus is generally not done. It is important to realize that the gastroesophageal junction can be visually identified at the area where the esophagus tapers, in the region of the lower esophageal sphincter. The tapering of the esophagus in the region of the lower esophageal sphincter may be difficult to determine when lower esophageal sphincter pressures are low; thus, we commonly say that Barrett's esophagus is defined as columnar mucosa 3 cm above the region where the gastric folds end.

Intestinal pseudo-obstruction has been associated with several types of underlying neoplasms and has been hypothesized to result from a paraneoplastic process in patients with small cell lung carcinoma and bronchial carcinoid. This article documents the first reported association of gastroparesis and a retroperitoneal leiomyosarcoma. A paraneoplastic process is the proposed basis of this relationship, inasmuch as these syndromes have been noted in other tumors of mesodermal origin. The resolution of intestinal dysmotility after tumor resection, as described here, has only rarely been reported.

Hepatic cavernous hemangioma must be included in the differential diagnosis of any hepatic solid mass. It is the second most common neoplasm of the liver, following intrahepatic metastases. With the exception of giant or symptomatic HCH, it does not require specific intervention. The ability to diagnose HCH radiologically (Table 2) has significant clinical importance. When confronted with clinical data and a preliminary radiologic study suggestive of HCH, serial planar blood-pool scintigraphy (with SPECT if the lesion is3-4 cm) should probably be the initial diagnostic examination. In comparison to MRI, it is safer, less expensive and easier for some patients to tolerate. For small, deep seated lesions or those adjacent to the heart or large vessels, MRI is the preferred test. Dynamic CT is probably most useful in patients with normal renal function in whom optimal imaging of the extrahepatic abdomen is desired. If the etiology of an incidental hepatic mass suspected to be an HCH is still not evident after these studies, angiography or biopsy are the remaining options. As described, angiography is sensitive and relatively specific for HCH. Although percutaneous biopsy may be associated with increased risk of bleeding, fine-needle biopsy has been shown to be safe for hemangiomas. However, fine-needle biopsy is more useful for confirming a suspected malignancy than for actually diagnosing hemangioma.

We report a patient with Crohn's disease manifesting as recurrent giant gastric ulcers, with subsequent perforation and gastric outlet obstruction. The ulcers contained granulomas, and the patient was achlorhydric. To our knowledge, this is the first report of giant ulcers in a patient with gastric Crohn's disease. This case demonstrates another gastric manifestation of Crohn's disease, it documents nonmalignant gastric ulcers in the setting of achlorhydria, and it raises the possibility of Crohn's disease in the differential diagnosis of giant gastric ulcers refractory to medical management.

We report the case of a 33-yr-old man who presented with an acute incomplete esophageal obstruction, mimicking food impaction, who was found to have a giant intramural esophageal leiomyoma. The leiomyoma was successfully removed through a longitudinal esophagotomy. This is the first report of a nonpedunculated intramural esophageal leiomyoma presenting as an acute esophageal obstruction.

Nine men with refractory condylomata acuminata were treated with intramuscular interferon alfa-n1 and the effect on their serum lipid levels was noted. Comparison of lipid panels before and after interferon revealed that all nine patients had an increase (median 62 mg/dl, p = 0.004) in their triglyceride level and a decrease (median 21 mg/dl, p = 0.004) in high-density lipoprotein cholesterol levels. Total cholesterol levels tended to decrease but the change was not statistically significant. This effect on serum lipids should be considered when interferon alfa-n1 is used in the treatment of genital warts.

To elucidate the in vivo role of natural killer (NK) cells, the growth of several murine and human tumors was studied in four variants of athymic, nude mice with different levels of NK activity. Beige-nude mice, homozygous for both the beige and the nude genes, had very low levels of NK activity, and their response to the B-cell mitogen, bacterial lipopolysaccharide, was lower than that of high-NK, adult NIH nude mice. Young and adult NIH nudes had different NK levels and showed different response in assays for K-cell, T-cell, and B-cell activity. The B-cell-defective NIH-II mice had slightly lower NK levels than adult NIH animals, but much lower response in the antibody-dependent cell-mediated cytotoxicity assay. No correlation was found between host NK activity and the s.c. growth of various human (LOX, CEM, K562) and murine (YAC-1) tumor cells. Low NK activity was not associated with increased lung colony formation in a metastasis model using i.v.-injected human (LOX) and murine (B16F10) melanoma cells. No relationship was found between host NK activity and the rate of elimination of i.v.-injected 5-iodo-2'-deoxyuridine-labeled LOX, B16F10, and YAC-1 cells from lungs, liver, or spleen. The results fail to support the view that NK cells exert significant direct effects on tumor cells in vivo.