Stromal-derived IGF2 promotes colon cancer progression via paracrine and autocrine mechanisms.

The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source. Further, we provide functional evidence that stromal IGF2, via the paracrine IGF1R/insulin receptor axis, activated pro-survival AKT signaling in CRC cell lines. In addition to its effects on malignant cells, autocrine IGF2/IGF1R signaling in CAFs induced myofibroblast differentiation in terms of alpha-smooth muscle actin expression and contractility in floating collagen gels. This was further augmented in concert with transforming growth factor-ß (TGFß) signaling suggesting a cooperative mechanism. However, we demonstrated that IGF2 neither induced TGFß/smooth muscle actin/mothers against decapentaplegic (SMAD) signaling nor synergized with TGFß to hyperactivate this pathway in two dimensional and three dimensional cultures. IGF2-mediated physical matrix remodeling by CAFs, but not changes in extracellular matrix-modifying proteases or other secreted factors acting in a paracrine manner on/in cancer cells, facilitated subsequent tumor cell invasion in organotypic co-cultures. Consistently, colon cancer cells co-inoculated with CAFs expressing endogenous IGF2 in mouse xenograft models exhibited elevated invasiveness and dissemination capacity, as well as increased local tumor regrowth after primary tumor resection compared with conditions with IGF2-deficient CAFs. In line, expression of IGF2 correlated with elevated relapse rates and poor survival in CRC patients. In agreement with our results, high-level coexpression of IGF2 and TGFß was predicting adverse outcome with higher accuracy than increased expression of the individual genes alone. Taken together, we demonstrate that stroma-induced IGF2 promotes colon cancer progression in a paracrine and autocrine manner and propose IGF2 as potential target for tumor stroma cotargeting strategies.

Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression.

The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. Here, we show for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma. The impact of stromal WNT2 on carcinoma formation or progression was not addressed so far. Canonical WNT/ß-catenin signaling was assessed using a 7TGP-reporter construct. Furthermore, effects of WNT2 on fibroblast migration and invasion were determined using siRNA-mediated gene silencing. Tumor cell invasion was studied using organotypic raft cultures and in vivo significance was assessed via a xenograft mouse model. We identified cancer-associated fibroblasts (CAFs) as the main source of WNT2. CAF-derived WNT2 activated canonical signaling in adenomatous polyposis coli/ß-catenin wild-type colon cancer cells in a paracrine fashion, whereas no hyperactivation was detectable in cell lines harboring mutations in the adenomatous polyposis coli/ß-catenin pathway. Furthermore, WNT2 activated autocrine canonical WNT signaling in primary fibroblasts, which was associated with a pro-migratory and pro-invasive phenotype. We identified FZD8 as the putative WNT2 receptor in CAFs. Three-dimensional organotypic co-culture assays revealed that WNT2-mediated fibroblast motility and extracellular matrix remodeling enhanced cancer cell invasion of cell lines even harboring mutations in the adenomatous polyposis coli/ß-catenin pathway. Thus, suggesting a tumor-promoting influence on a broad range of CRC. In line, WNT2 also promotes tumor growth, invasion and metastasis in vivo. Moreover, high WNT2 expression is associated with poor prognosis in human CRC. The identification of the pro-malignant function of stromal derived WNT2 in CRC classifies WNT2 and its receptor as promising stromal targets to confine cancer progression in combination with conventional or targeted therapies.

99mTc tetrofosmin myocardial perfusion scintigraphy in CAD. Performance with early and standard delayed acquisition and fractional flow reserve.

AIM: Early stress imaging (15 min after injection of the radiopharmaceutical) in 99mTc tetrofosmin myocardial perfusion scintigraphy (MPS) has been shown feasible in comparison to standard imaging after 45 minutes, but the effects on image quality and diagnostic accuracy ask for further evaluation. PATIENTS, METHODS: 97 patients (61 men, 36 women, age 69 ± 11 years) underwent both early (EA) and standard (SA) acquisition (after 14 ± 4 min and 43 ± 6 min, respectively) using 99mTc tetrofosmin gated SPECT with iterative reconstruction. Sub-diaphragmatic tracer activity and image quality was scored in a 4-point scale by blinded observers. Semiquantitative myocardial perfusion analysis was performed on a 17-segment model using standard cardiac quantification SPECT software (4 DM-SPECT). Stenoses of indeterminate haemodynamic significance were validated by measurement of fractional flow reserve (FFR). RESULTS: Extra-cardiac tracer activity was more commonly found in EA (43%) than in SA (38%), but without any diagnostic impact in > 95% of the patients. The mean summed stress score was significantly higher for early than standard imaging (6.4 ± 6.3 vs. 5.6 ± 6.1, p = 0.009). The amount of ischaemic area was not significantly different (EA: 9.1 ± 6.7 % vs. SA: 7.8 ± 6.9 %). The mean stress ejection fraction was 52 ± 11% (EA) compared to 55 ± 11 % (SA) (p = ns). FFR was inversely related to SDS at early (r = -0.704, p < 0.05) and standard (r = -0.678, p < 0.05) acquisition. All patients with a FFR < 0.8 (considered as hemodynamically significant stenoses) revealed a positive scan. CONCLUSION: Stress 99mTc tetrofosmin MPS with early acquisition is feasible and at least equally accurate when iterative reconstruction is applied.

Memorandum on the use of information technology to improve medication safety.

BACKGROUND: Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately. OBJECTIVES: To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts. METHODS: This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation. CONCLUSION: Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.

Fructose and lactose intolerance and malabsorption testing: the relationship with symptoms in functional gastrointestinal disorders.

BACKGROUND: The association of fructose and lactose intolerance and malabsorption with the symptoms of different functional gastrointestinal disorders (FGID) remains unclear. AIM: To investigate the prevalence of fructose and lactose intolerance (symptom induction) and malabsorption and their association with clinical gastrointestinal (GI) as well as non-GI symptoms in FGID and the outcome of dietary intervention. METHODS: Fructose and lactose intolerance (defined by positive symptom index) and malabsorption (defined by increased hydrogen/methane) were determined in 1372 FGID patients in a single centre using breath testing. Results were correlated with clinical symptoms in different FGID Rome III subgroups. The effectiveness of a targeted saccharide-reduced diet was assessed after 6-8 weeks. RESULTS: Intolerance prevalence across all FGIDs was 60% to fructose, 51% to lactose and 33% to both. Malabsorption occurred in 45%, 32% and 16% respectively. There were no differences in intolerance or malabsorption prevalence between FGID subgroups. FGID symptoms correlated with symptoms evoked during testing (r = 0.35-0.61. P < 0.0001), but not with malabsorption. Non-GI symptoms occurred more commonly in patients with intolerances. Methane breath levels were not associated with constipation using several cut-off thresholds. Adequate symptom relief was achieved in >80% of intolerant patients, irrespective of malabsorption. CONCLUSIONS: Fructose and lactose intolerances are common in FGID and associated with increased non-GI symptoms, but not with specific FGID subtypes. Symptoms experienced during breath testing, but not malabsorption, correlate with FGID symptoms. Effective symptom relief with dietary adaptation is not associated with malabsorption. Mechanisms relating to the generation of GI and non-GI symptoms due to lactose and fructose in FGID need to be explored further.

[Clinical relevance and indications for cardiac magnetic resonance imaging 2013: an interdisciplinary expert statement]. / Klinischer Stellenwert und Indikationen zur Magnetresonanztomografie des Herzens 2013: Ein interdisziplinäres Expertenstatement.

During the last years the indications of Cardiac Magnetic Resonance Imaging (CMRI) have been continuously expanded. However, the acceptance of the method by cardiologists and radiologists does not correlate with respect to the diagnostic potential. Several factors, such as expensive equipment, relatively long examination times, high technical know how and lack of remuneration, limit the application of CMRI in everyday clinical practice. Furthermore, doctors tend to apply more conventional, well established diagnostic procedures, the access to the method is still limited and there exist difficulties in the interdisciplinary collaboration. The interdisciplinary Austrian approach to Cardiac Imaging is aimed to improve the aforementioned problems and to support the implementation of CMRI in the diagnostic tree of cardiac diseases thus enabling a cost efficient management of patients in cardiology.

Adverse drug reactions (ADRs) associated with hospital admissions - elderly female patients are at highest risk.

BACKGROUND: ADRs represent a significant problem in drug utilisation. The prevalence of admissions caused by ADRs varies depending on the observational site, studied population, data collection method and the used definitions. Women seem to be more frequently affected than men. OBJECTIVE: To assess the incidence and quality of ADRs related to hospital admissions, to identify the drugs most commonly involved and to define risk factors and preventive strategies for those ADRs. MATERIAL AND METHODS: 3,190 medical records of all newly admitted internal ward patients were assessed in a prospective observational study in an internal hospital over 6 months. Potential ADRs at hospital admission were identified following a list of suspicious symptoms and laboratory results. Cases were evaluated by means of a computer tool and data-base specialized on detecting causality and severity of ADRs. RESULTS: 304 ADRs were identified in 242 patients (7.6%), with 60% directly leading to admission. More women than men encountered an ADR (10 vs. 6%, p < 0.005). Analyzed separately by age groups, this gender difference became significant at an age of ≥ 81 years. The most common ADRs were electrolyte imbalances and over-anticoagulation. Diuretics and vitamin K antagonists were significantly correlated with ADRs. 62% of all ADRs were severe or life-threatening. CONCLUSION: ADRs leading or related to hospital admission are highly prevalent. Older age and female gender are significantly associated with ADR related hospital admissions. Causative drugs are the ones prescribed most frequently. Multidisciplinary preventive strategies and surveillance methods are necessary to ensure better care and patient safety especially for elderly women.

No evidence of stimulation of human tumor cell proliferation by a standardized aqueous mistletoe extract in vitro.

The in vitro antiproliferative or stimulatory activity of an aqueous mistletoe extract (AME) with a defined content of bioactive mistletoe lectin (ML) was investigated in 6 human tumor cell lines, including two melanomas and leiomyosarcomas, each of which had previously been reported to show evidence of growth stimulation if treated with low concentrations of isolated ML. The effects of AME were compared to that of the standard cytotoxic agent adriamycin (ADR) using the well established propidium iodide and sulforhodamin B proliferation assays. The AME concentrations used ranged from 0.5 pg to 5 ng (0.82 fMol-85 pM) bioactive ML/ml in melanoma (HT-144, SK-MEL-28) and leiomyosarcoma (SK-MLS-1, S-UT-1B) cell lines and from 0.1-100 ng ML/ml (1.7 pM-1.7 nM) in MCF-7 breast cancer and SW620 colon carcinoma cell lines, respectively. The influence of AME on cell growth was determined at various time-points from 24 hours to 6 days of exposure. We found a time- and cell line-dependent inhibition of tumor cell growth, but no reproducible stimulation of tumor cell proliferation. Inhibitory concentrations 50% (IC50) for e.g. the SK-MEL-28 melanoma cell line, decreased from 4.1 ng ML/ml at 24 hours to 0.16 ng ML/ml at 72 hours and 0.18 ng ML/ml at 5 days. Our data clearly demonstrate that, by applying scientifically valid methods and procedures, the standardized AME did not stimulate tumor cell proliferation but showed time- and concentration-dependent antiproliferative effects.

Change in pharmacokinetic and pharmacodynamic behavior of gemcitabine in human tumor xenografts upon entrapment in vesicular phospholipid gels.

PURPOSE: The in vivo pharmacokinetics (PK), biodistribution and antitumor activity of a new liposomal formulation of gemcitabine (GemLip) were compared to the conventional (clinical) formulation of gemcitabine (GemConv). METHODS: Gemcitabine was entrapped in a vesicular phospholipid gel (VPG) consisting of densely packed liposomes. Redispersed VPG containing GemLip consisted of 33% liposomally entrapped and 67% free gemcitabine. The in vivo efficacies of GemLip and GemConv were compared using the subcutaneously growing human soft tissue sarcoma SXF 1301 and the orthotopically growing human bladder cancer BXF 1299T. PK and biodistribution were evaluated using radiolabeled drug and lipid in SXF 1301 tumor-bearing nude mice. RESULTS: GemLip was highly active in SXF 1301 at a gemcitabine dose of 6-9 mg/kg (days 1, 8 and 15; dose near the MTD). In the 6-mg/kg groups, complete tumor remissions were observed in seven of eight mice. Equimolar doses of GemConv resulted in only moderate tumor growth inhibition. Even at equitoxic doses (360 mg/kg given on days 1, 8 and 15, or 120 mg/kg on days 1, 5 and 8) GemConv was less active than GemLip. Furthermore, GemLip was active in the orthotopically growing BXF 1299T bladder cancer model at 6 mg/kg and prevented distant organ metastasis. In the PK study, GemLip achieved a 35-fold higher plasma AUC (1680 mg x h/ml) than GemConv (47.6 mg x h/ml). The serum half-lives were 0.15 h for free gemcitabine and 13.3 h for liposomal gemcitabine (6 mg/kg each i.v.). Moreover, gemcitabine levels in tumors were fourfold higher following injection of GemLip than following injection of GemConv. CONCLUSIONS: GemLip is a highly effective gemcitabine delivery system which results in superior gemcitabine pharmacodynamics and PK than GemConv. The enhanced in vivo efficacy might be explained by sustained release and passive tumor targeting.

Abnormal bone marrow stroma in mice deficient for nemo-like kinase, Nlk.

The stromal compartment of the bone marrow is composed of various cell types that provide trophic and instructive signals for hematopoiesis. The mesenchymal stem cell is believed to give rise to all major cellular components of the bone marrow microenvironment. Nemo-like kinase, Nlk, is a serine-threonine kinase that connects MAP kinase and Wnt signaling pathways; its in vivo function in mouse is unknown. We have generated mice with a targeted disruption of Nlk and find that the complex phenotype significantly varies with the genetic background. Whereas C57BL/6 mice lacking Nlk die during the third trimester of pregnancy, the 129/Sv background supports survival into adolescence; such mice are growth retarded and suffer from various neurological abnormalities. We show here that the Nlk deficiency syndrome includes aberrant differentiation of bone marrow stromal cells. Varying degrees of morphological abnormality, such as increased numbers of adipocytes, large blood sinuses and absence of bone-lining cells are observed in the bone marrow of mutant mice. Nlk deficient mice thus provide a novel model to study the genetic requirements for bone marrow stromal differentiation.

Antiproliferative activity of an aqueous mistletoe extract in human tumor cell lines and xenografts in vitro.

The in vitro antiproliferative activity of an aqueous mistletoe extract (AME) with a defined content of bioactive mistletoe lectin (ML) was tested in 25 human tumor cell lines, including 20 solid and 5 hematological malignancies and 47 human tumor xenografts. The antiproliferative activity of AME was compared to that of the standard cytotoxic agent doxorubicin (CAS 23214-92-8, adriamycin, ADR) using the sulforhodamin B, propidium iodide and soft agar colony forming assays, respectively. AME was highly cytotoxic in solid human tumors with mean IC70 values in the range of 0.17-1 ng ML/ml (2.8-17 pmol bioactive ML). On a molar basis, AME was 3 to 4 logs more potent than ADR and showed differential cytotoxicity towards tumors of the breast, small cell and non-small cell lung, prostate and renal cell cancers. AME was also highly active in hematological malignancies with steep dose response curves resulting in mean IC70 values of 0.12 ng ML/ml (2 pmol). The acute lymphoblastic leukemia cell line HL-60 was the most sensitive, the histiocytic lymphoma cell line U937 the most resistant hematological malignancy. It is important to stress that AME did not induce a biologically relevant increase of cell proliferation in any of the tumor cell lines tested. Our data suggest that AME has in vitro antitumor profiles similar to those of classical anticancer agents. Clear dose-response relationships were found in all of the performed experiments and interesting differential cytotoxicity patterns were observed. Experiments with sensitive tumor types identified in these in vitro studies are currently ongoing in order to demonstrate the anticancer activity of AME in different animal tumor models.

Anticancer activity of an aqueous mistletoe extract (AME) in syngeneic murine tumor models.

Mistletoe extracts have been used for decades for non-specific stimulation of the immune system in cancer therapy. Mistletoe lectins (ML) have been identified as the active principle with cytotoxic and immunomodulatory potencies. In the present in vivo experiments, the anticancer effects of an aqueous mistletoe extract (AME) were investigated in different subcutaneously growing syngeneic murine tumors such as Renca renal cell carcinoma, C8 colon 38 carcinoma, F9 testicular carcinoma, B16 melanoma and Lewis lung carcinoma. The animals used were immunocompetent mice of different strains (C57BL/6, BALB/c), depending on the type of tumor tested. After tumor transplantation, the mice were treated with AME at dose levels corresponding to 0, 0.3, 3, 30 or 300 ng ML/kg/d by the i.p. or s.c. route for a maximum of 4 consecutive weeks. The tumor volume was determined by serial caliper measurements and expressed relative to controls. Significant tumor growth inhibition was observed with the Renca , C8 colon 38 and F9 testicular carcinomas at 30 and 300 ng ML/kg/d. These findings were confirmed in independent repeat experiments. No inhibitory effects were seen with the Lewis lung carcinoma and B16 melanoma under the conditions described above. In conclusion, AME showed in vivo anticancer activity in different transplantable syngeneic murine tumor models following repeated parenteral treatment. In view of the low dose levels used, the effects are most likely due to the immunostimulatory rather than to the cytotoxic potencies of AME.

Non-invasive blood glucose monitoring by means of near infrared spectroscopy: investigation of long-term accuracy and stability.

Modern strategies in the treatment of Diabetes mellitus require frequent blood glucose tests. Near-infrared spectroscopy [NIR] is considered to be a method for non-invasive blood glucose testing. The present study evaluated the long-term accuracy and stability of the method. Spectra of 10 patients were recorded. An individual calibration models were calculated for each patient from spectra which were recorded at the beginning of the investigation. These models were then applied to calculate blood glucose values from spectra which were recorded 84 to 169 days later. The long-term accuracy and stability of the calibration models expressed as root mean squared error of prediction [RMSP] varied from 3.1 to 35.9 mmol/l and the error grid analysis [EGA] from 13 to 92% clinically acceptable values in zones A and B. The results of the investigation indicate that long-term monitoring of blood glocose by means of NIR-spectroscopy and individual calibration models over a period of 3 to 4 months is basically possible once long-term stability of the method will be improved. Further technological progress and a better understanding of the underlying physiological processes is necessary to achieve a level of accuracy, reliability and stability of the method as required for clinical application.

Adult rhabdomyoma of the extremity: a case report and review of the literature.

The adult rhabdomyoma is a rare, benign skeletal muscle neoplasm that usually occurs in the head and neck. A case report of an adult rhabdomyoma arising in the thigh is presented with a review of the literature. This is the first case of an extremity adult rhabdomyoma to be reported. It is also the largest at 13 centimeters. Distinction from a highly differentiated rhabdomyosarcoma is important. Recent chromosomal studies suggest that the adult rhabdomyoma is a true neoplasm. Total resection is curative but the lesion may recur if incompletely excised.

Free tissue transfer provides durable treatment for large nonhealing venous ulcers.

BACKGROUND: Most venous ulcers (VUs) will heal with conventional treatment, which focuses on improving regional venous hemodynamics. This treatment, however, often fails to heal large, recurrent VUs that are associated with severe lipodermatosclerosis (LDS). These complicated ulcers may require correction of local venous hemodynamics and replacement of the surrounding LDS with healthy tissue. We report our experience managing 24 especially difficult VUs with debridement and free flap coverage. PATIENTS AND METHODS: Between 1987 and 1997, 25 free flap procedures were performed in 22 patients for 24 recalcitrant VUs. Ulcers had been present for a mean of 5.24 years and had failed to heal with conservative therapy and split-thickness skin grafts (STSGs) (mean, 2.2). Eleven patients (46%) had exposed bone, tendon, or joint. At operation the area of LDS was excised, and all perforating veins were ablated. The defects after excision ranged from 100 to 600 cm(2) (mean, 237 cm(2)). The free flap was inset within the defect and covered with an STSG. RESULTS: We healed all 24 ulcers with free tissue transfer (one patient required a second flap after the first failed). There were no deaths. Local complications that required repeat STSG occurred in three (13%) of the 24 successful flap transfers. Four other flaps had minor local complications that healed with local wound care. Follow-up was available for 21 of the 24 successful flap transfers. No recurrent ulcers were identified in the territory of the flap after a mean of 58 months, but three patients had new ulcers in the same leg after 6 to 77 months. Patients with severe complications were hospitalized longer than those with minor or no complications (45.7 vs 12.8 days, P <.01), and their hospital charges were greater ($76,681 vs $30,428, P <.01). CONCLUSION: Free tissue transfer can provide rapid healing and long-term relief from severe VUs that are unable to be treated with conventional therapy. This technique improves venous hemodynamics, removes all liposclerotic tissue, provides an abundant blood supply, and resolves the tissue-related components of chronic ulceration. Although further work is needed to determine the optimal indications, this technique provides a durable treatment for especially recalcitrant ulcers.

Colloidal properties of human transferrin receptor in detergent free solution.

The colloidal properties of transferrin receptor, isolated from human placenta, in detergent free solution has been investigated by light scattering techniques and analytical ultracentrifugation. In detergent free solution at 293.2 K, hTfR forms stable aggregates with an apparent hydrodynamic radius of 17 nm. The molecular mass was determined by ultracentrifugation to lie between (1722+/-87) kDa (sedimentation equilibrium) and (1675+/-46) kDa (sedimentation velocity). This implies that the aggregates are build up from nine hTfR dimers. Based on model calculations, which are in good agreement with the experimental data, we propose a torus-like structure for the aggregates. Upon pH shift from pH 7.5 to 5.0 or removal of the N-linked carbohydrate chains, formation of larger aggregates is induced. These aggregates can be described in terms of porous fractal structures. We propose a simple model, which accounts for that behaviour assuming that the aggregation is mainly due to the reduction of negative surface charge.

Treatment options for perianal Bowen's disease: survery of American Society of Colon and Rectal Surgeons Members.

The aim of this study was to determine current management practices of physicians caring for patients with perianal Bowen's disease. A questionnaire was sent to 1,499 members listed in the 1997 American Society of Colon and Rectal Surgeons Directory asking them how many patients they have treated and which operative or nonoperative treatment option they choose for small (< or =3 cm), large (> 3 cm), and microscopic lesions. Of 1,499, 663 (44.2%) surgeons responded. Not all respondents answered each item. Seventy-five per cent of surgeons surveyed (n = 653) devote greater than 75 per cent of their practice to colon and rectal surgery. Of 642 respondents, 552 (86%) managed a total of <10 patients, and 90/642 (14%), > or =10 patients. Ninety-six per cent of respondents use wide local excision for patients with small lesions. Eighty-seven per cent of respondents use wide local excision for patients with large lesions. Seventy-four per cent treat patients with microscopic disease conservatively and without wide excision. The majority of surgeons caring for patients with perianal Bowen's disease are performing wide local excision for both small and large lesions. Microscopic disease was usually treated conservatively with observation alone.

Cecal necrosis: infrequent variant of ischemic colitis. Report of five cases.

PURPOSE: Spontaneous nonocclusive ischemic colitis involving only the right colon is an infrequent occurrence. Because this problem is less recognized than its counterpart involving the left colon, the correct diagnosis may not be considered. The purpose of this article was to describe the presentation and management of this unusual clinical problem. METHODS: Five cases of nonocclusive ischemic cecal necrosis are described. Four of the patients presented with right-sided abdominal pain, tenderness, and leukocytosis. The preoperative diagnosis was incorrect in all patients, although cecal necrosis was considered in one. Two patients were thought to have. appendicitis, two were thought to have carcinoma, and one was thought to have a perforated viscus. Each patient underwent a right hemicolectomy and four survived. RESULTS: Each of the patients had ischemic cecal necrosis without evidence of emboli or vasculitis. Although cecal gangrene may occur after systemic hypotension, no such event preceded these patients' presentation. We believe that the patients we treated had a form of nonocclusive ischemic colitis, which occasionally affects only the right colon. CONCLUSION: Ischemic necrosis of the cecum is an infrequent variant of ischemic colitis that should be considered in the differential diagnosis of the elderly patient presenting with right lower quadrant pain.