Pilot study of peripheral internal jugular venous catheters on a hospitalist-run medicine procedure service.

Providers caring for hospitalized patients with difficult intravenous access (DIVA) frequently use central venous catheters (CVCs). One potential alternative is a peripheral internal jugular (PIJ) catheter, which is less traumatic to place and has fewer lumens than a CVC. We describe the results of 2 years' experience from a pilot project of a medicine procedure service placing PIJ catheters in hospitalized patients with DIVA. We successfully placed 34/35 (97%) PIJ catheters in 32 patients with zero complications. Median duration of use was 2.5 days (range 0-53 days, IQR 1-5). Catheter failure rate within 7 days was 32.4%, though it varied across catheter types: 9.5% in 8-10 cm midline catheters versus 69.2% (p < .001) in 6 cm angiocatheter wire introducers or shorter peripheral intravenous catheters. Our results suggest that PIJ catheters may be an option to reduce the mechanical and infectious risks associated with CVCs in some hospitalized patients with DIVA.

Safety and predictors of the success of lumbar punctures performed by a medicine procedure service.

BACKGROUND: Medicine procedure services (MPS) increasingly perform bedside procedures, including lumbar punctures (LPs). Success rates and factors associated with LP success performed by MPS have not been well described. OBJECTIVE: We identified patients undergoing LP by an MPS September 2015 to December 2020. We identified demographic and clinical factors, including patient position, body mass index (BMI), use of ultrasound, and trainee participation. We performed multivariable analysis to identify factors associated with LP success and complications. MAIN OUTCOME AND MEASURES: We identified 1065 LPs among 844 patients. Trainees participated in 82.2%; ultrasound guidance was used in 76.7% of LPs. The overall success rate was 81.3% with 7.8% minor and 0.1% major complications. A minority of LPs were referred to radiology (15.2%) or were traumatic (11.1%). In multivariable analysis, BMI > 30 kg/m2 (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.21-0.48), prior spinal surgery (OR 0.50, 95% CI 0.26-0.87), and Black race (OR 0.62, 95% CI 0.41-0.95) were associated with decreased odds of successful LP; trainee participation (OR 2.49, 95% CI 1.51-4.12) was associated with increased odds. Ultrasound guidance (OR 0.53, 95% CI 0.31-0.89) was associated with lower odds of traumatic LP. RESULTS: In a large cohort of patients undergoing LP by an MPS, we identified high success and low complication rates. Trainee participation was associated with increased odds of success, while obesity, prior spinal surgery, and Black race were associated with decreased odds of success. Ultrasound guidance was associated with lower odds of a traumatic LP. Our data may help proceduralists in planning and assist in shared decision-making.

Faculty and Resident Perspectives on Teaching Pediatric Evidence-Based Medicine in the Clinical Setting: A Qualitative Study.

PURPOSE: To describe how pediatric educators effectively teach evidence-based medicine (EBM) in the clinical setting. Secondarily, to identify barriers hindering effective practice and teaching of EBM and strategies to overcome these barriers. METHODS: The authors conducted a cross-sectional multi-institutional qualitative study from July 2016 to December 2017 in which they interviewed pediatric educators across many subspecialties who were identified as exemplary teachers of EBM at 3 academic pediatric residency programs. Pediatric residents who had recently worked with these faculty members were also interviewed to allow triangulation between participants. Qualitative analysis was complete once saturation was achieved. RESULTS: Twenty-six pediatric educators identified as exemplary teachers of EBM and 10 residents who worked with those educators participated in the study. Thirteen explicit teaching strategies and 2 implicit teaching strategies, namely disclosure of uncertainty and role modeling, were identified. Barriers to practicing clinical EBM included balancing patient responsibilities, inadequate time, and personal knowledge. Barriers to teaching clinical EBM were inadequate time and learner engagement. To overcome these barriers, faculty limit and focus teaching points, attempt to make EBM relevant to patient care, and incorporate follow-up strategies. CONCLUSIONS: Numerous teaching strategies are available to faculty to improve the clinical teaching of EBM and to overcome commonly encountered clinical EBM barriers. Familiarity with these clinical EBM teaching strategies can be used for faculty development and to enhance the teaching of EBM to learners.

Digital image-assisted quantitative nuclear analysis improves diagnostic accuracy of thyroid fine-needle aspiration cytology.

BACKGROUND: Thyroid fine-needle aspiration (FNA) plays a key role in triaging thyroid nodules. Yet many cases are assigned to indeterminate categories. The new category "noninvasive follicular thyroid neoplasm with papillary-like features" (NIFTP) complicates thyroid cytology. Digital image-derived nuclear measurements might objectively distinguish papillary thyroid carcinoma (PTC) from benign nodules and NIFTP. METHODS: All thyroid FNAs from 2012 to 2016 of atypia of undetermined significance (A; n = 8) and suspicious for malignancy (S; n = 2) with sufficient cellularity and surgical follow-up, all FNAs preceding NIFTP (n = 6), and a random sample of PTC (n = 9) and benign (n = 10) cytology were studied. A modified Giemsa-stained slide from each case was scanned using the Aperio imaging system, and long (dl ) and short (ds )-axis diameters were measured for 125 nuclei per case. Nuclear area and elongation were calculated. RESULTS: Nuclear area was larger in PTC (mean, 77.2 µm2 [range, 70.6-86.0 µm2 ]) than benign (mean, 43.3 µm2 [range 38.2-52.2 µm2 ]) (P < .001). Nuclear areas from indeterminate FNAs segregated according to final histology (A/S PTC mean 72.7 µm2 , A/S benign mean 53.7 µm2 ; P = 0.004), and were not significantly different from definitive FNAs of the same diagnosis. NIFTP nuclear area was smaller than PTC (mean, 54.8 µm2 [range, 46.7-66.1 µm2 ]; P < .001). Nuclear elongation showed similar results, but with greater group overlap. CONCLUSION: Nuclear area and elongation can be calculated using a commercial digital imager; both correlate with the final surgical pathology diagnosis of PTC versus benign, including NIFTP. Area provides greater resolution than elongation. This technique could be used to resolve indeterminate cytology in which PTC is considered.

Distinguishing non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) from classic and invasive follicular-variant papillary thyroid carcinomas based on cytologic features.

INTRODUCTION: An international panel recently recommended reclassification of non-invasive follicular variant of papillary thyroid carcinoma (PTC) to non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). NIFTPs have little or no risk of recurrence and can be treated with lobectomy alone. Preoperative distinction of NIFTP from PTC will help avoid overtreatment. MATERIALS AND METHODS: All thyroid tumors with a histologic diagnosis of PTC and preceding diagnostic cytology (n = 299) over a 5-year period were identified. Cases meeting criteria for NIFTP were reclassified as such. All NIFTP cases with available cytology (n = 6) and a similar number of randomly selected invasive follicular variant of papillary thyroid carcinoma (IFVPTC; n = 9) and classic PTC (cPTC, n = 11) were evaluated for 18 cytologic features. RESULTS: A total of 35 (12%) lesions were reclassified as NIFTP, 194 (65%) were cPTC, and 70 (23%) were IFVPTC. The NIFTPs had a preceding cytologic interpretation of benign (31%), atypia of undetermined significance (34%), follicular neoplasm (9%), suspicious for malignancy (12%), or malignant (14%). Cytologically, NIFTP was distinguished from cPTC by absence of any architectural features in all 6 cases, and by absence of pseudoinclusions (P < 0.001) and multinucleated giant cells (P = 0.027) in nearly all. Nuclear pseudoinclusions (P = 0.001), marginal micronucleoli (P = 0.018), irregular branching sheets (P = 0.025), and linear arrangement (P = 0.025) favored IFVPTC over NIFTP. CONCLUSIONS: NIFTPs were originally assigned to a variety of cytologic categories. There are several cytologic differences between NIFTP and cPTC or IFVPTC. Our findings support restricting the definitive diagnosis of PTC to cases with architectural features of PTC and/or intranuclear pseudoinclusions.

Tissue Acquisition During EBUS-TBNA: Comparison of Cell Blocks Obtained From a 19G Versus 21G Needle.

BACKGROUND: Previous studies have shown that needle gauge size has no significant impact on diagnostic yield during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Our objective was to determine whether cell blocks obtained via the new Flex 19G EBUS-TBNA needle would contain more cellular material based on cell area compared with those obtained from a 21G needle. METHODS: A prospective analysis of patients undergoing EBUS-TBNA at our institutions was performed. Sampling of the same lesion(s) with both the Flex 19G and 21G needles was performed in an alternating manner. In total, 47 patients with suspected lung cancer or mediastinal/hilar lymphadenopathy were included with a total of 83 lesions biopsied. Cell block area was calculated using the Aperio ImageScope software. RESULTS: Mean cell area in the Flex 19G group was 7.34±12.46 mm compared with 5.23±10.73 mm in the 21G group (P=0.02). In the malignant subgroup, the average cell area was 16.16±16.30 mm in the Flex 19G group versus 11.09±15.55 mm in the 21G group (P=0.02). No significant difference was noted in the mean cell area within the nonmalignant subgroup, 1.80±3.01 mm in the 19G group versus 1.56±1.79 mm in the 21G group (P=0.60). CONCLUSION: The cell area obtained via the 19G needle was significantly larger than that obtained with the 21G needle. Further multicenter randomized studies are needed to identify the utility of the Flex 19G needle in diagnosing/subtyping lymphoproliferative disorders and adequacy for molecular testing in non-small cell lung cancer.

Neuroendocrine cell proliferations in lungs explanted for fibrotic interstitial lung disease and emphysema.

Using recently proposed pathological criteria, we determined the incidence of neuroendocrine cell proliferation in a series of explants with lung disease. Cases were defined as NECH (≥3 bronchioles with ≥5 endocrine cells), borderline diffuse neuroendocrine cell hyperplasia (DPNECH) (1-3 tumourlets with or without NECH), and DPNECH (≥3 tumourlets with NECH). Endocrine cells were identified by immunohistochemical staining for synaptophysin. There were 65 explants with interstitial lung disease (57 with non-sarcoid fibrotic lung disease, 8 with sarcoidosis), and 21 with centrilobular emphysema. Over one-third of all explant cases demonstrated histological criteria for NECH. There were three cases of DPNECH in the non-sarcoid fibrotic lung disease group (5%) and 20 cases of NECH (35%). The emphysema group had one case of DPNECH (5%), two cases of borderline DPNECH (10%), and seven cases with NECH (33%). The sarcoidosis group had two cases of DPNECH (25%) and three cases of NECH (38%). NECH is common in interstitial lung disease and emphysema. These results suggest that fibrotic lung disease is a predisposing factor for neuroendocrine cell proliferation, in addition to the known risk of epithelial neoplasms.

Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer patients with and without human immunodeficiency virus (HIV) infection.

OBJECTIVE: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in cancer immunology. There are limited but emerging data on expression of these molecules in HIV-infected lung cancer patients. MATERIALS AND METHODS: We reviewed archived lung cancer tissue samples from HIV-infected cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3, and percent of tumor infiltrating immune cells (TII) expressing PD-1 and PD-L1. Positive expression was defined as >5%. Statistical analysis was performed using the non-parametric Mann-Whitney test and the chi-square test. RESULTS: PD-L1 expression on tumor cells was positive in 23% of cases and 46% of controls. B7-H3 expression on tumor cells was positive in 92% of cases and 69% of controls. PD-1 expression on TII was positive in 69% of cases and 54% of controls. PD-L1 expression on TII was positive in 31% of cases and 69% of controls. B7-H3 percent expression on tumor cells was significantly higher in cases vs. controls (median 90% vs 20%, p = 0.005), but there were no significant differences in percent expression of PD-L1 on tumor cells, PD-1 on TII or PD-L1 on TII. CONCLUSION: HIV-infected lung cancer patients had significantly higher B7-H3 tumor expression compared to HIV-uninfected controls, with similar rates of tumor PD-L1 expression, as well as PD-1 and PD-L1 expression on TII. These results support inclusion of HIV-infected lung cancer patients in future immunotherapy trials.

Mice with Inflammatory Bowel Disease are Susceptible to Clostridium difficile Infection With Severe Disease Outcomes.

Background: Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases. Methods: We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created. Results: No CDI occurs in healthy control mice, wherease the incidence of CDI in IBD mice is 40%; however, in IBD mice that received antibiotics, the incidence of CDI is 100% and the disease is accompanied by high levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone, those IBD mice infected with C. difficile have more severe symptoms, toxemia, histopathological damage, and higher mortality. Moreover, several proinflammatory cytokines and chemokines are significantly elevated in the colon tissues from IBD mice infected with C. difficile. Conclusions: We, for the first time, demonstrate in an animal model that mice with dextran sulfate sodium induced-inflammatory bowel disease are significantly more susceptible to C. difficile infection, and that the bacterial infection led to more severe disease and death. These findings are consistent with clinical observations, thus, the animal model will permit us to study the pathogenesis of these concurrent diseases and to develop therapeutic strategies against the comorbidity of IBD and CDI.

Margin Analysis: Cutaneous Malignancy of the Head and Neck.

This article focuses only on margin analysis of the cutaneous malignancy of the skin. It discusses basal cell carcinoma, squamous cell carcinoma, and cutaneous melanoma. The management of the neck and distant disease are beyond the scope of this article, but it answers what is the appropriate surgical margin when excising these skin tumors, whether frozen sections are accurate for the analysis of these tumors, and treatment algorithm and rationale for a positive resection margin.

Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids.

Although epidemiological evidence in humans and bile acid feeding studies in rodents implicate bile acids as tumor promoters, the role of endogenous bile acids in colon carcinogenesis remains unclear. In this study, we exploited mice deficient in the ileal apical sodium-dependent bile acid transporter (ASBT, encoded by SLC10A2) in whom fecal bile acid excretion is augmented more than 10-fold. Wild-type and Asbt-deficient (Slc10a2 (-/-) ) male mice were treated with azoxymethane (AOM) alone to examine the development of aberrant crypt foci, the earliest histological marker of colon neoplasia and a combination of AOM and dextran sulfate sodium to induce colon tumor formation. Asbt-deficient mice exhibited a 54% increase in aberrant crypt foci, and 70 and 59% increases in colon tumor number and size, respectively. Compared to littermate controls, Asbt-deficient mice had a striking, 2-fold increase in the number of colon adenocarcinomas. Consistent with previous studies demonstrating a role for muscarinic and epidermal growth factor receptor signaling in bile acid-induced colon neoplasia, increasing bile acid malabsorption was associated with M3 muscarinic and epidermal growth factor receptor expression, and activation of extracellular signal-related kinase, a key post-receptor signaling molecule.

Postdischarge phone calls after pediatric hospitalization: an observational study.

OBJECTIVES: Difficulties with transition from inpatient to outpatient care can lead to suboptimal outcomes for patients. We implemented a protocol for systematic follow-up phone calls to families of pediatric patients after discharge, primarily to improve care transition. We also hypothesized that the phone calls would decrease readmissions and emergency department (ED) visits after discharge and improve patient satisfaction. METHODS: We conducted a quasi-experimental study examining the impact of routinely making follow-up phone calls, compared with historical control discharges. We implemented standardized attending physician phone calls to families of all patients discharged from a general pediatric hospitalist service. Calls were made within 72 hours of discharge to assess problems with transition. Charts were reviewed for documentation of difficulty with the care transition, 14-day and 30-day readmissions, ED visits, and Press-Ganey satisfaction scores. All results in the 12 months after the intervention were compared with the preceding12 months. RESULTS: We reached 78% of all patients' families by phone after discharge. Of the families reached, 19.9% needed an issue addressed, half of which were medication related. There were improvements in 14-day and 30-day readmissions and 14-day ED visit rates, as well as improvement in patient satisfaction scores, but none of these results reached statistical significance. CONCLUSIONS: Standardized, physician-performed, postdischarge phone calls identified frequent patient care issues related to difficulties with inpatient to outpatient transition, many of which were medication related. However, our study was underpowered to detect a statistically significant correlation with changes in readmission rates, ED visits, or patient satisfaction.

Biliary stent-related alterations can be distinguished from adenocarcinoma on bile duct brushings using a limited number of cytologic features.

INTRODUCTION: Although it is widely accepted that cytologic alterations secondary to a biliary stent can be difficult to distinguish from adenocarcinoma in pancreatobiliary exfoliative cytology, no systematic study has been undertaken to identify the cytologic features that best distinguish these entities. MATERIALS AND METHODS: A training set of 29 bile duct brushings (14 with biliary stents, originally classified as atypical or suspicious, with >6 months of benign clinical follow-up; and 15 diagnosed as adenocarcinoma with histologic confirmation) was evaluated for the following: nuclear enlargement, nuclear contour, nuclear overlap, chromatin distribution, nuclear-cytoplasmic ratio, anisonucleosis, macronucleoli, mitoses, acute inflammation, disorganization, necrosis, cell borders, single atypical cells, and 2 distinct cell populations. A distinct validation set of 31 equivocal stented brushings-13 later diagnosed with carcinoma and 18 with ≥6 months of benign follow-up-were similarly evaluated. Cases were categorized as benign or malignant using a scoring algorithm based on statistically significant features. RESULTS: Five features achieved statistical significance: atypical single cells (P = 0.0001), 2 distinct cell populations (P = 0.0007), and anisonucleosis (P = 0.0422) favored malignancy; distinct cell borders (P = 0.0018) and acute inflammation (P = 0.0035) favored benign. The algorithm correctly classified 12 of 14 benign and 15 of 15 malignant cases in the training set and 16 of 18 benign and 7 of 13 malignant cases in the validation set. CONCLUSIONS: Most bile duct brushings from patients with biliary stents could be definitively and correctly classified as either benign or malignant using 5 morphologic features: single atypical cells, binary cell population, anisonucleosis, distinct cell borders, and acute inflammation.

Ascending aortitis: a clinicopathological study of 21 cases in a series of 300 aortic repairs.

There are few single-institution clinicopathological series of aortitis. In this study, all ascending aneurysms were prospectively evaluated pathologically with ≥6 aortic sections over a 6-year period.Of 300 ascending aortic resections, there were 21 cases of aortitis (7%), in 11 women and 10 men (mean 67, range 41-88 years). There were 19 patients with aneurysms, and two patients with sclerosing periaortitis, clinically suspected to have intramural haematoma. Of the 19 patients with aneurysms (11 women), two had prior temporal arteritis, one ankylosing spondylitis, one IgA nephropathy, one undifferentiated autoimmune disease, one Lyme disease, and one fibromyalgia. In only two patients was aortitis suspected before surgery as the cause of aneurysm. Four patients developed distal aortic aneurysm requiring repeat surgery. Valve replacement or repair was necessary in nine patients, and two patients died after surgery. There were no significant differences between patients with and without autoimmune disease. The histological features were necrotising aortitis in 18 of 19 patients with aneurysmal aortitis, and there was one case of non-necrotising aortitis. One valve showed autoimmune valvulitis, congenitally bicuspid associated with ankylosing spondylitis. Necrotising aortitis was classified as acute (n = 5), healing (n = 9), and healed (n = 4). Acute necrotising aortitis was associated with need for valve replacement (p = 0.01) and younger age (p = 0.01). The healed phase had subtle histological features, sparse medial inflammation, marked medial attenuation, and chronic adventitial inflammation. Two patients with periaortitis demonstrated marked fibroinflammatory thickening of the adventitia with histological features typical of IgG4-related disease; neither had systemic symptoms. Ascending aortitis is histologically diverse, most frequently of the medial necrotising type, and is usually not suspected pre-operatively. Awareness of the histological spectrum is necessary for pathological diagnosis.

Divergent effects of muscarinic receptor subtype gene ablation on murine colon tumorigenesis reveals association of M3R and zinc finger protein 277 expression in colon neoplasia.

BACKGROUND: M3 and M1 subtype muscarinic receptors are co-expressed in normal and neoplastic intestinal epithelial cells. In mice, ablating Chrm3, the gene encoding M3R, robustly attenuates intestinal tumor formation. Here we investigated the effects of Chrm1 gene ablation, alone and in combination with Chrm3 ablation. METHODS: We used wild-type, Chrm1-/-, Chrm3-/- and combined Chrm1-/-/Chrm3-/- knockout (dual knockout) mice. Animals were treated with azoxymethane, an intestine-selective carcinogen. After 20 weeks, colon tumors were counted and analyzed histologically and by immunohistochemical staining. Tumor gene expression was analyzed using microarray and results validated by RT-PCR. Key findings were extended by analyzing gene and protein expression in human colon cancers and adjacent normal colon tissue. RESULTS: Azoxymethane-treated Chrm3-/- mice had fewer and smaller colon tumors than wild-type mice. Reductions in colon tumor number and size were not observed in Chrm1-/- or dual knockout mice. To gain genetic insight into these divergent phenotypes we used an unbiased microarray approach to compare gene expression in tumors from Chrm3-/- to those in wild-type mice. We detected altered expression of 430 genes, validated by quantitative RT-PCR for the top 14 up- and 14 down-regulated genes. Comparing expression of this 28-gene subset in tumors from wild-type, Chrm3-/-, Chrm1-/- and dual knockout mice revealed significantly reduced expression of Zfp277, encoding zinc finger protein 277, in tissue from M3R-deficient and dual knockout mice, and parallel changes in Zfp277 protein expression. Notably, mRNA and protein for ZNF277, the human analogue of Zfp277, were increased in human colon cancer compared to adjacent normal colon, along with parallel changes in expression of M3R. CONCLUSIONS: Our results identify a novel candidate mouse gene, Zfp277, whose expression pattern is compatible with a role in mediating divergent effects of Chrm3 and Chrm1 gene ablation on murine intestinal neoplasia. The biological importance of this observation is strengthened by finding increased expression of ZNF277 in human colon cancer with a parallel increase in M3R expression. The role of zinc finger protein 277 in colon cancer and its relationship to M3R expression and activation are worthy of further investigation.

Undifferentiated sarcoma of the liver: a case study of an erythropoietin-secreting tumor.

Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor usually found in children, with rare cases reported in adults. We present a case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL), which resembles UESL, who initially presented with a markedly elevated hematocrit (61.2%). Cytogenetic studies for polycythemia vera were negative, but the patient's erythropoietin (EPO) was elevated. A computed tomography scan and subsequent partial hepatectomy revealed a well-circumscribed, partially cystic mass in the right lobe of the liver measuring 34 cm. Following surgery, the patient's EPO level and hematocrit dropped to within normal range and remained so for 1 year, at which point it rose again. A subsequent magnetic resonance imaging scan showed a liver mass at the previous resection margin, consistent with a recurrence. In this case study, we describe the first reported USL resembling an UESL that secretes EPO, which was a useful marker of tumor recurrence.

Pearls and oy-sters: the utility of cytology and flow cytometry in the diagnosis of leptomeningeal leukemia.

Diagnosis of leptomeningeal leukemia (and more broadly, leptomeningeal metastasis [LM]) is based on:

Cholinergic muscarinic receptor activation augments murine intestinal epithelial cell proliferation and tumorigenesis.

BACKGROUND: Previously, we showed that M3 muscarinic receptor (M3R; gene name Chrm3) deficiency attenuates murine intestinal neoplasia, supporting the hypothesis that muscarinic receptors play an important role in intestinal tumorigenesis. METHODS: To test this hypothesis, in the present study we treated mice with bethanechol, a non-selective muscarinic receptor agonist without nicotinic receptor activity, and examined its effects on azoxymethane (AOM)-induced colon neoplasia. Mice were provided with drinking water containing 400 µg/mL bethanechol chloride or water without additions (control) for a total of 20 weeks, a period that included the initial 6 weeks when mice received intraperitoneal injections of AOM. RESULTS: When euthanized at week 20, control mice had 8.0 ± 1.3 tumors per animal, whereas bethanechol-treated mice had 10.4 ± 1.5 tumors per mouse (mean ± SE; P = 0.023), a 30% increase. Strikingly, tumor volume per animal was increased 52% in bethanechol-treated compared with control mice (179.7 ± 21.0 vs. 111. 8 ± 22.4 mm(3); P = 0.047). On histological examination, bethenechol-treated mice also had more adenocarcinomas per animal (8.0 ± 1.0 vs. 4.1 ± 0.6 for control mice, P = 0.0042). Cell proliferation in both normal mucosa and adenocarcinomas was increased in bethanechol-treated compared to control mice. Also, in tumors, bethanechol treatment increased expression of Chrm3, Egfr and post-Egfr signaling molecules Myc and cyclin D1. Bethanechol treatment increased the thickness of normal colonic mucosa and the expression of selected matrix metalloproteinase (Mmp) genes, including Mmp7, Mmp10 and Mmp13. CONCLUSIONS: These findings support a prominent role for muscarinic receptors in colon neoplasia, and identify post-receptor signaling molecules as potential therapeutic targets.

18F-FDG PET/CT in a recurrent diffuse malignant peritoneal mesothelioma.

Peritoneal mesothelioma is a rare and aggressive tumor. Early diagnosis of the disease is difficult, delaying effective treatment. We report a case of recurrent, biphasic, diffuse, malignant peritoneal mesothelioma. Initial abdominal computed tomography showed abnormal but nonspecific findings suggestive of an ovarian malignancy, with a negative endoscopy and laboratory studies. An abdominal exploratory laparotomy found widespread malignancy within the peritoneum with a pathological diagnosis of peritoneal mesothelioma. A PET/CT imaging showed diffusely increased metabolic activity throughout the peritoneum, with no evidence of thoracic or pleural involvement. This case demonstrates the PET/CT findings seen with malignant recurrent peritoneal mesothelioma.