Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

BACKGROUND: Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective. OBJECTIVE: This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens. DESIGN: Raters included surgeons, pathologists, pathology residents, pathologists' assistants, and pathologists' assistant trainees. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters postfixation. Four parameters were evaluated: mesorectal bulk, surface regularity, defects, and coning. Interrater agreement was measured using ordinal α-values. SETTING: The study was conducted at a single academic center. MAIN OUTCOME MEASURES: The primary outcome was agreement between individuals when grading total mesorectal excision specimens. RESULTS: A total of 37 total mesorectal excision specimens were assessed. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning, and overall grade were 0.85, 0.85, 0.92, 0.84, and 0.91. When compared with all raters, pathologists and residents had higher agreement and pathologists and surgeons had lower agreement. Ordinal α-values comparing pathologist and pathologist's assistant agreement for overall grade were similar pre- and postfixation (0.78 vs 0.80), but agreement for assessing defects decreased postfixation. Among pathologists' assistants, agreement was higher when grading specimens postfixation than when grading fresh specimens. LIMITATIONS: Assessment bias may have occurred because of the greater number of pathologists' assistants participating than the number of residents and pathologists. CONCLUSIONS: The results indicate good interrater agreement for the assessment of overall grade, with defects showing the best interrater agreement in fresh specimens. Although total mesorectal excision specimens may be consistently graded postfixation, the assessment of defects postfixation may be less reliable. This study highlights the need for additional knowledge-transfer activities to ensure consistency and accurate grading of total mesorectal excision specimens. See Video Abstract at http://links.lww.com/DCR/A497.

Inflammatory pseudotumours of the oesophagus--histological and immunohistochemical findings.

AIMS: Inflammatory oesophageal pseudotumours are rare lesions, thought to be reactive. Due to marked atypia of the stromal cells, these can be misdiagnosed as malignancies. The objective of this study was to characterize histological and immunohistochemical features of a series of inflammatory pseudotumours of the oesophagus. METHODS AND RESULTS: We present 12 cases of inflammatory oesophageal pseudotumours, occurring in seven females and five males, with a mean age of 57.3 years. Clinical presentations were variable; dysphagia, abdominal pain and weight loss and upper gastrointestinal bleed. In a majority of the cases, nodules or masses in the distal oesophagus were identified at endoscopy. Microscopically, the lamina propria in all 12 cases contained inflammation and granulation tissue. Ten of 12 cases showed mucosal ulceration and 11 of 12 cases had acutely inflamed epithelium. Markedly atypical pleomorphic stromal cells with prominent nucleoli were identified in all 12 cases. Immunohistochemistry showed uniform positivity for vimentin in 11 of 11 cases, and two of seven cases demonstrated weak focal positivity for smooth muscle actin. The cells were negative for all other markers. CONCLUSIONS: Reactive oesophageal lesions can show marked nuclear atypia in stromal fibroblasts/myofibroblasts, which are easily mistaken for malignancies. Pathologists must consider the diagnosis of an inflammatory pseudotumour if stromal atypia is present in an inflammatory background.

Severity of coeliac disease and clinical management study when using a non-metabolised medication: a phase I pharmacokinetic study.

OBJECTIVE: The non-metabolised antihistamine fexofenadine has oral absorption resulting from transporter activity. Uptake by enterocyte organic anion transporting polypeptides and efflux by an ATP-binding cassette transporter (P-glycoprotein) are primary determinants. Coeliac disease-mediated lesions to the small intestinal mucosa may alter oral absorption of the drug probe, fexofenadine. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study SETTING: London, Ontario, Canada PARTICIPANTS: Patients with coeliac disease (n=41) with positive serology and healthy individuals (n=48). MAIN OUTCOME MEASURES: Patients with coeliac disease-duodenal histology and oral fexofenadine pharmacokinetics within a 3-week period. Healthy individuals-oral fexofenadine pharmacokinetics with water and grapefruit juice. RESULTS: Patients with coeliac disease were stratified by disease severity: Group A (n=15, normal), B+C (n=14, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=12, moderate to severe villous blunting). Patients with coeliac disease in groups A, B+C and D and healthy individuals receiving water had similar fexofenadine AUC0-8 (2038±304, 2259±367, 2128±410, 1954±138 ng.h/mL; p>0.05; mean±SEM) and Cmax (440±73, 513±96, 523±104, 453±32 ng/mL; p>0.05), respectively. These four groups all had higher fexofenadine AUC0-8 (1063±59; p<0.01) and Cmax (253±18; p<0.05) compared with those for healthy individuals receiving grapefruit juice. Coeliac groups had a positive linear trend between disease severity and fexofenadine Tmax (2.0±0.3, 2.7±0.4, 3.1±0.5 hours; p<0.05). CONCLUSIONS: Coeliac disease severity based on duodenal histopathology did not affect oral fexofenadine bioavailability. Increased Tmax suggested absorption distal to the duodenum (jejunum + ileum), where histology seems more normal which may be the key determinant. Patients with coeliac disease may not require consideration for alternative clinical drug management for a number of non-metabolised and transport-mediated medications.

Reduction of liver ischemia reperfusion injury by silencing of TNF-α gene with shRNA.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a central mediator in the hepatic response to ischemia/reperfusion. Short hairpin RNA (shRNA) has been proven to be an effective means of harnessing the RNA interference pathway in mammalian cells. In the current study, we investigated whether silencing TNF-α gene with shRNA can prevent liver ischemic reperfusion injury (IRI). METHODS: Male BalB/c mice were randomized to TNF-α shRNA, scramble shRNA, or sham operation groups. TNF-α shRNA and scramble shRNA groups were injected 48 h before inducing IRI. IRI was induced via microaneurysm clamps applied to the left hepatic artery and portal vein. Six hours after reperfusion, IRI injury was examined by serum level of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver histopathology, MPO, and MDA level, as well as by relative quantities of TNF-α mRNA. RESULTS: TNF-α expression induced by ischemia reperfusion in the liver was significantly suppressed after treatment with TNF-α shRNA compared with the group treated with scramble shRNA (P < 0.001). Mice treated with TNF-α shRNA showed lower peak values of AST and ALT than scramble shRNA treated mice (P < 0.001). On histopathologic slides, mice treated with TNF-α shRNA had significantly less ischemia/reperfusion injury based on Suzuki score than the scramble shRNA group, 3.57 ± 2.30 and 8.83 ± 0.98 respectively (P < 0.001), while the sham group was not significantly different from the TNF-alpha shRNA group, 0 ± 0 and 3.57 ± 2.30, respectively (P = 0.075). Liver tissue MDA levels were significantly lower in mice treated with TNF-α shRNA as compared with the group treated with scramble shRNA (P < 0.01). Immunohistochemical staining for MPO was significantly lower in mice treated with TNF-α shRNA compared with the group treated with shRNA (compared with treated with scramble shRNA group.) CONCLUSIONS: Liver IRI can be minimized through gene silencing of TNF-α. This may represent a novel therapy in the setting of transplantation and in other conditions associated with IRI of the liver.

Globular glial tauopathy, a newly recognized white matter tauopathy, with depression/anxiety disorder: report and review of classification.

Several studies have recently described 4-repeat tauopathies that are characterized by the presence of globular glial inclusions. These inclusions are astrocytic or oligodendroglial, show extensive white matter involvement, and have a wide range of neuropathological and clinical presentations. Globular glial tauopathy (GGT) is classified into three subtypes according to clinical manifestations. Type I is characterized by frontotemporal lobar degeneration and represents a group of diseases with diverse clinical and histopathological features. Some of these disorders are associated with abnormal microtubule-associated protein tau gene. Type II presents as motor impairment due to pyramidal involvement, whereas type III is a combination of the features of types I and II. This report describes a rare case of GGT that manifested as depression and anxiety and demonstrates its neuropathological features. We have also compared the features of this case with those of previously reported cases and have revisited the classification.

Recurrent Hepatocellular Carcinoma After Liver Transplantation: Validation of a Pathologic Risk Score on Explanted Livers to Predict Recurrence.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation is a major cause of morbidity and mortality. To date, there is no widely accepted pathologic assessment tool to predict HCC recurrence. In 2007, we developed a pathologic risk score that stratified patients into low, intermediate, or high risk for recurrence based on explant pathology. The aim of this study was to externally validate this risk score. METHODS: We retrospectively evaluated 124 patients over a 10-year period who underwent liver transplantation for HCC. Using explanted pathology reports, each patient was stratified according to the pathologic risk score and followed over time for HCC recurrence. RESULTS: Recurrence occurred in 15 patients (12%) after a mean follow-up of 25 months. Using the pathologic risk score, 10 (8%), 21 (17%), and 93 (75%) patients were stratified into high, intermediate, and low risk of recurrence, respectively. Among these risk groups, recurrence occurred in 50%, 28.5%, and 4.3% (P < .01) of patients, respectively. Using the optimal cutoff value ≤3.5, our risk score had a sensitivity of 80% and specificity of 79% with an area under the receiver operator characteristic curve of 0.8. Those with lower risk scores had higher recurrence-free survival (P < .0001). CONCLUSIONS: Our pathologic risk score accurately risks stratified patients for HCC recurrence after liver transplant. It can be used to tailor surveillance strategies for those deemed to be at elevated risk for recurrence.

Complete duodenal necrosis associated with non-traumatic duodenal hematoma requiring emergent pancreatico-duodenectomy.

INTRODUCTION: Duodenal necrosis is a rare complication of acute pancreatitis but can occur given the shared blood supply to the head of the pancreas and the duodenum. PRESENTATION OF CASE: A 55-year-old male presented with acute-on-chronic pancreatitis and a duodenal hematoma. The hematoma expanded to occlude the biliary tree and, shortly after, the duodenum necrosed and perforated. The patient required an emergent pancreaticoduodenectomy performed in two stages. DISCUSSION: Surgical management is complex and a difficult challenge for a general surgeon. Many advocate for wide drainage to create a controlled fistula using a malecot through the wall defect/separate duodenotomy/a retrograde jejunostomy tube. This case represents an extreme variation on this issue which was best managed by definitive resection given the extent of the necrosis. CONCLUSION: This case report demonstrates that duodenal hematoma and necrosis should be recognized as part of the spectrum of consequences of acute pancreatitis. General surgeons should have a surgical approach to this complication whether that be diversion or definitive resection.

Severity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study.

OBJECTIVE: Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study. SETTING: London, Ontario, Canada. PARTICIPANTS: Patients with coeliac disease (n=47) with positive serology and healthy individuals (n=68). MAIN OUTCOME MEASURES: Patients with coeliac disease-upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals-oral felodipine pharmacokinetics study with water and grapefruit juice. RESULTS: Coeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0-8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0-8 (11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice. CONCLUSIONS: Increased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity.

Lobular capillary hemangioma of the liver.

BACKGROUND: Lobular capillary hemangioma (LCH) is a benign vascular tumor that is rare in adults and has never been reported in the liver. This vascular lesion usually presents on the skin or mucous membranes, and predominantly affects children. METHODS: LCH as a large asymptomatic hepatic mass was seen in a 35-year-old female. Imaging and pathologic characteristics of the mass are reviewed, and the relevant literature is also reviewed. RESULTS: A large vascular hepatic lesion was observed in an asymptomatic 35-year-old female. Pathologic examination after surgical resection revealed typical features of LCH. CONCLUSIONS: This is the first case of lobular capillary hemangioma seen as a liver lesion in an adult. Large vascular hepatic lesions pose significant difficulties in discerning benign from potentially malignant conditions. In this report we describe the pitfalls and radiological uncertainties with interpreting vascular lesions of the liver.

CDX2 and Muc2 immunohistochemistry as prognostic markers in stage II colon cancer.

The treatment for colorectal cancer is largely surgical followed by adjuvant chemotherapy in high-risk cases. In patients with stage II cancer, there is no clear benefit for chemotherapy, and the current tools for assessment of risk are inadequate. A recent study identified that colorectal cancer with a gene signature similar to undifferentiated colonic stem cells was associated with a worse outcome. It was later shown that loss of CDX2 detected by immunohistochemistry (IHC) alone resulted in a worse prognosis and that this could be used to predict patients who would benefit from chemotherapy. Having observed that CDX2 expression can be patchy, we elected to validate these prior results for clinical practice using whole-slide IHC. The pathology of all cases was reviewed, and 3 blocks were selected for CDX2 IHC. We also expanded the panel beyond CDX2 to assess whether other markers in the gene signature including CDX1, Muc2, GPX2, and villin could better predict outcome. Among 210 cases, CDX2 expression was diffusely lost in 11% and focally lost in 23% of cases. There was no difference in survival based on CDX2 expression, but Muc2 loss was associated with reduced survival (hazard ratio, 3.32; 95% confidence interval, 1.20 to 9.20). No significant differences in outcome were identified based on CDX1, GPX2, or villin expression. In keeping with this, assessment of The Cancer Genome Atlas gene expression data demonstrated that decreased Muc2 expression was associated with reduced overall survival. Our results with whole-slide IHC are different from the previous studies and caution against the use of CDX2 in isolation as a prognostic marker in clinical practice. We have identified that loss of Muc2 is associated with reduced survival. This supports the use of the colonic differentiation gene expression signature to identify high-risk patients but cautions against the use of any one IHC-based marker in isolation.

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between SSA and TSA, because these architectural abnormalities may well be a reflection of abnormalities in genetically programmed mucosal development.

Survivin and hedgehog protein expression in serrated colorectal polyps: an immunohistochemical study.

Sessile serrated adenomas and traditional serrated adenomas are pathogenetically related to inhibition of apoptosis. Survivin and hedgehog proteins, including sonic hedgehog, patched, and smoothened, inhibit apoptosis, with hedgehog proteins forming a signal transduction cascade implicated in digestive cancers. This study compares survivin and hedgehog protein expression in serrated polyps and tubulovillous adenomas. Biopsies of sessile serrated adenomas (48) and traditional serrated adenomas (10) diagnosed during 2005 were retrieved from our files. Biopsies of normal mucosa (10), hyperplastic polyps (14), and tubulovillous adenomas (22) were used for comparison. Immunohistochemistry for survivin, sonic hedgehog, patched, and smoothened was graded as high or low grade. chi(2) tests were used to evaluate correlation between polyp type and survivin and hedgehog expression. Traditional serrated adenomas were also compared to sessile serrated adenomas with foci of cytological dysplasia (11 cases) with respect to MLH1 and p53 expression. Sessile serrated adenomas showed high-grade nuclear and cytoplasmic expression of survivin at the bottom of crypts more frequently than tubulovillous adenomas (60% versus 18%, P = .001 [nuclear]; 54% versus 18%, P = .005 [cytoplasm]), the latter showing a top-heavy pattern of staining. Survivin expression in hyperplastic polyps was similar to sessile serrated adenomas, being bottom-heavy, whereas traditional serrated adenomas showed diffuse staining throughout crypts. Although traditional serrated adenomas showed high-grade expression of sonic hedgehog more frequently than tubulovillous adenomas (90% versus 18%; P < .001), sonic hedgehog, patched, and smoothened expression was low grade among normal mucosa, hyperplastic polyps, and sessile serrated adenomas. All cytological dysplasias showed increased p53 expression within dysplastic foci, and MLH1 was also lost within dysplastic foci in 4 cases; traditional serrated adenomas showed intact MLH1 expression and minimal p53 expression throughout. Survivin expression is localized to the bottom of crypts in sessile serrated adenomas and hyperplastic polyps, whereas tubulovillous adenomas show top-heavy expression. Traditional serrated adenomas express survivin throughout crypts, suggesting intersection between the serrated and conventional adenoma-cancer pathways. Sonic hedgehog up-regulation is characteristic of traditional serrated adenomas, distinguishing this entity from other colorectal polyps.

Pathological effects of drugs on the gastrointestinal tract: a review.

Drug-induced injury of the gastrointestinal (GI) tract is increasingly common but generally under-recognized. Although there is an overwhelming number of drugs that are associated with adverse GI effects, there is a limited number of characteristic injury patterns that should prompt consideration of drug-induced GI pathology. These include the following: erosions, ulcers, and strictures; crystal deposition; parietal cell changes; reactive gastropathy; pseudodysplastic changes; microscopic colitis; infectious or necrotizing enterocolitis; ischemic colitis; focal active colitis; and increased epithelial apoptosis. This article reviews morphological and pathophysiological features of some of the more common and pathologically recognizable drug-related injury patterns and provides a practical guide for the recognition and diagnosis of drug-induced pathology in the upper and lower GI tract.

The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment.

Total mesorectal excision (TME) refers to the surgical removal of the complete perirectal soft tissue envelope, using sharp instruments under direct vision, and has become the contemporary standard of care for patients with rectal cancer. Pathologists play a key role in the evaluation of these specimens, including the quality assurance of surgical performance, as well as evaluation of the circumferential radial margin (CRM). While the latter is the most significant predictor of local recurrence, the quality of the excised mesorectum is another important factor in assessing the risk of local recurrence in patients with a negative CRM. Since proper pathological assessment of the TME specimen provides important prognostic information, as well as critical feedback to surgeons regarding technical performance, it is important to have adequate guidelines for the macroscopic handling of these specimens. The CLASSICC study of the Medical Research Council in the United Kingdom, as well as the Dutch TME trial have introduced a new standard for the pathological assessment of TME specimens, including an approach that involves assessment in both the fresh and fixed states, at least 48 hours of fixation of an intact specimen, with observations made on both the external appearance and cross-sectional slices. This article reviews the pathological assessment of the TME specimen, including basic definitions, current international guidelines, an approach to evaluating the mesorectum and a discussion of special issues relating to margins, lymph node retrieval and effects of neoadjuvant therapy.

The impact of knowledge transfer on the detection of venous invasion in colorectal cancer.

Venous invasion (VI) is an independent predictor of hematogenous metastasis and mortality in colorectal cancer (CRC) yet remains widely underreported. Its detection may require recognition of subtle morphologic clues, which at times are only unmasked with an elastin stain. This study evaluates the impact of a knowledge transfer initiative (KTI) on VI detection in a "real-world" pathology practice setting. Following participation in an interobserver variability study of VI detection (Kirsch et al, 2013), 12 participants received educational materials highlighting key issues in VI detection. Eighteen months later, participants were invited to submit pathology reports from all CRC resections signed out 18 months prior to and 18 months following the KTI (n = 266 and n = 244, respectively). Nine pathologists participated. Reports were reviewed for VI and other established prognostic factors. Numbers of elastin stains and tumor-containing blocks were also recorded. Comparative analyses were adjusted for baseline differences in tumor, lymph node, and metastasis stage; tumor location; use of neoadjuvant therapy; and number of tumor-containing blocks. VI detection increased significantly post-KTI versus pre-KTI (39.3% versus 18.4%, adjusted odds ratio [OR] 2.86 [1.91-4.28], P < .001). Increased VI detection post-KTI was observed in both stage II (31.8% versus 12.5%, adjusted OR 3.27 [1.45-7.42], P = .004) and stage III CRC (62.4% versus 28.2%, adjusted OR 4.23 [2.37-7.55], P < .001). All pathologists demonstrated increased VI detection post-KTI. Use of elastin stains was significantly higher post-KTI versus pre-KTI (61.5% versus 5.3% of cases respectively, P < .001). This study demonstrates the effectiveness of knowledge transfer in increasing VI detection in routine pathology practice.

Gastrointestinal stromal tumors: a contemporary review.

The literature on gastrointestinal stromal tumors (GISTs) has rapidly expanded and has demonstrated how scientific advancements in diagnosis can revolutionize the understanding of disease, while paving the way for effective treatment. While KIT (CD117) immunohistochemistry has established our definition of GISTs, molecular genetics continue to refine it. Elucidation of the aberrant receptor tyrosine kinase (RTK) model of GIST pathogenesis through mutations in c-kit and platelet-derived growth factor alpha PDGFRalpha proto-oncogenes has been prerequisite to the use of imatinib mesylate (STI571, Gleevec; Novartis, Switzerland), a molecular inhibitor of several tyrosine kinases, in the treatment of GISTs. In addition to providing a means for effective treatment, clarification of the molecular pathology of GISTs may potentially offer a new classification of these tumors by correlating genotype with histological, immunohistochemical, and clinical phenotype. This article seeks to review current knowledge of GISTs, offering a practical guide to their diagnosis and describing current epidemiological, molecular biological, and therapeutic aspects.

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers. CASE PRESENTATION: A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-alpha immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery. CONCLUSION: This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.

Increasing incidence of adenocarcinoma of the gastroesophageal junction and distal stomach in Canada -- an epidemiological study from 1964-2002.

BACKGROUND: The increasing incidence of esophageal and proximal gastric (cardia) adenocarcinoma and the decreasing incidence of distal gastric (antropyloric) adenocarcinoma has been documented in several populations. The aim of the present study was to examine incidence trends of these neoplasms in Ontario, Canada's most populous province, over a 39-year period. METHODS: Analyses were based on data obtained from the Ontario Cancer Registry of Cancer Care Ontario. Number of cases and rates per 100,000 age-adjusted to the 1996 Canadian standard, were obtained for all esophageal and gastric carcinoma cases reported between 1964 and 2002. Rates were grouped into five-year periods to analyze trends over the 39-year period. Point and 95% CI estimates of average annual percentage change in incidence rates were calculated with a log-linear regression model. RESULTS: The incidence of adenocarcinoma of the distal esophagus increased in men and women (average annual increase of 9.5% in men; 4.3% in women). The incidence of adenocarcinoma of the cardia increased in men and women (average annual increase of 7.3% in men; 5.8% in women). The incidence of antropyloric adenocarcinoma increased in men and women (average annual increase of 4.4% in men; 5.3% in women). The incidence of esophageal squamous cell carcinoma remained stable. CONCLUSIONS: There has been a significant increase in the incidence of adenocarcinoma around the gastroesophageal junction in men over the 39-year study period. The increase in incidence of distal gastric adenocarcinoma is unexpected and may relate to a reclassification phenomenon, immigration trends in Ontario and a rising incidence of diffuse/signet ring cell adenocarcinoma.

The Future Liver Remnant in Patients Undergoing the Associating Liver Partition with Portal Vein Ligation for Staged Hepatectomy (ALPPS) Maintains the Immunological Components of a Healthy Organ.

BACKGROUND AND AIMS: A short-interval, two-stage approach termed associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) increases the number of patients with extensive malignant disease of the liver and a small future liver remnant (FLR) that can undergo liver resection. While this approach results in accelerated liver hypertrophy of the FLR, it remains unknown whether this phenomenon is restricted to liver parenchymal cells. In the current study, we evaluated whether ALPPS alters the immunological composition of the deportalized lobe (DL) and the FLR. METHODS: In this prospective, single-center study, liver tissue from the DL and the FLR were collected intra-operatively from adult patients undergoing ALPPS for their liver metastases. The extent of hypertrophy of the FLR was determined by volumetric helical computed tomography. Flow cytometry and histological analyses were conducted on liver tissues to compare the frequency of several immune cell subsets, and the architecture of the liver parenchyma between both stages of ALPPS. RESULTS: A total of 12 patients completed the study. Histologically, we observed a patchy peri-portal infiltration of lymphocytes within the DL, and a significant widening of the liver cords within the FLR. Within the DL, there was a significantly higher proportion of B cells and CD4(+) T cells as well innate-like lymphocytes, namely mucosa-associated invariant T (MAIT) cells and natural killer T (NKT) cells following ALPPS. In contrast, the frequency of all evaluated immune cell types remained relatively constant in the FLR. CONCLUSION: Our results provide the first description of the immunological composition of the human liver following ALPPS. We show that following the ALPPS procedure, while the immune composition of the FLR remains relatively unchanged, there is a moderate increase in several immune cell populations in DL. Overall, our results support the continued utilization of the ALPPS procedure.

In-situ and invasive carcinoma within a phyllodes tumor associated with lymph node metastases.

BACKGROUND: Phyllodes tumors (cystosarcoma phyllodes) are uncommon lesions in the female breast. Rarely, the occurrence of carcinoma within a phyllodes tumor has been reported in the literature, but has never been associated with lymph node metastases. CASE PRESENTATION: A 26-year-old woman presented with a firm, mobile, non-tender mass in the left breast and palpable lymph nodes in the left axilla. The excised lesion appeared well circumscribed and lobulated, with variable fleshy and firm areas. Microscopic examination showed a circumscribed fibroepithelial lesion with a well developed leaf-like architecture, in keeping with a benign phyllodes tumor. The epithelial component showed extensive high grade ductal carcinoma in-situ (DCIS) and invasive carcinoma of no special type, located entirely within the phyllodes tumor. Subsequent axillary lymph node dissection revealed metastatic carcinoma in four lymph nodes. CONCLUSIONS: Although rare, phyllodes tumors may harbor DCIS and invasive carcinoma, with potential for lymph node metastasis.