IQGAP1 and IQGAP2 are reciprocally altered in hepatocellular carcinoma.

BACKGROUND: IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC. METHODS: IQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of the Iqgap2 promoter was determined by pyrosequencing of bisulfite-treated genomic DNA. RESULTS: IQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although the Iqgap2 promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6). CONCLUSIONS: We conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of the Iqgap2 promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.

Solitary synovial osteochondroma.

Solitary synovial osteochondroma (SSO) is a rare variant of extraskeletal osteochondroma. The aim of this study was to review 5 cases of SSO, including clinical, radiographic, and histopathologic features. Five cases of SSO were retrieved from our files. Histopathologic and radiographic findings were reviewed, and a clinicopathologic correlation was performed. Patients' ages ranged from 33 to 63 years. Knee mass was the most common presentation. All cases were well circumscribed and had multiple cartilaginous lobules surrounded by fibroadipose tissue. Microscopically, lobulated adult-type hyaline cartilage with central calcification was noted. Cytologic atypia was present in one case, but malignant features were absent. Two cases were suggestive of chondrosarcoma on imaging studies. Patients underwent surgery, which was curative in cases for which follow-up was available. In conclusion, SSO is a rare lesion that may mimic low-grade chondrosarcoma at times. Correct recognition of SSO depends on radiographic and clinicopathologic analysis.

Differences in ablation size in porcine kidney, liver, and lung after cryoablation using the same ablation protocol.

OBJECTIVE: The purpose of our study was to assess the variation in size of acute necrosis and the variation in thermal map measured during cryoablation in multiple organs using the same ablation protocol for each organ. MATERIAL AND METHODS: Eight female pigs underwent one cryoablation per organ of kidney, lung, and liver performed with open surgery with a 2.4-mm cryoprobe. A 12- and 8-minute double-freeze cycle was used. Intratissue temperatures were monitored using 16-gauge thermometers spaced at 5.0-mm increments from the cryoprobe. The comparison of results among tissues was performed using the multiple analysis of variance. The -20 degrees C thermal diameter was correlated with tissue damage. The kidneys, lungs, and liver were removed and examined histologically for a pathologic complete coagulative necrosis zone. RESULT: A single 2.4-mm cryoprobe had a mean ice ball diameter in kidney, lung, and liver of 38.5 +/- 4.7, 35.5 +/- 3.6, and 32.5 +/- 2.7 mm, respectively. A mean -20 degrees C thermal diameter was achieved at 24.07 +/- 1.38 mm in kidney, 12.76 +/- 3.0 mm in lung, and 8.8 +/- 3.7 mm in liver by means of regression analysis. The acute pathologic complete coagulative necrosis zone size was 21.0 +/- 1.56 mm (kidney), 11.6 +/- 1.48 mm (lung), and 8.0 +/- 1.20 mm (liver). CONCLUSION: The inherent characteristics of different organs manifest different ablation zone sizes during cryoablation despite the same ablation protocol being used. This information should be factored into planning for ablation procedures.

Clinical, pathologic, and outcome study of hyperplastic and sessile serrated polyps in inflammatory bowel disease.

There is evidence that some cancers in patients with inflammatory bowel disease (IBD) develop via the serrated pathway of carcinogenesis. This study examined the clinicopathological features and outcome of 115 IBD patients (65 with ulcerative colitis, 50 with Crohn disease), all with at least 1 serrated polyp at endoscopy or colon resection, including the presence of synchronous and metachronous conventional neoplastic lesions (dysplasia or adenocarcinoma), over an average follow-up period of 56.4 months. Conventional neoplasia was categorized as flat dysplasia (low or high grade), sporadic adenoma, adenoma-like dysplasia-associated lesion or mass, or adenocarcinoma. Overall, 97% of patients had at least 1 hyperplastic polyp (HP), 6% had a sessile serrated adenoma/polyp, and none had a traditional serrated adenoma. Eight patients (7%) had a synchronous conventional neoplastic lesion; only 1 had flat dysplasia (1%) and 2 had adenocarcinoma (2%). Thirteen patients developed a metachronous conventional neoplastic lesion, with 8 developing their conventional neoplasm within an area of previous or concurrent colitis; only 1 patient developed flat dysplasia (1%), and none developed adenocarcinoma. A higher proportion of patients with both an HP and a synchronous conventional neoplastic lesion at index developed a metachronous conventional neoplastic lesion, compared with those with an index HP only (25% versus 7%). These results suggest that IBD patients (both ulcerative colitis and Crohn disease patients) with HP have a very low risk of developing a conventional neoplastic lesion (flat dysplasia or adenocarcinoma) that would warrant surgical resection.

Blood-based biomarkers can differentiate ulcerative colitis from Crohn's disease and noninflammatory diarrhea.

BACKGROUND: Blood gene expression profiling has been used in several studies to identify patients with a number of conditions and diseases. A blood test with the ability to differentiate Crohn's disease (CD) from ulcerative colitis (UC) and noninflammatory diarrhea would be useful in the clinical management of these diseases. METHODS: Affymetrix U133Plus 2.0 GeneChip oligonucleotide arrays were used to generate whole blood gene expression profiles for 21 patients with UC, 24 patients with CD, and 10 control patients with diarrhea, but without colonic pathology. RESULTS: A supervised learning method (logistic regression) was used to identify specific panels of probe sets which were able to discriminate between UC and CD and from controls. The UC panel consisted of the four genes, CD300A, KPNA4, IL1R2, and ELAVL1; the CD panel comprised the four genes CAP1, BID, NIT2, and NPL. These panels clearly differentiated between CD and UC. CONCLUSIONS: Gene expression profiles from blood can differentiate patients with CD from those with UC and from noninflammatory diarrheal disorders.

Adenocarcinoma in ectopic prostatic tissue at dome of bladder: a case report of a patient with urothelial carcinoma of the bladder and adenocarcinoma of the prostate.

We report a case of ectopic prostate tissue with an associated prostatic adenocarcinoma occurring in the dome of the urinary bladder. A 62-year-old man presented with a 4-month history of persistent microscopic hematuria following a urinary tract infection. Other complaints included frequent urination, but there was neither dysuria nor gross hematuria. Digital rectal examination revealed a smooth prostate of normal size. Cystoscopic examination revealed a sessile lesion of the anterior bladder neck and multiple smaller papillary lesions throughout the bladder. Following a transurethral resection of the bladder tumor with a diagnosis of muscle-invasive transitional cell carcinoma grade 3, a radical cystoprostatectomy was performed. The diagnosis of transitional cell carcinoma was confirmed, but in addition, a different lesion was also incidentally found in the dome of the bladder. This incidental lesion showed a prostatic adenocarcinoma arising from ectopic prostatic tissue within the bladder submucosa. The prostate also showed prostatic adenocarcinoma, but this was minimal, low grade, and confined to the prostate gland, and thus it was felt to be unlikely to have metastasized to the bladder dome. Adenocarcinoma arising in ectopic prostatic tissue is a rare finding and to our knowledge only 1 case has been previously described, occurring in the soft tissue adjacent to the prostate. We report the first case of adenocarcinoma arising in ectopic prostatic tissue within the bladder.

Sarcomatoid chromophobe renal cell carcinoma with heterologous sarcomatoid elements. A case report and review of the literature.

Chromophobe renal cell carcinoma (CRCC) is a distinct subtype of renal cell carcinoma (RCC) that is well known for its relatively good prognosis. Sarcomatoid transformation in this tumor, although rare, has been well documented in the literature and, as in other types of RCC, carries an ominous prognosis for the patient. The finding of heterologous elements in the sarcomatoid component of CRCC is an extraordinary event, which has been reported in only 2 previous cases. Here, we present the third such case, occurring in the left kidney of a previously healthy 63-year-old woman. The nephrectomy specimen showed CRCC with extensive sarcomatoid changes displaying heterologous elements in the form of chondrosarcomatous and osteosarcomatous differentiation. As in other sarcomatoid RCCs, this tumor behaves aggressively, with frequent distant metastases. It is important to recognize the sarcomatoid component in these tumors because of its consequential adverse prognosis for the patient.

Retrospective study of clinicopathologic features and prognosis of high-grade neuroendocrine carcinoma of the esophagus.

Clinicopathologic features of esophageal neuroendocrine carcinoma (NEC), apart from those of small-cell carcinoma, have not been characterized. We evaluated the clinicopathologic features and prognosis including overall survival of NEC of the esophagus. We identified 40 patients with esophageal NEC from our institutional database. All cancers had been clinically staged using endoscopic ultrasonography, computed tomography, and positron emission tomography. Neuroendocrine differentiation was confirmed by immunohistochemical staining. The NEC component was classified into small-cell and large-cell subtypes, and non-neuroendocrine components were evaluated. Patients with locoregional disease were treated with chemoradiation with or without surgery or with surgery only. Patients with distant metastasis were treated with systemic therapy. The extent of residual tumors was evaluated in esophagectomy specimens after preoperative chemoradiation. Twenty-seven patients had large-cell NEC, and 13 had small-cell neuroendocrine carcinoma. An adenocarcinoma component was present in 15 patients and squamous carcinoma component in 1 patient. Synaptophysin was positive in all cases, and chromogranin was positive in 31 cases. Seventeen patients had distant metastasis, and 21 had locoregional disease. Seventeen patients with locoregional disease received preoperative chemoradiation. Disease progressed in 7 patients, and 10 had residual tumor in resection specimens. Overall survival was better with locoregional disease than with distant metastasis (P=0.006). Overall survival was better in patients with non-neuroendocrine component than in patients with pure NEC (P=0.031). There was no difference in prognosis between patients with large-cell NEC and those with small-cell neuroendocrine carcinoma. Esophageal NEC is an aggressive tumor, and patients with mix NEC have better outcome.

Thermal maps around two adjacent cryoprobes creating overlapping ablations in porcine liver, lung, and kidney.

PURPOSE: To determine cryoprobe spacing requirements in order to achieve overlapping ablation zones using the same ablation protocol in porcine liver, lung, and kidney. MATERIALS AND METHODS: Six female pigs underwent cryoablation of the liver, lung, and kidney. Two 2.4-mm cryoprobes were spaced 20-mm apart with seven 16-gauge thermometers placed linearly and in axis with the cryoprobes at 5-mm increments from one another. The placement of the thermometers was such that three were placed between the two probes and two were placed laterally to each probe. Simultaneous use of the cryoprobes, using 12- and 8-minute double-freeze cycles, was performed with intratissue temperature monitoring during the procedure. RESULTS: The center temperatures between the two cryoprobes in kidney, lung, and liver were -25.87( degrees )C +/- 1.91, -6.47(degrees )C +/- 3.94, and 0.48( degrees )C +/- 6.69, respectively. Dual 2.4-mm cryoprobes in our model achieved acute pathological complete coagulative necrosis zone at the center of the ablation zone between the cryoprobes only in the kidney tissue where a mean diameter of the acute complete coagulative necrosis zone was 39.6 mm +/- 0.76 mm. CONCLUSIONS: The critical temperature of -20 degrees C was not reached at the midpoint between the probes with the 20-mm spacing arrangement in the lung and liver. These results emphasize the need for individualized organ ablation treatment protocols.