Adenomyomas of the Gallbladder: An Analysis of Frequency, Clinicopathologic Associations, and Relationship to Carcinoma of a Malformative Lesion.

CONTEXT.­: The nature and associations of gallbladder (GB) "adenomyoma" (AM) remain controversial. Some studies have attributed up to 26% of GB carcinoma to AMs. OBJECTIVE.­: To examine the true frequency, clinicopathologic characteristics, and neoplastic changes in GB AM. DESIGN.­: Cholecystectomy cohorts analyzed were 1953 consecutive cases, prospectively with specific attention to AM; 2347 consecutive archival cases; 203 totally embedded GBs; 207 GBs with carcinoma; and archival search of institutions for all cases diagnosed as AM. RESULTS.­: Frequency of AM was 9.3% (19 of 203) in totally submitted cases but 3.3% (77 of 2347) in routinely sampled archival tissue. A total of 283 AMs were identified, with a female to male ratio = 1.9 (177:94) and mean size = 1.3 cm (range, 0.3-5.9). Most (96%, 203 of 210) were fundic, with formed nodular trabeculated submucosal thickening, and were difficult to appreciate from the mucosal surface. Four of 257 were multifocal (1.6%), and 3 of 257 (1.2%) were extensive ("adenomyomatosis"). Dilated glands (up to 14 mm), often radially converging to a point in the mucosa, were typical. Muscle was often minimal, confined to the upper segment. Nine of 225 (4%) revealed features of a duplication. No specific associations with inflammation, cholesterolosis, intestinal metaplasia, or thickening of the uninvolved GB wall were identified. Neoplastic change arising in AM was seen in 9.9% (28 of 283). Sixteen of 283 (5.6%) had mural intracholecystic neoplasm; 7 of 283 (2.5%) had flat-type high-grade dysplasia/carcinoma in situ. Thirteen of 283 cases had both AM and invasive carcinoma (4.6%), but in only 5 of 283 (1.8%), carcinoma arose from AM (invasion was confined to AM, and dysplasia was predominantly in AM). CONCLUSIONS.­: AMs have all the features of a malformative developmental lesion, and may not show a significant muscle component (ie, the name "adeno-myoma" is partly a misnomer). While most are innocuous, some pathologies may arise in AMs, including intracholecystic neoplasms, flat-type high-grade dysplasia or carcinoma in situ, and invasive carcinoma (1.8%, 5 of 283). It is recommended that gross examination of GBs include serial slicing of the fundus for AM detection and total submission if one is found.

Reappraisal of T1b gallbladder cancer (GBC): clinicopathologic analysis of 473 in situ and invasive GBCs and critical review of the literature highlights its rarity, and that it has a very good prognosis.

There are highly conflicting data on relative frequency (2-32%), prognosis, and management of pT1b-gallbladder carcinoma (GBC), with 5-year survival ranging from > 90% in East/Chile where cholecystectomy is regarded as curative, versus < 50% in the West, with radical operations post-cholecystectomy being recommended by guidelines. A total of 473 in situ and invasive extensively sampled GBCs from the USA (n = 225) and Chile (n = 248) were re-evaluated histopathologically per Western invasiveness criteria. 349 had invasive carcinoma, and only 24 were pT1. Seven cases previously staged as pT1b were re-classified as pT2. There were 19 cases (5% of all invasive GBCs) qualified as pT1b and most pT1b carcinomas were minute (< 1mm). One patient with extensive pTis at margins (but pT1b focus away from the margins) died of GBC at 27 months, two died of other causes, and the remainder were alive without disease (median follow-up 69.9 months; 5-year disease-specific survival, 92%). In conclusion, careful pathologic analysis of well-sampled cases reveals that only 5% of invasive GBCs are pT1b, with a 5-year disease-specific survival of > 90%, similar to findings in the East. This supports the inclusion of pT1b in the "early GBC" category, as is typically done in high-incidence regions. Pathologic mis-staging of pT2 as pT1 is not uncommon. Cases should not be classified as pT1b unless extensive, preferably total, sampling of the gallbladder to rule out a subtle pT2 is performed. Critical appraisal of the literature reveals that the Western guidelines are based on either SEER or mis-interpretation of stage IB cases as "pT1b." Although the prognosis of pT1b-GBC is very good, additional surgery (radical cholecystectomy) may be indicated, and long-term surveillance of the biliary tract is warranted.

Radiomics of locally advanced rectal cancer: machine learning-based prediction of response to neoadjuvant chemoradiotherapy using pre-treatment sagittal T2-weighted MRI.

PURPOSE: Variable response to neoadjuvant chemoradiotherapy (nCRT) is observed among individuals with locally advanced rectal cancer (LARC), having a significant impact on patient management. In this work, we aimed to investigate the potential value of machine learning (ML)-based magnetic resonance imaging (MRI) radiomics in predicting therapeutic response to nCRT in patients with LARC. MATERIALS AND METHODS: Seventy-six patients with LARC were included in this retrospective study. Radiomic features were extracted from pre-treatment sagittal T2-weighted MRI images, with 3D segmentation. Dimension reduction was performed with a reliability analysis, pair-wise correlation analysis, analysis of variance, recursive feature elimination, Kruskal-Wallis, and Relief methods. Models were created using four different algorithms. In addition to radiomic models, clinical only and different combined models were developed and compared. The reference standard was tumor regression grade (TRG) based on the Modified Ryan Scheme (TRG 0 vs TRG 1-3). Models were compared based on net reclassification index (NRI). Clinical utility was assessed with decision curve analysis (DCA). RESULTS: Number of features with excellent reliability is 106. The best result was achieved with radiomic only model using eight features. The area under the curve (AUC), accuracy, sensitivity, and specificity for validation were 0.753 (standard deviation [SD], 0.082), 81.1%, 83.8%, and 75.0%; for testing, 0.705 (SD, 0.145), 73.9%, 81.2%, and 57.1%, respectively. Based on the clinical only model as reference, NRI for radiomic only model was the best. DCA also showed better clinical utility for radiomic only model. CONCLUSIONS: ML-based T2-weighted MRI radiomics might have a potential in predicting response to nCRT in patients with LARC.

Gastrointestinal tract schwannomas and brief review of literature.

Schwannomas originating from Schwann cells arise from the peripheral nerve sheath and are slow-growing, benign tumors that originate mostly from the mesenchyme. It appears equally in both sexes. Schwannomas are often seen in the 3rd and 5th decades of life. Schwannomas can be seen everywhere where peripheral nerves are seen. Gastrointestinal schwannomas constitute 2-6% of all submucosal masses, and the stomach is the most common region (60-70%). Endoscopic Ultrasound (EUS)-guided sampling of gastrointestinal submucosal lesions has made it possible to achieve preop- erative differential diagnosis. Patients diagnosed with gastrointestinal schwannomas between January 2005 and December 2017 were included in this study. Three out of six patients were females. Median age was 52.5 (44-76) years. Schwannomas were found in two patients in the gastric region, one patient in the appendiceal region, two patients in the colon and one patient in the perianal region. Primary schwannomas are usually benign. Radical resection with free margin is necessary because of the risk of malignant degeneration; chemo and radiotherapy response is indeterminate, and local recurrence rates are high.

Intracholecystic tubular non-mucinous neoplasm (ICTN) of the gallbladder: a clinicopathologically distinct, invasion-resistant entity.

Preinvasive tumor-forming gallbladder neoplasms that are composed of small, non-mucinous tubules with complex architecture remain a poorly characterized group. Here, we evaluated the clinicopathological characteristics of this entity. Twenty-eight examples were analyzed. Tumors were invariably pedunculated polyps with thin stalks, often presented as loosely attached intraluminal nodules, with cauliflower architecture (akin to cholesterol polyps) comprised of compact, back-to-back acinar-like, small tubular units with minimal/no cytoplasm showing variable complexity, creating a picture distinct from the other tubular type dysplasia in the gallbladder. Their limited stroma showed distinctive amorphous amyloid-like hyalinization (39%). While some had round nuclei with single prominent nucleoli, others exhibited slightly more elongated nuclei with washed out chromatin reminiscent of papillary thyroid carcinoma. Squamoid/meningothelial-like morules (71%) and subtle neuroendocrine cell clusters (39%) were frequent. The level of cytoarchitectural atypia qualified as high-grade dysplasia (HGD) in all cases, but none were invasive. The background mucosa showed no dysplasia, but cholesterolosis. The majority (n = 8/12) showed diffuse MUC6 expression and lacked MUC5AC expression. Based on these observations, 635 gallbladder carcinomas were re-analyzed for residual/adjacent lesions with entity-defining characteristics disclosed here, and none could be identified. Preinvasive tubular non-mucinous neoplasm of the gallbladder, which we propose to classify as intracholecystic tubular non-mucinous neoplasm, is a clinicopathologically discrete entity, which tends to occur in uninjured gallbladders and in association with cholesterol polyps. By being tubular, non-mucinous and MUC6-positive, it is akin to intraductal tubulopapillary neoplasms of pancreatobiliary tract, but it is also different in many other aspects. Although their cytoarchitectural complexity warrants an HGD/carcinoma classification, they do not show invasion and their distinct characteristics warrant their separate classification.

Mural Intracholecystic Neoplasms Arising in Adenomyomatous Nodules of the Gallbladder: An Analysis of 19 Examples of a Clinicopathologically Distinct Entity.

Intracholecystic neoplasms (ICNs) (pyloric gland adenomas and intracholecystic papillary neoplasms, collectively also called intracholecystic papillary/tubular neoplasms) form multifocal, extensive proliferations on the gallbladder mucosa and have a high propensity for invasion (>50%). In this study, 19 examples of a poorly characterized phenomenon, mural papillary mucinous lesions that arise in adenomyomatous nodules and form localized ICNs, were analyzed. Two of these were identified in 1750 consecutive cholecystectomies reviewed specifically for this purpose, placing its incidence at 0.1%. Median age was 68 years. Unlike other gallbladder lesions, these were slightly more common in men (female/male=0.8), and 55% had documented cholelithiasis. All were characterized by a compact multilocular, demarcated, cystic lesion with papillary proliferations and mucinous epithelial lining. The lesions' architecture, distribution, location, and typical size were suggestive of evolution from an underlying adenomyomatous nodule. All had gastric/endocervical-like mucinous epithelium, but 5 also had a focal intestinal-like epithelium. Cytologic atypia was graded as 1 to 3 and defined as 1A: mucinous, without cytoarchitectural atypia (n=3), 1B: mild (n=7), 2: moderate (n=2), and 3: severe atypia (n=7, 3 of which also had invasive carcinoma, 16%). Background gallbladder mucosal involvement was absent in all but 2 cases, both of which had multifocal papillary mucosal nodules. In conclusion, these cases highlight a distinct clinicopathologic entity, that is, mural ICNs arising in adenomyomatous nodules, which, by essentially sparing the "main" mucosa, not displaying "field-effect/defect" phenomenon, and only rarely (16%) showing carcinomatous transformation, are analogous to pancreatic branch duct intraductal papillary mucinous neoplasms.

Gallbladder polyps: Correlation of size and clinicopathologic characteristics based on updated definitions.

BACKGROUND: Different perspectives exist regarding the clinicopathologic characteristics, biology and management of gallbladder polyps. Size is often used as the surrogate evidence of polyp behavior and size of ≥1cm is widely used as cholecystectomy indication. Most studies on this issue are based on the pathologic correlation of polyps clinically selected for resection, whereas, the data regarding the nature of polypoid lesions from pathology perspective -regardless of the cholecystectomy indication- is highly limited. METHODS: In this study, 4231 gallbladders -606 of which had gallbladder carcinoma- were reviewed carefully pathologically by the authors for polyps (defined as ≥2 mm). Separately, the cases that were diagnosed as "gallbladder polyps" in the surgical pathology databases were retrieved. RESULTS: 643 polyps identified accordingly were re-evaluated histopathologically. Mean age of all patients was 55 years (range: 20-94); mean polyp size was 9 mm. Among these 643 polyps, 223 (34.6%) were neoplastic: I. Non-neoplastic polyps (n = 420; 65.4%) were smaller (mean: 4.1 mm), occurred in younger patients (mean: 52 years). This group consisted of fibromyoglandular polyps (n = 196) per the updated classification, cholesterol polyps (n = 166), polypoid pyloric gland metaplasia (n = 41) and inflammatory polyps (n = 17). II. Neoplastic polyps were larger (mean: 21 mm), detected in older patients (mean: 61 years) and consisted of intra-cholecystic neoplasms (WHO's "adenomas" and "intracholecystic papillary neoplasms", ≥1 cm; n = 120), their "incipient" version (<1 cm) (n = 44), polypoid invasive carcinomas (n = 26) and non-neoplastic polyps with incidental dysplastic changes (n = 33). In terms of size cut-off correlations, overall, only 27% of polyps were ≥1 cm, 90% of which were neoplastic. All (except for one) ≥2 cm were neoplastic. However, 14% of polyps <1 cm were also neoplastic. Positive predictive value of ≥1 cm cut-off -which is widely used for cholecystectomy indication-, was 94.3% and negative predictive value was 85%. CONCLUSIONS: Approximately a third of polypoid lesions in the cholecystectomies (regardless of the indication) prove to be neoplastic. The vast majority of (90%) of polyps ≥1 cm and virtually all of those ≥2 cm are neoplastic confirming the current impression that polyps ≥1 cm ought to be removed. However, this study also illustrates that 30% of the neoplastic polyps are <1 cm and therefore small polyps should also be closely watched, especially in older patients.

Tubular gastric adenocarcinoma: machine learning-based CT texture analysis for predicting lymphovascular and perineural invasion.

PURPOSE: Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poor prognosis in gastric cancers. In this work, we aimed to investigate the potential role of computed tomography (CT) texture analysis in predicting LVI and PNI in patients with tubular gastric adenocarcinoma (GAC) using a machine learning (ML) approach. METHODS: Sixty-eight patients who underwent total gastrectomy with curative (R0) resection and D2-lymphadenectomy were included in this retrospective study. Texture features were extracted from the portal venous phase CT images. Dimension reduction was first done with a reproducibility analysis by two radiologists. Then, a feature selection algorithm was used to further reduce the high-dimensionality of the radiomic data. Training and test splits were created with 100 random samplings. ML-based classifications were done using adaptive boosting, k-nearest neighbors, Naive Bayes, neural network, random forest, stochastic gradient descent, support vector machine, and decision tree. Predictive performance of the ML algorithms was mainly evaluated using the mean area under the curve (AUC) metric. RESULTS: Among 271 texture features, 150 features had excellent reproducibility, which were included in the further feature selection process. Dimension reduction steps yielded five texture features for LVI and five for PNI. Considering all eight ML algorithms, mean AUC and accuracy ranges for predicting LVI were 0.777-0.894 and 76%-81.5%, respectively. For predicting PNI, mean AUC and accuracy ranges were 0.482-0.754 and 54%-68.2%, respectively. The best performances for predicting LVI and PNI were achieved with the random forest and Naive Bayes algorithms, respectively. CONCLUSION: ML-based CT texture analysis has a potential for predicting LVI and PNI of the tubular GACs. Overall, the method was more successful in predicting LVI than PNI.

Follicular Cholecystitis: Reappraisal of Incidence, Definition, and Clinicopathologic Associations in an Analysis of 2550 Cholecystectomies.

CONTEXT.: Follicular cholecystitis (FC) is a poorly characterized entity. OBJECTIVE.: To determine its frequency/clinicopathologic associations. DESIGN.: A total of 2550 cholecystectomy specimens were examined. Two hundred three of these were consecutive routine cholecystectomies submitted entirely for microscopic examination to determine the relative frequency of incidental pathologies in gallbladders (GBs). The remainder had representative sampling. Underlying conditions were nonobstructive pathologies (1270 nonspecific cholecystitis), obstructive (62 distal biliary tract tumors, 35 primary sclerosing cholangitis, and 31 autoimmune pancreatitis), and neoplastic (n = 949). FC was defined as 3 distinct lymphoid follicles (LFs)/centimeter. RESULTS.: In the GBs totally submitted for microscopic examination, the true frequency of FC was found to be 2.5% (5/203), and in the representatively sampled group, it was 1.9%, with similar frequencies in nonobstructive, obstructive, and neoplastic cases (2.3%, 3.1%, and 1.3%, respectively, P = .77). When the 39 FC in nonneoplastic GBs contrasted with ordinary chronic cholecystitis, they were associated with older age (68 vs 49 years, P < .0001), similar gallstone frequency (68 vs 81%), female/male ratio (2.7 vs 2.6), and wall thickness (4 mm for both). None had lymphoma/parasites/Salmonella infection. Of 17 cases who had undergone gastric biopsy, 5 had chronic gastritis (2 with Helicobacter pylori). Microscopically, the LFs were the main inflammatory process often with minimal intervening inflammation. IgG4-positive plasma cell density was low (<10/high-power field) in 21/24(87.5%) cases. CONCLUSIONS.: Follicular cholecystitis is seen in 2% of cholecystectomies, typically in significantly older patients, suggesting a deranged immune response. A third of the patients reveal biopsy-proven gastritis. FC does not seem to be associated with autoimmunity, lymphoma, or obstructive pathologies.

Epstein-Barr virus infection in patients with chronic gastritis without Helicobacter pylori infection.

BACKGROUND/AIMS: The association of Epstein-Barr virus (EBV) with gastric malignancies has been proven by many studies in the literature. However, information about EBV-associated inflammation/gastritis remains limited. The aim of this study is to establish the prevalence of latent EBV infection in patients with chronic gastritis without H. pylori infection. MATERIALS AND METHODS: In this study, 119 patients with gastritis without H. pylori infection were included. Furthermore, 28 patients with H. pylori gastritis were included in the study as a control group. Chromogenic in situ hybridization (EBV-encoded RNA) and immunohistochemistry (LMP-1 antibody) were performed in all 147 cases. The prevalence of EBV and its relationship with age, sex, the affected part of the stomach, the density of inflammation, inflammatory activity, intestinal metaplasia, and atrophy were analyzed. RESULTS: In this study, 14 cases showed positive immunostaining for EBV. EBV positivity was seen mostly in the lymphoid tissue (13 cases), but it was also detected at the gastric epithelium (7 cases). The mean age of the patients was 44 years, which was slightly younger than that of the EBV-negative cases (48 years). The inflammation density was higher in EBV-positive cases than the EBV-negative gastritis cases (p=0.002). Intestinal metaplasia was detected in 7% of the cases. EBV-positive cases had a higher incidence of atrophy without intestinal metaplasia (21% vs 3.8% without EBV). CONCLUSION: EBV was detected in 12% of the cases with gastritis without H. pylori infection. Endoscopic follow-up may be appropriate for patients with gastritis, who have atrophy without intestinal metaplasia and are H. pylori negative but EBV positive.

Computed tomography texture analysis in patients with gastric cancer: a quantitative imaging biomarker for preoperative evaluation before neoadjuvant chemotherapy treatment.

PURPOSE: The aim of the study is to explore the role of computed tomography texture analysis (CT-TA) for predicting clinical T and N stages and tumor grade before neoadjuvant chemotherapy treatment in gastric cancer (GC) patients during the preoperative period. MATERIALS AND METHODS: CT images of 114 patients with GC were included in this retrospective study. Following pre-processing steps, textural features were extracted using MaZda software in the portal venous phase. We evaluated and analyzed texture features of six principal categories for differentiating between T stages (T1,2 vs T3,4), N stages (N+ vs N-) and grades (low-intermediate vs. high). Classification was performed based on texture parameters with high model coefficients in linear discriminant analysis (LDA). RESULTS: Dimension-reduction steps yielded five textural features for T stage, three for N stage and two for tumor grade. The discriminatory capacities of T stage, N stage and tumor grade were 90.4%, 81.6% and 64.5%, respectively, when LDA algorithm was employed. CONCLUSION: CT-TA yields potentially useful imaging biomarkers for predicting the T and N stages of patients with GC and can be used for preoperative evaluation before neoadjuvant treatment planning.

The Role of 18F-FDG PET/CT in staging of gallbladder carcinomas.

BACKGROUND/AIMS: Gallbladder Carcinoma (GBC) is the most common and aggressive tumor of the biliary tract. Patients are typically diagnosed during advanced stages, and the mean overall survival is short. In our study, we aimed to demonstrate the uptake patterns of 18F-FDG PET/CT in GBC, as well as its association with survival and diagnostic value during the initial stage. MATERIALS AND METHODS: Overall, 17 patients with GBC were retrospectively included in the study. 18F-FDG PET/CT study was performed for pretreatment staging. Two different standardized uptake values (SUVmax and SUVmean), metabolic tumor volume 40% (MTV40), and tumor lesion glycolysis (TLG) of the primary tumors were compared between the clinical and histopathological groups. RESULTS: Of the 17 patients, 11 were women (64.7%), and 6 (35.3%) were men. The mean age of the patients was 69.7±8.8 years. 18F-FDG uptake was detected in all lesions. Mean SUVmax was calculated to be 15.4±13.7 (median=10.6, range=3.4-46.8). All distant metastases (52.9%) were detected in the liver. Semiquantitative metabolic parameters (SUVmax and SUVmean, MTV40, and TLG) obtained from patients with distant metastasis were not significantly higher than those without distant metastasis. Similar results were obtained in patients with and without nodal metastasis. No statistically significant intergroup difference was observed regarding metabolic parameters. However, a statistically significant negative correlation was observed between the patient's age and the SUVmax of the primary lesion and metastatic lymph nodes (r=-0.564, p=0.018). During 10.7±10.4 months of mean follow-up, the mean survival of patients with distant metastases (6.1±11.0 months) was significantly shorter than that of patients with no organ metastases (15.8±7.1 months). CONCLUSION: In our study, distant metastases and age were observed to be crucial prognostic factors in patients with gallbladder carcinoma (GBC). In addition, we believe that 18F-FDG PET/CT imaging will help to stage the GBC, detect nodal and distant metastasis, and evaluate the metabolic state of gallbladder lesions.

The Prognostic Value of 18F-FDG PET/CT and KRAS Mutation in Colorectal Cancers

Objective: Prognostic effect of KRAS mutation and side of tumor in colorectal cancer is a highly controversial subject. Therefore, we evaluated the association between FDG uptake pattern in 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging and KRAS mutation and tumor localization in patients with a diagnosis of colon cancer and assessed the effects of these three factors on prognosis and survival. Methods: Eighty-three patients with colorectal cancer were retrospectively included in this study. 18F-FDG PET/CT study was performed for pretreatment staging. The maximum standardized uptake value (SUVmax) of the primary tumor and survival data of patients were compared between groups. KRAS mutations were detected with the help of real-time Polymerase Chain Reaction technique through genomic DNA extracted from paraffin-embedded tumor tissue blocks. Tumor lesions with potential KRAS mutations were classified as mutant KRAS and wild type. Results: Twenty five patients were female while 58 were male. The mean age of the patients was 59.8±11.3 years. Mean follow-up was 35.5±18.9 months. Primary tumor was localized in the left colon in 83.1% of patients and in the right colon in 16.9%. KRAS mutation was detected in 54.2% (n=45) of patients. Mean SUVmax of patients with primary tumor was estimated to be 21.1±9.1 (range= 6.0-47.5). Mean tumor SUVmax of patients with a KRAS mutation (24.0±9.0) was found to be significantly higher than those without KRAS mutation (17.7±8.2) (p=0.001). Mean survival was significantly shorter in patients with locoregional nodal metastasis than in patients without locoregional nodal metastasis as well as in patients with distant nodal metastasis than in patients without distant nodal metastasis and in patients with organ metastasis in initial PET/CT than in patients without organ metastasis. Also, mean survival was nearly statistically-significantly shorter in patients with tumors located in left colon (34.2±19.4) than in right colon (43.2±14.6) (p=0.059). However, we found no significant impact of KRAS mutation on survival. Conclusion: In our study, we found that tumor localization had no significant effect on prognosis in patients with colon cancer. On the other hand, FDG uptake was observed to be higher in the presence of KRAS mutation and it was concluded that coexistence of KRAS mutation with higher SUVmax is a negative prognostic factor.

Metabolic Characteristics and Diagnostic Contribution of 18F-FDG PET/CT in Gastric Carcinomas

Objectives: The aim of this study was to evaluate 18F-fluoro-2-deoxy-glucose (FDG) uptake patterns in primary tumors and metastatic lesions, and also to assess the diagnostic contribution of positron emission tomography/computed tomography (PET/CT) in the initial staging of gastric cancer (GC). Methods: The total number of 341 patients with GC were included in this study. All 18F-FDG PET/CT imagings were performed for initial staging. The maximum standardized uptake value (SUVmax) of primary tumor, obtained from 18F-FDG PET/CT imaging was compared between subtypes of GC. Results: Mean SUVmax of 339 patients' primary tumor was 12.9±8.6. The highest mean SUVmax was detected in patients with medullary subtype GC (17.8±9.9) while the lowest mean SUVmax (9.7±7.6) was seen in signet ring cell carcinoma (SRCC). The primary mean SUVmax was found statistically higher in tubular adenocarcinoma (TAC) group than SRCC group (p<0.001). Higher SUVmax values were found statistically significantly correlated with advanced age (aged ≥60) and increased tumor size (>3 cm) in patients with TAC (p=0.03). Primary tumor SUVmax was found statistically higher in regional lymph node (RLN) positive patients than in RLN negative patients in TAC and SRCC groups (p<0.001 and p=0.012, respectivelly). Also, in patients with SRCC, SUVmax was significantly higher in the distant metastatic group than in the group without metastasis (p=0.025). Conclusion: Increased primary tumor SUVmax was associated with some of clinical parameters such as age and RLN metastasis in patients with TAC. However, there was no relationship between distant metastatic state and primary tumor 18F-FDG uptake in TAC. However, high SUVmax of primary tumor in SRCC was associated with regional and distant metastasis, and primary tumor 18F-FDG uptake may be a prognostic value for this subgroup.

Non-neoplastic Polyps of the Gallbladder: A Clinicopathologic Analysis of 447 Cases.

There is no systematic histopathologic analysis of non-neoplastic polyps in the gallbladder. In this study, in addition to a computer search for cases designated as "polyp," a systematic review of 2533 consecutive routinely sampled archival and 203 totally submitted prospective cholecystectomies were analyzed for >2 mm polyps (cut-off was based on radiologic sensitivity). A total of 447 non-neoplastic polyps were identified. The frequency was 3% in archival cases and 5% in totally submitted cases. Only 21 (5%) were ≥1 cm. The average age was 52 years, and the female to male ratio was 3.1. Two distinct categories were delineated: (1) injury-related polyps (n=273): (a) Fibro(myo)glandular polyps (n=214) were small (mean=0.4 cm), broad-based, often multiple (45%), almost always (98%) gallstone-associated, and were composed of a mixture of (myo)fibroblastic tissue/lobular glandular units with chronic cholecystitis. Dysplasia seen in 9% seemed to be secondary involvement. (b) Metaplastic pyloric glands forming polypoid collections (n=42). (c) Inflammatory-type polyps associated with acute/subacute injury (11 granulation tissue, 3 xanthogranulomatous, 3 lymphoid). (2) Cholesterol polyps (n=174) occurred in uninjured gallbladders, revealing a very thin stalk, edematous cores devoid of glands but with cholesterol-laden macrophages in 85%, and cholesterolosis in the uninvolved mucosa in 60%. Focal low-grade dysplasia was seen in 3%, always confined to the polyp, unaccompanied by carcinoma. In conclusion, non-neoplastic polyps are seen in 3% of cholecystectomies and are often small. Injury-related fibromyoglandular polyps are the most common. Cholesterol polyps have distinctive cauliflower architecture, often in a background of uninjured gallbladders with cholesterolosis and may lack the cholesterol-laden macrophages in the polyp itself. Although dysplastic changes can involve non-neoplastic polyps, they do not seem to be the cause of invasive carcinoma by themselves.

The Effects of Local and Systemic Administration of Proline on Wound Healing in Rats.

Purpose: Wound healing consists of a sequence of complex molecular and cellular events. Collagen is composed mainly of proline and hydroxyproline. Proline and hydroxyproline constitute 1/3 of the amino acids in collagen, which makes up approximately 30% of the proteins within the body. The hydroxylation of proline found in collagen determines the stability of the triple helical structure of collagen. In this study, we examined the effects of local and systemic administration of proline on wound healing. Materials and Methods: 24 female Sprague-Dawley rats were used in the study and divided into three groups. Group 1: The defect created in the backs of the subjects was left to secondary healing. Group 2: 200 µl proline per day was administered topically for 30 days on the defect in the backs of the subjects. Group 3: 200 µl per day was administered intraperitoneally for 30 days on the defect in the backs of the subjects. Results: On day 21, there was a statistically significant difference between the groups in terms of the mean re-epithelialization score. On days 7 and 14, there was a statistically significant difference between the groups in terms of the mean granulation score. On days 7, 14, and 21, there was a statistically significant difference between the groups in terms of the mean collagen accumulation score. On day 30, there was a statistically significant difference between Groups 1 and 3 in terms of the mean E-mode score on mechanical tensile test. Conclusion: Our study confirmed that proline has positive effects on wound healing. However, it revealed that systemic administration of proline is more effective than local administration of proline.

Effects of Intracordal Estradiol and Dexamethasone Injection on Wound Healing in Vocal Fold Injuries.

OBJECTIVE: The aim of this study was to investigate the effects of intracordal estradiol and dexamethasone injection on wound healing in vocal fold injuries. STUDY DESIGN: A prospective controlled animal study was carried out. SETTING: This study was conducted at a tertiary center. SUBJECTS-METHODS: Ten rabbits were randomly divided into two groups. As surgical procedure, cordotomy technique was performed in the middle third of the vocal folds bilaterally. In the first group, 0.1 mL of dexamethasone was injected into the right side, and 0.1 mL of saline was injected into the left side. In the second group, 0.1 mL of estradiol was injected into the right side, and 0.1 mL of saline was injected into the left side. Animals were sacrificed after 1 month and laryngeal specimens were evaluated histopathologically. RESULTS: No statistically significant difference was observed in terms of inflammatory response, epithelial thickness, type I and III collagen, and hyaluronic acid parameters in dexamethasone and estradiol injections compared to the saline injection. In terms of elastin level, estradiol injection demonstrated statistically higher values compared to the saline injection. Elastin level of dexamethasone injected vocal folds was not statistically different compared to the saline injection. No significant differences were observed in terms of inflammatory response, epithelial thickness, type I and III collagen, and hyaluronic acid parameters between the estradiol and dexamethasone injected vocal folds. CONCLUSION: It is thought that the effects of estradiol or dexamethasone injections may have similar effects on wound healing in vocal fold injuries. Intracordal estradiol injection has positive effects on tissue elastin levels.

Cytokeratin 17 and Ki-67: Immunohistochemical markers for the differential diagnosis of keratoacanthoma and squamous cell carcinoma.

The clinical and histopathological distinction between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is essential, but frequently difficult to make. The utility of CK17 and Ki-67 expression in distinguishing between KA and SCC was investigated. Immunohistochemical staining patterns for CK17 and Ki-67 were evaluated in 24 KA and 27 SCC cases. The pattern of staining was evaluated as central, peripheral or diffuse, according to the basal/peripheral and suprabasal/central cell staining of tumor lobules. The sensitivity and specificity of the central CK17 staining pattern in the identification of KA were 92 and 70%, respectively. Additionally, the sensitivity and specificity of the diffuse Ki-67 staining pattern in the identification of SCC were 81 and 100%, respectively. The results of the present study suggest that a diffuse Ki-67 staining pattern may be used to diagnose SCC, while a central CK17 staining pattern indicates KA. However, the KA-like SCC cases exhibited mixed patterns, which limits the effectiveness of these markers.