Association of Gut Lachnospiraceae and Chronic Spontaneous Urticaria.

(1) Background: Chronic spontaneous urticaria (CSU) has been linked to the dysbiosis of the gut microbiota. Furthermore, various studies have highlighted the anti-inflammatory properties of short-chain fatty acids (SCFAs), whose production is primarily regulated by the gut microbiota. However, only a few studies have investigated the role of major SCFA producers, such as Lachnospiraceae, in skin inflammatory diseases. (2) Goal: This study aimed to compare the abundance of Lachnospiraceae between CSU patients and healthy controls (HCs). (3) Material and methods: In this case-control study, 16S rRNA sequencing was performed to compare the composition of the gut microbiome between 22 CSU patients and 23 HCs. (4) Results: Beta-diversity revealed significant clustering (p < 0.05) between the CSU patients and HCs. Alpha diversity in the CSU group was significantly decreased according to the Evenness index (p < 0.05). The linear discriminant analysis effect size (LEfSe) identified the significant depletion of the Lachnospiraceae family in CSU patients. (5) Conclusion: Our study revealed the dysbiosis of the gut microbiota in CSU patients, including decreased levels of Lachnospiraceae members, responsible for SCFA production, suggesting that SCFAs may contribute to immune dysfunction in the pathogenesis of CSU. We speculate that the modulation of SCFAs could serve as a prospective additional option in CSU treatment.

Gender Difference in Distribution of Estrogen and Androgen Receptors in Intestinal-type Gastric Cancer.

BACKGROUND: Gender difference in survival of patients with gastric cancer is not well investigated. The aim of this study was to analyze the gender-related distribution of estrogen receptor alpha (ERα) and androgen receptor (AR) in the epithelium and stroma of intestinal-type gastric cancer. MATERIALS AND METHODS: Immunohistochemical analysis was performed in 60 patients (42% females). RESULTS: In gastric cancer patients, frequency of ERα-positive cells was lower in epithelium than in healthy individuals, but not significantly. In stroma and epithelium, AR-positive cells were absent from samples of women with T1 and T2 stage disease, while in men, their frequency was significantly increased in stroma of those with T3 and T4 stages and was significantly higher compared to women. AR-positive cells in stroma were fibroblasts, myofibroblasts and mast cells. CONCLUSION: To our knowledge, this study is the first to show gender differences in the distribution and frequency of AR-positive cells in neoplastic stroma of gastric cancer.

Biliary leakage after urgent cholecystectomy: Optimization of endoscopic treatment.

AIM: To investigate the results of endoscopic treatment of postoperative biliary leakage occurring after urgent cholecystectomy with a long-term follow-up. METHODS: This is an observational database study conducted in a tertiary care center. All consecutive patients who underwent endoscopic retrograde cholangiography (ERC) for presumed postoperative biliary leakage after urgent cholecystectomy in the period between April 2008 and April 2013 were considered for this study. Patients with bile duct transection and biliary strictures were excluded. Biliary leakage was suspected in the case of bile appearance from either percutaneous drainage of abdominal collection or abdominal drain placed at the time of cholecystectomy. Procedural and main clinical characteristics of all consecutive patients with postoperative biliary leakage after urgent cholecystectomy, such as indication for cholecystectomy, etiology and type of leakage, ERC findings and post-ERC complications, were collected from our electronic database. All patients in whom the leakage was successfully treated endoscopically were followed-up after they were discharged from the hospital and the main clinical characteristics, laboratory data and common bile duct diameter were electronically recorded. RESULTS: During a five-year period, biliary leakage was recognized in 2.2% of patients who underwent urgent cholecystectomy. The median time from cholecystectomy to ERC was 6 d (interquartile range, 4-11 d). Endoscopic interventions to manage biliary leakage included biliary stent insertion with or without biliary sphincterotomy. In 23 (77%) patients after first endoscopic treatment bile flow through existing surgical drain ceased within 11 d following biliary therapeutic endoscopy (median, 4 d; interquartile range, 2-8 d). In those patients repeat ERC was not performed and the biliary stent was removed on gastroscopy. In seven (23%) patients repeat ERC was done within one to fourth week after their first ERC, depending on the extent of the biliary leakage. In two of those patients common bile duct stone was recognized and removed. Three of those seven patients had more complicated clinical course and they were referred to surgery and were excluded from long-term follow-up. The median interval from endoscopic placement of biliary stent to demonstration of resolution of bile leakage for ERC treated patients was 32 d (interquartile range, 28-43 d). Among the patients included in the follow-up (median 30.5 mo, range 7-59 mo), four patients (14.8%) died of severe underlying comorbid illnesses. CONCLUSION: Our results demonstrate the great efficiency of the endoscopic therapy in the treatment of the patients with biliary leakage after urgent cholecystectomy.

Estrogen and androgen receptors in inflammatory fibroid polyp (Vanek's tumor): case report.

BACKGROUND/AIM: Vanek's tumor is an inflammatory fibroid polyp (IFP) of very low incidence, which originates in the submucosa of the stomach, duodenum, jejunum and ileum. The etiology of this tumor is still unknown. Histologically, IFP is characterized by submucosal spindle cell proliferation in fibromyxoid stroma with inflammatory infiltrate. The aim of the present study was to investigate the presence of estrogen and androgen receptors in IFP and compare it with its proliferative loci. PATIENTS AND METHODS: The study analyzed a 79-year-old patient suffering from IFP. Analyses were performed by immunohistochemistry. RESULTS: Androgen-positive spindle cells were detected at the periphery of onion skin-like formations. Estrogen receptor-positive cells were not detected and Ki67 showed low proliferative activity. CONCLUSION: This case report shows for the first time the presence of androgen receptor-positive cells whose location corresponds with the distribution of Ki67-positive cells in IFP.

Periprosthetic bone loss following hemiarthroplasty: a comparison between cemented and cementless hip prosthesis.

The aim of this prospective randomized clinical study was to evaluate the magnitude of bone mineral changes as well as the clinical results after cemented and cementless haemiarthroplasty (HA) for femoral neck fracture. The study was comprised of 60 patients (mean age 85.2 years); 30 of them underwent cemented HA and 30 cementless HA. All patients underwent osteodensitometry for the purpose of Bone Mineral Density (BMD) evaluation. BMD was measured with dual-energy X-ray absorptiometry test (DEXA scans), which was scheduled at 1 month, 6 months and 1 year after surgery. BMD was evaluated at each of the seven Gruen zones. Harris Hip Score (HHS) at 3 months, 6 months and 12 months was used for evaluation of functional outcome. No difference was found between the two groups of patients in terms hospital stay, morbidity and mortality. The procedure took longer time in group A (cemented HA) compared to group B (cementless HA) (79.03 ± 3.59 vs 68.02 ± 5.97 minutes; p = 0.00). The Harris hip score averaged 76.97 ± 7.49 one year after surgery. At each follow - up examination the HHS was significantly higher in patients with cemented HA. We noted a trend of less intensive BMD reduction in all Gruen zones in group A compared to group B. However, the difference in BMD reduction between these two groups was significant only in zones 2, 3 and 4. Our results support the view that cemented hemiarthroplasty should be used for the management of displaced femoral neck fractures providing better functional outcomes and lower periprosthetic bone loss.

Internal fixation with locking plate of 3- and 4-part proximal humeral fractures in elderly patients: complications and functional outcome.

Despite recent advances in operative techniques, internal fixation of (3- and 4-part) displaced proximal humeral fractures in elderly patients with osteoporotic bone remains controversial, sometimes followed by poor results. The aim of the present study was to evaluate outcomes of internal fixation with locking plate of multi-fragment proximal humeral fractures in elderly patients. The study cohort comprised 59 consecutive patients (mean age 70.1) with 3- and 4-part fractures who had undergone open reduction and internal fixation with locked plate at Sestre milosrdnice University Hospital Center in Zagreb, Croatia. All patients were invited for follow-up examinations and underwent standard x-ray examination preoperatively to assess fracture pattern in the operating theatre as well as at 6 weeks, 3 and 6 months, 1 year, and then annually after surgery to assess fracture healing or complications. Clinical outcomes were measured by constant score. Patients were followed-up for 14 to 36 months. The overall complication rate was 27.1%. The mean constant score at 1-year follow-up was 70.2 points for 3-part fractures vs. 64.2 for 4-part fractures (p < 0.0001). In conclusion, despite a relatively high overall complication rate, internal fixation with locking plate provided moderate to good functional results in the treatment of osteoporotic complex proximal humeral fractures.

Approach to distal femur by osteotomy of the patellar distal pole and internal fixation with basket plate in complex articular fracture: report of five cases.

According to AO classification, 33-C3 (complete articular multifragmentary) fracture of distal femur is characterized by complex articular involvement, along with short distal femoral block with multiple small fragments and usually with severe soft tissue abruption. In such cases of complex articular fracture of distal femur with extensive comminution of the femur condyle that is often seen in these fractures, anatomical reduction is quite difficult. Minimal fixation strategies sometimes do not provide an optimal degree of reduction and stability of the distal femoral block osteosynthesis. We describe 5 cases of treatment of the 33-C3 distal femoral fractures using arthrotomy of the knee joint by osteotomy of the distal pole of the patella and internal fixation with basket plate as an alternative approach for anatomical reduction of the comminuted articular surface.

[Adrenal myelolipoma--report of 15 patients]. / Mijelolipomi nadbubrezne zlijezde--prikaz serije od 15 bolesnika.

Myelolipoma is a rare, benign, non-functioning tumor most frequently located in the adrenal cortex. It consists of mature fatty tissue with components of hematopoietic tissue in different proportions. There are certain ambiguities related to the diagnosis and therapy of myelolipoma, and it is therefore important to keep in view all the aspects of the lesion and the circumstances in which it develops. This paper presents a series of 15 patients with myelolipoma diagnosed at the Ljudevit Jurak Department of Pathology, Sestre milosrdnice University Hospital Center. Out of 15 patients, 10 were men (one of them with bilateral tumor) aged 41 to 73, and 5 were women aged 51 to 54. Macroscopically, the tumors were oval, encapsulated, yellowish, soft masses located in the adrenal glands. The diameter of the tumors ranged between 0.5 and 13.9 cm. Microscopically, they consisted of multiplied mature adipose cells combined with myeloid tissue composed largely of megakaryocytes, erythroid cells and lymphocytes. In all patients, the postoperative course was uneventful with no recurrences.

Giant mixed-type liposarcoma of the mesentery: case report.

Primary mesenteric liposarcomas are very rare, especially when they are of mixed histologic pattern. Patient prognosis is based upon the most aggressive histologic type of liposarcoma. A case is reported of a 77-year-old man with a history of slowly increasing abdominal volume over 3 years. The diagnosis of giant intra-abdominal mass suspect of liposarcoma was confirmed by computed tomography and ultrasound scans. The patient underwent resection of 24 tumor masses weighing together 23.5 kg. The microscopic diagnosis was mixed-type liposarcoma of the mesentery. Although this type of tumor is rare, tumor tissue should be thoroughly collected and analyzed on histologic examination to reach definitive diagnosis. Recognition of the underappreciated subtype of liposarcoma is important for proper prognosis and treatment of the patient. According to our knowledge, this is the largest size of mixed-type mesenteric liposarcoma described in the English literature.

hGH and GHR expression in large cell neuroendocrine carcinoma of the colon and rectum.

Large cell neuroendocrine carcinoma (LCNEC) is an aggressive neoplasm with a low frequency of occurrence in the digestive tract. We present a series of eight patients diagnosed with LCNEC of the colon and rectum. Grossly, tumors were presented as endophytic/ulcerative, annular and polypoid masses, with a gray-white color and necrosis in most cases. Histologically, they were high-grade tumors composed of large cells of organoid, nesting, trabecular, rosette-like and palisading patterns, with a high mitotic rate. Tumors were immunoreactive for neuroendocrine markers, including chromogranin A (2/8), synaptophysin (7/8), and neuron-specific enolase (8/8). Moreover, we analyzed the expression of growth hormone (hGH) and growth hormone receptor (GHR) in colorectal LCNECs and six tumors were immunoreactive for hGH, while five tumors were immunoreactive for GHR. To our knowledge hGH and GHR expression has not been previously analyzed in colorectal LCNEC. Their overexpression suggests a role of hGH and GHR in the development of colorectal LCNEC.

A case of signet-ring cell carcinoma of the gallbladder: immunohistochemistry and differential diagnosis.

The morphological spectrum of gallbladder carcinoma is broad and variable. Most of these tumors are tubular adenocarcinomas. There are some tumors with unusual morphology that may be difficult to classify due to their rarity. One of such tumors is the signet-ring cell carcinoma, which is a highly aggressive, mucin producing variant of gallbladder adenocarcinoma predominantly or exclusively composed of signet-ring cells. Histologically, these tumors are similar to their counterparts in other organs such as stomach, colon and breast, and should not be misinterpreted as metastatic carcinoma from one of these primary sites. The literature about this variant of carcinoma is sparse and little is known about it. We found only three cases of signet-ring cell carcinoma of the gallbladder previously reported. We present the case of an 86-year-old woman with signet-ring cell carcinoma of the gallbladder and discuss the potential diagnostic dilemmas

Synchronous rectal adenocarcinoma and bilateral clear cell renal carcinoma.

A 69-year-old man was admitted for resection of rectal adenocarcinoma diagnosed by colonoscopy. Preoperative computed tomography scan and abdominal ultrasonography revealed bilateral renal tumors measuring up to 2 and 2.8 cm in largest diameter, respectively. The patient underwent partial colectomy and bilateral partial nephrectomy. Microscopically, rectal adenocarcinoma penetrated the submucosa, without invasion of the muscularis propria. Both renal tumors were clear cell renal carcinomas of Fuhrmann nuclear grade 2. To our knowledge, this is the first case of synchronous adenocarcinoma of the rectum and bilateral clear cell renal cell carcinoma described in the literature to date.

Low-grade periductal stromal sarcoma of the breast with myxoid features: Immunohistochemistry.

A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to 'fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment.

Expression of growth hormone receptor and growth hormone in colorectal carcinoma.

BACKGROUND/AIMS: The aims of this study were to determine and compare the expression of growth hormone and growth hormone receptor in primary colorectal adenocarcinoma, regional lymph node metastases and unaffected adjacent bowel wall, and to correlate the expression of growth hormone and growth hormone receptor with clinicopathologic and survival data of the patients. METHODOLOGY: Expression of growth hormone and growth hormone receptor were immunohistochemically analyzed in tumor, lymph node metastases and unaffected adjacent colorectal mucosa from 48 patients with colorectal carcinoma. Only the patients with long-term follow-up and known modalities of treatment and outcome were included in the study. RESULTS: Increased expression of growth hormone receptor showed statistically significant correlation with recurrence of the disease and survival (p < 0.05), while expression of growth hormone had no significant connection with same data (p > 0.05). There was no significant difference between the expression of growth hormone and growth hormone receptor and the age, and gender of the patients, tumor diameter, and Dukes and Astler-Coller stage (p > 0.05). CONCLUSIONS: Our data demonstrate that growth hormone receptor and growth hormone are frequently expressed in colorectal carcinomas. Patients with increased expression of growth hormone receptor had more common recurrence of the disease and shorter survival.

Peritumoral retraction clefting correlates with advanced stage squamous cell carcinoma of the esophagus.

The present study was designated to analyze correlation between the presence and extent of peritumoral retraction clefting and various clinicopathologic features in esophageal squamous cell carcinoma (ESCC), and to possibly establish the significance of this phenomenon in ESCC. Fifty-four consecutive patients with advanced ESCC were included in the study. The presence of peritumoral retraction clefting was classified on the basis of the proportion of tumor nests exhibiting this phenomenon. Tumors with clefts that affected up to 25% of tumor nests were classified as group I; with clefts that affected >25% to 50% of tumor nests as group II; with clefts that affected >50% to 75% of tumor nests as group III; and tumors with clefts that affected more than 75% of tumor nests were classified as group IV. Statistical analysis showed a correlation between presence and extent of peritumoral clefting and lymph node metastasis. T3 tumors and tumors with lymph node metastasis had significantly more pronounced peritumoral clefting compared with T2 tumors and tumors without lymph node metastasis. The presence of peritumoral clefting was not associated with the number of affected lymph nodes. There was no correlation between the presence and extent of peritumoral clefting with patient age and sex, and tumor location, diameter and grade. The association of peritumoral retraction clefting in ESCC with local invasiveness and lymph node metastasis indicated that peritumoral clefting could be a simple and useful morphological feature of tumor aggressiveness and may contribute to the pathological and clinical assessment of patients with ESCC.

Pleomorphic ductal carcinoma of the breast with predominant micropapillary features.

An 83-year-old woman with long-standing chronic ischemic cardiac and obstructive pulmonary disease, presented with a painless tumor in her right breast. Microscopically the tumor consisted of micropapillary formations and loosely cohesive nests and strands of large, highly pleomorphic cells. Micropapillary formations were surrounded by peritumoral retraction clefting, and the papillae lacked a true fibrovascular core. Multinucleated giant and bizarre tumor cells were also present and numerous. Within the tumor a high-grade intraductal component with the same cell morphology and necrosis and mucin production was found. Micropapillary pattern occupied approximately 60% of the tumor mass, loosely cohesive nests and strands approximately 20% and an intraductal component was noted in approximately 20% of the tumor mass. On immunohistochemistry the tumor cells were positive for pan-cytokeratin, epithelial membrane antigen (EMA), S100 protein and E-cadherin while estrogen and progesterone receptors, HER2-neu and Bcl2 were negative. EMA staining was diffuse and observed in the outer and inner margins of neoplastic nests. The diagnosis of pleomorphic breast carcinoma with predominant micropapillary features was established. In summary, micropapillary carcinoma can be distinguished from other types of breast carcinoma with micropapillary growth pattern on the basis of reverse cell polarity, which is easily confirmed on immunohistochemistry.

Axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia.

Apocrine carcinomas represent a rare group of tumors with a potential for destructive local invasion, regional and distant metastases, and are equally common in both sexes. A case of a 79-year-old woman with axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia is presented. To our knowledge, this is the first case diagnosed in a Caucasian and also the first case diagnosed in a female patient. Grossly, the tumor measured 3.2x1.5x1.2 cm and on cut section appeared granular, white to gray-tanned. Microscopically, the tumor was located in the dermis, poorly demarcated, focally necrotic with ulcerated overlying skin. It was predominantly composed of complex, closely packed tubuloglandular structures but in few areas papillary structures were also observed. The cells contained abundant eosinophilic, finely granular cytoplasm with pleomorphic nuclei and showed apocrine-like decapitation. The cytoplasm contained periodic acid Schiff diastase resistant granules. Mitoses were frequent and some were atypical. In one area, the tumor was lobular and composed of tubular structures lined with one layer of uniform cuboidal or columnar eosinophilic cells, indicating a pre-existing apocrine adenoma. Beneath the tumor, in the deep dermis and subcutaneous tissue, hyperplastic apocrine glands were also found. No additional therapy was used, and one year after the surgery the patient was alive and showed no signs of tumor spread. This and previously reported cases suggest that apocrine hyperplasia and apocrine adenoma may represent successive steps in the development of apocrine carcinoma.

Morphometric analysis of renal arteries in patients with renal cell carcinoma.

The aim of this study was to analyze morphometric parameters of renal arteries (longest diameter and tunica media thickness) in patients with renal cell carcinoma (RCC), to look into their relationship to tumor necrosis and to compare them with morphometric parameters recorded in a control group. We analyzed archival cases of RCC diagnosed in 2003 that also contained routinely sampled specimens of distal segments of renal artery. The control group consisted of specimens from both renal arteries obtained from 16 patients at routine autopsy during 2004-2005. Autopsy, as well as further histological analysis, did not disclose any malignant disease in the control group. Morphometric analysis of diameter and thickness of the renal artery tunica media was performed using Issa 3.1 software (Vamstek 2002, Zagreb, Croatia). The comparison of tunica media thickness showed that renal arteries from RCC cases were significantly thicker compared to distal parts of renal arteries in the control group (p=0.0002). Although renal artery samples from cases with necrotic tumor areas were thicker than those without tumor necrosis, the difference was not statistically significant. It is concluded that significantly thicker tunica media characterizes renal arteries in the group of patients with RCC when compared with the control group.

Stable and unstable chromosome aberrations measured after occupational exposure to ionizing radiation and ultrasound.

AIM: To evaluate chromosome aberration and fluorescent in situ hybridization (FISH) assays as a method to estimate of health risk, we monitored 9 male subjects occupationally exposed to low doses of both ionizing radiation and ultrasound during a period of over 3 years. METHODS: Sampling was performed at 6-month intervals during a three-year period. First we used conventional chromosomal aberrations analysis. When the aberration frequency for a particular subject reached the background, we measured translocations in the final sample, using fluorescence in situ hybridization. Chromosome painting probes for chromosomes 1, 2, and 4 were used simultaneously. RESULTS: Dicentric and ring chromosomes were eliminated within a year. Translocations persisted and deviated from control values in all examinees. Translocations were detected long after unstable aberrations decreased to the background level. CONCLUSION: Fluorescence in situ hybridization-based translocation detection was a reliable method for monitoring chronic occupational clastogen exposure. Chromosome aberration assay correlated with translocation frequency. Stable chromosomal aberrations reflected cumulative genome damage during job exposure.