Identification of New Prognostic Markers and Therapeutic Targets for Non-Muscle Invasive Bladder Cancer: HER2 as a Potential Target Antigen.

Bacillus Calmette-Guérin (BCG) is the gold standard adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC). However, given the current global shortage of BCG, new treatments are needed. We evaluated tumor microenvironment markers as potential BCG alternatives for NMIBC treatment. Programmed death-ligand 1, human epidermal growth factor receptor-2 (HER2), programmed cell death-1 (PD1), CD8, and Ki67 levels were measured in treatment-naïve NMIBC and MIBC patients (pTa, pT1, and pT2 stages). Univariate and multivariate Cox proportional hazard models were used to determine the impact of these markers and other clinicopathological factors on survival, recurrence, and progression. EP263, IM142, PD1, and Ki67 levels were the highest in the T2 stage, followed by the T1 and Ta stages. HER2 and IM263 expressions were higher in the T1 and T2 stages than in the Ta stage. In NMIBC, the significant prognostic factors for recurrence-free survival were adjuvant therapy, tumor grade, and HER2 positivity, whereas those for progression-free survival included age, T-stage, and IM263. Age, T-stage, EP263, PD1, CD8, and Ki67 levels were significant factors associated with overall survival. IM263 and HER2 are potential biomarkers for progression and recurrence, respectively. Therefore, we propose HER2 as a potential target antigen for intravesical therapeutics as a BCG alternative.

Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. METHODS: Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23 kg/m2), "overweight" (23-27.5 kg/m2), and "obese" (≥ 27.5 kg/m2). Among the 389 patients included in this study, 108 were classified as normal, while 227 and 54 patients were classified as overweight and obese, respectively. The relationships between clinicopathological factors and biochemical recurrence were analyzed by univariate and multivariate Cox ≤ proportional hazard models. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ≥ 0.2 ng/mL. RESULTS: In univariate analysis, the categorical variables of "overweight" and "obese" were significant prognostic factors for biochemical recurrence. In multivariate analysis models including PSA density [hazard ratio (HR) 1.8, p = 0.01], extraprostatic extension (HR 2.0, p < 0.001), Gleason score (HR 1.7, p = 0.01), surgical margin positivity (HR 2.46, p < 0.001), and lymphovascular invasion (HR 2.53, p < 0.001), the categorical variables of "overweight" (HR 1.6, p = 0.03) and "obese" (HR 1.76, p = 0.035) were prognostic factors for biochemical recurrence. CONCLUSION: The obesity status of patients with prostate cancer as "overweight" and "obese" was a risk factor for biochemical recurrence after adjusting for other clinicopathological factors.

Osteochondrolipoma Presenting as a Popliteal Cyst.

Here, we describe a popliteal mass that was initially misdiagnosed as a simple popliteal cyst, which finally turned out to be osteochondrolipoma. A 63-year-old housewife presented with sustained knee pain in association with a palpable mass on the popliteal fossa. The mass was in the posteromedial area and soft, non-tender, non-movable in the posteromedial area. Using plain radiography, the mass appeared as a round, soft tissue density lesion containing bony fragments. We performed an ultrasound-guided needle biopsy in conjunction with magnetic resonance imaging, followed by an open excisional biopsy. Microscopically, histological sections showed a lipoma with cartilaginous and osseous differentiation, finally diagnosed as osteochondrolipoma. In conclusion, popliteal masses are not always simple cysts, and the evaluation of masses in the popliteal fossa is always necessary.

Prognostic implications of EGFR and HER-2 alteration assessed by immunohistochemistry and silver in situ hybridization in gastric cancer patients following curative resection.

BACKGROUND: The aim of this study was to use immunohistochemistry (IHC) and silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in gastric cancer in order to determine the relationship with prognosis in gastric cancer patients following curative resection. PATIENTS AND METHODS: In this study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III gastric cancer patients who underwent curative surgery. RESULTS: Thirteen cases (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease (P < 0.001). The patients with operable state gastric cancer who had EGFR alteration had an unfavorable prognosis, and multivariate analysis confirmed that EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was associated with older age (P = 0.006), well or moderately differentiated histology (P < 0.001) and intestinal type (P = 0.002). CONCLUSION: HER-2 alteration is not an independent prognostic factor for curatively resectable gastric cancer. We observed EGFR alteration in a subset of cases with operable state gastric cancer and determined that it was associated with an unfavorable prognosis.

Colorectal micropapillary carcinomas are associated with poor prognosis and enriched in markers of stem cells.

Colorectal micropapillary carcinoma has recently been reported as an aggressive variant of adenocarcinoma with a high incidence of lymph node metastasis, but has not been well investigated in terms of survival analysis. This study analyzed the clinicopathological characteristics, including survival data, of the patients with micropapillary carcinoma. We hypothesized that the aggressive features of micropapillary carcinoma might be related to the presence of more tumor cells with stem cell phenotype in colorectal cancer. Fifty-five (10%) micropapillary carcinoma cases were identified among 561 cases of colorectal cancer. We compared the clinicopathological characteristics, including survival data and immunohistochemical profiles of stem cell markers (SOX2, NOTCH3, CD44v6, CD166, ALDH1) of micropapillary carcinomas with those of randomly selected 112 conventional adenocarcinomas lacking micropapillary carcinoma components (non-micropapillary carcinoma) in the colorectum. To exclude the possibility of dilution of control group by patients with microsatellite instability-high carcinomas, we divided non-micropapillary carcinomas into microsatellite instability-high carcinoma and microsatellite stable tumors. Micropapillary carcinomas were characterized by more frequent lymphovascular invasion (P<0.0001) and lymph node metastasis (P<0.0001), higher pathological T and tumor node metastasis stages (P=0.047 and P=0.001), and more frequent SOX2 (P=0.038) and NOTCH3 expressions (P=0.005). Overall 5-year survival rate for patients with micropapillary carcinoma (37%) was significantly lower than for microsatellite instability-high carcinoma and microsatellite stable carcinoma patients (92 and 72%, P<0.0001). The presence of the micropapillary carcinoma component was shown to be associated with a significantly worse survival rate in univariate (P<0.0001) and multivariate (P=0.003, Cox hazard ratio 2.402) analyses. In conclusion, recognition of the micropapillary carcinoma component in colonic adenocarcinoma is very important, because the micropapillary carcinoma has been associated with a significantly worse prognosis. We also found a higher expression rate of cancer stem cell markers in micropapillary carcinomas, suggesting their potential contribution to the survival disadvantage of micropapillary carcinoma.

Male breast adenoid cystic carcinoma.

INTRODUCTION: Adenoid cystic carcinoma (ACC) of the breast is a rare condition, and cases in male patients are even less common. CASE: We describe a case of ACC of the breast with axillary lymph node metastasis, disseminated osteolytic bone metastasis and bone marrow involvement in a 41-year-old man. CONCLUSION: Male breast ACC is an extremely rare malignancy; there can be difficulty in obtaining a final diagnosis. We report this case because of its rarity.

Gastric micropapillary carcinoma: A distinct subtype with a significantly worse prognosis in TNM stages I and II.

Micropapillary carcinoma (MPC) is an aggressive variant of adenocarcinoma, with a high incidence of lymph node (LN) metastasis in several organs, although not yet well described in the stomach. Thus, we compared the clinicopathologic characteristics, including survival data and immunohistochemical profiles of cell adhesion molecules (E-cadherin, ß-catenin, IQGAP-1, and CD44v6), of MPCs with those of adenocarcinomas lacking MPC components (non-MPC) in the stomach. We compared 72 MPC cases with 160 non-MPC cases. Most gastric MPCs arose from tubular or papillary adenocarcinomas, and the proportion of MPC components ranged from 5% to 80%. MPCs were characterized by more frequent lymphovascular invasion and LN metastasis (P<0.0001), higher tumor node metastasis (TNM) stage (P=0.019), advanced age (>65 y; P<0.0001), and more frequent CD44v6 and aberrant ß-catenin expression (P<0.0001). The overall 5-year survival rates for patients with MPC were significantly worse than those with non-MPC (30% vs. 67%; P=0.002). Furthermore, when it was stratified by TNM stages, the survival rates were distinguished between MPC and non-MPC groups in TNM stages I to II (P=0.0003), but not in TNM stages III to IV. The presence of the MPC component was associated with a significantly worse patient survival by univariate (P=0.0003) and multivariate (P=0.04) analyses in patients with stages I to II gastric carcinoma. In conclusion, recognition of the MPC component in gastric carcinoma is critical, because the MPC component is associated with more frequent LN metastasis and a worse prognosis, especially in stages I to II gastric cancer.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix: a case report.

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma.

Unusual bronchopulmonary foregut malformation associated with pericardial defect: bronchogenic cyst communicating with tubular esophageal duplication.

We report a case of unusual bronchopulmonary foregut malformation composed of a mediastinal bronchogenic cyst with sequestrated lung tissue and communicating tubular esophageal duplication associated with complete pericardial defect. A 18-yr. old man, who had suffered from dry cough and mild dyspnea, was admitted because of an incidentally detected chest mass. A computed tomography scan demonstrated a cystic mass with an air fluid level connected with esophagus in the middle mediastinum. The surgically resected mass was a pleural invested accessory lobe of the lung (8.0 x 7.0 x 4.5 cm) connected with the esophageal wall by a tubular structure (3.0 cm in length and 2.0 cm in diameter). A complete left pericardial defect was also identified. Histologically, the cystic wall was composed of fibrovascular connective tissue with a smooth muscle layer, mixed seromucous glands and cartilage, and the inner surface of the cyst was lined by ciliated pseudostratified columnar epithelium. The inner surface of the tubular structure was lined by non-keratinizing or keratinizing squamous epithelium, and the wall contained submucosal mucous glands, muscularis mucosa, and duplicated muscularis propria. This case is important in understanding the embryological pathogenesis of the variable spectrum of the bronchopulmonary foregut malformation.

Torsion of the gallbladder: report of a case.

Torsion of the gallbladder is a rare entity that is difficult to diagnose preoperatively. The condition occurs most often in the elderly. Although its etiology is unknown, a constant finding is the presence of the gallbladder on a mobile mesentery (floating gallbladder). Torsion, or volvulus, of the gallbladder occurs when it twists axially, with the subsequent occlusion of bile and/or blood flow. Herein, a case of torsion of the gallbladder is presented where preoperative computed tomographic scan and laparoscopy were successfully used to diagnose and treat this condition without the usual requirement of open exploration. Given the possibility of laparoscopic cholecystectomy and the increasing incidence with which torsion of the gallbladder is being witnessed today, the importance of a preoperative computed tomographic scan is emphasized when there is a high index of clinical suspicion.

Aneurysm of the popliteal artery in neurofibromatosis.

The neurofibromatoses are a heterogeneous set of genetic disorders having clinical manifestations that involve the skin, the nervous system, or both. In addition, the disease can be confounded by a broad spectrum of complications, such as various kinds of osseous lesion, vascular lesions, aqueduct stenosis, optic glioma, and learning disabilities. Neurofibromatosis results in vascular involvement in approximately 10% of cases. Stenotic lesions predominate, but aneurysms have been documented as well. Rarely noted, however, have been peripheral aneurysms. In this report, we discuss the case of a 66-year-old woman with type 1 neurofibromatosis and a popliteal artery aneurysm who was operated upon because of threatened limb ischemia. Histological findings confirmed neurofibromatous invasion of the vessel wall.

Mesenteric involvement of acute-stage Buerger's disease as the initial clinical manifestation: report of a case.

Buerger's disease is almost always a disease of the blood vessels in the extremities. Conversely, mesenteric involvement of Buerger's disease is rare, and no true series have been reported. We report the case of a 37-year-old man with clinical symptoms of upper extremity Buerger's disease, who underwent surgery for extensive small bowel infarction. Histopathologic findings revealed that the mesenteric arteries were swollen and infiltrated with neutrophils, but not associated with fibrinoid necrosis. The lumen was occluded by a highly cellular thrombus with the appearance of a microabscess. These findings were compatible with acute-stage mesenteric Buerger's disease and postoperative studies revealed multiple occluded segments in the small and medium-sized arteries of both legs and the left arm, suggestive of Buerger's disease in the extremities.

Staged surgery for chronic primary aortoduodenal fistula in a septic patient.

Aortoenteric fistula is one of the most challenging problems that confront the vascular surgeons. Controversy remains over the optimal treatment because of the continued publication of series with high mortality, amputation, and aortic disruption rates. A positive preoperative blood culture is the best predictor of mortality with increased amputation rates due to infection of the extra-anatomic bypass. Therefore, in selected cases with sepsis, a prudent management protocol is required. We report a 68-yr-old male presenting with a chronic primary aortoduodenal fistula extensively involving the duodenum and Gram-negative sepsis. We planned a staged operation. Initially, an emergency laparotomy and control of the aorta allowed stabilization of the patient, identification of the fistula, and direct in situ placement of the prosthetic graft followed by an en bloc resection of the aneurysm and the surrounding structures. After he recovered from sepsis and had been stabilized, a staged extra-anatomic bypass followed by transabdominal removal of the temporarily placed graft was done. This management plan will allow the highest success rate and may be a prudent management protocol for these difficult cases.

Superficial endobronchial lung cancer: radiologic-pathologic correlation.

OBJECTIVE: To analyze the plain chest radiographic and CT findings of superficial endobronchial lung cancer and to correlate these with the findings of histopathology. MATERIALS AND METHODS: This study involved 19 consecutive patients with pathologically proven lung cancer confined to the bronchial wall. Chest radiographs and CT scans were reviewed for the presence of parenchymal abnormalities, endobronchial nodules, bronchial obstruction, and bronchial wall thickening and stenosis. The CT and histopathologic findings were compared. RESULTS: Sixteen of the 19 patients had abnormal chest radiographic findings, while in 15 (79%), CT revealed bronchial abnormalities: an endobronchial nodule in seven, bronchial obstruction in five, and bronchial wall thickening and stenosis in three. Histopathologically, the lesions appeared as endobronchial nodules in 11 patients, irregular thickening of the bronchial wall in six, elevated mucosa in one, and carcinoma in situ in one. CONCLUSION: CT helps detect superficial endobronchial lung cancer in 79% of these patients, though there is some disagreement between the CT findings and the pathologic pattern of bronchial lesions. Although nonspecific, findings of bronchial obstruction or bronchial wall thickening and stenosis should not be overlooked, and if clinically necessary, bronchoscopy should be performed.