Independent verification of circulating miRNA as diagnostic biomarkers for urothelial carcinoma.

Urothelial carcinoma (UC) is an umbrella term for bladder cancers (BCa) and upper-tract urothelial carcinoma (UTUC), with BCa and UTUC sometimes detected concomitantly. The methods of detection for UC are often inaccurate or highly invasive, and, therefore, are thought to be unsatisfactory. Previously, we reported seven serum miRNAs as diagnostic markers for BCa. Here, we re-evaluated potential diagnostic miRNAs in different institutions. We prospectively analyzed serum samples obtained from 126 UC patients (BCa: 106 samples; UTUC: 14 samples; UTUC with BCa: six samples) and 50 noncancer controls by microarray analysis. We randomly assigned these samples into a training or a validation set. Biomarker candidate miRNAs were selected based on cross-validation scores in the training set of samples, with diagnostic power confirmed in the validation set. Among the diagnostic miRNAs identified in this way, miR-1343-5p and miR-6087 had been identified as potential diagnostic miRNAs in our previous study. In addition, we evaluated the association between the serum levels of identified miRNAs and the presence of UC risk conditions. The expression levels of several miRNAs correlate with the risk factors in participants without UC, which may be explained by the presence of a microscopic tumor or a precancerous lesion. In conclusion, we identified two robust miRNA diagnostic markers for UC detection. Further functional analysis is required to elucidate the mechanism by which alterations in the expression of these miRNAs occur.

Pyoderma Gangrenosum after Breast Cancer Resection: A Less-invasive and Early Treatment Using the Skin around Ulcers.

Surgical invasion is a risk factor of pyoderma gangrenosum (PG). A total of 25% of postoperative PG cases were reported to occur after breast surgeries, including bilateral breast reduction and breast reconstruction following cancer resection. Immunosuppressive therapy and less-invasive wound therapy are necessary; however, the complete healing of ulcers takes 5.1 months on average. We herein report a case of skin grafting under a surgical concept of less-invasive and short-term treatment. An 82-year-old woman complained of a high fever and severe pain at her breast wounds after bilateral breast cancer resection. Although we performed emergency debridement surgery to remove the necrotic tissue, suspecting surgical site infection and inflammation, her high fever persisted. She was diagnosed with PG because of the physical findings of characteristic painful, sterile ulcerations, bullae and pustules, and the pathological abundance of neutrophils in the absence of infection and vasculitis. Oral administration of prednisolone 30 mg/day improved the symptoms, and we applied negative-pressure wound therapy (NPWT) from day 16 following debridement surgery. After the gradual reduction of oral steroid intake to 12.5 mg/day, we performed skin grafting surgery. To limit the surgical invasion, we used the surplus skin around the ulcers. Split-thickness mesh skin grafts were fixed by NPWT to avoid the use of tie-over sutures. We achieved short-term treatment of PG with a less-invasive surgical strategy using skin around the ulcers and NPWT.

Clinical findings and treatment of disseminated 'Mycobacterium avium subspecies hominissuis' infection in a domestic cat.

A cat was referred because of diffuse parenchymal lung disease. Close examinations revealed a swollen abdominal lymph node and multiple nodules of the liver. Mycobacterium avium subspecies hominissuis infection was confirmed by culture and single nucleotide polymorphism analysis of samples recovered from the liver and bronchoalveolar lavage. After administration of combination antibiotics for 6 months, culture results were negative. Though atonic seizures were observed during the treatment, it disappeared after isoniazid discontinuation and pyridoxal phosphate administration. On day 771 of illness, no clinical signs, lung diseases, or obvious swelling of lymph nodes was observed. This is the first report to confirm Mycobacterium avium subspecies hominissuis infection in cats through gene analysis and to completely cure it with combination antibiotics.

Case report: retroperitoneal aspergilloma in a patient with rheumatoid arthritis presenting as malignant tumor.

BACKGROUND: Aspergillosis in patients with impaired immunity usually presents with invasive pulmonary infection and dissemination to a variety of organs via hematogenous spread. Aspergilloma in the retroperitoneal cavity is a rare disease with only a few cases reported in the literature. To the best of our knowledge, the present case of a retroperitoneal aspergilloma with no surgical history is only the second report in the literature. CASE PRESENTATION: A 65 year-old man, who had been receiving immunosuppressive treatment for rheumatoid arthritis with vasculitis for 9 years, was referred to the Urology Department with a retroperitoneal mass. This was confirmed by computed tomography performed during treatment for pulmonary aspergilloma. Because it was not possible to rule out malignant disease (e.g., liposarcoma), surgical exploration was performed. Pathological examination revealed aspergillus hyphae with fat necrosis, and retroperitoneal aspergilloma was diagnosed and appropriately treated. The tumor did not recur subsequently. CONCLUSION: Our present case emphasizes that pharmacological treatments for aspergilloma in the retroperitoneal cavity have poor drug transitivity, so the relative effectiveness of pharmacological response is not useful for differentiating retroperitoneal aspergilloma from malignant disease.

[An Intravesical Foreign Body after Caesarean Section and Tissue Fixing System (TFS) Operation : Two Case Reports].

Foreign body in the bladder is a relatively rare case. We encountered two cases of foreign bodies in the bladder after gynecological surgery. Case 1 was a 72-year-old woman. When she was 70 years old,an operation for her pelvic organ prolapse was performed. She visited our hospital because of discomfort in urination. We performed a transurethral lithotripsy of the bladder stone and detected a foreign body,and it was an anchor used for the Tissue Fixation System(TFS)operation (a pelvic organ prolapse operation). Case 2 was a 34-year-old woman. She delivered a baby by Caesarean section when she was 30 years old. She visited our hospital because of recurring urinary tract infection. The ultrasound examination of the bladder showed high echoic area in the posterior bladder wall. The cystoscope examination showed a small black foreign body that was protruding from the posterior wall of the bladder. The foreign body in the bladder was a surgical suture. The component of the suture was similar to silk. The foreign body in the bladder may have been the cause of infection. Artificial material used for an operation of an organ in the pelvic area sometimes slips into the bladder and causes inflammation. If a patient had undergone an operation for an organ in the pelvic area in the past,and there is recurring urinary tract infection,the presence of a foreign body in the bladder should be suspected.

Neutrophil CD64 is upregulated in RA patients with lymphoma but not in other solid cancers.

OBJECTIVE: To evaluate the utility of quantifying CD64 expression on neutrophils in rheumatoid arthritis patients with malignancy, especially its diagnostic role in lymphoma. METHODS: We used flow cytometry to quantify CD64 expression on neutrophils from patients diagnosed with malignancy during the follow-up period prior to initiating treatment. RESULTS: Neutrophils from 18 patients with lymphoma expressed significantly higher levels of CD64 (9635.6 ± 2123.7 molecules/cell) than those from 32 patients with other solid cancers (carcinoma) (1250.5 ± 91.1 molecules/cell) (p < 0.001). When the cutoff value was set at 2060 molecules/cell, the sensitivity and specificity of CD64 for diagnosing lymphoma was 88.9% and 94.4%, respectively. CONCLUSIONS: The quantitative measurement of neutrophil CD64 by flow cytometry may be useful as a subsidiary diagnostic marker in patients with suspected lymphoma. Although neutrophil CD64 is currently a well-known marker of infection, it is necessary to bear in mind that lymphoma is also a candidate in differential diagnosis when CD64 expression on neutrophils is upregulated.

Clinical application of neutrophil CD64 quantification for differential diagnosis of acute scrotum.

The management of acute scrotum can be challenging, especially in infants or patients with a neurological or neurodevelopmental disorder in whom presentation, diagnosis and definitive management tends to be delayed. This leads to poor outcomes, such as loss of the affected testis. Here we present two cases of testicular torsion in patients with neurodevelopmental disorders, and a further two cases of epidydimo-orchitis in whom measurement of CD64 expression on neutrophils was helpful for differential diagnosis. These data suggest that the levels of expression of CD64 by neutrophils, known as a marker of infection, could also be useful for differentiating between testicular torsion and infection in acute scrotum.

[Unilateral adrenal tuberculosis: a case report].

Computed tomography (CT) performed for a 75-year-old man as a follow-up examination for deep vein thrombosis in October 2010 revealed a left adrenal mass (diameter, 8 mm). In December 2012, the adrenal mass increased to 28 mm in diameter, and he was referred to our department. Several blood examinations revealed that the adrenal mass was non-functioning, and only peripheral lesions were observed to be enhanced by using CT in the arterial phase. Malignancy was suspected due to the irregular shape and growth of the mass, and left adrenalectomy was performed in February 2013. The histopathological diagnosis was adrenal mycobacteriosis, and clinical diagnosis was adrenal tuberculosis. No other tuberculosis infection-related lesion was detected, and the patient was treated with multidrug antituberculous chemotherapy.

Androgen deprivation therapy prevents bladder cancer recurrence.

Although accumulating preclinical evidence indicates the involvement of androgen receptor signals in bladder cancer (BC) development, its clinical relevance remains unclear. We aimed to evaluate the predictive role of androgen deprivation therapy (ADT) in BC recurrence in prostate cancer (PC) patients. We retrospectively reviewed 20,328 patients with PC diagnosed during 1991-2013 and identified 239 (1.2%) men having primary BC. After excluding ineligible patients, 162 patients made up a final cohort. With a median follow-up of 62 months, 38 (50%) of 76 control patients without ADT experienced BC recurrence, while 19 (22%) of 86 did in ADT group. Thus, patients having received ADT for their PC showed a significantly lower risk of BC recurrence (5-year actuarial recurrence-free survival: 76% v 40%; P < 0.001) and also had a significantly smaller number of recurrence episodes (5-year cumulative recurrence: 0.44 v 1.54; P < 0.001), compared to the control patients. A multivariable analysis revealed ADT as an independent prognosticator (hazard ratio, 0.29; 95% confidence interval, 0.17-0.49) for BC recurrence. This is the first clinical study showing that ADT significantly reduces the risk of BC recurrence.

[Malignant priapism due to metastatic papillary renal cell carcinoma : a case report].

A 70-year-old man presented in December, 2010 with priapism persistent for over a month. The patient had no history of medications for erectile dysfunction, penis trauma, or traumatic sexual activities. A blood gas measurement of the cavernosum was performed, but only fibrosis tissue was aspirated and no blood was obtained. Color-flow Doppler imaging of the penis revealed blood flow in the corpora cavernosa of the penis, suggesting the occurrence of nonischemic priapism. Enhanced chest and abdominal computed tomography revealed a left renal cyst, and the wall of the cyst showed contrast enhancement. No other obvious obstructive mass or tumor was detected in the pelvic cavity. Gradually, necrotic changes of the glans penis appeared, and total penectomy was performed. Histopathological examination of penectomy tissue specimens suggested papillary renal cell carcinoma metastases to the penis. Consequently, open left radical nephrectomy was performed. Pathological diagnosis revealed papillary renal cell carcinoma pT2, and the patient was diagnosed with stage IV (pT2N0M1) renal cell carcinoma. Treatment was provided by intravenous temsirolimus therapy that resulted in partial remission and stable disease, which in turn relieved cancer pain.

[The use of negative pressure wound therapy to treat wound necrosis and groin lymphorrhea after inguinal lymph nodes dissection: a case report].

Wound necrosis and groin lymphorrhea after inguinal lymph nodes dissection are serious complications. But treatment options for these complications are somewhat controversial. We report a patient who underwent an inguinal lymph node dissection for a regional metastasized squamous cell carcinoma of penis. Unfortunately, a extensive wound necrosis occurred with lymphorrhea (300 cc daily). After operative debridement, negative pressure wound therapy was started. We had used the instrument "V.A.C. (Vacuum Assisted Closure) ATS Therapy System" (KCI U.S.A.). After 11 days of negative pressure wound therapy, the good formation granulation tissue was observed and the lymphatic leakage was prominently decreased. This therapy was performed without serious complications but tolerable localized pain due to negative pressure. There were only seven reports that gave the description of an approach using negative pressure wound therapy for the less invasive treatment of lymphocutaneous fistulas and evaluated the efficacy of this therapy as an alternative medical procedure for treating lymphorrhea. This case suggested that negative pressure wound therapy could not only promote wound healing but also improve intractable lymphorrhea.

A case of squamous cell carcinoma arising from a suprapubic cystostomy tract.

BACKGROUND: Patients with spinal cord injury and a chronic indwelling urinary catheter are known to have an increased risk of bladder malignancy. However, squamous cell carcinoma (SCC) of the epidermis around a suprapubic cystostomy is relatively rare. Here, we report a case of lower abdominal SCC arising from the suprapubic cystostomy tract. CASE PRESENTATION: A 58-year-old man with a complete spinal cord injury was referred to our hospital with a chief complaint of an abdominal mass. Abdominal enhanced computed tomography (CT) showed a 7-cm mass surrounding the suprapubic cystostomy and bilateral inguinal and para-aortic lymph nodes metastasis. Histopathological examination of percutaneous biopsy specimens was performed. The diagnosis was stage IV (cT4N1M1) epidermal SCC, which was treated with palliative external radiation therapy. CONCLUSION: The SCC in this case was thought to arise from mechanical stimulus of the suprapubic cystostomy. Physicians and patients should pay careful attention to any signs of neoplasms with long-term indwelling catheters, such as skin changes around the suprapubic cystostomy site. This case presentation is only the fourth report of SCC arising from the suprapubic cystostomy tract in the literature. In cases of unresectable tumors and contraindications to chemotherapy, palliative radiotherapy may lead to disease remission and symptom relief.

[A case of dedifferentiated liposarcoma of the spermatic cord].

We report a case of dedifferentiated liposarcoma of the spermatic cord. A 79-year-old man was referred to our hospital with the chief complaint of a painless right scrotal swelling. A hard mass was palpable beside the soft mass which was suspected of lipoma or liposarcoma, and under this mass there was right testis. Therefore, we performed a right radical orciectomy. Histopathological diagnosis was dedifferentiated liposarcoma of the spermatic cord. Dedifferentiated liposarcoma of the spermatic cord was rare, and preoperative diagnosis was difficult.

[Case of recurrent retroperitoneal malignant paraganglioma 25 years after surgery].

A 41-year-old man was referred to our hospital for a left renal mass detected by screening computed tomography for hypertension. He had undergone surgery for left pheochromocytoma at 16 years of age in 1981, and the last follow-up was in 1986. Although a 131I-metaiodebenzylguanidine (MIBG) scintigram did not show abnormal uptake, elevated levels of serum cathecholamines were demonstrated. The left renal mass positioned in the upper pole and inside of the kidney had invaded the pancreas, colon and spleen. Surgical resection was done under a diagnosis of recurrent pheochromocytoma, and the tumor was removed with other organs, including normal left adrenal gland that was confirmed histologically. Histologically and immunohistochemically, the resectioned tumor was invasive malignant paraganglioma and diagnosed as the local recurrence or metastasis of previously resectioned retroperitoneal paraganglioma, which was believed to have grown slowly.

Muscle and small intestinal metastasis of renal cell carcinoma markedly responsive to interferon-alpha therapy: a case report.

Skeletal muscle and small intestine are rare sites of metastasis in renal cell carcinoma. Therefore very few reports of interferon-alpha (IFN-alpha) therapy exist for these types of metastasis. Here, a case of metastatic renal cell carcinoma to muscle and jejunum is reported. After IFN-alpha therapy for 9 weeks, muscle metastasis completely disappeared and intestinal lesions were markedly reduced. However, subsequent patient compliance for this therapy was poor, resulting in death after relapse of the RCC.

[Pheochromocytoma manifested by traumatic adrenal hemorrhage].

The presentation of pheochromocytoma is quite variable. We report a case of previously undiscovered pheochromocytoma which was manifested by traumatic retroperitoneal hemorrhage. A 79-year-old man fell from his bicycle and was admitted to the emergency room complaining of right flank pain. Enhanced computed tomography (CT) revealed hemorrhage around the right adrenal gland. Since the plasma catecholamine levels were elevated, we suspected the presence of pheochromocytoma. After absorption of the hematoma, the tumor appeared clearly. The diagnosis of pheochromocytoma was confirmed through urine catecholamine testing and 131I-MIBG scintigraphy. Six months after the injury, the tumor was surgically resected. Traumatic hemorrhage of pheochromocytoma is extremely rare; only 3 cases have been reported in the literature.

[Small cell carcinoma of the bladder: a case report].

A 61-year-old man was referred to our hospital with a complaint of gross hematuria and lower abdominal discomfort. Ultrasonography, magnetic resonance imaging and cystoscopy revealed a nodular invasive tumor in urinary bladder. The histopathological findings of transurethral-biopsy specimen was the small cell carcinoma and transitional cell carcinoma of the bladder infiltrating into smooth muscle layer. Total cystectomy with ileal conduit was performed following 1 course of neoadjuvant chemotherapy (M-VAC). Computed tomography (CT) before adjuvant chemotherapy revealed tiny lung metastasis in left peripheral lung area. As postoperative adjuvant therapy, 4 courses of chemotherapy (etoposide and calboplatin) were performed with 50 Gy of extra beam radiotherapy to the lung metastasis. Follow up CT revealed disapperance of lung metastasis, and the patient has been free from disease for one year after chemotherapy.

Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo.

Silencing of gene expression by small interfering RNAs (siRNAs) is rapidly becoming a powerful tool for genetic analysis and represents a potential strategy for therapeutic product development. However, there are no reports of systemic delivery for siRNAs toward treatment of bone-metastatic cancer. Accordingly, we report here that i.v. injection of GL3 luciferase siRNA complexed with atelocollagen showed effective reduction of luciferase expression from bone-metastatic prostate tumor cells developed in mouse thorax, jaws, and/or legs. We also show that the siRNA/atelocollagen complex can be efficiently delivered to tumors 24 h after injection and can exist intact at least for 3 days. Furthermore, atelocollagen-mediated systemic administration of siRNAs such as enhancer of zeste homolog 2 and phosphoinositide 3'-hydroxykinase p110-alpha-subunit, which were selected as candidate targets for inhibition of bone metastasis, resulted in an efficient inhibition of metastatic tumor growth in bone tissues. In addition, upregulation of serum IL-12 and IFN-alpha levels was not associated with the in vivo administration of the siRNA/atelocollagen complex. Thus, for treatment of bone metastasis of prostate cancer, an atelocollagen-mediated systemic delivery method could be a reliable and safe approach to the achievement of maximal function of siRNA.

[Giant seminoma in abdominal retention of the testis manifested with unilateral leg pain: a case report].

A 26-year-old man was admitted to the department of surgery of our hospital with a complaint of intermittent left leg pain for the past two weeks. Ultrasonography revealed reduced blood flow to the tibial artery, which suggested a vascular disease like arteriosclerosis obliterans. Enhanced computed tomography (CT) revealed a huge abdominal tumor and a 3-dimensional CT scan showed a feeding artery from the left renal artery to the huge tumor. Findings of routine blood and urine examinations were elevated levels of lactate dehydrogenase, alkaline phosphatase, and C-reactive protein. Surgical exploration revealed a giant tumor with clouded ascites in the abdominal cavity containing class V cells revealed by cytological examination. The tumor was easily resected. Its vascular pedicle was thick and hypertrophied. Thus, it could be traced to the origin of left gonadal artery. At this time, the surgeon incidentally noticed the absence of left testis in the patient's scrotum. The resected specimen was 25 x 18 x 12 cm in size, and it weighed 3000 gm. The histological finding was pure seminoma invaded to peritoneum. His leg pain was relieved after the tumor resection.