E2F target score is associated with cell proliferation and survival of patients with hepatocellular carcinoma.

BACKGROUND: E2F target genes are essential for the cell cycle. A score that quantifies its activity is expected to reflect the aggressiveness and prognosis of hepatocellular carcinoma. METHODS: Cohorts of hepatocellular carcinoma patients (total n = 655) from The Cancer Genome Atlas, GSE89377, GSE76427, and GSE6764 were analyzed. The cohorts were divided into high versus low by the median. RESULTS: All the Hallmark cell proliferation-related gene sets were consistently enriched in hepatocellular carcinoma with high E2F targets score, and E2F score was associated with grade, tumor size, American Joint Committee on Cancer staging, proliferation score, and MKI67 expression, as well as with less abundance of hepatocytes and stromal cells. E2F targets enriched DNA repair, mTORC1 signaling, glycolysis, and unfolded protein response gene sets and were significantly associated with the higher intratumoral genomic heterogeneity, homologous recombination deficiency, and progression of hepatocellular carcinoma. On the other hand, there was no relationship between E2F targets and mutation rates or neoantigens. High E2F hepatocellular carcinoma did not enrich any of the immune-response-related gene sets but was associated with high infiltration of Th1, Th2 cells, and M2 macrophage; however, there was no difference in cytolytic activity. In both early (I and II) and late (III and IV) stages of hepatocellular carcinoma, a high E2F score was associated with worse survival and was an independent prognostic factor for overall and disease-specific survival in patients with hepatocellular carcinoma. CONCLUSION: The E2F target score, associated with cancer aggressiveness and worse survival, could be used as a prognostic biomarker in patients with hepatocellular carcinoma.

Repeated Small Bowel Obstruction Caused by Chestnut Ingestion without the Formation of Phytobezoars.

A small number of cases of small bowel obstruction caused by foods without the formation of phytobezoars have been reported. Repeated small bowel obstruction due to the ingestion of the same food is extremely rare. We present the case of 63-year-old woman who developed small bowel obstruction twice due to the ingestion of chestnuts without the formation of phytobezoars. This is the first reported case of repeated small bowel obstruction caused by chestnut ingestion. Careful interviews are necessary to determine the meal history of elderly patients and psychiatric patients.

A new treatment for retroperitoneal fibrosis: initial experiences of using Seprafilm® to wrap the ureter.

OBJECTIVE: To confirm the efficacy of using Seprafilm® (Genzyme Corp., Cambridge, MA, USA) for wrapping the ureter to treat the ureteric stenosis caused by retroperitoneal fibrosis (RPF). PATIENTS AND METHODS: Between August 2010 and September 2012, 11 ureters in eight patients with RPF (seven males and one female, mean age 65 years) were treated. The mean (range) length of the narrow segment of the ureter was 30 (10-90) mm. During surgery, after having been released from adhesive tissue, the stenotic segment of the ureter was wrapped with Seprafilm to isolate it from the surrounding tissue. A radiographic follow-up was performed every 6 months using computed tomography, i.v. pyelography and/or (99m) Tc-mercapto-acetylglycyl-glycyl-glycine ((99m) Tc-MAG3) renal scintigraphy. RESULTS: For the unilateral operations, the mean estimated blood loss was 39 mL, and the mean operating time was 154 min. All ureters were isolated from the fibrotic tissue and wrapped with Seprafilm successfully without major complications. During the mean follow-up period of 17 months, no ureteric restenoses were observed in the affected sides, but new stenosis occurred in the contralateral side of the ureter in one patient. CONCLUSIONS: Although the follow-up period is still limited, we believe that the use of Seprafilm has the potential to become an effective option in the treatment of ureteric stenosis caused by RPF, when the omentum cannot be used. To establish the relative advantages of using Seprafilm over performing a standard omental wrap, further experimentation will be required to compare the two techniques.

[A case of carcinomatous cardiac tamponade caused by breast cancer treated with instillations of OK-432 and mitomycin C].

The patient was a 36-year-old female who had undergone Auchincloss operation for left breast cancer at another hospital when 29 years old. Three years ago she was transferred from another hospital to our department complaining of dyspnea. Under the diagnosis of cardiac tamponade, we treated her with pericardial drainage and systemic chemotherapy (intravenous dosage of trastuzumab and vinorelbine: VNR), and then pericardial effusion disappeared. Further medical treatment was continued on an outpatient basis. One year later, cardiac tamponade developed again. We performed echo-guided pericardiocentesis and removed 600 mL of bloody effusion. The cytology of the effusion showed class V. Pericardial effusion recurred, so we instilled OK-432 and mitomycin C (MMC) twice. After that the cytology diagnosis became negative, and the heart shadow in chest X-P reduced. The pericardial effusion has never occurred until now. We also gave her systemic chemotherapy (intravenous dosage of trastuzumab)and endocrine therapy (peroral administration of medroxyprogesterone acetate). She made a remarkable recovery with these treatments and could go back to work.

[A case of nonresected gastric cancer with peritoneal dissemination effectively treated by S-1/DOC and PTX/ CDDP combination chemotherapy with good QOL].

We performed combination chemotherapy in the outpatient clinic on a 47-year-old man with nonresected gastric cancer accompanied by peritoneal dissemination. At first we administered S-1/DOC combination chemotherapy. Afterwards a rise of tumor marker (CEA) occurred accompanying taste disorder and edema of the lower limbs, so we changed to combination chemotherapy for PTX/CDDP. Since the only side effect was numbness, the patient was treated on an outpatient basis while working. The case achieved good QOL by these combination chemotherapy methods for 1 year 10 months post exploratory laparotomy.

[Periconceptional intake of folate reduces the risk of neural tube defects: awareness among urologists in 2007].

AIMS: Folic acid is one of water-soluble Vitamin B group and plays an important role in proliferating cells of the fetus. A multicentered, randomized control trial proved in 1991 that folic acid supplements of 4 mg per day periconceptionally administered to 1031 women who were recruited from 7 countries and had afflicted prior pregnancy successfully prevented 72% of recurrence of neural tube defects. As a primary prevention method, the Government has recommended to take 400 microgram of folate supplements per day from 4 weeks before and 12 weeks after conception. Because of huge amount of folate being demanded in the first trimester, this vitamin is called as "vitamin for women" or "vitamin for fetuses". We herewith report results of questionnaire study performed among urologists. MATERIALS AND METHODS: A questionnaire was sent July 2007 to 400 urologists randomly selected from the Membership Directory of the Japanese Urological Association 2006 whether they are aware of the role of folic acid and how they guide young women or pregnant women on their life style. One hundred sixty-one responses were obtained (40%). RESULTS: Thirty-six percent of urologists were aware of the important role of folic acid in the critical stage of fetal development, which was significantly elevated compared to 26% observed in 2002 (p = 0.037). Fifty-seven percent of urologists acquired this information through Japanese Urological Association or medical journals, 17% through mass media, and 7% through internet. Those who guided young women or pregnant women to refrain from smoking, to abstain from alcohol, to take well-balanced meals and to take folate supplements were 73%, 62%, 67% and 7%, respectively. Ninety-two percent of urologists agreed to provide this information to young women or pregnant women. CONCLUSION: Birth incidence of spina bifida has been increasing in Japan. In order to suppress incidence of this congenital anomaly, Urologists are requested to send young women a message that maternal periconceptional intake of folate will suppress the risk of congenital anomalies.

[Renal cell carcinoma presenting high serum level of CA19-9 due to hydronephrosis: a case report].

A 58-year old female was referred to our hospital due to left renal cyst that was pointed out at her health check-up. Abdominal CT scan showed left hydronephrosis with a 20 x 12 x 11cm tumor. The serum CA19-9 level elevated to 4,400 U/ml. Urinary cytology in the left renal pelvis was negative, therefore we could not diagnose whether the mass was renal cell carcinoma or renal pelvic tumor before surgery. She underwent left radical nephrectomy, and frozen section revealed renal cell carcinoma. Immunohistological stain clarified CA19-9 was limited to epithelium lining the renal pelvis and was not contained in carcinoma cells. After the surgery, the serum CA19-9 decreased to the normal range. Serum CA19-9 is known to be sometimes elevated in patients with urothelial carcinoma, but rarely elevated in those with renal cell carcinoma. We thought that hydronephrosis by tumor occlusion caused CA19-9 elevation in our case.

[A case of metastasis to the diaphragm from ascending colon cancer].

We reported a case of metastatic tumor to the diaphragm discovered by rising CEA after operation of ascending colon cancer. A 72-year-old female underwent right hemicolectomy on January 2005. After discharge, she received adjuvant chemotherapy by S-1, but a rise of CEA was shown. Based on exploratory findings, laparotomy was done with the diagnosis of metastasis to the liver(S7). A tumor was present in the right diaphragm, and contacted the liver(S7). Partial resection of the right diaphragm was performed. The removed specimen revealed the same histological findings of the last operated ascending colon. Metastasis to the diaphragm is very rare, especially a solitary one as in this case. Etiologically speaking, the tumor cells might be absorbed or have strayed into peritoneal stomata of the diaphragm.

[Triple cancer in the urinary system: a case report].

A 74-year-old male was referred to our hospital due to microhematuria that was pointed out at his health check-up. Cystoscopy showed many papillary bladder tumors under 5 mm in size. Intravenous pyelography also showed deformity of the right kidney and shadow defects in the left renal pelvis. Abdominal computed tomography revealed an 8 cm tumor invading the renal vein in the right kidney, and a 3 cm tumor in the left renal pelvis. Prostate biopsy was performed with PSA 3.4 ng/ml, and he was also diagnosed with prostate carcinoma. First, he received right radical nephrectomy, and secondly left nephroureterectomy and cystectomy. Our case should be called triple cancer because bladder cancer was thought to be daughter tumor of renal pelvic tumor. This is, to our knowledge, the 11th case report that occurred in the urinary tact, and the first case that needed total resection of urinary tract.

[Radical prostatectomy for prostate carcinoma with ectopic ureter ; a case report].

A 71-year old male visited our hospital with a chief complaint of pollakisuria. The needle biopsies of the prostate were performed with PSA 8.0 ng/ml, and he was diagnosed as moderately differentiated adenocarcinoma. Imaging techniques revealed a right complete duplicated upper urinary system with an ectopic ureter draining to the prostatic urethra. He received radical prostatectomy with concomitant anastomosis of ureter to ureter. There is no evidence of hydronephrosis or tumor recurrence 11 months after operation. This is, to our knowledge, the second case report describing the association of radical prostatectomy and ectopic ureter.

Efficacy, safety and hospital costs of tension-free vaginal tape and pubovaginal sling in the surgical treatment of stress incontinence.

AIM: The efficacy, safety and hospital costs of the tension-free vaginal tape procedure were compared with the pubovaginal sling operation. METHODS: A total of 60 women urodynamically diagnosed as having stress or mixed urinary incontinence were operated on using either the tension-free vaginal tape or pubovaginal sling operation in a prospective manner. Preoperative characteristics of the women were not significantly different for the groups. The women were followed for up to 24 months. RESULTS: In the tension-free vaginal tape group, the operation time was shorter, numbers of analgesics postoperatively required were less and hospital charges were less expensive compared to those in the pubovaginal sling operation (P < 0.01). Kaplan-Meier survival analysis showed a marginal significant difference (P = 0.059) in the objective cumulative cure rates at 24 months between the groups receiving the former (70.3%) and latter (48.3%) procedures. Subjective cure rates were not significantly different (P = 0.101). In both groups, an improvement in quality of life was significant and surgical complications were identical. De novo urge incontinence developed in 6% and 10% in the former and latter, respectively. CONCLUSIONS: The tension-free tape was significantly superior to the pubovaginal sling in terms of operation time, postoperative pain, and hospital charges, but not in cure rates. A longer follow up with a larger sample size is necessary to draw definite conclusions.

[Giant condyloma with malignant degeneration: a case report].

We report a case of giant condyloma with malignant degeneration. A 56-year-old male was referred to our hospital due to a penile infection that was resistant to antibiotic therapy for more than a year. The swelling appeared to be a penile cancer. We suspected malignancy and performed penile biopsies twice; however, the histopathological diagnosis was condyloma acuminatum and malignant findings were absent. We continued the antibiotic therapy for 3 months; however, no improvement was achieved. Therefore, total penectomy and urinary diversion were performed. The pathological diagnosis of the resected tissues was not only condyloma but also squamous cell carcinoma, and cancer cells appeared on the cut surface of the specimens. We added radiation therapy. There was no evidence of recurrence or metastasis at 18 months after surgery.

[Retroperitoneal liposarcoma: a case report].

We report a case of retroperitoneal liposarcoma. A 66-year-old male was referred to our hospital for a retroperitoneal tumor that was detected during gallbladder stone examination. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an extrarenal lipomatous tumor, 20 x 14 x 8 cm in size, in the right retroperitoneal space. He underwent surgical excision of the tumor with concomitant resection of the right kidney and adrenal gland. The resected tissue weighed 730 g. Histological examination revealed a well differentiated liposarcoma. He received no adjuvant therapy.

[Primary undifferentiated carcinoma of the ureteral stump; a case report].

A 72-year-old man referred our hospital with the chief complaint of macroscopic hematuria. He had undergone simple left nephrectomy for left renal stone when he was 27-years-old. His urine cytology showed class IIIb. They were 4 times. We performed random biopsy of the bladder and retrograde pyelography of the right But they were no positive findings for the cause of hematuria and for the existence of malignancy. After 2 months, he had macroscopic hematuria again. Cystoscopic re-examination revealed a fibrin out of the residual left ureteral orifice. Computed tomographic scan showed a perivesical mass. The diagnosis was the carcinoma of the ureteral stump. We performed ureterectomy. The pathological study revealed the undifferentiated carcinoma. This case is the first report of the undifferentiated carcinoma occurred on the residual ureteral stump in the Japanese literature.

[Awareness of periconceptional consumption of folic acid among urologists and a group of laymen].

OBJECTIVE: The Ministry of Health, Labour and Welfare announced that periconceptional consumption of folic acid will reduce risks of having babies afflicted with Neural Tube Defects (NTDs) in the year of 2000. We assessed awareness of the role of folic acid among urologists and a patient group, how urologists give advices on lifestyle to young women, and what lifestyle the patient group currently maintains. MATERIALS AND METHODS: A postal questionnaire survey was conducted involving 400 urologists randomly selected and a group of 250 female patients afflicted with NTDS and 250 mothers who had given birth to babies having NTDs during the past 7 years. Eighty-four percent of urologists aged 40 years and over and 76% of the patient group aged in their 20s and 30s. Response rates were 56% in the former and 52% in the later. RESULTS: Twenty-six percent of urologists and 92% of the patient group knew an important role folic acid played in prevention of neural tube defects. While 10% of urologists advised to consume multi-vitamins containing folic acid or folic acid supplements, 25% of myelodysplastics and the mothers took them. Sixty-eight percent of doctors advised to take well-balanced food and 82% of the patent group answered that they do. Over 80% of the doctors and the patient group believed that a folic acid campaign is to be organized to inform young women of childbearing age of possible reduction of the risk. CONCLUSION: It is found that proportion of urologists who are aware of a role of periconceptional consumption of folic acid is significantly lower than that of the group of patients (p < 0.0001). Urologists are expected to recognize specific benefits of folic acid in the prevention of NTDs, to advise young women of childbearing age to take well-balanced meals, and to recommend those who wish to be pregnant to consume 400 micrograms of folic acid supplements from 4 weeks before to 12 weeks after conception.

[Folic acid reduces risks of having fetus affected with neural tube defects: dietary food folate and plasma folate concentration].

OBJECTIVES: Risk of having fetus affected with neural tube defects can be reduced by maternal periconceptional folic acid supplementation. The purpose of the present study is to investigate how folate is taken from diets and to measure plasma folate concentrations. SUBJECTS AND METHODS: A total of 222 women comprising 5 groups, i.e., healthy women, mothers of myelodysplastic patients, pregnant women, myelodysplastic patients, nurse students, participated in our study. Food frequency questionnaires kept 3 days were analyzed based on the 5th standard table of food composition in Japan. Plasma folate concentrations were measured by means of chemiluminescent immunoassay method. Changes in plasma folate concentrations and possible adverse effects following the folic acid supplementation for 16 weeks were also investigated. RESULTS: The dietary intake of folate, plasma folate concentration and energy intake averaged 293 micrograms/day, 8.1 ng/ml and 1,857 Kcal, respectively, among the subjects. Pregnant women took the largest amount of folate from diets and demonstrated the highest plasma folate concentration among the groups. The dietary folate in myelodysplastic patients and nurse students was significantly lower compared to that of healthy women. The Recommended Dietary Allowance of folate was not fulfilled in 22% of non-pregnant adult women and 72% of pregnant women. The dietary folate was mainly taken from the 3rd food group but the 4th group of food was consumed most. Mean folate intake was significantly correlated with circulating concentrations of serum folate (p = 0.012 r = 0.186). The consecutive administration of 400 micrograms supplements for 16 weeks increased a baseline plasma value of 8.7 ng/ml to 32.6 but fell down rapidly to 17.3 24 hours later without any adverse effects. CONCLUSIONS: The dietary folate and serum folate concentrations averaged 293 micrograms/day and 8.1 ng/ml, respectively. The former is the first report based on the 5th standard table of food composition in Japan. Majority of pregnant women took less dietary folate than what recommended by the government. Those who are capable of becoming pregnant are recommended to consume much of the 3rd food group and those who are planning to become pregnant are recommended to take 400 micrograms of folic acid supplements from 4 weeks before to 12 weeks after conception.

[A case in which severely irritable bladder following intravesical instillation of Bacillus Calmette Guerin was successfully treated by steroid therapy].

We report a patient whose irritable bladder symptoms following Bacillus Calmette Guerin (BCG) instillation were satisfactorily treated by steroid administration. A 59-year-old male had undergone transurethral resection for the bladder carcinoma recurred three times. The histopathological examination revealed the tumor as transitional cell carcinoma, G1 to G2, and pTa. Subsequently an instillation of 80 mg BCG into the bladder was planned 8 times every 7 days. After the 5th instillation he presented with gross hematuria, painful micturition, pollakisuria, urgency and reduced bladder capacity of 15 ml. The dose was reduced to 40 mg and another 3 instillations were accomplished. Since conventional treatments of anti-cholinergics, analgesics and epidural anesthesia were of little help for the subjective symptoms, he was put on the steroid pulse therapy 2 weeks after completion of the BCG regimen. The treatment gradually improved the subjective symptoms and increased the bladder capacity up to 160 ml. In conclusion, we believe that the steroid pulse therapy deserves considering in the early stage of irritable bladder symptoms following BCG instillation.

Focal segmental sclerotic lesions of the glomerulus in transplanted kidneys assessed using computerized image analysis.

Mechanisms responsible for the development of focal segmental sclerotic lesions of the glomerulus (FSGS lesions) in transplanted kidneys were investigated by morphometric analysis. The mean glomerular area and the interstitial area were measured using computerized image analysis to compare implantation biopsies (so-called 1-h biopsies; 1Bx) with later biopsies (episode Bx; EBx) that had been taken for diagnostic purposes to identify the cause of deteriorating renal function. Groups of patients with (group A, n = 15) or without (group B, n = 10) FSGS lesions were compared. Twelve of 15 in group A and all in group B had lost graft function due to chronic allograft nephropathy. It was found that neither the mean glomerular area nor the interstitial area differed significantly between the two groups in either 1Bx or EBx. The interstitial area was significantly increased (P = 0.007) and the mean glomerular area tended to be increased (P = 0.085) in EBx compared with 1Bx in group A but not in group B. The serum creatinine level at the time of EBx in group A correlated with the interstitial area (P = 0.031) but not the mean glomerular area. However, there was no similar correlation in group B. In conclusion, factors for the development of FSGS lesions in transplanted kidneys may be the increase in interstitial area and possible glomerular hypertrophy following transplantation, rather than pre-existing reduced renal mass of the donor kidneys.

[Urolithiasis in those patients with myelodysplasia].

OBJECTIVE: To evaluate incidence and treatments of urolithiasis in myelodysplastic patients. PATIENTS AND METHODS: During the past 27 years 303 myelodysplastic patients, 160 men and 143 women, have been treated and 50 of them were operated on with bladder augmentation procedures. Their medical records were retrospectively reviewed. RESULTS: Urolithiasis occurred 20 times in 15 patients, 11 men and 4 women, where calculi developed 18 times in the bladder and twice in the kidney. Prevalence of urolithiasis was 20% (10/50) in those who had undergone bladder augmentation and 2% (5/253) in those who had not had this surgery, where the difference was statistically significant between the two groups (p < 0.01). Overall, 5% of all the patients suffered from stones in the urinary tract. Bladder calculi were endoscopically treated in 11 occasions or were resolved with suprapubic lithotomy in 4 cases. Small stones in the bladder were spontaneously delivered 3 times and extracorporeal shock wave lithotripsy (ESWL) was necessary for a renal calculus in one patient. The last patient having a renal stone has been put under care. Majority of stone compositions consisted of magnesium ammonium phosphate (MAP). CONCLUSION: It was found that urolithiasis was 10 times more prevalent in those patients operated on with enterocystoplasty than those without bladder augmentation and that intermittent clean catheterization and regular bladder irrigation were of necessity to prevent urolithiasis for those having enterocystoplasty.