Hydrodissection performed safely with an injection catheter during robot-assisted radical prostatectomy.

To facilitate nerve preservation during robot-assisted radical prostatectomy (RP), hydrodissection (HD) using an injection catheter was performed. HD during RP is a nerve-sparing technique in which an epinephrine solution is injected into the lateral prostatic fascia to separate it from the prostatic capsule. Although the beneficial effects of HD on postoperative sexual function have been reported, HD has rarely been used in robot-assisted RP. The primary reason may be the potential benefits of robotic surgery, such as less bleeding, magnified surgical view, and fine movement of instruments; another possible reason is the difficulty of handling sharp needles in a narrow intra-abdominal surgical space of robot-assisted RP. For safe fluid injection, we performed HD using an injection catheter - commonly used for endoscopic upper gastrointestinal hemostasis - during robot-assisted RP. The required time to accomplish HD and the safety of the procedure were examined in 15 HD of 11 patients. Approximately 2 minutes (median, 118 seconds; interquartile range, 106-174 seconds) were needed for HD using the injection catheter. All patients had no complications, such as injuries to the intestine, vessels, or other organs. Postoperative bleeding did not occur in any patients. HD with an injection catheter enables surgeons to perform simple and safe nerve preservation during robot-assisted RP.

Novel quantitative software for automatically excluding red bone marrow on whole-body magnetic resonance imaging in patients with metastatic prostate cancer: A pilot study.

OBJECTIVES: To establish a novel quantitative method that automatically excludes the red bone marrow and accurately quantifies the tumor volume on whole-body magnetic resonance imaging using updated imaging software. To also evaluate the association between the quantified tumor volume and the prognosis of patients with metastatic prostate cancer. METHODS: This prospective analysis included patients diagnosed with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer between 2017 and 2022. We developed an imaging software (Attractive BD_Score) that analyzed whole-body diffusion-weighted and in-phase and opposed-phase T1-weighted images to automatically exclude the red bone marrow. The quantified tumor volume was compared with that quantified by traditional whole-body diffusion-weighted imaging without red bone marrow exclusion. Prostate-specific antigen progression-free survival, time-to-pain progression, and overall survival were evaluated to assess the prognostic value of the quantified tumor volume. RESULTS: The quantified tumor volume was significantly smaller than that quantified by the traditional method in metastatic hormone-sensitive (median: 81.0 ml vs. 149.4 ml) and metastatic castration-resistant (median: 29.4 ml vs. 63.5 ml) prostate cancer. A highly quantified tumor volume was associated with prostate-specific antigen progression-free survival (p = 0.030), time-to-pain progression (p = 0.003), and overall survival (p = 0.005) in patients with metastatic hormone-sensitive prostate cancer and with poor prostate-specific antigen progression-free survival (p = 0.001) and time-to-pain progression (p = 0.005) in patients with metastatic castration-resistant prostate cancer. CONCLUSIONS: Our imaging method could accurately quantify the tumor volume in patients with metastatic prostate cancer. The quantified tumor volume can be clinically applied as a new prognostic biomarker for metastatic prostate cancer.

Importance of considering interest in sex when evaluating satisfaction after robot-assisted radical prostatectomy.

OBJECTIVES: To assess the impact of patients' interest in sex on the satisfaction after robot-assisted radical prostatectomy, longitudinal changes of urinary and sexual functions and bothers were evaluated. METHODS: A total of 101 patients underwent robot-assisted radical prostatectomy in our institution. Based on sexual interest, they were divided into the high-interest and low-interest groups. Overall satisfaction, urinary function, urinary bother, sexual function, and sexual bother were evaluated using the expanded prostate cancer index composite questionnaire preoperatively and at 1, 3, 6, and 12 months after robot-assisted radical prostatectomy. We investigated the associations between the overall satisfaction and urinary function/urinary bother/sexual function/sexual bother scores (with higher score indicating better function and less impairment). RESULTS: In the high-interest group (n = 45), satisfaction correlated with high urinary function and urinary bother scores early after robot-assisted radical prostatectomy (urinary function: 1 and 3 months, urinary bother: 3 months postoperatively; P < 0.05) and then with high sexual bother score thereafter (sexual bother at 6 and 12 months after surgery; P < 0.05). Sexual function score did not correlate with satisfaction. In the low-interest group (n = 56), satisfaction correlated with high urinary function and urinary bother scores over time (urinary function: 3 and 6 months, urinary bother: at 3, 6 and 12 months postoperatively; P < 0.05). Neither sexual function nor sexual bother correlated with satisfaction postoperatively in the low-interest group. CONCLUSIONS: The impact of urinary and sexual functions and bothers on patients' overall satisfaction differed between patients with high- and low-interest in sex. The patient's interest in sex should be considered when assessing satisfaction after robot-assisted radical prostatectomy.

Use of the SAND balloon catheter for safe and easy laparoscopic removal of adrenal cysts.

INTRODUCTION: Surgical resection should be considered for giant adrenal cysts if they are functional, if malignancy cannot be ruled out, or if there is a risk of bleeding. However, preventing cyst damage, including fluid leak, and ensuring a good field of view could be challenging in laparoscopic surgery. We report on our successful use of the SAND balloon catheter in laparoscopic adrenalectomy. CASE PRESENTATION: The patient was a 40-year-old man with a right adrenal cyst that exhibited growth tendency. We performed laparoscopic adrenalectomy using a SAND balloon catheter through a preexisting port. Use of the catheter allowed for not only aspiration of the cyst fluid without leakage into the operative field but also gentle grasping of the cyst wall, which enabled us to easily remove the adrenal gland, including the cyst. CONCLUSION: Use of the SAND balloon catheter facilitates safe and easy laparoscopic resection of giant adrenal cysts.

Undifferentiated pleomorphic sarcoma of the prostate in a young man.

INTRODUCTION: Prostate sarcoma is an extremely rare disease with a poor prognosis. Undifferentiated pleomorphic sarcoma has never been described in the prostate.Case presentation: A 27-year-old man complained of frequent urination and dysuria for several years. Various examinations were suggestive of prostate sarcoma. The pathological diagnosis was confirmed as prostate sarcoma via ultrasound-guided transrectal needle biopsy. Because the location of the tumor in the prostate was confirmed by magnetic resonance imaging, we performed robot-assisted radical prostatectomy. The final pathological diagnosis was undifferentiated pleomorphic sarcoma. Local recurrence occurred at the front of the rectum 2 months after surgery. Although chemotherapy and radiotherapy were initially effective, he died 18 months after surgery. CONCLUSION: Undifferentiated pleomorphic sarcoma of the prostate is believed to have a poor prognosis. When selecting the surgical procedure, functionality should be considered for individual cases with complete resection.

Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1.

In a previous study, we found that DNAJB8, a heat shock protein (HSP) 40 family member is expressed in kidney cancer stem-like cells (CSC)/cancer-initiating cells (CIC) and that it has a role in the maintenance of kidney CSC/CIC. Heat shock factor (HSF) 1 is a key transcription factor for responses to stress including heat shock, and it induces HSP family expression through activation by phosphorylation. In the present study, we therefore examined whether heat shock (HS) induces CSC/CIC. We treated the human kidney cancer cell line ACHN with HS, and found that HS increased side population (SP) cells. Western blot analysis and qRT-PCR showed that HS increased the expression of DNAJB8 and SOX2. Gene knockdown experiments using siRNAs showed that the increase in SOX2 expression and SP cell ratio depends on DNAJB8 and that the increase in DNAJB8 and SOX2 depend on HSF1. Furthermore, treatment with a mammalian target of rapamycin (mTOR) inhibitor, temsirolimus, decreased the expression of DNAJB8 and SOX2 and the ratio of SP cells. Taken together, the results indicate that heat shock induces DNAJB8 by activation of HSF1 and induces cancer stem-like cells.

Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8.

OBJECTIVES: To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. MATERIALS AND METHODS: To induce DNAJB8-specific immune reaction, we stimulated human CD8+ lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8. We evaluated CTL induction with the peptide immunization in mouse model. RESULTS: We confirmed peptide-specific interferon-γ secretions and cytotoxic activities of induced human CTLs. In vivo immunization with the peptide to mice, peptide-specific CTL response could be observed in mouse CD8+ T cells. Furthermore, immunization with the peptide showed significant anti-tumor effects compared with negative controls. CONCLUSION: DNAJB8-derived peptide is a novel candidate for CSCs-targeting immunotherapy, and mouse models can be used to evaluate CSCs-targeting immunotherapy.

Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of gynecologic cancer stem cells through expression of HSP27.

Cancer stem-like cells (CSCs)/ cancer-initiating cells (CICs) are defined by their higher tumor-initiating ability, self-renewal capacity and differentiation capacity. CSCs/CICs are resistant to several therapies including chemotherapy and radiotherapy. CSCs/CICs thus are thought to be responsible for recurrence and distant metastasis, and elucidation of the molecular mechanisms of CSCs/CICs are essential to design CSC/CIC-targeting therapy. In this study, we analyzed the molecular aspects of gynecological CSCs/CICs. Gynecological CSCs/CICs were isolated as ALDH1high cell by Aldefluor assay. The gene expression profile of CSCs/CICs revealed that several genes related to stress responses are preferentially expressed in gynecological CSCs/CICs. Among the stress response genes, a small heat shock protein HSP27 has a role in the maintenance of gynecological CSCs/CICs. The upstream transcription factor of HSP27, heat shock factior-1 (HSF1) was activated by phosphorylation at serine 326 residue (pSer326) in CSCs/CICs, and phosphorylation at serine 326 residue is essential for induction of HSP27. Immunohistochemical staining using clinical ovarian cancer samples revealed that higher expressions of HSF1 pSer326 was related to poorer prognosis. These findings indicate that activation of HSF1 at Ser326 residue and transcription of HSP27 is related to the maintenance of gynecological CSCs/CICs.

Prognostic factors and risk stratification in patients with castration-resistant prostate cancer receiving docetaxel-based chemotherapy.

BACKGROUND: While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for castration-resistant prostate cancer (CRPC) patients. Despite the excellent anti-tumor effect of docetaxel, its severe adverse effects sometimes distress patients. Therefore, it would be very helpful to predict the efficacy of docetaxel before treatment. The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy. METHODS: This study included 79 patients with CRPC treated with docetaxel. The variables, including patient characteristics at diagnosis and at the start of chemotherapy, were retrospectively collected. Prognostic factors predicting OS were analyzed using the Cox proportional hazard model. Risk stratification for overall survival was determined based on the results of multivariate analysis. RESULTS: PSA response ≥50 % was observed in 55 (69.6 %) of all patients, and the median OS was 22.5 months. The multivariate analysis showed that age, serum PSA level at the start of chemotherapy, and Hb were independent prognostic factors for OS. In addition, ECOG performance status (PS) and the CRP-to-albumin ratio were not significant but were considered possible predictors for OS. Risk stratification according to the number of these risk factors could effectively stratify CRPC patients treated with docetaxel in terms of OS. CONCLUSIONS: Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS. ECOG PS and the CRP-to-albumin ratio were not significant, but were considered possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating overall survival.

Dnajb8, a Member of the Heat Shock Protein 40 Family Has a Role in the Tumor Initiation and Resistance to Docetaxel but Is Dispensable for Stress Response.

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined by their abilities of tumor initiation, self-renewal and differentiation. In a previous study, we showed by gene knockdown using siRNA and gene overexpression experiments that Dnaj (Hsp40) homolog, subfamily B, member 8 (DNAJB8), a role in the maintenance, of renal cell carcinoma CSCs/CICs. In the present study, we established Dnajb8 knockout (KO) renal cell carcinoma (RCC) line cells (RenCa cells) and analyzed the cells to confirm the function of Dnajb8 in RCC CSCs/CICs. Dnajb8 KO cells showed reduced ratios of side population cells and reduced sphere forming ability. An in vivo single cell tumor initiation assay revealed that the numbers of CSCs/CICs were 3 in 4 wild-type RenCa cells and 1 in 4 Dnajb8 KO cells. Dnajb8 KO cells showed sensitivity to Docetaxel. On the other hand, Dnajb8 KO cells did not show any sensitivities to stresses including low pH, low glucose, heat shock and sensitivity to cisplatin. The results indicate that Dnajb8 has a role in tumor initiation, side population ratio and sphere formation but it is dispensable for stress responses.

Transplantation of Horseshoe Kidney from Living, Genetically Unrelated Donor.

We report a case of renal transplantation using a horseshoe kidney from a living, genetically unrelated donor. The recipient was a 60-year-old man with diabetic nephropathy, and the donor was the 63-year-old wife of the recipient with a horseshoe kidney free of complications. Computed tomography showed two renal arteries and one renal vein on the left side, and the isthmus was perfused by several accessory arteries and veins. To demarcate the boundary of the isthmus, the left renal artery was ligated and cannulated for in situ perfusion. Furthermore, the isthmus was clamped, and the boundary of the isthmus was confirmed. The kidney was divided at the left margin of the perfused boundary. The cut ends of the isthmus were closed by sutures. The left kidney was transplanted into the right iliac fossa of the recipient. Asymptomatic fluid collection occurred on the cut surface at the isthmus of the donor, and this fluid decreased in due course. On the other hand, the recipient experienced no surgical complication or rejection, while maintaining serum creatinine levels of 2.00-2.20 mg/dL over a 22-month follow-up period. Horseshoe kidneys may be used for transplantation in selected cases after a detailed preoperative evaluation.

External validation of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment scoring models to predict recurrence and progression in Japanese patients with non-muscle invasive bladder cancer treated with bacillus Calmette-Guérin.

OBJECTIVE: To validate two prediction models (European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment) for recurrence and progression of non-muscle invasive bladder cancer in Japanese patients who underwent bacillus Calmette-Guérin instillation therapy. METHODS: From March 1985 to April 2007, data were analyzed from 366 patients who underwent transurethral resection of bladder tumor followed by bacillus Calmette-Guérin instillation therapy. The ability of two scoring models to predict recurrence and progression was assessed by concordance index. RESULTS: For recurrence probability, the concordance index of the European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.514 and 0.576, respectively, which was lower than that (0.604) of a selected single prognostic factor (age) by our multivariate analysis. For progression probability, the concordance index of European Organization for Research and Treatment of Cancer and Spanish Urological Club for Oncological Treatment models was 0.693 and 0.764, respectively, which was higher than that (0.633) of a selected single factor (T stage) by our multivariate analysis. The Spanish Urological Club for Oncological Treatment scoring system resulted in better stratification of tumor recurrence and progression when compared with the European Organization for Research and Treatment of Cancer model, probably because more patients underwent bacillus Calmette-Guérin treatment in the Spanish Urological Club for Oncological Treatment cohort than in the European Organization for Research and Treatment of Cancer cohort. CONCLUSIONS: The Spanish Urological Club for Oncological Treatment scoring system is a good predictor of tumor recurrence and progression in Japanese patients who underwent bacillus Calmette-Guérin immunotherapy. A large prospective study is warranted to confirm the efficacy of this system.

O(log2 M) self-organizing map algorithm without learning of neighborhood vectors.

In this letter, a new self-organizing map (SOM) algorithm with computational cost O(log2 M) is proposed where M2 is the size of a feature map. The first SOM algorithm with O(M2) was originally proposed by Kohonen. The proposed algorithm is composed of the subdividing method and the binary search method. The proposed algorithm does not need the neighborhood functions so that it eliminates the computational cost in learning of neighborhood vectors and the labor of adjusting the parameters of neighborhood functions. The effectiveness of the proposed algorithm was examined by an analysis of codon frequencies of Escherichia coli (E. coli) K12 genes. These drastic computational reduction and accessible application that requires no adjusting of the neighborhood function will be able to contribute to many scientific areas.

Characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer: the pathogenesis of bone destruction.

Disseminated carcinimatosis of the bone marrow is accompanied by solid tumors, and gastric cancer accounts for the majority. The prognosis of this condition is poor, however, the pathogenesis for wide-spread bone lesions has yet to be elucidated. In 9 patients with gastric cancer demonstrating disseminated carcinomatosis of the bone marrow, the characteristic clinicopathological features were examined. Immunohistochemistry for receptor activator of NF-kappaB ligand (RANKL) and parathyroid hormone-related protein was also performed on gastric cancer tissue and bone marrow specimens to identify the factors responsible for the occurrence of bone lesions in patients presenting with this condition. The characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer include a yonger patient age, an elevation of serum alkaline phosphatase and/or lactate dehydrogenase levels, wide-spread bone metastases with osteolytic bone destruction, a low incidence of hypercalcemia and a histological gastric cancer type of either signet ring cell carcinoma or poorly diffentiated adenocarcinoma. The expression of RANKL, which is one of the master regulators of osteoclastic bone resorption in bone metastasis, was also found in gastric cancer cells obtained from such patients. The RANKL expressed in gastric cancer may therefore play a critical role in the promotion of osteoclast formation, which has been suggested to be involved in the pathogenesis of bone lesions.

Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas.

Metastasis-associated protein MTA1 and histone deacetylase form a protein complex with histone deacetylase activity that plays an important role in histone deacetylation, alteration of chromatin structure and transcriptional control. The precise role of the MTA1 protein in the malignant progression of human cancers remains unknown, however, especially its overexpression and relationship with histone acetylation/deacetylation in experimental and clinical tumors. The expression levels of MTA1 protein and the acetylation levels of histone H4 were examined in 70 cases of surgically resected esophageal squamous cell carcinomas, using immunohistochemistry. The intensities of immunostaining of MTA1 protein and acetylated histone H4 in carcinoma tissues (Ca) were compared to normal epithelium (N) contained in the same section. Thirty of 70 cases (42.9%) displayed overexpression of MTA1 protein (N < Ca). Cancers overexpressing MTA1 protein invaded deeper into the esophageal wall (p < 0.005) and showed significantly higher degrees of lymph node metastasis (p < 0.01), higher pathological stage, more lymphatic involvement and poorer prognosis (p < 0.05) than the remaining cases. The acetylation levels of histone H4 inversely correlated to the depth of cancer invasion and pathological stage (p < 0.05), and the patients with higher level of histone H4 acetylation had a better prognosis (p < 0.05). Furthermore, immunostaining patterns of MTA1 and acetylated histone H4 were inversely correlated (p < 0.001), demonstrating the relationship of deacetylation of histone H4 in MTA1-overexpressing carcinomas. In conclusion, the data suggest that the overexpression of MTA1 protein and acetylation level of histone H4 protein, both of which are closely related, might be useful predictors of malignant potential of esophageal squamous cell carcinomas. Thus, strategies involving inhibition of MTA1 function as well as inhibition of histone deacetylation could be novel approaches for the treatment of esophageal squamous cell carcinomas.

Polyps with different grades of dysplasia and their distribution in the colorectum.

BACKGROUND/AIMS: To determine the role of adenomatous polyps in the development of colorectal cancers, we examined the relationship between the distribution and polyps with different grades of dysplasia (low, high), or/and cancers in the colorectum. METHODOLOGY: The distribution of 527 polyps with low-grade dysplasia was compared with that of 121 polyps with high-grade dysplasia, and 10 colorectal cancer lesions with adenomatous polyps in 361 patients who underwent total colonoscopy. RESULTS: The distribution rate of polyps at the distal colon and rectum into polyps with high-grade dysplasia significantly increased in comparison to that into polyps with low-grade dysplasia, respectively (p<0.002). The percentage of polyps with high-grade dysplasia measuring >1 cm significantly increased in comparison to that with low-grade dysplasia measuring >1 cm (p<0.00001). In patients with both adenomatous polyps and colorectal cancers, the polyps with high-grade dysplasia at the distal sites of cancerous lesions increased significantly more than at the proximal sites of cancerous lesions (p<0.05). Polyps with high-grade dysplasia have malignant potentials to intermediate between polyps with low-grade dysplasia and colorectal cancers in our study. CONCLUSIONS: The different distributions of different grades thus suggested that polyps with different grades of dysplasia at various colorectal sites were found to have different malignant potentials for cancer development.

[A case of recurrent gallbladder cancer responding to low-dose 5-FU and CDDP therapy].

We treated a patient with a postoperative local recurrence of gallbladder cancer who showed a long-term response to low-dose 5-fluorouracil (5-FU) and cisplatin (CDDP) therapy. A 60-year-old woman was diagnosed with advanced gallbladder cancer, for which she underwent an extended cholecystectomy, bile duct resection and a partial resection of the duodenum in March 2000. The pathological diagnosis was well differentiated tubular adenocarcinoma of si, ly1, v1, hinf2, binf2, n0. Eight months later, she presented with cholangitis and obstructive jaundice due to a local recurrence of the gallbladder cancer and her serum CA19-9 level had increased to 1,991.6 U/ml. The biliary obstruction was treated by PTCD and a subsequent self-expanding metallic stent. In addition, she was also placed on combined chemotherapy with low-dose 5-FU and CDDP. Her serum CA19-9 level thereafter gradually decreased, so that after eight months it was within the normal range, and the recurrent tumor at the hepatic hilus was also observed to have decreased in size on the CT scan. As of this writing she has undergone eight courses of low-dose 5-FU and CDDP therapy over about a year and has been able to maintain a good quality of life without any severe adverse effects.

Gastric metastasis from lung carcinoma. Case report.

We report here gastric metastasis from lung carcinoma in an 80-year-old man. His chief complaint was epigastric pain from metastases in the stomach. Although metastasis from primary carcinoma of the lung to the small intestine is more common than has been previously suspected, symptoms are rare. Such a metastasis may present as bowel perforation. To find cases of lung carcinoma metastasis to the gastrointestinal tract is clinically rare, and there have been few reports in the English literature. This report describes the gastrointestinal metastasis from lung carcinoma.