Yuji Nishizawa

CD133 expression in rectal cancer after preoperative chemoradiotherapy.

CD133‐positive cells have been reported to possess a cancer‐initiating‐cell phenotype and the property of resistance to chemoradiation therapy in colorectal cancer. The aim of the present study was to evaluate quantitative and locational changes in CD133‐positive cells in rectal cancer patients who received preoperative chemoradiation therapy. The prognostic significance of CD133 expression in patients with preoperative chemoradiation therapy was also analyzed. Immunohistochemical staining for CD133 and cancer‐initiating‐cell marker CD44 were performed in 92 surgically resected rectal cancers. Of the 92 cases, 43 patients received preoperative chemoradiation therapy and 49 patients underwent surgery alone. Forty pretherapic biopsy specimens from 43 patients in preoperative chemoradiation therapy group were also analyzed. CD133‐positive cases were more common in the preoperative chemoradiation therapy group than in the surgery‐alone group (P = 0.03). Further, CD133‐positive cases were more common in the preoperative chemoradiation therapy group than in pretherapic biopsy specimens (P = 0.02). In the preoperative chemoradiation therapy group, the CD133‐positive cases showed poorer prognosis than the CD133‐negative cases. On the other hand, the frequency of CD44‐positive case within cancer tissue was similar between the preoperative chemoradiation therapy group and the surgery‐alone group. CD44 expression in the preoperative chemoradiation therapy group was not associated with prognosis. CD44‐ and CD133‐positive cells were distributed evenly within the tumor both in the preoperative chemoradiation therapy group and surgery‐alone group, and locational alteration was not observed. The therapy‐resistant ability of CD133‐positive cells can be associated with poor outcome in the patients with preoperative chemoradiation therapy.

Bladder-sparing extended resection of locally advanced rectal cancer involving the prostate and seminal vesicles.

PurposeTotal pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE.MethodsEleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively.ResultsCysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR).ConclusionThese bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control.

The association between anal function and neural degeneration after preoperative chemoradiotherapy followed by intersphincteric resection.

BACKGROUND: Preoperative chemoradiotherapy for rectal cancer is administered to improve local control, but it can also induce severe anal dysfunction after surgery. OBJECTIVE: The goals of the study were to assess the influence of preoperative chemoradiotherapy on pathological findings and to examine the correlation of these findings with the cause of severe anal dysfunction after intersphincteric resection. DESIGN: Peripheral nerve degeneration was evaluated histopathologically with the use of hematoxylin and eosin-stained sections of surgical specimens after intersphincteric resection, based on karyopyknosis, vacuolar degeneration, acidophilic degeneration of cytoplasm, denucleation, and adventitial neuronal changes. Each item was scored to quantify the level of neural degeneration, and the relationship between degeneration and anal function was examined at 12 months after closure of the stoma. Anal function was assessed by questionnaire, and incontinence was evaluated based on the Wexner score. SETTING: This study was conducted at the National Cancer Center Hospital East from 2001 to 2006. PATIENTS: The subjects were 68 patients with lower rectal cancer who underwent intersphincteric resection with (n = 47) or without (n = 21) preoperative chemoradiotherapy. MAIN OUTCOME MEASURES: The findings in the 2 groups were compared to clarify the association between the degree of histological degeneration and postoperative anal function. RESULTS: Neural degeneration was significantly higher in the chemoradiotherapy group, and the neural degeneration and Wexner scores had a significant correlation (P = .003, r = 0.477). CONCLUSION: Preoperative chemoradiotherapy induced marked neural degeneration around the rectal tumor. The significant correlation between the degeneration score and postoperative anal function suggests that this score may be a useful marker to predict the influence of preoperative chemoradiotherapy on anal function after surgery.

Saturated Salt Solution Method: A Useful Cadaver Embalming for Surgical Skills Training

AbstractThis article evaluates the suitability of cadavers embalmed by the saturated salt solution (SSS) method for surgical skills training (SST).SST courses using cadavers have been performed to advance a surgeons techniques without any risk to patients. One important factor for improving SST is the suitability of specimens, which depends on the embalming method. In addition, the infectious risk and cost involved in using cadavers are problems that need to be solved.Six cadavers were embalmed by 3 methods: formalin solution, Thiel solution (TS), and SSS methods. Bacterial and fungal culture tests and measurement of ranges of motion were conducted for each cadaver. Fourteen surgeons evaluated the 3 embalming methods and 9 SST instructors (7 trauma surgeons and 2 orthopedists) operated the cadavers by 21 procedures. In addition, ultrasonography, central venous catheterization, and incision with cauterization followed by autosuture stapling were performed in some cadavers.The SSS method had a sufficient antibiotic effect and produced cadavers with flexible joints and a high tissue quality suitable for SST. The surgeons evaluated the cadavers embalmed by the SSS method to be highly equal to those embalmed by the TS method. Ultrasound images were clear in the cadavers embalmed by both the methods. Central venous catheterization could be performed in a cadaver embalmed by the SSS method and then be affirmed by x-ray. Lungs and intestines could be incised with cauterization and autosuture stapling in the cadavers embalmed by TS and SSS methods.Cadavers embalmed by the SSS method are sufficiently useful for SST. This method is simple, carries a low infectious risk, and is relatively of low cost, enabling a wider use of cadavers for SST.

Association between Anal Function and Therapeutic Effect after Preoperative Chemoradiotherapy followed by Intersphincteric Resection

Background/Aims: Preoperative chemoradiotherapy (CRT) for rectal cancer improves local control, but can also induce severe anal dysfunction after surgery. The goal of the study was to assess the relationship of the therapeutic effect of CRT with anal function and prognosis after intersphincteric resection (ISR). Methods: The subjects were 37 patients with lower rectal cancer who underwent ISR with preoperative CRT. The rectal cancer regression grade (RCRG) was quantified based on histologic features of surgical specimens. The relationships of RCRG with anal function (assessed by questionnaire) and incontinence (Wexner score) were examined at 12 months after surgery. Results: The median Wexner scores at 12 months after stoma closure in RCRG1, -2, and -3 cases were 18.0, 7.5, and 4.5, respectively, and anal function differed significantly among these groups (p = 0.001). Four cases had local recurrence, but 5-year local recurrence rates did not differ significantly among the groups. The 5-year disease-free survival rates were 88.9, 50.8, and 50.0% and the 5-year overall survival rates were 100, 77.3, and 66.7% in RCRG1, -2, and -3 cases, respectively, with no significant differences among the groups. Conclusion: Postoperative anal function is decreased when the effect of preoperative CRT is strong in patients treated with ISR.

Gene expression profile in the activation of subperitoneal fibroblasts reflects prognosis of patients with colon cancer

Tumors can create a heterogenetic tumor microenvironment. We recently identified the pathologically unique cancer microenvironment formed by peritoneal invasion (CMPI), and revealed that subperitoneal fibroblasts (SPFs) within peritoneal tissue play a crucial role in tumor progression through their interaction with cancer cells. Therefore, the genes in SPFs altered by cancer stimulation may include some biologically important factors associated with patient prognosis. In this study, we aimed to identify new biomarkers using genes specifically upregulated in SPFs by cancer‐cell‐conditioned medium (CCCM) stimulation (SPFs CCCM response genes; SCR genes) in colon cancer (CC). We constructed two frameworks using SCR gene data: a publicly released microarray dataset, and validation cases with freshly frozen CC samples to identify genes related to short recurrence‐free survival (RFS). In the first framework, we selected differentially expressed genes between the high and low SCR gene expression groups. In the second framework, genes significantly related to short RFS were selected by univariate analysis using all SCR genes, and multivariate analysis was performed to select robust genes associated with short RFS. We identified CTGF, CALD1, INHBA and TAGLN in the first framework, and PDLIM5, MAGI1, SPTBN1 and TAGLN in the second framework. Among these seven genes, high expression of three genes (CALD1, TAGLN and SPTBN1) showed a poor prognosis in our validation cases. In a public microarray dataset, SCR gene expression was associated with the expression of ECM component, EMT, and M2‐macrophage associated genes, which was concordant with the pathological features of CMPI. Thus, we successfully identified new prognostic factors.

Hands-free interface for surgical procedures based on foot movement patterns.

A hands-free interface has been developed to allow a single surgeon to control a locally operated forceps manipulating robot. It is based on the use of a pressure sensor sheet placed on the floor to measure temporal changes in the center of gravity of the operators foot, in addition to the applied force. Pattern recognition was carried out during trials with endoscope specialists and students for six different types of foot movements. The specialist patterns were then used to develop an interface for controlling a robot with five degrees of freedom. Using this control interface, it was found that the robot could successfully handle a model organ during simulated surgery.

Rectoseminal vesicle fistula as a rare complication after low anterior resection: a report of three cases

A rectoseminal vesicle fistula is a rare complication after a low anterior resection for rectal cancer, usually developing in the outpatient postoperative period with pneumaturia, fever, scrotal swelling or testicular pain. A diagnostic water-soluble contrast enema, cystography and computed tomography reveal a tract from the rectum to the seminal vesicle. Anastomotic leakage is thought to be partially responsible for the formation of such tracts. This report presents three cases of rectoseminal vesicle fistula, and the presumed course of the disease and optimal treatment options are discussed.

Area of residual tumor beyond the muscular layer is a useful predictor of outcome in rectal cancer patients who receive preoperative chemoradiotherapy.

The purpose of the present study was to determine whether the amount and the location of residual tumor are associated with outcome in surgically treated rectal cancer patients who receive preoperative chemoradiation therapy. Forty‐three rectal cancer patients who underwent sphincter‐saving operations after preoperative chemoradiation therapy were enrolled in the study. The total area of residual tumors was measured using morphometry software, and then the area of the residual tumors located within and beyond the muscular layer was also determined. Associations between clinicopathological features were evaluated. The results showed that the total area of residual tumor and area of residual tumor within the muscular layer were associated with TNM stage, tumor regression, and microscopy features, but not with patient disease‐free survival. The area of the residual tumor located beyond the muscular layer was significantly associated with pathological ypT, ypN stage, tumor downstaging, perineural invasion, and the depth of tumor invasion beyond the muscular layer (P < 0.05). Further, large residual tumor area beyond the muscular layer was associated with shorter disease‐free survival (P < 0.05). Morphometry of residual tumor area beyond the muscular layer is a new pathological prognostic factor for rectal cancer patients receiving preoperative chemoradiation therapy.

Differences in tissue degeneration between preoperative chemotherapy and preoperative chemoradiotherapy for colorectal cancer

PurposePreoperative chemoradiotherapy (CRT) for rectal cancer is administered to improve local control, but can also induce severe anal dysfunction after surgery, while preoperative chemotherapy that significantly reduces the primary lesion in rectal cancer has recently been developed. The aim of the study was to examine differences in the effects of preoperative CRT and chemotherapy on tissue degeneration of patients with colorectal cancer.MethodsThe subjects were 91 patients, including 68 with rectal cancer who underwent internal sphincteric resection with (n = 47, CRT group) or without (n = 21, control group) preoperative CRT, and 23 with colorectal cancer who received preoperative FOLFOX treatment. Peripheral nerve degeneration was evaluated histopathologically using H&E-stained sections, based on karyopyknosis, disparity of the nucleus, denucleation, vacuolar or acidophilic degeneration of the cytoplasm, and adventitial neuronal changes.ResultsThe incidence of neural degeneration was significantly higher in the CRT group than in the control group and FOLFOX group. There were no differences in any items of neural degeneration between the FOLFOX and control groups.ConclusionCRT induced marked neural degeneration around the rectal tumor. FOLFOX treatment produced mild neural degeneration similar to that in the control group.