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Biomedical subjects

Yoshihiro Moriya

Publications and source records attributed to Yoshihiro Moriya.

At least 19 recordsLinked to original sources

Abdominal sacral resection for posterior pelvic recurrence of rectal carcinoma: analyses of prognostic factors and recurrence patterns.

BACKGROUND: Local recurrence of rectal cancer presents challenging problems. Although abdominal sacral resection (ASR) provides pain control, survival prolongation, and possibly cure, reported morbidity and mortality are still high, and survival is still low. Thus, appropriate patient selection and adjuvant therapy based on prognostic factors and recurrence patterns are necessary. The purpose of this study was to evaluate the results of ASR for posterior pelvic recurrence of rectal carcinoma and to analyze prognostic factors and recurrence patterns. METHODS: Forty-four patients underwent ASR for curative intent in 40 and palliative intent in 4 cases. All but one could be followed up completely. Multivariate analyses of factors influencing survival and positive surgical margins were conducted. RESULTS: Morbidity and mortality were 61% and 2%, respectively. Overall 5-year survival was 34%. The Cox regression model revealed a positive resection margin (hazard ratio, 10 [95% confidence interval, 3.8-28]), a local disease-free interval of <12 months (4.2 [1.8-9.8]), and pain radiating to the buttock or further (4.2 [1.6-11]) to be independently associated with poor survival. The logistic regression model showed that macroscopic multiple expanding or diffuse infiltrating growths were independently associated with a positive margin (7.5 [1.4-40]). Of the patients with recurrence, 56% had failures confined locally or to the lung. CONCLUSIONS: ASR is beneficial to selected patients in terms of survival. To select patients, evaluation of the resection margin, the local disease-free interval, pain extent, and macroscopic growth pattern is important. To improve survival, adjuvant treatment should be aimed at local and lung recurrences.

Adult↗

Second hepatectomy for recurrent colorectal liver metastasis: analysis of preoperative prognostic factors.

BACKGROUND: Second hepatectomy is a potentially curative treatment for patients with hepatic recurrence of colorectal cancer. However, there is still no consensus about the patient selection criteria for second hepatectomy under these circumstances, and the factors affecting prognosis after second hepatectomy remain uncertain. METHODS: Clinicopathologic data for 111 consecutive patients with colorectal liver metastasis who underwent second hepatectomy at a single institution between 1985 and 2004, and for whom complete clinicopathologic reports were available, were subjected to univariate and multivariate analyses. RESULTS: The morbidity and mortality rates were 14% and 0%, respectively, and the overall 5-year survival rate was 41%. Multivariate analysis revealed that synchronous resection for the first liver metastasis (hazard ratio, 1.8), more than three tumors at the second hepatectomy (1.9), and histopathological involvement of the hepatic vein and/or portal vein by the first liver metastasis (1.7) were independently associated with poor survival. We used these three risk factors to devise a preoperative model for predicting survival. The 5-year survival rates of patients without any risk factors, and with one, two, or three risk factors, were 62%, 38%, 19%, and 0%, respectively. CONCLUSIONS: Second hepatectomy is beneficial for patients without any risk factors. Before second hepatectomy, chemotherapy should be considered for patients with any of these risk factors, especially with two or three factors, in the adjuvant or neoadjuvant setting to prolong survival. These results need to be confirmed and validated in another data set or future prospective trial according to the scoring scheme we outline.

Biomarkers, Tumor↗

A case of resected huge ileocolonic mesenteric liposarcoma which responded to pre-operative chemotherapy using doxorubicin, cisplatin and ifosfamide.

Primary mesenteric liposarcoma is a rare entity that has been reported only 14 times in English literature. The treatment strategy for mesenteric liposarcoma is, if no distant metastases are detected, surgical resection with a wide surgical margin, often followed by radiation and/or adjuvant chemotherapy for high-risk patients. However, the efficacy of pre-operative chemotherapy is unknown. If the tumor is shrunk by pre-operative chemotherapy, we could achieve complete surgical resection, which is difficult when the tumor is too large or is invading neighboring organs. We herein describe a case of huge mesenteric liposarcoma that showed significant tumor shrinkage by pre-operative chemotherapy using doxorubicin, cisplatin and ifosfamide, allowing a margin-negative operation.

Adult↗

Adjuvant chemotherapy with uracil-tegafur for pathological stage III rectal cancer after mesorectal excision with selective lateral pelvic lymphadenectomy: a multicenter randomized controlled trial.

BACKGROUND: Although adjuvant radiotherapy was proved to be effective for local control of rectal cancer even after standardized mesorectal excision, the role of adjuvant chemotherapy after such standardized surgery remains to be clarified. We aimed to assess the efficacy of a combination of uracil and tegafur for pathological stage III rectal cancer treated by standardized mesorectal excision with selective lateral pelvic lymphadenectomy. METHODS: We randomly assigned patients with completely resected stage III rectal cancer, who underwent standardized mesorectal excision with selective lateral pelvic lymphadenectomy, to receive either oral uracil-tegafur (400 mg/m2 tegafur per day) for one year or no treatment. Standardization and quality control of the surgery and pathological techniques were ensured by use of the guidelines of the Japanese Society for Cancer of the Colon and Rectum. The primary endpoint was relapse-free survival. The secondary endpoint was overall survival. RESULTS: We enrolled and randomized 276 patients. Excluding two ineligible patients, 274 were included in the analysis. Planned interim analysis 2 years after accrual termination revealed significant prolongation of relapse-free survival (P = 0.001) and overall survival (P = 0.005) in the uracil-tegafur group. The 3-year relapse-free survival and overall survival rates were 78 and 91% in the chemotherapy group and 60 and 81% in the surgery-alone group, respectively. Local recurrence rates were low in both groups. Grade 3 events occurred in 17% of the chemotherapy patients, but no grade 4 or more events occurred. CONCLUSION: Adjuvant chemotherapy with uracil-tegafur improves survival of patients with stage III rectal cancer after standardized mesorectal excision with selective lateral pelvic lymphadenectomy.

Adult↗

Function preservation in rectal cancer surgery.

When total mesorectal excision (TME) is accurately performed, dysfunction, theoretically, does not occur. However, there are differences among individuals in the running patterns and the volumes of nerve fibers, and if obesity or a narrow pelvis is present, nerve identification is difficult. Currently, the rate of urinary dysfunction after rectal surgery ranges from 33% to 70%. Many factors other than nerve preservation play a role in minor incontinence. Male sexual function shows impotence rates ranging from 20% to 46%, while 20%-60% of potent patients are unable to ejaculate. In women, information on sexual function is not easily obtained, and there are more unknown aspects than in men. As urinary, sexual, and defecation dysfunction due to adjuvant radiotherapy have been reported to occur at a high frequency, the creation of a protocol that enables analysis of long-term functional outcome will be essential for future clinical trials. In the treatment of rectal cancer, surgeon-related factors are extremely important, not only in achieving local control but also in preserving function. This article reviews findings from recent studies investigating urinary, sexual, and defecation dysfunction after rectal cancer surgery and discusses questions to be studied in the future.

Digestive System Surgical Procedures↗

Intersphincteric resection in patients with very low rectal cancer: a review of the Japanese experience.

PURPOSE: This study was designed to evaluate the feasibility and oncologic and functional outcomes of intersphincteric resection for very low rectal cancer. METHODS: A feasibility study was performed using 213 specimens from abdominoperineal resections of rectal cancer. Oncologic and functional outcomes were investigated in 228 patients with rectal cancer located <5 cm from the anal verge who underwent intersphincteric resection at seven institutions in Japan between 1995 and 2004. RESULTS: Curative operations were accomplished by intersphincteric resection in 86 percent of patients who underwent abdominoperineal resection. Complete microscopic curative surgery was achieved by intersphincteric resection in 225 of 228 patients. Morbidity was 24 percent, and mortality was 0.4 percent. During the median observation time of 41 months, rate of local recurrence was 5.8 percent at three years, and five-year overall and disease-free survival rates were 91.9 percent and 83.2 percent, respectively. In 181 patients who received stoma closure, 68 percent displayed good continence, and only 7 percent showed worsened continence at 24 months after stoma closure. Patients with total intersphincteric resection displayed significantly worse continence than patients with partial or subtotal resection. CONCLUSIONS: Curability with intersphincteric resection was verified histologically, and acceptable oncologic and functional outcomes were obtained by using these procedures in patients with very low rectal cancer. However, information on potential functional adverse effects after intersphincteric resection should be provided to patients preoperatively.

Adult↗

The risk of multiple primary malignancies with colorectal carcinoma.

PURPOSE: With advances in diagnostic techniques and treatment modalities, the number of patients identified with colorectal carcinoma who develop multiple primary malignancy during long-term follow-up has been increasing. We investigated multiple primary malignancies occurring in a large number of colorectal carcinoma patients who had undergone surgery in the 1980s at our institution. METHODS: A total of 1,304 Japanese patients with colorectal carcinoma treated between January 1980 and December 1989 were prospectively followed to investigate the situations in which multiple primary malignancies occurred. To determine whether the incidence of multiple primary malignancies in this series was higher than expected, we calculated the expected numbers of carcinoma occurrences and evaluated these findings by exact binomial test. RESULTS: The median follow-up period was 95 months. The incidence of multiple primary malignancy was 18.7 percent (143/765) among males and 14.7 percent (79/539) among females. The most common site of multiple primary malignancy among males was the stomach, followed by the lung, prostate, larynx, liver, esophagus, and urinary bladder. The most common site among females was the uterus, followed by the stomach, breast, and liver. The sites that showed a higher incidence of multiple primary malignancy than the expected value were: the prostate, larynx, urinary bladder, oral cavity/pharynx and thyroid among males, and the uterus and oral cavity/pharynx among females. CONCLUSIONS: Fifteen to 20 percent of Japanese colorectal carcinoma patients experienced multiple primary malignancies. Postoperative long-term screening methods should be established considering the actual occurrence numbers and risk rate of multiple primary malignancies in addition to metachronous colorectal carcinoma.

Aged↗

Treatment strategy for locally recurrent rectal cancer.

Despite radical surgery, up to 33% of patients with rectal cancer will develop locoregional relapse. The management of these patients is particularly challenging. Surgery is the mainstay of treatment for those with a mobile recurrence. However, the majority of patients develop recurrence involving the pelvic wall. In these patients, multimodality therapy including radical surgery and intraoperative radiotherapy have been reported with 5-year survival of up to 31% and local control rates of 50-71%. The most important factor for obtaining long-term local control and survival is R0 resection. Extended surgery such as abdomino-sacral resection has not been popular because of 5-year survival rates of 16-31%, and significant postoperative morbidity. Re-recurrence following surgery occurs locally and in the lung, and remains a significant problem. In surgical treatment for local recurrence, surgeon-related factors are crucial. A staging system using degree of fixation and other prognostic factors should be developed so that appropriate treatment modalities are applied to each case.

Combined Modality Therapy↗

Randomized controlled trial to evaluate laparoscopic surgery for colorectal cancer: Japan Clinical Oncology Group Study JCOG 0404.

A randomized controlled trial was started in Japan to evaluate whether laparoscopic surgery is the optimal treatment for colorectal cancer. Patients with T3 or deeper carcinoma in the colorectum without transverse and descending colons are pre-operatively randomized to either open or laparoscopic colorectal resection. Surgeons in 24 specialized institutions will recruit 818 patients. The primary end-point is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the proportion of conversion from laparoscopic surgery to open surgery, and the proportion of completion of laparoscopic surgery.

Adult↗

CD10 expression in colorectal carcinoma correlates with liver metastasis.

PURPOSE: If it were possible to identify the features of primary colorectal carcinoma that were associated with liver metastasis, these features could be used as predictors of liver metastasis. METHODS: From January 1995 to December 1997, 648 consecutive cases of colorectal carcinoma were recorded at the Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. We evaluated clinicopathologic and immunohistochemical factors (age, gender, tumor location, gross type, size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and expression of CD10, MUC2, and human gastric mucin) in 505 of these patients who had undergone resection of T2/T3/T4 colorectal carcinomas to clarify the correlation between these factors and liver metastasis. RESULTS: Liver metastases, including unresectable, were detected in 122 patients (24 percent), all of whom had been followed for at least five years. Univariate analysis revealed that liver metastasis was significantly associated with tumor size, histologic type, dedifferentiation of invasive front, depth of invasion, lymphatic invasion, venous invasion, lymph-node metastasis, and CD10 expression. Multivariate analysis revealed that invasion deeper than the subserosa, venous invasion, lymph-node metastasis, and CD10 expression were significantly associated with liver metastases. CONCLUSIONS: CD10 expression in colorectal carcinoma is a good predictor of liver metastasis.

Adenocarcinoma↗

A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis.

BACKGROUND & AIMS: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. METHODS: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. RESULTS: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. CONCLUSIONS: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer.

Adult↗

Safety of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis.

To assess the feasibility and analyze the short-term outcomes of laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis, a review was performed of a prospective registry of 67 patients who underwent laparoscopic sigmoidectomy and anterior resection with intracorporeal rectal transection and double-stapling technique anastomosis between July 2001 and January 2004. Patients were divided into 3 groups: sigmoid colon/rectosigmoid carcinoma, upper rectal carcinoma, and middle/lower rectal carcinoma. A comparison was made of the short-term outcomes among the groups. The number of cartridges required in bowel transection was significantly increased in patients with middle/lower rectal carcinoma, and significant differences were observed in the length of the first stapler cartridge fired for rectal transection. Furthermore, mean operative time and blood loss were also significantly greater in the middle/lower rectum group; however, complication rates and postoperative course were similar among the 3 groups. No anastomotic leakage was observed. Laparoscopic intracorporeal rectal transection with double-stapling technique anastomosis can be performed safely without increased morbidity or mortality.

Adult↗

[Selection and techniques of surgical procedures based on the mode of cancer spread of rectal cancer].

The author reviewed recent results of Japanese and international studies on preoperative staging, pathology of bisopied specimens, sentinel node navigation surgery, and single tumor cells in rectal cancer. Preoperative staging with high accuracy is possible using high spatial MRI imaging. Examination of circumferential resection margins is incompatible with that of lymph nodes Intersphincteric resection can be an alternative to abdominoperineal resection for selected rectal tumors located at the anorectal junction without compromising the chance for cure. Although information on sentinel node navigation surgery and isolated single cells has accumulated, the selection of surgical procedures should not be based on these investigations. We emphasize that multiinstitutional clinical trials of adjuvant chemoradiotherapy and surgical treatment are indispensable for developing treatments for rectal cancer in Japan.

Digestive System Surgical Procedures↗

Total pelvic exenteration with distal sacrectomy for fixed recurrent rectal cancer in the pelvis.

PURPOSE: This study evaluates the effectiveness of total pelvic exenteration with distal sacrectomy for fixed recurrent tumor that developed from primary rectal cancer. METHODS: We investigated surgical indications, techniques to minimize blood loss and reduce complications, and oncological outcomes in 57 patients who underwent total pelvic exenteration with distal sacrectomy between 1983 and 2001. RESULTS: Forty-eight patients (84 percent) had negative margins. A comparison between two periods (1983-1992 and 1993-2001) showed that mean blood loss decreased from 4,229 to 2,500 ml (P = 0.002), indicating a favorable learning curve in minimizing blood loss. Two hospital deaths were observed in the earlier period and none in the later period. The most common sacral amputation level was the S3 superior margin, followed by the S4 inferior margin and the S2 inferior margin. The most frequent complication was sacral wound dehiscence in 51 percent, followed by pelvic sepsis in 39 percent. The incidence of pelvic sepsis in the later period was significantly decreased to 23 percent, compared with 72 percent in the earlier period (P = 0.046). Multivariate analysis showed that negative margins and negative carcinoembryonic antigen predicted improved survival. In 48 patients with negative margins, three-year and five-year disease-specific survival rates were 62 percent and 42 percent, respectively. CONCLUSION: Strict patient selection makes total pelvic exenteration with distal sacrectomy a feasible radical approach for fixed recurrent tumor. Careful performance of this surgical procedure along with the proper steps to decrease blood loss should achieve a favorable learning curve and low rate of surgical complications.

Adult↗

Extensive but hemiallelic methylation of the hMLH1 promoter region in early-onset sporadic colon cancers with microsatellite instability.

BACKGROUND AND AIMS: Methylation of the hMLH1 promoter region is frequently observed in microsatellite instability (MSI)-positive sporadic colorectal carcinomas. We studied hMLH1 promoter methylation in peripheral blood lymphocytes of 87 index patients representing 29 cases of hereditary nonpolyposis colorectal cancers (HNPCCs), 28 cases of atypical HNPCCs, and 30 sporadic cases of the development of early-onset colorectal carcinomas or multiple primary cancers. METHODS: Methylation of the hMLH1 promoter region was analyzed by Na-bisulfite polymerase chain reaction/single-strand conformation polymorphism analysis or methylation-specific polymerase chain reaction. MSI, allelic status of the hMLH1 locus, and loss of hMLH1 protein expression were examined in cases for which tumor tissues were available. RESULTS: Extensive methylation of the hMLH1 promoter was detected in peripheral blood lymphocytes of 4 of 30 patients with sporadic early-onset colon cancer, among whom multiple primary cancers (1 colon and 1 endometrial cancer) developed in 2 cases. This methylation was not detected in analyses of HNPCC or atypical HNPCC groups or healthy control subjects. MSI was positive, and extensive methylation was detected in both cancers (colon and endometrial cancer) and normal tissues (colon, gastric mucosa, endometrium, and bone marrow) in all of the examined cases (3 of 3). Analysis of a polymorphic site in the hMLH1 promoter in 2 informative cases showed that methylation was hemiallelic. In 1 case, the unmethylated allele was lost in the colon cancer but not in the metachronous endometrial cancer. CONCLUSIONS: Constitutive, hemiallelic methylation of the hMLH1 promoter region was shown to be associated with carcinogenesis in sporadic, early-onset MSI-positive colon cancers.

Adaptor Proteins, Signal Transducing↗

Prospective evaluation of prognostic factors in patients with colorectal cancer undergoing curative resection.

BACKGROUND AND OBJECTIVES: Streak type, defined by the presence of white streaks at the advancing margin of tumor invasion; focal dedifferentiation, seen as undifferentiated cancer cells with an infiltrative pattern at the invasive front; and perineural invasion have been demonstrated to be prognostic factors in patients with colorectal cancer. We performed a prospective study to examine the usefulness of these features as prognostic factors. METHODS: We reviewed a total of 391 patients who underwent curative surgery for colorectal cancer between May 1997 and June 1999. Of these, 50 patients with multiple cancers were excluded, and a total of 341 patients were finally entered into the study. RESULTS: Of the prognostic factors investigated, depth of invasion, lymph node status, lymphatic invasion, venous invasion, growth type, streak type, focal dedifferentiation, and perineural invasion were significant prognostic factors in univariate analysis. In multivariate analysis, lymph node status, depth of invasion, and perineural invasion were significant prognostic factors. The survival of patients with perineural invasion was significantly poorer than that of patients without perineural invasion in both stage II and III cancer. CONCLUSIONS: Perineural invasion status can be used to facilitate the selection of colorectal cancer patients for adjuvant chemotherapy and should be described in routine pathology reports.

Colorectal Neoplasms↗