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RalA protein, a member of the Ras superfamily of small GTPases, is a tumor antigen that induces serum RalA antibodies (s-RalA-Abs). The present study explored the clinicopathological and prognostic significance of s-RalA-Abs in patients with colorectal cancer. Serum samples were obtained from 314 patients with colorectal cancer at stage 0/I (n=71), stage II (n=86), stage III (n=78), stage IV (n=64) and recurrence (n=15). Samples were analyzed for the presence of s-RalA-Abs using ELISA. The cutoff optical density value was fixed at 0.324 (mean of heathy controls + 3 standard deviations). The overall positive rate for serum anti-RalA antibodies was 14%. The presence of s-RalA-Abs was not significantly associated with clinicopathological characteristic factors. Additionally, the s-RalA-Abs(+) group demonstrated significantly poor relapse-free survival rates. The s-RalA-Abs (+)/carcinoembryonic antigen (CEA)(+) group exhibited the worst prognosis and s-RalA-Abs(+)/CEA(+) was an independent risk factor for poor relapse-free survival. Although the positive rate was not high, s-RalA-Abs may be a useful predictor of poor relapse-free survival in patients with colorectal cancer. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to identify risk factors for postoperative recurrence (PR) after Altemeier's and Delorme's procedures for full-thickness rectal prolapse (FTRP)., Methods: We enrolled 127 patients who underwent Altemeier's and Delorme's procedures for FTRP between April 2008 and September 2021. We divided the 127 patients into recurrence and non-recurrence groups and conducted univariate and multivariate analyses. We used six independent variables: age, body mass index (BMI), history of surgical repair for FTRP, coexistence of prolapse in other organs, poor fixation of the rectum on defecography before surgery, length of the prolapsed rectum, and type of surgical procedure (Altemeier's or Delorme's procedures)., Results: PR developed in 51 (40.1%) patients during a mean follow-up period of 453 (range, 9-3616) days. Comparing the recurrence group (n=51) with the non-recurrence group (n=76), significant difference was observed regarding the coexistence of prolapse in other organs (p=0.017) in the univariate analysis. In the multivariate analysis, significant differences were observed in BMI (OR 1.18, 95% CI 1.030-1.350, p=0.020), coexistence of prolapse in other organs (OR 3.38, 95% CI 1.200-9.500, p=0.021), length of the prolapsed rectum (OR 1.030, 95% CI 1.010-1.060, p=0.015), poor fixity of the rectum on defecography (OR 0.332, 95% CI 0.129-0.852, p=0.022), and surgical procedures (OR 0.192, 95% CI 0.064-0.573, p=0.003)., Conclusions: The study suggested that increasing BMI, coexistence of prolapse in other organs, length of the prolapsed rectum, poor fixation of the rectum on defecography before surgery, and types of surgical procedure might be risk factors of PR after perineal surgery for FTRP., Competing Interests: Conflicts of Interest K. Funahashi received a research grant from Taiho pharmaceutical Co., Ltd. The other authors declare that they have no conflicts of interest to disclose., (Copyright © 2024 The Japan Society of Coloproctology.)

BACKGROUND Although recurrence after surgery for esophagogastric junction (EGJ) adenocarcinoma frequently develops in the mediastinal and para-aortic lymph nodes (LN), distant LN recurrence in the mesocolon is rare. We report a rare case of ileocecal LN metastasis in the ascending mesocolon after radical surgery for an EGJ adenocarcinoma. CASE REPORT We performed subtotal esophagectomy with mediastinal and para-gastric LN dissection in a patient with an advanced EGJ adenocarcinoma. Clinicopathologically, the patient was diagnosed with type I EGJ adenocarcinoma based on Siewert's classification (pathological T3N1M0). One year after surgery, computed tomography showed enlarged lymph nodes around the ileocolic artery, and further examination was performed. Although positron emission tomography-computed tomography showed that the lesion had moderate uptake of fluorodeoxyglucose, we did not find the reason for the enlarged lymph nodes. Finally, laparoscopic ileocecal resection was performed for diagnostic and therapeutic purposes. Clinicopathological tests revealed that the specimen was a moderately differentiated adenocarcinoma, which was strongly suspected to be a metastasis of the EGJ adenocarcinoma. CONCLUSIONS We encountered a rare case of EGJ adenocarcinoma that spread to the ileocecal LN in the ascending mesocolon. To the best of our knowledge, this is the first such report in the literature to date. Laparoscopic ileocecal resection for metastasis to the ascending mesocolon seems reasonable as a local control.

Objectives The current carbohydrate antigen 125 (CA125) cutoff value demonstrated high specificity but low sensitivity. Therefore, we used new cutoff values to evaluate the clinical impact of perioperative CA125 in gastric cancer. Methods This study retrospectively analyzed 525 patients with gastric cancer (349 males and 176 females), of whom 445 patients underwent R0 resection and 80 patients underwent R1/R2 resection between 2011 and 2020. The receiver operating characteristic curve indicated preoperative and postoperative cutoff CA125 values of 15.7 IU/mL and 17.3 IU/mL, respectively, to predict overall survival. Furthermore, we analyzed changes in postoperative CA125 levels and evaluated their prognostic impact using multivariate analysis. Results The preoperative CA125-positive rate was 25%. Males, advanced TNM factors, and noncurative resection cases demonstrated significantly higher positive rates than the other group. The preoperative CA125-positive group exhibited a significantly higher noncurative resection rate than the preoperative CA125-negative group (32% versus 10%, P < 0.01). Preoperatively, CA125-positive status was an independent poor prognostic factor (P < 0.01), and at three months postoperatively, it tended to be a poor prognostic factor. Conclusions High preoperative CA125 (>15.7 IU/mL) was a significant predictor for noncurative resection and poor overall prognosis in gastric cancer. Furthermore, postoperative CA125-positive status three months postoperatively was also a potential predictor of recurrence and poor prognosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethics Committee of Toho University Omori Medical Center (Tokyo, Japan) issued approval M20196 19056 18002. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Moriyama et al.)

A 27-year-old man was referred to our hospital for a detailed examination of abdominal distention, bloody stool, anorectal pain, and weight loss. A colonoscopy revealed a circumferential type 2 tumor at 9 cm from the anal verge which was diagnosed as an adenocarcinoma based on biopsy. Contrast-enhanced CT of the abdomen showed an elevated perineal lipid concentration in the rectum(Ra)which was suspicious for clinical T4a stage, and simultaneous S7/8 liver metastasis. We strongly suspected familial adenomatous polyposis(FAP)because his mother had a past history of total proctocolectomy for FAP. We decided to first create a loop stoma at the transverse colon for the obstructive rectal cancer, and then administer neoadjuvant chemotherapy(mFOLFOX6 plus panitumumab). We performed total proctocolectomy with permanent stoma and S8 ventral resection for the liver metastasis after 5 courses of mFOLFOX6 plus panitumumab. As for clinicopathological findings, round 50 polyps were identified in the colon and rectum, and rectal cancer invaded into the muscularis propria. Finally, the patient was diagnosed as a clinically attenuated FAP with ypT2 rectal cancer.

Biosimilar(BS)drugs have recently been introduced owing to concerns with healthcare economics. In this report, we present a case in which a patient discontinued bevacizumab treatment following an allergic reaction to a BS formulation of bevacizumab but was able to safely continue treatment by switching to an original bevacizumab formulation in the late-line setting. The patient was a 66-year-old man diagnosed with unresectable colorectal cancer with synchronous multiple liver metastases. After primary tumor resection, chemotherapy including the original bevacizumab formulation was initiated. Allergic reactions to the BS formulation of bevacizumab occurred during the second-line treatment; however, in the late-line setting, switching back to the original bevacizumab formulation enabled the safe continuation of therapy. Overall, our case study suggests that switching of biologic agents may contribute to the ongoing management of chemotherapy.

We experienced a case of resection of a metastatic umbilical tumor(Sister Mary Joseph's nodule: SMJN)derived from a pancreatic tail carcinoma. The patient was a 70-year-old woman. She visited her previous doctor with a chief complaint of lower abdominal pain and came to our hospital due to suspicion of pancreatic tail cancer. She was found to have metastases to multiple organs which was unresectable by surgery. After chemotherapy up to the second-line of treatment, she was diagnosed to have progressive disease. The decision was made to provide the best supportive care for the patient. Thereafter, the patient developed SMJN. She had hemorrhage from the tumor accompanied by body movement, and her activity of daily living became impaired. She had difficulty controlling the bleeding despite repeated hemostatic treatment at the outpatient clinic and at her home. However, she required frequent blood transfusions for her severe anemia. Therefore, we performed a resection of the SMJN to control bleeding and to relieve her symptoms. She had a good postoperative course and was discharged on the fifth postoperative day. Due to deterioration of her general condition, she expired on the 59th day after surgery. However, the patient was able to live at home without bleeding or pain by the umbilical tumor. The local resection was considered to be useful as a palliative surgical treatment for SMJN.

Objectives: We evaluated the prognostic impact of a novel C-reactive protein (CRP) cut-off value (0.6 mg/dl) and carcinoembryonic antigen (CEA)/carbohydrate antigen 19-9 (CA19-9) in stage II/III colorectal cancer., Methods: Four hundred ninety-eight patients with stage II (n = 275) or stage III (n = 223) colorectal cancer, surgically treated between January 2010 and December 2016, were analyzed. The optimal CRP cut-off value was fixed at 0.6 mg/dl to predict recurrence based on the receiver operating characteristic curve. Prognostic factors, including CRP/CEA/CA19-9 status, for relapse-free survival (RFS) were evaluated by multivariate analysis., Results: Recurrent rates were 15% and 32% in stages II and III, respectively. In stage II, CRP, CEA, and CA19-9 were not significant prognostic factors for RFS. In stage III, the RFS of the low CRP group was significantly better than that of the high CRP group ( p = 0.002). In stage III, the RFS of CRP(-)/CEA(-) or CRP(-)/CA19-9(-) was significantly better than the other group, as opposed to the RFS of the CEA(-)/CA19-9(-) group that was not. The CRP(-)/CEA(-)/CA19-9(-) group recurrence rate in stage III was significantly better than the CRP(+)/CEA(-)/CA19-9(-) group (20% vs. 50%, p = 0.006). Multivariate analysis revealed that CRP(-)/CEA(-)/CA19-9(-) ( p = 0.04) and non-T4 ( p < 0.001) were good independent prognostic factors in stage III. The CRP(-)/CEA(-)/CA19-9(-)/non-T4 group recurrence rate in stage III was 11% (8 out of 73)., Conclusions: In stage III, the CRP(-)/CEA(-)/CA19-9(-)/non-T4 group is favorable risk for recurrence., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2022 The Japan Society of Coloproctology.)

Objective: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors., Methods: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53., Results: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer., Conclusion: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.

Purpose: Hypercalcemia has been reported as a poor prognostic factor in malignant tumors. However, no report has shown the clinical impact of serum calcium levels on patients with esophageal cancer. We evaluated the prognostic impact of preoperative serum calcium levels on patients with esophageal cancer., Methods: We evaluated 240 patients (197 men, 43 women; mean age, 66 years; age range, 34-85 years) with esophageal cancer who underwent radical surgery between September 2008 and December 2017. After assigning the patients to two groups (high calcium group, 8.8 mg/dL or more and low calcium group, 8.7 mg/dL or less), we compared the groups' overall survival and the clinicopathological features. The clinicopathological and prognostic significance of preoperative serum calcium levels were evaluated in a univariate and multivariate analysis., Results: The patients with deep tumors showed low serum calcium levels significantly more frequently (P <0.05). The low calcium group showed a significantly worse prognosis than the high calcium group (P <0.05). However, low serum calcium level was not an independent poor prognostic factor., Conclusions: Preoperative low serum calcium levels were associated with advanced tumors. Low serum calcium might be associated with esophageal cancer progression.

Case: An 83-year-old female. At 82 years of age, the patient sought evaluation with a complaint of rectal bleeding. A 35-mm rectal gastrointestinal stromal tumor(GIST)was treated by laparoscopic ultra-low rectal resection and transanal anastomosis following trans-anal rectal dissection by perineal manipulation. Approximately 1 year later, a 20-mm metastatic lymph node within the right lateral lymph node group at the pelvic cavity was detected. The patient was diagnosed with a recurrence of rectal GIST. The patient had no symptoms and did not wish to undergo surgery. After 7 weeks of treatment with an imatinib dose reduction(200 mg), the dosage was increased and the patient was admitted to the hospital with edema of the face and lower limbs, and pleural and pericardial effusions(grade 2). After discharge from the hospital, the medication was terminated early at the patient's request. One year later, the lymph nodes had decreased in size to 7.5 mm, indicating a partial response. The treatment-free period continued, and after 5 years at 89 years of age the lymph nodes had not enlarged, thus the patient was thought to be clinically cured. We report a rare case of long-term tumor suppression using short-term low-dose imatinib therapy.

The case is a 59‒year‒old woman. A detailed examination of fecal occult blood revealed a diagnosis of cStage Ⅳ sigmoid colon cancer cT3N1M1b(liver H2, hilar liver and celiac artery lymph nodes). After excision of the primary lesion, decided to give chemotherapy. The gene test was RAS gene mutation negative and EGFR positive, and mFOLFOX6 plus panitumumab (pani)was started as the first‒line treatment. Imaging tests at the end of 13 courses showed that the maximum diameter of liver metastases was reduced from 54 mm to 16 mm, and CEA was normalized from 93.9 ng/mL. However, metastasis was found in the hilar lymph nodes, it was judged that hepatectomy is not indicated, radiofrequency ablation therapy was performed. But FOLFIRI plus pani was restarted because metastatic liver tumor relapsed on CT 5 months later. After 6 courses, she felt tired, so I consulted her and changed to TAS‒102 plus bevacizumab. Sudden headache and vomiting appear during 3 courses, head CT revealed subarachnoid hemorrhage. No brain metastases or organic lesions such as cerebral aneurysms and stenotic lesions, the relationship with bevacizumab was strongly suspected.

The patient was a 77-year-old woman who visited our hospital with a chief complaint of blood in the stool. The patient had a colonoscopy 2 years earlier, which led to suspicions of total colitis-type ulcerative colitis(UC). However, the histological findings did not lead to a definitive diagnosis. Upon the withdrawal of urine in an outpatient visit, fecaluria was noted. Based on various examinations, we diagnosed this patient with Rs, cT4b(bladder), cN0, cM0 adenocarcinoma. We then performed Hartmann operation with partial cystectomy. The pathological findings indicated colorectal cancer with ulcerative colitis (CAC)(low grade and high grade dysplasia and carcinoma). Postoperative examinations of the oral side of the colon revealed a flat squamous elevated lesion in the ascending colon, which was diagnosed as adenocarcinoma. Therefore, we waited for the improvement of performance status and performed additional total colectomy with resection of the anus and ileostomy. We experienced a case of progressive CAC due to the difficulty of histological diagnosis via biopsy and a lack of appropriate surveillance post clinical suspicions. In cases of colitis-type UC, appropriate surveillance by endoscopists and pathologists is important.

An 84-year-old woman presented with a 9mm sized solitary liver metastasis in liver S8 18 months after the surgery for sigmoid colon cancer. The patient was treated with stereotactic body radiation therapy(SBRT)for local control, because the patient chose not to undergo surgery or chemotherapeutic treatment for metastatic liver cancer. SBRT is a minimally invasive treatment with a very short treatment period. Therefore, it may be considered as an alternative treatment for patients who are not suitable for surgery.

A 60-year-old woman was administered mFOLFOX6 therapy as postoperative adjuvant chemotherapy for fStage III a ascending colon cancer. The patient developed a disorder of consciousness(Japan Coma Scale[JCS]III-200)immediately after the completion of the therapy. Blood ammonia levels were high at 319 mg/dL, and a diagnosis of disturbance of consciousness due to hyperammonemia was made. The patient's state of consciousness improved on the following day as blood ammonia levels decreased due to treatment with branched chain amino acid(BCAA)formulation and oxygen. Two months later, mFOLFOX6 therapy was again administered with strengthening measures for side effects to nausea and vomiting and reducing 5-FU, but the patient again developed a disorder of consciousness(JCS III-200). The 5-FU administration rate was considered as a potential cause of hyperammonemia. Hyperammonemia induced by 5-FU is relatively rare, with a reported incidence of 5-9%; however, caution is required with high dosage regimens of 5-FU that are currently recommended for colorectal cancer therapy because hyperammonemia is an important side effect.

When a medical provider(medical personnel)becomes a medical receiver(patient), does the consciousness about chemotherapy change ? If yes, what is the main reason ? In this study, we conducted a questionnaire on the consciousness of doctors and pharmacologists engaged in chemotherapy for gastric and/or colorectal cancer. The number of questionnaires collected was 83 and 92 for gastric and colorectal cancer, respectively. In adjuvant chemotherapy, 5%and 4%do not want to receive any chemotherapy for gastric and colorectal cancer if they are patients. The main reasons are binding hours, side effects, and no wish for life extension. About 11%and 9%change their consciousness regarding chemotherapy according to whether they are care providers or receivers. The main reasons are medical perspective and their sense of duty. In chemotherapy for advanced cancer, 6% and 5% of gastric and colorectal cancer patients, do not want to receive any chemotherapy. The main reasons are low expectations for being cured, binding hours, and no wish for life extension. Further, 21%and 14%wish to have limited chemotherapy. As regards consciousness on chemotherapy, 26% and 18% reported changes according to whether they are providers or receivers. The main reasons are medical perspective and their sense of duty. As for the purpose of chemotherapy for advanced gastric and colorectal cancer, 96% and 43% answered prolonging life and relief, respectively. The proportion of persons who answered complete cure is statistically higher in colorectal(32%)than in gastric cancer(18%). The most common answer for an adverse event they want to avoid if they are patients is peripheral neuropathy. These results clearly demonstrate that a considerable proportion of medical personnel hold a negative attitude against or are reluctant to receiving chemotherapy, especially for advanced gastric and colorectal cancer. It is of great importance to make use of these results in clinical practice.

Objectives: Intersphincteric resection (ISR) for low-lying rectal cancer (LRC) may induce major problems associated with anorectal function. In this study, we assessed the severity of ISR-induced impairment in anorectal function., Methods: In total, 45 patients followed up regularly ≥2 years after diverting ileostoma closure were eligible. The patients underwent ISR (n=35) or conventional coloanal anastomosis without resection of the internal anal sphincter (IAS) (n=10) for treatment of LRC from January 2000 to December 2011. We retrospectively compared anorectal function [stool frequency, urgency, Wexner incontinence scale (WIS) score, and patient satisfaction with bowel movement habits on a visual analog scale (VAS) score] for ≥2 years after stoma closure between the two groups., Results: The median follow-up period was 4.0 years (range, 2.0-6.5 years). Of the total, 17 (48.6%) patients who underwent ISR had poor anorectal function, including two with complete incontinence. Significant differences were found between the groups in the incidence of urgency ( p =0.042), WIS score ( p =0.024), and defecation disorder with a WIS score of ≥10 ( p =0.034) but not in stool frequency. Based on the VAS score, 45.7% of patients who underwent ISR were dissatisfied with their bowel movement habits ( p =0.041)., Conclusions: Extensive resection of the IAS has negative short- and long-term effects on anorectal function., Competing Interests: Conflicts of Interest The authors declare that there are no conflict of interest., (Copyright © 2017 by The Japan Society of Coloproctology.)

We report a case of aortoesophageal fistula rupture during the course of chemotherapy following colon cancer resection. The patient was a 77-year-old woman. Following recurrence of cancer of the sigmoid colon, the patient received a course of XELOX plus bevacizumab(Bmab)to treat peritoneal dissemination and lung metastases. She was brought by ambulance to our hospital's emergency department 55 days after the last dose of Bmab, with a chief complaint of hematemesis. Hematolo- gy results showed severe anemia with a hemoglobin level of 4.0 g/dL. Descending thoracic aortic dissection was noted on chest CT with contrast, and the patient was diagnosed with an aortoesophageal fistula rupture. She underwent emergent endovascular chest stent grafting to control the bleeding. Although the ruptured esophagus was a potential source of infection, the patient and family members chose palliative treatment. Therefore, conservative treatment was administered without removing the esophagus. The patient's postoperative course was good; instead of resuming oral intake, the patient was discharged on home IVH 59 days after surgery. Outpatient follow-up continued, but multiple metastases led to gradual worsening of the patient's general condition. She died 168 days after being admitted for surgery.

Background/aims: KRAS mutation is an important prognostic factor for patients with metastatic colorectal cancer receiving anti-epidermal growth factor receptor therapy. However, the influence of KRAS mutation on the response to mFOLFOX6 ± bevacizumab remains unclear., Methodology: We retrospectively analyzed 49 patients who received modified FOLFOX6 (mFOLFOX6) ± bevacizumab as first-line therapy. Genetic analysis showed that 30 patients had wild-type (WT) KRAS and 19 patients hadKRAS mutations (MT). These two groups were compared with regard to the response rate (RR), progression-free survival (PFS), and overall survival (OS)., Results: The RR was not significantly different between the WT and MT groups, but PFS and OS were significantly better in the WT group than the MT group (PFS: 11.8 months vs. 8.7 months, p<0.01; OS: 37.8 months vs. 29.3 months, p<0.0385). A similar analysis of 27 patients who were treated with mFOLFOX6 + bevacizumab showed a better prognosis for WT patients. Multivariate analysis also revealed that KRAS mutation was an independent factor with a significant relation to PFS., Conclusions: These results suggest that KRAS mutation may be a useful prognostic marker for patients with metastatic colorectal cancer receiving mFOLFOX6 ± bevacizumab therapy, especially for patients treated with mFOLFOX6 + bevacizumab.

Background/aims: In Japan lateral pelvic lymph node dissection has been actively performed with total mesorectal excision for low rectal cancer. However, its definitive efficacy remains unclear. This study is to evaluate clinical significance of lateral pelvic lymphatic drainage in low rectal cancer patients by 99mTc-Sn colloid radioactive tracers., Methodology: Intraoperatively detecting rectal lymphatic drainage using 99mTc-Sn colloid radioactive tracer in 39 low rectal cancer patients, we performed lateral pelvic lymph node dissection in lateral pelvic lymphatic flow-positive patients., Results: Lateral pelvic lymphatic flow was detected in 11 patients (28%). In four (36%) of 11 patients, tumor cells were histologically identified in lateral pelvic lymph nodes. A median size of metastatic lateral pelvic lymph nodes was 7.5 (range, 2-150) mm, and all but one overlooked patient could not be detected by routine preoperative imaging scans retrospectively. The five-year disease-free survival rate of lateral pelvic lymphatic flow-positive patients was significantly poorer (45% vs. 75%, p = 0.0044)., Conclusions: Tumor cells potentially extended beyond the fascia propria recti in low rectal cancer with lateral pelvic lymphatic flow. Preoperative chemoradiation therapy and adjuvant therapy are considered to be reasonable to improve a poor prognosis of low rectal cancer patients with lateral pelvic lymphatic flow.

Background/aims: A phase I study was performed to evaluate the dose-limiting toxicity and the recommended dose of the oral fluoropyrimidine S-1 when administered concurrently with radiation therapy to 9 Japanese patients with low rectal cancer., Methodology: S-1 was given orally for a total of 9 weeks (4 weeks alone and 5 weeks during radiation therapy) at oral doses of 65 mg/m2/day (n = 3 patients) or 80 mg/m2/day (n = 6 patients). Radiation therapy was administered in 1.5 gray fractions five times weekly (Monday to Friday) for a total dose of 45 gray., Results: All patients achieved the planned 45 gray of radiation therapy. There was no grade > or = 3 toxicity. The recommended dose of S-1 was determined to be 80 mg/m2/ day. The dose intensity of S-1 was well maintained, and the combination of S-1 plus radiation therapy was well tolerated by all patients. Sphincter-preserving procedures were possible in all but one (89%) patient. High rates of tumor shrinkage and nodular downstaging were achieved. The histological response rate was 78%, including one complete response., Conclusions: The recommended dose of S-1 with concurrent radiation therapy was 80 mg/m2/day. Pre-operative chemoradiation therapy with S-1 was feasible and well tolerated by patients with low rectal cancer.

A 74-year-old woman was diagnosed with advanced rectal cancer and stenosis. To resolve the rectal stenosis, we successfully placed an expandable metallic stent across the stenosis. After stent placement, food intake improved, and a good quality of life was maintained. Subsequently, the patient received systemic chemotherapy with modified FOLFOX6 (mFOLFOX6). The tumor responded remarkably to chemotherapy, and the patient did not experience any complications. After 2 courses of mFOLFOX6, the patient underwent high anterior resection. The postoperative course was satisfactory, and she has now been disease-free for 6 months after surgery.

Unlabelled: We report 5 cases of colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) oxaliplatin after systemic infusion chemotherapy failure. Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (L-OHP 100 mg/body, 2 hours) combined with intravenous (iv) levofolinate calcium (175 mg/body, 2 hours) and iv bolus 5-FU (500 mg/body) every 2 weeks., Result: An average age was 58 years. All patients had previously received FOLFOX. Lung metastases had already existence before HAI oxaliplatin in 4 patients. A median of 10 treatments were administered (range 5-14). Serum level of CEA was decreased in 4 cases. In 2 patients, lung metastasis developed while a PR was obtained in the liver metastasis. Progress disease (PD) was confirmed in other 3 patients. No major toxicity was presented. The median time to progression free survival was 3.0 months and the median overall survival was 7.1 months., Conclusion: HAI oxaliplatin might be beneficial as a salvage therapy for CRLM without extrahepatic metastasis, which demonstrated an acceptable tolerability and maintenance of QOL.

Purpose: Fecal incontinence is a frequently observed symptom after lower rectal surgery with sphincter manipulation. The aim of this study was to evaluate a proposed modification to the fecal incontinence quality of life (FIQL) scale for the assessment of the quality of life among patients with very low rectal cancer who have undergone intersphincteric resection., Methods: A single 14-item composite scale was prepared that was derived from items in the "Lifestyle" and "Coping" subscales of the original FIQL. The scale was tested with a convenience sample of 152 postoperative patients. In addition to classic psychometric evaluation, newer statistical techniques, such as a multiple correspondence analysis and partial credit model, were performed to evaluate the item response patterns., Results: The proposed scale exhibited an item-rest correlation of 0.66-0.84 and a Cronbach's alpha of 0.96, and was correlated with concurrently measured Social Functioning subscale of the Medical Outcomes Study Short Form 36 (-0.70), physical role limitation (-0.61), and Wexner continence grading scale (-0.61). Multiple correspondence analysis supported a uni-dimensional construct, and the partial credit model showed a varying yet overlapping range of item response thresholds across items. Several items, such as "Locating bathroom whenever going out", reflected more a serious condition than items such as "Avoiding eating-out." Weighted item scores based on estimated thresholds provided results comparable with those based on non-weighted scores., Conclusions: The proposed modification to the FIQL scale exhibited high internal consistency and satisfactory concurrent and convergence validity. The modified scale is practical to administer and is sensitive to a range of functional problems associated with fecal incontinence among patients who have undergone intersphincteric resection.

Most tumors of patients with Lynch syndrome and a fraction of sporadic colorectal cancers (CRCs) exhibit high levels of microsatellite instability (MSI) at mono- and dinucleotide repeat loci. A different type of instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been found in non-colonic cancers. Our previous study demonstrated that EMAST is common in sporadic CRC. Here, we focused on the relationships between EMAST and other genomic instability parameters or clinicopathological features in an unselected series of 88 sporadic CRCs. Of the tumors in the sample, 4 (4.5%) were MSI-high (MSI-H), 9 (10.2%) were MSI-low (MSI-L) and 75 (85.2%) were microsatellite stable. EMAST status was determined using 7 EMAST markers. Fifty-three (60.2%) tumors without MSI-H showed instability at >or=1 EMAST loci. All 4 MSI-H tumors showed instability at several EMAST loci. Instability profiles of MSI-H tumors at EMAST loci were more complex than those of non-MSI-H tumors. A tendency of positive association was observed between MSI-L and EMAST (P=0.023). The frequency of loss of heterozygosity (LOH) for the 14 loci in EMAST-positive tumors was significantly higher than negative tumors (P=0.048). Among the clinicopathological parameters, only tumor location at the distal colon was associated with EMAST-negative tumors (P=0.0084, one-tailed). A relatively higher frequency of well-differentiated adenocarcinomas was observed in EMAST tumors as opposed to non-EMAST tumors, though the survival rate was similar. These results suggest that overlapping mechanisms that cause MSI-L, EMAST and LOH in CRCs may exist.

We experienced a case in which the hepatic artery catheter system could be used long term. Even after 5 years and five months, there was no damage to the hepatic artery, and we could still use this system. For insertion of the catheter, a fine catheter with the tip tapered at 2.7 F was selected. This catheter was inserted into the hepatic artery peripheral branch in the liver, after a side hole was created 11 cm from the tip, and the side hole was adjusted to stay in the common hepatic artery. We speculated that the reason for little injury to the hepatic artery was use of a fine catheter despite possible damage to the hepatic artery wall like saw cutting in this case. We classified the patterns according to which a catheter damaged the inner wall of the hepatic artery into 5: "straight punch type", "hook punch type", "whiplash type", "elbow blow type", "and saw type".

Metastasis to the regional lymph nodes is an important prognostic factor in colorectal cancer, and nodal evaluation is essential for accurate staging. In colorectal cancer, the aim of evaluating sentinel lymph nodes (SLNs) is the selection of patients for adjuvant therapy and the detection of aberrant lymphatic drainage patterns, leading to modification of the initial therapeutic plan. In a review of the literature, tracer, technique, tumor-related factors (location and size of tumor, T stage, status of lymph node metastasis), neoadjuvant chemoradiation therapy, and body mass index were important factors in the accurate diagnosis of SLNs in colorectal cancer. In recent multicenter SLN trials, ultrastaging has been possible in 10-38% of NO colon cancer patients. Most recently, the trial conducted by Bilchik et al., which investigated the prognostic significance of micrometastases in SLNs in colon cancer patients, found that all NO colon cancer patients with recurrence had positive SLN findings after reverse transcriptase-polymerase chain reaction (RT-PCR)-ultrastaging, whereas none of those with negative SLN findings in immunohistologic staining had recurrence, and there was only a significant correlation between recurrence and molecular markers in RT-PCR. However, further prospective multicenter trials are warranted to evaluate the ultimate clinical relevance of SLN diagnosis in colorectal cancer including anal cancer.

We report 27 cases of liver metastases treated with transarterial chemoembolization (TACE) with CPT-11, DSM, and mitomycin C (CPT-DSM therapy). In the 27 patients with liver metastases from colorectal cancer, CPT-DSM therapy was performed 47 times. All of these patients were a contra indication of hepatectomy. We compared a tumor marker before and after the treatment, and measured a serum level of SN-38, which is an active substance of CPT-11 and resolved from CPT-11. Although the level of CPT-11 was wearing off after CPT-DSM therapy, the peak of SN-38 level delayed 1 hour after the infusion. The CEA and CA19-9 levels were decreased to 54.2% and to 45.1% of the level before the treatment, respectively. Nine of the partial response and stable disease patients underwent surgery. The response rate was 59%. A 3-year survival rate was 20%. These results suggest that CPT-DSM therapy is one of the most effective anticancer agents. This TACE can be a feasible therapy for colorectal liver metastases as the first-line therapy.

Purpose: This study was designed to examine the draining lymph node basin at highest risk of metastasis in lower rectal cancer using 99 mTc-tin colloid., Methods: In 43 patients, the area with highest hot nodes density was defined as the draining lymph node basin using a gamma probe. Metastatic states of all removed lymph nodes were examined histologically., Results: A total of 203 hot nodes were identified in 39 patients (91 percent) with a mean of 5.2 nodes. The number of removed lymph nodes was 808 nodes: 670 nodes in the mesorectum, and 138 nodes in the pelvis. In 21 patients, the metastatic states of 119 nodes were investigated histologically. From the distribution of the identified hot nodes, the draining lymph node basins were classified into two patterns: lateral type (n = 17), and mesorectal type (n = 22). Only 20 (17 percent) of 119 positive nodes were identified as hot node. Tumor cells that occupied the lymph node diffusely or massively probably interfered with the exact diagnosis of metastasis. Lymph node metastasis in the pelvis was observed in 5 patients (13 percent). One false negative was of the mesorectal type with diffuse metastases in the para-aortic lymph nodes. The remaining four patients were of the lateral type and all positive lymph nodes, including positive nonhot nodes, were located within the draining lymph node basin. Consequently, in 20 (95.2 percent) of 21 patients with lymph node metastasis, all positive lymph nodes were located within the draining lymph node basin of the tumor., Conclusions: Two types of the draining lymph node basin of advanced lower rectal cancer were identified using this method. The concordance between lymph node metastases and the draining lymph node basin is good.

In the surgical treatment of advanced rectal cancer, wide lymphadenectomy has been replaced by autonomic nerve preservation because of serious problems such as postoperative urinary and sexual dysfunction. This may offer a considerable clue to as whether metastasis of lateral lymph node can be diagnosed by a new technique in order to provide more benefits to many patients with advanced rectal cancer. Moreover the sentinel lymph node (SLN) concept has lately attracted attention as a new technique. We studied SLN in 40 patients with advanced lower rectal cancer using 99mTc-Sn colloid as a tracer. SLN was successfully identified in 35 (87.5%) of 40 patients, and the mean number of SLNs identified per patient was 5.6 lymph nodes (range 1-14). In this study overall accuracy was 86%, and it was suggested that lateral lymphadenectomy was excluded in 91%, thanks to application of the SLN technique. Although the role this technique plays in the individualization of the therapy for rectal cancer will be large in the near future, many problems remain to be solved in the exact identification of SLN.

We measured TS and DPD activities in 40 patients with colorectal cancer who had undergone surgical reduction in our department between May 1997 and April 1998, including 26 patients with preoperative UFT (450 mg/body/day) chemotherapy for 2 weeks, and evaluated the clinical significance of TS and DPD activities as predictive factors of UFT sensitivity. TS activity was collated with histological type from a clinical pathological examination (p = 0.0103). Also, the tendency for TS activity to become high with the stage was observed. According to the evaluation of pathological response, histological effectiveness greater than grade 2 was noted in 7.7%. The apoptosis index (AI) in tumors with preoperative UFT chemotherapy was higher than those without such treatment, which showed a higher correlation with DPD activity of tumor tissue than TS activity (p = 0.0465). Recurrence was seen in 7 cases (lung metastasis: 2, liver metastasis: 4, and local recurrence: 1) in the preoperative chemotherapy group. TS activity was high in all patients with recurrence. TS showed significantly high activity in patients with recurrence compared with the non-recurrence (p = 0.0034) patients. Therefore, these results suggested that activity of both TS and DPD was a key factor for anti-tumor effectiveness of UFT. In particular, TS activity was an important predictive factor for effectiveness of UFT in recurrences.

We report a case in which low-dose CPT-11 chemotherapy was effective for metastatic liver tumor of sigmoid colon cancer. A 49-year-old male with metastatic liver tumor, who had undergone sigmoidectomy with D2 lymphadenectomy, was treated by low-dose CPT-11 chemotherapy (CPT-11 30 mg/m2 x 3 days, every 2 weeks). After 7 courses of this chemotherapy, CT and ultrasound examinations showed a reduction of tumor size in the liver. This chemotherapy also showed no high grade toxicities. Therefore, low-dose CPT-11 chemotherapy seems to be effective for metastatic colorectal cancer, and safe in view of toxicities.