Kenji Katsumata

Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial

Objective: The aim of the study was to confirm the noninferiority of mesorectal excision (ME) alone to ME with lateral lymph node dissection (LLND) in terms of efficacy. Background: Lateral pelvic lymph node metastasis is occasionally found in clinical stage II or III lower rectal cancer, and ME with LLND is the standard procedure in Japan. ME alone, however, is the international standard surgical procedure for rectal cancer. Methods: Eligibility criteria included histologically proven rectal cancer at clinical stage II/III; main lesion located in the rectum, with the lower margin below the peritoneal reflection; no lateral pelvic lymph node enlargement; Peformance Status of 0 or 1; and age 20 to 75 years. Patients were intraoperatively allocated to undergo ME with LLND or ME alone in a randomized manner. The primary endpoint was relapse-free survival, with a noninferiority margin for the hazard ratio of 1.34. Secondary endpoints included overall survival and local-recurrence-free survival. Analysis was by intention to treat. Results: In total, 701 patients were randomized to the ME with LLND (n = 351) and ME alone (n = 350) groups. The 5-year relapse-free survival in the ME with LLND and ME alone groups were 73.4% and 73.3%, respectively (hazard ratio: 1.07, 90.9% confidence interval 0.84–1.36), with a 1-sided P value for noninferiority of 0.0547. The 5-year overall survival, and 5-year local-recurrence-free survival in the ME with LLND and ME alone groups were 92.6% and 90.2%, and 87.7% and 82.4%, respectively. The numbers of patients with local recurrence were 26 (7.4%) and 44 (12.6%) in the ME with LLND and ME alone groups, respectively (P = 0.024). Conclusions: The noninferiority of ME alone to ME with LLND was not confirmed in the intent-to-treat analysis. ME with LLND had a lower local recurrence, especially in the lateral pelvis, compared to ME alone.

Detection and evaluation of epithelial cells in the blood of colon cancer patients using RT-PCR.

BackgroundAs a mode of colorectal cancer recurrence, liver metastasis plays an important role. One of the factors reported to predict liver metastasis is the detection of trace amounts of tumor cells in the blood. For this purpose, cancer cell-induced cytokeratins (CKs) are generally identified, using the reverse transcriptase-polymerase chain reaction (RT-PCR). In the present study, we aimed to detect trace amounts of tumor cells, based on CK20, in the circulating venous blood, and we examined pathological factors, liver metastasis, and prognosis.MethodsThe subjects were 57 colorectal cancer patients who had undergone operation. We examined the cancer-induced marker (CK20) in circulating venous blood by RT-PCR and investigated the relationships between this marker, pathological factors, and prognosis.ResultsDetection ratio of CK20 mRNA was 42.1%, and CK20 was significantly correlated with the pathological factor of lymph node metastasis(P = 0.037). The 5-year survival rate for CK20-positive patients was 62.5% and that for the CK20-negative patients was 87.5%; there was a significant difference(P = 0.048) between the two groups. Recurrence was recognized in six patients; two were positive for CK20 and four were negative for CK20.ConclusionsThese findings indicate that CK20 is strongly related to lymph node metastasis and prognosis, suggesting its usefulness for the diagnosis of colorectal cancer recurrence. However, CK20 did not predict liver metastasis.

Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502

While adjuvant chemotherapy is preferable for colon cancer, treatment duration is controversial. This phase III trial is investigated optimal duration of adjuvant chemotherapy for Stage IIB/III colon cancer. Eighteen-month treatment with UFT/LV did not improve DFS compared with 6-month UFT/LV treatment. This study suggests that 6 months treatment duration is enough for Stage IIB/III colon cancer.

Induction of apoptosis by p53, bax, bcl-2, and p21 expressed in colorectal cancer

BackgroundWe investigated the influence of genes on the apoptosis of colorectal tumor cells, based on DNA and mRNA kinetics.MethodsIn 30 colorectal cancer patients, we examined the mRNA expression of p53, bax, bcl-2, and p21WAF1, and we also investigated the development of tumor cell apoptosis, using a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method.ResultsTUNEL-positive cells showed a positive correlation with bax (P = 0.010) and a negative correlation with p21 (P = 0.04). We also investigated the relationship between p53 point mutation, p21 immunostaining degree, and apoptosis, based on DNA ladder expression. A remarkable correlation (P = 0.0090) was found between p21 and apoptosis.ConclusionsThe present study findings suggest that tumor cell apoptosis is (1) strongly inhibited by p21, (2) induced by bax, and (3) influenced by bcl-2, which, presumably, inhibits tumor cell apoptosis.

Complete laparoscopic resection of the rectum using natural orifice specimen extraction

AIM To investigate how complete laparoscopic anterior resection with natural orifice specimen extraction (NOSE), as a novel minimally invasive surgery, compares to conventional laparoscopic surgery. METHODS Twenty patients who underwent complete laparoscopic anterior resection with NOSE and 50 patients who underwent laparoscopic assisted anterior resection by the conventional method between 2011 and 2012 were studied. Selection for complete laparoscopic anterior resection with NOSE was decided on the basis of tumor size, localization of the tumor, and body mass index. Outcomes related to surgery, including operation time, postoperative wound pain, hospital stay after surgery, the number of totally dissected lymph nodes, postoperative complications (suture failure and wound infection), and anal function, were reviewed retrospectively. Anal function was assessed at 3 and 6 mo after surgery using the Wexner fecal incontinence scoring system. RESULTS Complete laparoscopic resection with NOSE was performed to completion in all 20 patients. There was no patient emergency that required conversion to conventional laparoscopic surgery or open surgery. The comparison between complete laparoscopic resection with NOSE and conventional laparoscopic surgery showed no significant differences in the maximal diameter of the tumor, number of totally dissected lymph nodes, bleeding volume, mean operation time, time to start of oral ingestion, postoperative hospital stay, and postoperative complications. On the other hand, with regard to pain after epidural anesthesia, the total usage of analgesia in this novel surgical technique was 1.85 ± 1.8 times, whereas it was 5.89 ± 2.86 in conventional laparoscopic surgery (P < 0.001). The postoperative pain period was 1.9 ± 1.9 d in this novel surgical technique, whereas it was 3.43 ± 1.41 d in conventional laparoscopic surgery (P < 0.004). In complete laparoscopic surgery with NOSE, the mean postoperative follow-up period was 20 mo (range: 12-30 mo). Neither local recurrence nor remote metastasis was observed during the follow-up period. CONCLUSION Complete laparoscopic anterior resection using NOSE does not require any incision and has excellent cosmetic properties, with mitigated postoperative pain.

Analysis of Autonomic Nerve Preservation and Pouch Reconstruction Influencing Fragmentation of Defecation after Sphincter-Preserving Surgery for Rectal Cancer

Our questionnaire survey on defecation disorders after rectal cancer surgery revealed that 66.7% of postoperative patients were most annoyed with fragmentation of defecation. Therefore, we performed a change-over-time analysis on the relationship of fragmentation and factors including location of rectal cancer, surgical technique, anastomosis method, pouch reconstruction, extent of lymph node dissection, and degree of pelvic and colonic nerve preservation surrounding the superior mesenteric artery. The fragmentation decreased over time at the postoperative time points of 6 months, 2 and 5 years. A statistical analysis of factors influencing fragmentation revealed that location of cancer, reconstruction technique, anastomosis method and degree of pelvic nerve preservation were significant factors for the entire patient population and that colonic nerve preservation was a significant factor 5 years after surgery. Analysis of patients with lower rectal cancer only showed that in addition to surgical technique and anastomosis method, pouch reconstruction was effective and autonomic nerve preservation was effective 5 years after surgery. As a result, when the anastomotic site was closer to the anus, the frequency of fragmentation increased; we concluded that pouch reconstruction was an effective surgical technique and colonic nerve preservation was effective in the longer term.

Carcinosarcoma of the Sigmoid Colon: Report of a Case.

Our case was a 65-year-old male, with the chief complaints of diarrhea and abdominal distention. Three years earlier, the patient had undergone transcatheter arterial embolization and radiofrequency treatment based on a diagnosis of hepatocellular carcinoma due to hepatitis B by another doctor. In October 2007, the patient developed diarrhea and increased abdominal distention. In December, CT examination conducted by the previous doctor revealed a 20-cm tumor within the pelvis. The patient was diagnosed with sigmoid colon cancer based on barium enema examination using gastrografin, and was introduced to our hospital for treatment. He was diagnosed with low-differentiated carcinoma by biopsy of the colon during endoscopy and underwent sigmoidectomy based on a diagnosis of sigmoid colon cancer. The tumor had infiltrated the bladder, and a tumorectomy was conducted through partially combined resection. The tumor was a huge lesion occupying the inside of the lumen, and histopathological findings revealed that the tumor, the main part of which lay beneath the mucous membrane, had a transitional image composed of both spindle-shaped atypical cells and sarcomatoid shape. The result of immunostaining was CK7(+), CK20(–), AFP(–), and the patient was diagnosed as having carcinosarcoma of the colon. Carcinosarcoma of the colon is a malignant tumor with poor prognosis, and the mean survival period in past reports was approximately 6 months. The patient was treated with FOLFIRI+Bevacizumab therapy according to chemotherapy for colon cancer, but he was refractory to the therapy.

Liver metastasis of pancreatic cancer managed by intra-arterial infusion chemotherapy combined with degradable starch microspheres.

Abstract. A patient with liver metastasis of pancreatic cancer received chemotherapy using mitomycin C and degradable starch microspheres. The patient was a 52-year-old woman who had undergone surgery for cancer of the head of the pancreas in October 1996. She had stage III disease and was followed up as an outpatient on oral therapy with a combined uracil and tegafur preparation. In October 2000, abdominal computed tomography (CT) scans detected multiple liver metastases. Three courses of intra-arterial infusion of mitomycin C and microspheres (1000 mg) resulted in regression of her tumor and a decrease of tumor marker levels. After three more courses of this therapy, the patient developed bile duct necrosis and died of disseminated intravascular coagulation. As her metastases were controlled for about 7 months, hepatic arterial infusion of mitomycin C and degradable starch microspheres appears to be useful for treating liver metastasis of pancreatic cancer, but careful attention should be paid to the risk of severe complications such as bile duct necrosis.

Correlations of Clinicopathological Factors with Protein Expression Levels of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase and Orotate Phosphoribosyltransferase in Colorectal Cancer

Background: Expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) have been reported to be associated with tumor response to 5-fluorouracil (5-FU). Method: We investigated correlations of clinicopathological factors with protein expression levels of TS, DPD, OPRT in colorectal cancer (CRC). The subjects were 202 patients who had undergone CRC resection. Result: There was a negative correlation between DPD and OPRT protein levels, but no correlation of TS levels with either OPRT or DPD levels. The DPD levels in women was significantly lower than that in men. The DPD level was significantly lower in colonic tumors than in rectal tumors, while the OPRT level was significantly higher in colonic tumors than in rectal tumors. The TS level did not correlate with any clinicopathological factors. Conclusion: DPD and OPRT protein levels in CRC suggest that female gender and colonic tumors are positive prognostic factors in patients who receive chemotherapy with 5-FU.

Examination of prognostic factors in patients undergoing surgery for colorectal perforation: A case controlled study

OBJECTIVE To determine if the POSSUM, SOFA, MPI, and SAS scores provide a better measure of severity for patients with prognostic factors undergoing surgery for colorectal perforation. SUBJECTS Fifty-nine patients who underwent surgery between 1996 and 2012. METHODS We retrospectively reviewed background factors, blood and physiological test results, and intraoperative findings of patients who survived and those who died. We also compared the POSSUM, SOFA, MPI, and SAS scores. Multivariate analysis was performed for factors that were significant by univariate analysis, and selected factors were used to produce a predictive prognostic model. RESULTS Univariate analysis revealed significant differences in age, anticoagulant/steroid administration, serum creatinine level, PF ratio, base excess (BE), chest radiography, pulse rate, and severity of peritoneal soiling. Age, serum creatinine level, pulse rate, and severity of peritoneal soiling were selected for multivariate analysis; only pulse rate was significantly different. There were significant differences between the two groups in POSSUM PS, OSS, SOFA, and MPI scores, and a comparison in terms of the ROC curve showed that our model had the highest peak; the area under the curve was 94.8% compared with 70-80% for the other systems, suggesting that our model is better than those systems. CONCLUSIONS POSSUM and SOFA are valid methods of evaluating risk from colorectal perforation, but our study revealed addition risk factors: (1) the PF ratio and BE, which are not included in POSSUM; (2) the pulse rate and severity of peritonitis, which are not included in SOFA; and (3) anticoagulant/steroid hormone administration.