Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212).

BACKGROUND: Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. METHODS: Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. RESULTS: A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). CONCLUSION: Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.

ANTECEDENTES: El JCOG0212 (ClinicalTrials.gov: NCT00190541) fue un ensayo fase III de no inferioridad en pacientes con cáncer de recto en estadio clínico II/III sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. El ensayo comparó la escisión del mesorrecto (mesorectal excision, ME) con la ME con disección de los ganglios linfáticos laterales (lateral lymph node dissection, LLND), siendo el criterio de valoración principal la supervivencia libre de recidiva (recurrence free survival, RFS). El análisis primario planificado a los 5 años de seguimiento no pudo confirmar la no inferioridad de la ME frente a la ME con LLND. Este estudio tuvo como objetivo comparar la ME como procedimiento único y la ME con LLND utilizando datos de seguimiento a largo plazo del ensayo JCOG0212. MÉTODOS: En este estudio se incluyeron pacientes con cáncer de recto en estadio clínico II/III por debajo de la reflexión peritoneal sin ganglios linfáticos aumentados de tamaño en la pared pélvica lateral. Después de que los cirujanos confirmaran la resección R0 mediante la ME, los pacientes fueron asignados al azar al brazo de ME sola o al brazo de ME con LLND. El criterio de valoración principal fue la supervivencia libre de recidiva (RFS). RESULTADOS: Un total de 701 pacientes de 33 instituciones fueron asignados al azar para ser tratados mediante una ME con LLND (n = 351) o EM sola (n = 350) entre junio de 2003 y agosto de 2010. Las tasas de RFS a 7 años fueron del 71,1% para ME con LLND y 70,7 % para ME sola (cociente de riesgos instantáneos, hazard ratio, HR: 1,09 (i.c. del 95% 0,84-1,42), no inferioridad P = 0,064)). El análisis de subgrupos mostró una mejor RFS entre los pacientes en estadio clínico III que se sometieron a ME con LLND en comparación con ME sola (HR: 1,49 (i.c. del 95%: 1,02-2,17)). CONCLUSIÓN: Los datos de seguimiento a largo plazo no justificaron la no inferioridad de la ME en comparación con la ME con LLND. Se recomienda la ME con LLND para pacientes en estadio clínico III, mientras que LLND podría omitirse para pacientes en estadio clínico II.

FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: The efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectable and borderline resectable pancreatic cancer is important for predicting outcomes after radical surgery, but few clinical indicators predict outcome before resection. This study examined the utility of FDG-PET in predicting the efficacy of NACRT and outcome after radical surgery. METHODS: Eighty-three pancreatic cancer patients who underwent FDG-PET before and after NACRT and had positive standard uptake values (SUVs) before NACRT were enrolled in this study. Peri-operative clinical factors, including FDG-PET findings, were examined to predict the efficacy of NACRT and outcome after surgery. RESULTS: Evans grade I, IIA, IIB, III, and IV was determined in 11, 31, 27, 11, and 3 patients, respectively. The maximum SUVs after NACRT (post SUV-max) and tumor size were significantly decreased compared to pretreatment values (p < 0.001 and p = 0.007, respectively). The post SUV-max and regression index were significantly related to grade III/IV (p = 0.04 and p < 0.001, respectively), but only the regression index predicted NACRT efficacy (p = 0.002). The AUC of the regression index for the detection of grade III/IV was 0.822, and 13 of 14 grade III/IV patients were picked up using 50% as the threshold (p < 0.001). Patients with a regression index >50% had a significantly better prognosis after radical resection than patients with <50% (p = 0.032). Regression index as well as pathological lymph node status and resectability status were independent prognostic factors in multivariate analysis (exp 2.086, p = 0.043). CONCLUSION: The regression index is potentially a good indicator of the efficacy of NACRT and outcome after radical resection for pancreatic cancer.

Novel prognostic prediction models for patients with stage IV colorectal cancer after concurrent curative resection.

BACKGROUND: We developed a prediction tool for recurrence and survival in patients with stage IV colorectal cancer (CRC) following surgically curative resection. PATIENTS AND METHODS: From January 1983 to December 2012, 113 patients with CRC and synchronous liver and/or lung metastatic CRC were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. All patients underwent curative resection of primary and metastatic lesions. In the group of patients who underwent surgery from 1983 to 2008, a Cox regression model was used to develop prediction models for 1-year, 3-year and 5-year cancer-specific survival (CSS) and relapse-free survival (RFS). In the other group of patients who underwent surgery from 2009 to 2012, the developed prediction model was validated. RESULTS: Univariate analysis of clinicopathological factors showed that the following factors were significantly correlated with CSS and RFS: preoperative serum carcinoembryonic antigen level, tumour location, pathologically defined tumour invasion and lymph node metastasis, and synchronous metastatic lesions. Using these variables, novel prediction models predicting CSS and RFS were constructed using the Cox regression model with concordance indexes of 0.802 for CSS and 0.631 for RFS. The prediction models were validated by external data sets in an independent patient group. CONCLUSIONS: We developed novel and reliable personalised prognostic models, integrating tumour, node, metastasis (TNM) factors as well as the preoperative serum carcinoembryonic antigen level, tumour location and metastatic lesions, to predict patients' prognosis following surgically curative resection. This individualised prediction model may help clinicians in the treatment of postoperative stage IV CRC following surgically curative resection.

Male sexual dysfunction after rectal cancer surgery: Results of a randomized trial comparing mesorectal excision with and without lateral lymph node dissection for patients with lower rectal cancer: Japan Clinical Oncology Group Study JCOG0212.

BACKGROUND: We conducted a randomized controlled trial (JCOG0212) to determine whether the outcome of mesorectal excision (ME) alone for rectal cancer is not inferior to that of ME with lateral lymph node dissection (LLND). The present study focused on male sexual dysfunction after surgery. METHODOLOGY: Eligibility criteria included clinical stage II/III rectal cancer, the lower margin of the lesion below the peritoneal reflection, the absence of lateral pelvic lymph node enlargement, and no preoperative radiotherapy. After confirmation of R0 resection by ME, patients were intraoperatively randomized. Questionnaires using the International Index of Erectile Function (IIEF-5) about the sexual function of men were collected before and 1 year after surgery. Sexual dysfunction incidence was defined as the ratio of patients showing sexual dysfunction after surgery relative to the number who had no erectile dysfunction before surgery. RESULTS: Among 701 patients enrolled between June 2003 and August 2010, 472 males were included. Among them, 343 (73%) completed preoperative and postoperative questionnaires. According to the study protocol, the incidences of sexual dysfunction in patients who underwent ME alone and ME with LLND were 68% (17/25; 95%CI, 47-85%) and 79% (23/29; 95%CI, 60-92%), respectively (p = 0.37). Incidences of sexual dysfunction in patients with no or only mild erectile dysfunction before surgery who underwent ME alone and ME with LLND were 59% (48/81) and 71% (67/95), respectively (p = 0.15). Multivariate analysis identified age as the only risk factor for sexual dysfunction after surgery (p = 0.02). CONCLUSIONS: LLND may not increase sexual dysfunction incidence after rectal cancer surgery. This incidence is associated with increased age. This trial is registered with ClinicalTrials.gov, number NCT00190541 and University Hospital Medical Information Network Clinical Trials Registry, number C000000034.

Prevention of gastroduodenal content reflux and delayed gastric emptying after esophagectomy: gastric tube reconstruction with duodenal diversion plus Roux-en-Y anastomosis.

Reflux of gastroduodenal contents and delayed gastric emptying are the most common and serious problems after esophagectomy with gastric reconstruction. However, attempts to reduce the above symptoms, surgically as well as non-surgically, had no or limited effect. To address this issue, we performed retrosternal gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis (RY) in eight patients with thoracic esophageal cancer and compared the outcomes with control patients who underwent standard reconstruction. The procedure is simple, safe, and not associated with any postoperative complications. The pancreatic amylase concentrations in the gastric juice samples on postoperative day 2 were slightly lower in the non-RY group than in the RY group (1884 ± 2152 vs. 25,790 ± 23,542IU/mL, respectively, P= 0.07). Postoperative endoscopic examination showed neither reflux esophagitis nor residual gastric content in the RY group. Quality of life assessed by the Dysfunction After Upper Gastrointestinal Surgery-32 questionnaire postoperatively was significantly better in the RY group than in the non-RY group for 'decreased physical activity,''symptoms of reflux,''nausea and vomiting,' and 'pain.' The results of this pilot study suggest that gastric reconstruction with duodenal diversion plus RY seems effective in improving both the reflux and delayed gastric emptying. The benefits of this procedure need to be further assessed in a large-scale, randomized controlled trial.

The significance of abdominal para-aortic lymph node metastasis in patients with lower thoracic esophageal cancer.

Para-aortic lymph node (PALN) recurrence is often seen in patients with lower thoracic esophageal cancer treated by esophagectomy with extended lymph node dissection. However, the clinicopathological characteristics of patients with PALN metastasis and the significance of PALN dissection are unknown. A total of 283 patients with lower thoracic esophageal cancer underwent esophagectomy with lymphadenectomy at our hospital between April 1984 and March 2007. Among these 283 patients, 60 patients were enrolled in this retrospective study according to following criteria: (i) clinical T2 to T4 tumor, (ii) no clinical PALN metastasis, and (iii) received PALN dissection. PALN dissection was indicated by a tumor depth of at least T2 and no severe complications. The clinicopathological data, recurrence pattern, and overall survival were compared between patients with PALN and without PALN metastasis. The mean length of surgery was 587 min and the mean blood loss was 1383 mL. The morbidity was 33.3% and mortality was 5% in this series. Sixteen patients (26.7%) had PALN metastasis; these showed significantly more lymph node metastases (15.8 ± 13.2 vs. 3.0 ± 3.2, P < 0.0001) and significantly worse survival rates (53.3% vs. 79.9% at 1 year, 6.7% vs. 62.0% at 3 years, P < 0.0001) than patients without PALN metastasis. The incidence of lymph node recurrence (P < 0.0001) and hematogenous recurrence (P= 0.0487) was also higher in patients with PALN metastasis than in patients without PALN metastasis. Among the 16 patients with PALN metastasis, a univariate analysis revealed total number of metastatic nodes < 8 (P= 0.0325) to be a significant prognostic factor. A multivariate logistic regression analysis of the regional lymph nodes identified the invasion of the lower mediastinal nodes (hazard ratio = 6.120) and retroperitoneal nodes (hazard ratio = 15.167) to be significantly correlated with PALN metastasis. PALN metastasis is suggested to be related to the systemic spread of lymphatic metastasis even in lower thoracic esophageal cancer. PALN dissection for pathological PALN(+) patients should not be performed. It remains to be determined in future prospective studies whether patients without pathological PALN metastasis, but showing PALN micrometastasis, could achieve improved survival with PALN dissection.

The indications for a diverting stoma in low anterior resection for rectal cancer: a prospective multicentre study of 222 patients from Japanese cancer centers.

AIM: The aim of the study was to determine the present state of diverting stoma construction in Japanese cancer centres and to investigate the relationship between symptomatic leakage and diverting stoma after low anterior resection for rectal cancer. METHOD: Two hundred and twenty-two consecutive patients undergoing low anterior resection for rectal cancer located within 10 cm from the anal verge were investigated in a prospective, multicenter study. RESULTS: The overall leakage rate was 9.0% (20/222). Of 31 cases with an anastomosis within 2.0 cm from the anal verge, 22 (71%) had a diverting stoma. Of cases anastomosed within 5.0 cm, the absence of a diverting stoma and tumour size were significantly related to an increased rate of leakage [leakage in 13 (12.7%) of 102 cases without a diverting stoma; in three (3.8%) of 80 cases with a diverting stoma]. Among anastomoses within 2.0 cm from the anal verge, leakage occurred in four (44.4%) of nine cases without and in none (0%) of 22 cases with a diverting stoma. CONCLUSION: We recommend a diverting stoma for an anastomosis within 5.0 cm of the anal verge and strongly recommend it for a very low anastomosis within 2.0 cm.

Can ultrasonographic evaluation of subcutaneous fat predict pressure ulceration?

High-resolution ultrasound may be able to detect pressure ulcers before clinical signs emerge. This retrospective study found that one such early indicator is inflammatory oedema in the subcutaneous fat, which resolves as healing occurs.

Analgesic and chondroprotective effects of risedronate in osteoarthritis assessed by electroalgometry and measurement of collagen type II fragments in urine.

We evaluated the effect of the bisphosphonate, risedronate, on pain and cartilage metabolism in 33 patients with osteoarthritis of the knee, randomized into two groups. Group RC was treated with risedronate (2.5 mg/day) and calcium (900 mg/day); group C received calcium (900 mg/day) alone. Pain on exercise was estimated using a subjective visual rating scale (VRS) and an electroalgometric method of measuring decrease in skin impedance, previously shown to be indicative of pain. We measured urinary excretion of cartilage-specific collagen type II fragments as a marker of cartilage degradation. Multiple regression analysis revealed that pain alleviation as measured by skin impedance, but not VRS, was associated with a decrease in collagen fragment excretion. This suggests that, for pain evaluation, reduction in skin impedance may have a greater physiological basis compared with VRS-based evaluation. We consider that the chondroprotective and analgesic effects of risedronate may be related.

Correlation between pretherapeutic d-dimer levels and response to neoadjuvant chemotherapy in patients with advanced esophageal cancer.

Neoadjuvant chemotherapy may improve survival of responders in esophageal cancer patients but is useless and harmful in non-responders. Thus, it is important to predict the effect of the chemotherapy, and that any predictor must be applicable clinically. The aim of this study is to examine the correlation between pretherapeutic hypercoagulopathy as determined by plasma d-dimer levels and response to chemotherapy. In 71 patients with esophageal cancer who underwent neoadjuvant chemotherapy (cisplatin, adriamycin and 5-fluorouracil) followed by surgery, plasma d-dimer levels were measured before chemotherapy and the clinical and pathological responses to chemotherapy were assessed at 4 weeks after therapy (after surgery). Pretherapeutic plasma d-dimer level was significantly lower in clinical responders (complete response/partial response [CR/PR]; 0.62 +/- 1.10 microg/mL, mean +/- SD) than in non-responders (no change/progressive disease [NC/PD]; 1.15 +/- 1.08 microg/mL, P = 0.0491), and in pathological responders (Grade 1b-3; 0.62 +/- 1.11 microg/mL) and non-responders (Grade 0-1a; 1.15 +/- 1.05 microg/mL, P = 0.0107). The optimal cut-off level of the plasma d-dimer levels for predicting clinical and pathological responses was 0.6 microg/mL. Then, sensitivity and specificity for the prediction of CR/PR were 68% and 73%, and those for Grade 1b-3 were 91% and 69%, respectively. Our results suggested that pretherapeutic plasma d-dimer level correlated significantly with clinical and pathological responses to chemotherapy. Pretherapeutic plasma d-dimer level can be used as a predictor for chemosensitivity.

Evaluation of the technical difficulty performing laparoscopic resection of a rectosigmoid carcinoma: visceral fat reflects technical difficulty more accurately than body mass index.

BACKGROUND: In general, visceral fat and adhesion greatly influence the technical difficulty in performing abdominal surgery. Body mass index (BMI) has been widely used to express the degree of obesity, but it does not always properly reflect the degree of visceral fat. This retrospective study investigated the impact of visceral fat on the operation time to examine whether a quantified visceral fat area (VFA) could be used as a sensitive predictor of technical difficulty in performing a laparoscopic resection of rectosigmoid carcinoma. METHODS: Between February 1999 and April 2004, 58 consecutive patients underwent a laparoscopically assisted sigmoidectomy or anterior resection. After a review of the medical charts, the relationship between the operation time and the following variables was analyzed: sex, depth of invasion, approach (medial-to-lateral, lateral-to-medial), subjectively graded degree of visceral fat and adhesion, history of previous abdominal surgery, and BMI. The correlations between VFA, VFA/body surface area (BSA) measured by the "FatScan," software package for quantifying the VFA from the preoperative CT images, and operation time were investigated. Next, the impact of the VFA amount on the early surgical outcome was examined. RESULTS: According to the intraoperative findings, two patients with a severe adhesion required a significantly longer operation time. A history of previous abdominal surgery was not a significant factor in the operation time. Instead, the VFA/BSA had a stronger correlation with the operation time than the BMI. A significantly longer operation time (209 +/- 42 vs 179 +/- 37 min; p = 0.031) was observed for the patients in the high VFA/BSA group (> or =85 cm(2)/m(2)) group than in the normal VFA/BSA group (<85 cm(2)/m(2)). CONCLUSION: For predicting the technical difficulty of performing a laparoscopic resection of rectosigmoid carcinoma, VFA/BSA may be a more useful index than BMI.

Preoperative chemotherapy for clinically node-positive patients with squamous cell carcinoma of the esophagus.

Lymph node metastasis is one of the strongest prognostic factors for patients with esophageal cancer. Whether neoadjuvant chemotherapy is effective for metastatic nodes and improves the prognosis of clinically node-positive patients is unknown. Seventy-seven patients with clinically node-positive esophageal cancer, who were given preoperative chemotherapy (5-fluorouracil, cisplatin and adriamycin) followed by surgery, were retrospectively analysed. The histological effectiveness of the chemotherapy against the main tumor in the resected specimen was correlated with nodal status and prognosis. Of the 77 patients, the histological effects in the main tumors were grade 3 in one patient (1.3%), grade 2 in 10 (13.0%), grade 1b in seven (9.1%), grade 1a in 50 (64.9%) and grade 0 in nine (11.7%). Eleven patients (14.3%) were found to be pathologically node-negative. The pathological stages were significantly earlier in responders (grades 3-1b) than in non-responders (grades 1a-0) (P = 0.0001). The responders showed a significantly lesser degree of lymph node metastasis (P = 0.0005), fewer metastatic nodes (2.2 +/- 3.1 vs. 12.0 +/- 20.5, P = 0.0482) and better survival (P = 0.002) than the non-responders. The most common failure pattern for the non-responders was lymphatic recurrence, with an incidence of 47.5% (28/59), while that for the responders was 16.7%. Responders to neoadjuvant chemotherapy show fewer metastatic nodes and better prognosis than non-responders. Neoadjuvant chemotherapy may offer clinical benefit to responders.

Prognosis of patients who develop cervical lymph node recurrence following curative resection for thoracic esophageal cancer.

Patients with esophageal cancer often display relapse at cervical nodes after surgery, but their prognosis and a suitable therapy remains unknown. We retrospectively reviewed the records for 35 patients who underwent esophagectomy with lymphadenectomy who then displayed relapse at the cervical lymph nodes alone between 1985 and 2003 in order to observe the prognostic factors for such patients. Median survival time from the date of recurrence for all 35 patients was 12 months with 1-year, 2-year, 3-year and 5-year survival rate of 47.2%, 26.5%, 17.7% and 8.8%, respectively. With regard to the initial treatment against cervical node recurrence, 15 patients were treated by radiotherapy alone, eight by chemoradiotherapy, 11 by surgery and one by chemotherapy alone. Univariate analysis revealed that cervical node dissection at the prior esophagectomy (yes/no, P = 0.0178), time to recurrence (> 9 months or < 9 months, P = 0.0497) and the number of relapsed nodes (solitary/multiple, P = 0.0029) were significant prognostic factors. Among these factors, the number of relapsed nodes (solitary/multiple) was found to be the only significant prognostic factor with an odds ratio of 2.409 and 95% confidence interval of 1.033-5.619 by multivariate analysis. In conclusion, cervical node metastasis is generally considered to be distant organ metastasis. However, if it is a solitary node recurrence, substantial survival can be attained by appropriate loco-regional therapy.

Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11.

This open label pilot study evaluated the safety and efficacy of the oral 5-HT3 receptor antagonist granisetron for prophylaxis of delayed chemotherapy-induced nausea and vomiting (CINV) in 30 patients with advanced or recurrent colorectal cancer. Patients were studied during two cycles of a 5-week regimen with irinotecan (CPT-11) and UFT. Patients received prophylactic anti-emetic therapy that included intravenous granisetron. If Grade 1 or higher severity gastrointestinal symptoms occurred during 6 days after CPT-11 administration in Cycle 1, then oral granisetron was administered daily for the following 5 days of CPT-11 in Cycle 2. Sixteen patients (53.3%) experienced delayed CINV in Cycle 1. The incidence of Grade 2 or higher vomiting was 32.1% and 27.7% in Cycles 1 and 2 in males (P = 0.554) respectively, and 54.6% and 32.4% in females (P = 0.001) respectively. Granisetron is effective against delayed Grade 2 or higher vomiting induced by CPT-11/UFT in female patients, although granisetron alone may not sufficiently control nausea induced by this regimen.

Feasibility of autonomic nerve-preserving surgery for advanced rectal cancer based on analysis of micrometastases.

BACKGROUND: Autonomic nerve preservation has been advocated as a means of preserving urinary and sexual function after surgery for rectal cancer, but may compromise tumour clearance. The aim of this study was to determine the incidence of micrometastasis in the connective tissues surrounding the pelvic plexus. METHODS: The study included 20 consecutive patients who underwent rectal surgery with bilateral lymph node dissection for advanced cancer. A total of 78 connective tissues medial and lateral to the pelvic plexus and 387 lymph nodes were sampled during surgery. All connective tissue samples and 260 lymph nodes were examined for micrometastases by reverse transcriptase-polymerase chain reaction (RT-PCR) after operation. All patients were followed prospectively for a median of 36.0 months. RESULTS: Of 245 histologically negative lymph nodes, 38 (15.5 per cent) were shown by RT-PCR to harbour micrometastases. However, micrometastases to tissues surrounding the pelvic plexus were detected in only two (3 per cent) of 78 tissues, that is in two of 20 patients. Clinical follow-up showed that the two patients had a poor prognosis owing to distant metastases. CONCLUSION: Autonomic nerve-preserving surgery may be feasible for advanced rectal cancer, but study of more patients positive for micrometastases is required.

Identification of differentially expressed genes involved in colorectal carcinogenesis using a cDNA microarray.

To identify candidate genes involved in human colorectal carcinogenesis, we constructed the gene expression profiles of 50 colorectal cancers (CRCs) and 12 normal colorectal epithelia using a cDNA microarray specially constructed for CRC. Hierarchical clustering analysis and principal component analysis could clearly distinguish the gene profiles of cancer tissues from those of normal tissues. Our results confirm there are indeed differences in gene expression between cancer and normal mucosa. Our cDNA microarray identified 22 up-regulated genes and 32 down-regulated genes in CRC. Many of these genes have been previously identified in relation to human carcinogenesis, 68% and 78%, respectively. Subsequent validation of selected genes by serial analysis of gene expression and reverse transcription polymerase chain reaction, demonstrated expression patterns that were almost identical to our microarray analysis. Using a four-fold larger sample relative to that used in our previous study, candidate genes involved in human colorectal carcinogenesis were reproducibly identified. Further studies of comprehensive gene expression using our technique may elucidate the mechanism of CRC tumorigenesis.

A novel case with germline p53 gene mutation having concurrent multiple primary colon tumours.

During a search for causative genes in patients with concurrent multiple primary colon tumours, we found a novel case with a germline mutation of the p53 gene, from GCC (Ala) to GTC (Val) at codon 189. Of the six primary colon tumours that this patient had, one large advanced carcinoma exhibited a somatic p53 mutation and a somatic APC mutation, in addition to the germline p53 mutation. Two early carcinomas and three adenomas had somatic APC mutations but no somatic p53 mutation or loss of the p53 allele. K-ras-2 mutations were detected in an advanced carcinoma and an early carcinoma. The present results suggest that a patient with a certain type of germline p53 mutation is predisposed to concurrent multiple colon tumours. It is also suggested that in such a patient, a somatic APC mutation is involved in tumour formation and that an additional somatic p53 mutation contributes to tumour progression.

[Clinical trial of thermoradiotherapy and internal iliac arterial infusion of 5-FU for unresectable pelvic tumor].

Clinically, unresectable pelvic tumor is difficult to treat because the patients have poor prognosis and often suffer from severe pain and edema of the lower limbs due to the tumor invasion of the pelvic bone and the sciatic nerve. To improve QOL of such patients, we performed thermoradiotherapy (RTHT) or internal iliac arterial infusion of 5-FU (IIAI) for 7 patients who developed unresectable pelvic tumors which relapsed after surgery for 6 colorectal cancers and one leiomyosarcoma of the uterus. The mean tumor diameter was 10.2 cm and an evaluation by computed tomography revealed 2 of 6 tumors had a partial response (PR) and 3 no change (NC). Each of the 4 patients who had been ill in bed recovered to the point of being able to walk with a cane or wheel themselves in a wheelchair after the therapy.

[Minimally invasive treatment of colorectal cancer].

It may be widely interpreted that minimally invasive treatment of colorectal cancer includes endoscopic mucosal resection, transanal endoscopic microsurgery (TEM), laparoscopic surgery and open reduction-surgery as well as adjuvant treatments such as chemotherapy, radiotherapy and thermotherapy. With the development of medical technology and instruments, we have now a wide and new range of choices for each cancer stage of patients. However, it is not yet clear that minimally invasive treatment necessarily leads to better results in survival and recurrent rates of the patients, as compared with conventional surgery. We should therefore take into full consideration the lingering problems in selecting the new therapies. In this paper, we show the strong and weak points of laparoscopic surgery, TEM, right hemi-colectomy preserving Bauhin's valve and adjuvant radiotherapy for lower rectal cancer, and discuss ongoing problems.

Bone marrow micrometastases detected by RT-PCR for mammaglobin can be an alternative prognostic factor of breast cancer.

PURPOSE: To evaluate a new prognostic factor of breast cancer, bone marrow micrometastases which was detected by RT-PCR for mammaglobin, a sensitive molecular marker of breast cancer, was examined. MATERIALS AND METHODS: One hundred and eleven samples from stage I-III breast cancer patients were examined. Bone marrow micrometastases and clinicopathological parameters, which were age, tumor size, lymph node metastasis and status of the estrogen receptor, were evaluated for the prognostic factor by statistical analysis. RESULTS: Median follow-up time was 21.1 months. Thirty-three (29.7%) out of 111 samples were RT-PCR positive. Eight cases (24.2%) in this group showed recurrent lesions in the distant organs. Whereas six (7.7%) out of 78 RT-PCR negative patients had distant recurrences. In the premenoposal patients, and in the patients with axillary lymph node metastases, RT-PCR positive cases showed significantly higher distant recurrent rate. Bone marrow micrometastases, axillary nodal status, and estrogen receptor were independent prognostic factors for breast cancer by both univariate and multivariate analysis. CONCLUSIONS: Bone marrow micrometastases detected by RT-PCR for mammaglobin can be a useful predictive marker for early distant recurrence of breast cancer.