Prognostic impact of micrometastases in colon cancer: interim results of a prospective multicenter trial

OBJECTIVE: The 25% rate of recurrence after complete resection of stage II colon cancer (CC) suggests the presence of occult nodal metastases not identified by hematoxylin and eosin staining (H&E). Interim data from our ongoing prospective multicenter trial of sentinel node (SN) biopsy indicate a 29.6% rate of micrometastases (MM) identified by immunohistochemical staining (IHC) of H&E-negative SNs in CC. We hypothesized that these MM have prognostic importance. METHODS: Between March 2001 and August 2006, 152 patients with resectable colorectal cancer were enrolled in the trial. IHC and quantitative RT-PCR (qRT) assay were performed on H&E-negative SNs. Results were correlated with disease-free survival. RESULTS: The sensitivity of lymphatic mapping was significantly better in CC (75%) than rectal cancer (36%), P<0.05. Of 92 node-negative CC patients 7 (8%) were upstaged to N1 and 18 (22%) had IHC MM. Four patients negative by H&E and IHC were positive by qRT. At a mean follow-up of 25 months, 15 patients had died from noncancer-related causes, 12 had developed recurrence, 5 had died of CC (2 with macrometastases, 3 with MM), and 7 were alive with disease. The 12 recurrences included 4 patients with SN macrometastases and 6 with SN MM (2 by IHC, 4 by qRT). One of the 2 SN-negative recurrences had other positive lymph nodes by H&E. All patients with CC recurrences had a positive SN by either H&E/IHC or qRT. No CC patient with a negative SN by H&E and qRT has recurred (P=0.002). CONCLUSION: This is the first prospective evaluation of the prognostic impact of MM in colorectal cancer. These results indicate that the detection of MM may be clinically relevant in CC and may improve the selection of patients for adjuvant systemic chemotherapy. Patients with CC who are node negative by cumulative detection methods (H&E/IHC and qRT) are likely to be cured by surgery alone.     

Semen cryopreservation for patients with malignant or non-malignant disease: our 14-year experience

We retrospectively analyzed 163 patients who had been cryopreservating their sperm one year or more. They consisted of 72, 76 and 15 patients with a germ cell tumor, hematologic cancer and other diseases, respectively. Forty-eight patients (29.4%) were still cryoperservating their sperm, and the average period of cryoperservation was 4.7 +/- 3.0 years (1-13.1 years). Only 6 patients (3.7%) had used their cryopreserved sperm and the average preserved period was 6.0 years (1.3-12 years). In 115 of the 163 cases, the cryopreserved sperm was abandoned, and the main reason was the recovery of spermatogenesis. Of the cases that underwent semen analysis after treatment, 20.9% of the patients with testicular cancer and 57.9% of the patients with hematologic cancer, have not recovered spermatogenesis. Because chemotherapy to the testicular tumor and leukemia risk injuring testiclar function, cryopreservation of the sperm before treatment should be recommended. Because the preservation period tends to be prolonged, development of a system for long-time preservation is awaited.     

Survey of nerve injury associated with epidural/spinal anesthesia in Japan which occurred in the year 2004

BACKGROUND: The incidence of nerve injury associated with epidural/spinal anesthesia has not been sufficiently investigated in Japan. PURPOSE: The incidence of nerve injury caused by inappropriate epidural/spinal puncture or catheter placement was examined using data obtained by a survey conducted by the Japanese Society of Anesthesiologists for the year 2004. METHODS: In a survey for the year 2004, 1,218,371 anesthetic procedures were registered, among which 548,819 patients were estimated to be anesthetized under epidural/spinal procedures with or without general anesthesia. Twenty nine patients were reported to have incurred nerve injury due to inappropriate epidural/spinal puncture or catheter placement. RESULTS: Seven cases of spinal cord and 22 cases of peripheral nerve injury were reported, with estimated incidences of 1/78,000 and 1/25,000 procedures, respectively. Spinal cord injury developed before the start of surgery in 4 cases, intraoperatively in 1 case, and after the end of surgery in 2 cases. Permanent nerve damage developed in 4 patients with spinal cord injury and 7 patients with peripheral nerve injury. Eighty three percent of these events were reported to be preventable. CONCLUSIONS: The incidence of nerve injury caused by regional anesthesia in Japan seems to be comparable to those reported in the developed countries. To reduce the incidence of this complication, cautious evaluation of the risk/benefit balance in performing regional anesthesia, improving education and supervision of the procedures, and establishing better communication between anesthesiologists and surgeons concerning the timing of catheter removal and the postoperative coagulation state seem to be important.     

Cerebrovascular accidents developing in the operating theater: a JSA survey for the year 2004

BACKGROUND: The incidence of cerebrovascular accidents (CVA) developing in the operating theater has not been investigated on a large scale. In 2004, the Japanese Society of Anesthesiologists (JSA) started to survey neurological as well as life-threatening events in the operating theater. The incidence of CVA developing in the operating theater was examined using data obtained by the 2004 survey. METHODS: JSA has conducted annual surveys of life-threatening and neurological events in the operating theater by sending and collecting confidential questionnaires to all JSA certified training hospitals. The recovery rate was 91% (874/960 hospitals) in 2004. Seven hundred fourteen hospitals sent valid responses, and 1,218,371 anesthesias were registered. Among these cases, 123 patients were reported to have developed CVA in the operating theater. Incidences according to age class, ASA PS and surgical sites, causes, and their outcome were investigated. The patients with ASA PS 1 or 2 were classified as having good physical status, and those with ASA PS 3-5 were classified as having poor physical status. The causes of events were classified as follows: totally attributable to anesthetic management (AM), mainly to intraoperative pathological events (IP), to preoperative co-morbidity (PC), and to surgical management (SM). RESULTS: Overall incidence of CVA was 1.01/10,000 anesthesias. The incidence in patients aged 66 years or above was 2.00/10,000 anesthesias, which was 3.83-(95% confidential interval 2.57-5.71) fold higher than that in patients aged between 19 and 65 years. The incidences in elective and emergency patients with poor physical status were 3.27 and 7.91/10,000 anesthesias, respectively, which was 7.04- (4.56-10.87) and 17.06-(10.90-26.69) fold higher than that in elective patients with good physical status, respectively. The incidences in patients undergoing thoracotomy combined with laparotomy, craniotomy, or cardiovascular surgery were 2.76, 5.96 and 11.65/10,000 anesthesias, respectively, which were 7.22- (1.64-31.76), 15.59- (8.14-29.86), and 30.52- (16.80-55.44) fold higher than that in patients undergoing laparotomy alone. Among cardiovascular surgery, thoracic aortic surgery showed the highest number of incidents (57.98/10,000 anesthesias), followed by on-pump coronary artery bypass (11.07/10,000 anesthesias). Only one patient undergoing off-pump coronary artery bypass developed CVA, resulting in an 8.14- (1.00-66.18) fold lower incidence of CVA compared to that of on-pump coronary artery bypass. AM, IP, PC and SM were responsible for 4.1%, 24.4%, 27.6% and 35.0% of CVA. The incidence of CVA caused by AM or IP was calculated to be 0.29/ 10,000 anesthesias. If patients undergoing cardiovascular surgery or craniotomy were excluded, the incidence of CVA caused by AM or IP was calculated to be 0.13/ 10,000 anesthesias (15/ 1,134,398 anesthesias). The overall outcome of CVA was as follows: uneventful recovery 9.8%, death within 30 post-operative days 26.0%, vegetative state 6.5%, and sequelae involving deficits in the central nervous system 52.0%. The outcome of CVA caused by AM or IP was as follows: uneventful recovery 20.0%, death within 30 post-operative days 22.9%, vegetative state 8.6%, or sequelae involving deficits in central nervous system 45.7%. Twenty-seven point six percent of reported CVA were considered to have been preventable. CONCLUSIONS: The overall incidence of CVA developing in the operating theater in Japan was reported to be 123 among 1.2 million anesthesias. The incidence was high in elderly patients, in patients with poor physical status, and in patients undergoing cardiovascular surgery. Because the prognosis of CVA developing in the operating theater was poor, clinical strategies for prevention, early detection, prompt diagnosis, and appropriate treatment of CVA should be established.     

Anesthesia machine malfunction caused by the blockade of an exhaust gas port

We report an intraoperative case of anesthesia machine (ACOMA ANESPIRATOR KMA-1300III, ACOMA Medical Industry Co., Ltd., Tokyo) malfunction. The ventilator, which had run normally on the preanesthetic inspection, suddenly went out of order showing the negative circuit pressure. This accident was caused by the obstruction of the exhaust gas port with a vinyl bag, resulting in the failure in expansion of ventilator bellows. While minute volume exceeds fresh gas flow, the bellows are replenished with gases from the exhaust gas pocket connected to both the exhaust gas port and the excess gas aspirator. Mannual ventilation could be properly carried out. Our incident led the manufacturer to provide a safety device and to issue the notice of trouble.     

Recent changes in the incidence of life-threatening events in the operating room: JSA surveys between 2001 and 2005

BACKGROUND: In Japan, the number of medical staff charged with criminal liability has been increasing since 2000, and this medico-legal trend seems to be promoting topics of medical risk management in government, academic meetings and individual hospital. A survey conducted by the Japanese Society of Anesthesiologists (JSA) has been widely accepted among JSA-certified training hospitals, and its denominator has exceeded one million since 2001. The purpose of this investigation is to examine changes in the incidence of life-threatening events in the operating theater between 2001 and 2005 based on the data of the surveys. METHODS: JSA has conducted annual surveys of life-threatening and neurological events in the operating theater by sending and collecting confidential questionnaires to all JSA certified training hospitals. Cases of life-threatening events between 2001 and 2005 were analyzed. The recovery rates ranged from 76.2% (in 2005) to 91.6% (in 2002), and the annual patient numbers available for analysis ranged from 1,051,245 (in 2005) to 1,367,790 (in 2003) during the study period. The patients with ASA PS 1 or 2 were classified as having good physical status, and those with ASA PS 3 or 4 were classified as having poor physical status. Because mortalities (within 7 postoperative days) are more common in patients with poor physical status, in emergency patients, in neonate, in the elderly, and in patients undergoing cardiovascular surgery, the mortality rate in these patients were investigated. The recovery rate from cardiac arrest without any sequelae was also investigated. The causes of events were classified as follows: totally attributable to anesthetic management (AM), mainly to intraoperative pathological events (IP), to preoperative co-morbidity (PC), and to surgical management (SM). IP consists of pulmonary thromboembolism, acute coronary syndrome, anaphylaxis and so on. The incidence of cardiac arrest and mortality are indicated per 10,000 patients. Odds ratio and 95% confidential interval are shown in comparison with the incidence in 2001 to that in 2005. RESULTS: The incidences of cardiac arrest were 6.12 in 2001, 5.79 in 2002, 5.89 in 2003, 5.09 in 2004, and 4.24/10,000 patients in 2005, respectively (odds ratio 0.69; CI 0.62-0.78). The incidences of death within 7 postoperative days due to intraoperative life-threatening events were 6.41 in 2001, 6.31 in 2002, 6.61 in 2003, 5.88 in 2004, and 4.91/10,000 patients in 2005, respectively (OR 0.77; CI 0.69-0.85). The incidences of death in patients with poor physical status (from 35.48 to 26.87/10,000 patients; OR 0.76; CI 0.66-0.86), in emergency patients (from 37.25 to 30.55/10,000 patients; OR 0.82; CI 0.72-0.93), in neonates (from 70.09 to 31.70/10,000 patients; OR 0.45; CI 0.22-0.91) and in the elderly (from 11.03 to 8.75/10,000 patients; OR 0.79; CI 0.68 to 0.92) decreased. The incidence of death in patients undergoing cardiovascular surgery ranged between 61.22 and 76.88/10,000 patients, and has not shown any significant decline. The incidences of death due to IP (from 0.65 to 0.42/10,000 patients; OR 0.64; CI 0.44-0.92), PC (from 4.14 to 3.30/10,000 patients; OR 0.80; CI 0.70-0.91) and SM (from 1.49 to 1.02/10,000 patients; OR 0.68; CI 0.54-0.87) decreased. However, the incidence of death due to AM ranged between 0.07 and 0.11/10,000 patients, and has not shown any significant decline partly because of the small number of deaths from this cause. Although recent trends in life-threatening events seemed to be favorable, the recovery rate from cardiac arrest decreased from 40.3% in 2001 to 30.7% in 2005 (OR 0.66; CI 0.51-0.84). CONCLUSIONS: The incidence of life-threatening events in the operating room and mortality due to these events seemed to have decreased during the recent five years, probably because of progress in risk management in JSA-certified training hospitals. The decrease was obvious in the recent two years. However, the results should be interpreted cautiously, because the response rate to the questionnaire in 2005 was the lowest. To confirm this trend, we should perform a follow-up survey for 2006 and continue the survey. The reasons for the deterioration in the recovery rate from cardiac arrest should also be examined.