Shigeo Ohki

Results of aggressive resection of lung metastases from colorectal carcinoma detected by intensive follow-up.

AbstractPURPOSE: Although outcome of resection for colorectal carcinoma has improved, about 30 percent of patients develop metastatic lesions. Small pulmonary metastases 1 cm or less in diameter now can be detected by diagnostic tests including chest radiography and computed tomography. We evaluated results of our strategy for intensive follow-up after resection of colorectal cancer and aggressive resection of lung metastases disclosed by these periodic examinations. METHODS: Our follow-up program for lung metastasis includes a serum carcinoembryonic antigen assay every two months and chest radiography every six months. Surgical resection of lung metastases was performed if the primary and any nonpulmonary metastases had been controlled, lung metastases numbered four or fewer, and pulmonary functional reserve was adequate. Standard operation for lung metastasis was lobectomy, and lymph node dissection was added in cases of tumor size over 3 cm. Forty-two patients underwent 50 lung resections for metastatic colorectal cancer between 1992 and 1999. Long-term survival was assessed in terms of clinical variables. RESULTS: Overall five-year survival rate after resection of lung metastases from colorectal cancer was 63.7 percent. Variables significantly affecting postthoracotomy survival were primary tumor histology, number of nodules, and disease-free interval up to appearance of the lung metastases, and primary tumor histology was an independent prognostic factor. CONCLUSION: Intensive follow-up for lung metastases after resection of colorectal cancer and aggressive resection improved postoperative survival rate. Patients with well-differentiated adenocarcinoma of primary tumor, a solitary metastatic nodule, and disease-free interval of at least two years after initial surgery are likely to be long-term survivors.

Outcome of Total Pelvic Exenteration for Primary Rectal Cancer

AbstractPURPOSE: This retrospective study identifies the clinicopathologic factors (age, gender, size of tumor, location, tumor stage, lymph node metastasis, histologic differentiation, and adjuvant therapies) that are useful in predicting long-term survival in patients undergoing total pelvic exenteration for advanced primary rectal cancer. METHODS: We reviewed the medical records of 71 patients with stage T3 or T4 primary rectal cancer who underwent a curative total pelvic exenteration. The effects of various clinical variables on long-term survival were analyzed. RESULTS: The postoperative mortality, hospital death, and morbidity rates were 1.4, 4.2, and 66.2 percent, respectively. The overall five-year survival rate after total pelvic exenteration was 54.1 percent. The five-year survival rate was 65.7 percent for patients with T3 lesions and 39 percent for patients with T4 lesions. A univariate analysis showed that postoperative survival was affected by age, tumor stage, and lymph node metastasis, while a multivariate analysis showed that age and lymph node metastasis were independent prognostic factors. CONCLUSION: Total pelvic exenteration may enable long-term survival in younger patients with stage T3 or T4 primary rectal cancer and little or no lymph node metastasis.

VEGF receptor antisense therapy inhibits angiogenesis and peritoneal dissemination of human gastric cancer in nude mice.

The efficacy of a phosphorothioate antisense oligonucleotide (ASO) for KDR/Flk-1 (KDR/Flk-1-ASO), an endothelial cell–specific vascular endothelial growth factor (VEGF) receptor, was investigated on the peritoneal dissemination and angiogenesis of a human gastric cancer cell line in nude mice. Green fluorescent protein (GFP)–transduced NUGC-4 (NUGC-4-GFP) human gastric cancer cells were implanted into the peritoneal cavity of nude mice. KDR/Flk-1-ASO, -SO, or phosphate-buffered saline was administrated from days 7 to 14, 200 μg/mouse, once a day. The mice were sacrificed on day 28. Disseminated peritoneal tumor nodules expressing GFP were visualized by fluorescence microscopy. KDR/Flk-1-ASO significantly decreased the extent of peritoneal dissemination of the tumors. The number of cells undergoing apoptosis was significantly increased in the KDR/Flk-1-ASO–treated tumors. Microvessel density was significantly reduced in the KDR/Flk-1-ASO–treated tumor nodules. The KDR/Flk-1 antisense strategy, therefore, decreases tumor dissemination apparently by inhibiting angiogenesis.

Anisakidosis: a cause of intestinal obstruction from eating sushi

We report a case of strangulating small bowel obstruction in a 60-yr-old Japanese woman caused by anisakidosis (previously known as anisakiasis). With the increasing popularity of Japanese cuisine such as sushi in the United States, the incidence of anisakidosis is expected to increase. Intestinal anisakidosis can now be treated temporarily, but this condition may cause a serious obstruction afterwards, as evidenced by this particular case. Over 13,500 cases were reviewed in both the Japanese and English literature, and we discuss the prevention of anisakidosis without negatively altering the taste of the raw fish.

Amphiregulin Is a Promising Prognostic Marker for Liver Metastases of Colorectal Cancer

Purpose: Aberrant activation of epidermal growth factor receptors (EGFR/HER1) by ligand stimulation or heterodimerization with human epidermal growth factor 2 (HER2) is considered to play an important role in the development of colorectal carcinoma. Amphiregulin (AR) is a ligand of EGFR that might be related to the development and progression of gastrointestinal tumors. The aim of this study was to determine the AR, EGFR, and HER2 protein expression levels and to evaluate their prognostic relevance to the clinical course of colorectal cancer. Experimental Design: The AR, EGFR, and HER2 protein levels in primary tumors of colorectal cancer (n = 106) were examined using immunohistochemistry. Metastatic sites in liver specimens (n = 16) were also analyzed in the same manner. Results: Thirteen (81.6%) metastatic lesions of the liver stained positive for AR. Among the primary lesions of colorectal cancer, 58 (54.7%) stained positive for AR, 13 (12.3%) stained positive for EGFR, and 5 (4.7%) stained positive for HER2. When the relationships between each protein expression level and the clinicopathologic factors were examined, only the AR expression level was significantly related to liver metastasis (P = 0.0296). A multivariate analysis of liver metastasis proved that AR expression was an independent prognostic factor of liver metastasis from colorectal cancer (P = 0.0217). Conclusions: AR expression in primary lesions of colorectal cancer is an important predictive marker of liver metastasis.

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.

Right hepatic lobectomy and removal of inferior vena caval tumor embolus in a patient with hepatocellular carcinoma, using veno-venous bypass while preserving perfusion in the remnant liver: A case report

We describe a successful hepatectomy and the removal of a tumor embolus in a 43-year-old woman with hepatocellular carcinoma occupying the right lobe extending to the right branch of the portal vein and the inferior vena cava (IVC). Intraoperative echography revealed the tumor embolus in the IVC to originate from the main tumor via the right inferior hepatic vein, which extended cephalad from the confluence of the right hepatic vein to the IVC. Right hepatc lobectomy was performed via the anterior approach. Using femoro-axillary veno-venous bypass, we opened the IVC at the root of the inferior right hepatic vein to remove the tumor embolus after oblique clamping of the IVC between the right and middle hepatic veins was carried out to preserve perfusion in the remnant liver. Preserving perfusion in the remmant liver in radical hepatectomy for hepatocellular carcinoma with tumor embolism in the IVC appears to be a safe and advantageous technique in patients with poor liver reserve.

Recent Advance of Autonomic Nerve Preserving Operation for Rectal Cancer.

われわれは自律神経温存術を排尿機能と男性性機能 (勃起と射精) の維持を目的とする自律神経全温存術と排尿機能のみの維持を目的とする骨盤神経叢部分温存術の2つの分けている. これらの術式について図示し述べた. 全温存術で射精機能が維持されるためには腰部交感神経が温存されなければならない. 腰部交感神経は下腸間膜動脈IMA根部に接しているものと離れているものがありIMAを切断する前にtapingして温存する必要がある. 部分温存術ではS2, S3, S4から出現する骨盤内臓神経をあらかじめtapingし癌の下縁の高さまで神経を切除して直腸周囲組織を切除しリンパ節を郭清する. このような方法で自律神経温存術を行ったところ局所再発率は1.9%(2/104) であった. 術後射精機能は91%(70歳以下男性, 全温存例) に維持された.

Pelvic Exenteration for Primary Rectal Carcinoma.

教室で1974年より1991年までに骨盤内臓全摘術を施行し組織学的に治癒切除となった進行直腸癌58例の治療成績と, 治療成績の向上のための骨盤内持続温熱腹膜灌流法, 肝動注, 門注, 内腸骨動静脈合併切除, 仙骨合併切除などを併用した骨盤内臓全摘術9例の治療成績を検討した.骨盤内臓全摘術後の累積生存率は1年91.1%, 3年76.8%, 5年67.1%であった.直死, 入院死亡を除く56例中18例 (32.1%) に再発が見られ, その再発型式は局所再発が8例, 肝転移が4例に見られた.局所再発は深達度がa2以上の例またはリンパ節転移陽性例で高率であった.また, 肝転移は上部直腸の例や深達度a2以上のリンパ節転移陽性例で多かった.また骨盤内持続温熱腹膜灌流法, 肝動注, 門注を併用した骨盤内臓全摘治癒手術の5例では最長16か月の観察期間であるが現在まで再発を認めておらず, 本治療は高度進行直腸癌治療成績の向上に有用と思われた.

Clinical studies on recurrence of colorectal cancer.

大腸癌根治手術後の再発の防止および早期発見による治療成績の向上を目的として治癒手術後3年以上経過例における再発について検討を行った. 再発は415例中145例 (34.9%) にみられ約80%は2年以内, 約90%は3年以内にみられた. 再発形式は結腸癌では肝再発が半数をしめ, 直腸癌では局所再発が最も高頻度であった. 再発後5年生存例は3例のみであり, 再発死亡例129例の平均生存期間は11.6ヵ月であった. carcinoembryonic antigen, computed tomographyの導入により特に肝再発の切除率の向上がみられ, 再発巣の切除により生存期間が延長したと考えられる症例もあり, 腫瘍マーカー測定や画像診断などによる定期的なフォローアップを行い早期に再発を診断することが重要であると考えられた.