Katsuji Okui

A histopathologic study of 102 cases of intrahepatic cholangiocarcinoma: Histologic classification and modes of spreading

In our survey of 102 cases of intrahepatic cholangiocarcinoma, 71 peripheral type cases and 31 hilar type cases were observed, the former being prone to metastasize to remote organs and lymph nodes when compared with the latter. These cases were histologically classified into nine histologic types according to the predominant features and rearranged into three groups (well-differentiated, less-differentiated, and uncommon). Although most of these cases were mucin-producing adenocarcinomas with variable grades of differentiation (92 of 102; 90%), several uncommon types were also encountered (ten of 102; 10%), such as adenosquamous, squamous, mucinous, or anaplastic carcinoma. Remote organ metastases were observed more frequently in the less-differentiated group than in the well-differentiated group. In regard to intrahepatic tumor spreading, expansion via sinusoidal spaces (93%), vascular (52%) or lymphatic (18%) involvement, perineural invasion (16%), replacing growth in the bile duct (12%), and permeation in the portal connective tissue (19%) were observed. The cholangiocarcinomas with the vascular involvement presented a higher tendency of intrahepatic as well as extrahepatic metastasis. For correct diagnosis and treatment of cholangiocarcinoma, it seems to be important to possess some knowledge of these histologic types, including their variations and patterns of intrahepatic spread.

Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding

Fifteen patients with far-advanced gastric cancer were given surgical treatment followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature of 44.7 to 48.7 C, using equipment designed for treatment of cancerous peritoneal seeding as a closed circuit, and under hypothermie general anesthesia at 30 to 31 C. In nine of the 15 patients with peritoneal seeding and/or ascites, cancerous ascites was absent after this treatment. In all cases, repeated cytologie examinations of the lavage from Douglass pouch were negative. The postoperative courses were uneventful except for Patients 1 and 10, in whom slight leakage occurred. All patients were discharged and are in good health at the time of this writing, 7.2 ± 4.6 months after the treatment. The Case 4 Patient recently died in a traffic accident. In all patients, transient hepatic dysfunction and hypoproteinemia occurred after the operation. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe antitumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.

Evaluation of echographic diagnosis of rectal cancer using intrarectal ultrasonic examination

Ultrasonic examinations conducted in order to diagnose the depth of invasion and local lymph node metastases of rectal cancer. The intrarectal approach was performed preoperatively in 99 patients with rectal cancer, using either an Olympus-Aloka ultrasonic endoscopeTM (7.5 MHz) or other probes (Aloka, 7.5 MHz, 5 MHz). Through this method, intrapelvic organs were detected clearly, and hypoechoic findings due to tumors were detected in all patients. The normal rectal wall was echogenically divided into five layers, the third layer being the submucosal and the fourth layer being the proper muscle layer. In some cases, the proper muscle layer was divided into three layers in the echogram. In 79 of 88 patients, the diagnosis of depth of invasion, classified into three groups, was possible. Metastatic lymph nodes were shown as a hypoechoic round mass. In 52 of 71 patients proven to have local lymph node metastases in surgical specimens, lymph node metastases were diagnosed preoperatively. Thus, intrarectal ultrasonography provides valuable information concerning the choice of operating methods for rectal cancer.

Positive results of combined therapy of surgery and intraperitoneal hyperthermic perfusion for far-advanced gastric cancer.

To evaluate the clinical efficacy of intraperitoneal hyperthermic perfusion (IPHP) for far-advanced gastric cancer, particularly with peritoneal seeding, we investigated the survival times of 59 patients who underwent distal subtotal gastrectomy, total gastrectomy, or total gastrectomy combined with concomitant resection of some of the remaining intra-abdominal organs. In all the 30 patients given IPHP, no cancer cells were present posthyperthermically in the lavage from the Douglas pouch. The 30 patients given IPHP lived longer than the 29 patients not given IPHP (p = 0.001), with a 1-year survival rate of 80.4% in the former group compared to 34.2% in the latter. With respect to a comparison of survival time of patients with peritoneal seeding, 7 patients not given IPHP had a 6-month survival rate of 57.1% and did not survive more than 9 months, whereas 20 patients given IPHP had 1- and 2-year survival rates of 78.7% and 45.0%, respectively; here the difference was significant (p = 0.001). The IPHP and control groups without peritoneal metastasis included 10 and 22 patients, respectively, and the 1-year survival rates are 85.4% and 45.3%, respectively. The survival rates of the former exceeded those of the latter, with p = 0.015 by the generalized Wilcoxon test. Thus this combined therapy offers the promise of extended survival for patients with far-advanced gastric cancer.

Biodegradable mitomycin C microspheres given intra-arterially for inoperable hepatic cancer. With particular reference to a comparison with continuous infusion of mitomycin C and 5-fluorouracil

Thirty‐two patients with inoperable hepatic cancer underwent intra‐arterial hepatic infusion using mitomycin C (MMC) and 5‐fluorourcil (5‐FU) or intra‐arterial hepatic chemoembolization using heated albumin microspheres containing MMC with an average diameter 45 ± 8 μm. Nineteen of the 32 patients received the MMC microsphere treatment and another 13 received the conventional infusion treatment, lasting for 3.4 months. The administered doses of MMC microspheres were 11.7 ± 11.1 mg as MMC in the 12 with metastatic cancer and 6.9 ± 2.1 mg as MMC in the 7 with hepatocellular cancer (HCC). On the contrary, the 13 patients who underwent conventional infusion had average doses of MMC 34.5 ± 17.3 mg and of 5‐FU 13.4 ± 7.7 g, over 3.4 months. An objective tumor response was obtained in 13/19 (68.4%) under MMC microsphere chemoembolization, compared to 6/13 (46.2%) under the conventional infusion. The average level of CEA in the 12 with metastatic cancer, who underwent MMC microsphere therapy, dropped from 57.7 ng/ml to 16.5 ng/ml, while that in the 10 patients on conventional infusion dropped from 24.0 ng/ml to 17.4 ng/ml; that of alpha‐fetoprotein dropped in all 7 with HCC on MMC microsphere chemoembolization, compared to a fall in 1/3 on conventional infusion. With the MMC microsphere treatment, 5 patients from colorectal cancer lived for 15.6 ± 7.6 months, 2 are alive with a long life expectancy; and 7 patients from gastric or pancreatic cancer lived for only 9.3 ± 3.3 months. In case of conventional infusion, 6 patients from colorectal cancer survived for 8.6 ± 3.2 months; and 4 patients from gastric or gallbladder cancer survived for 6.0 ± 1.0 months. The MMC microsphere treatment is superior at P = 0.059 in survival duration to the conventional infusion treatment. However, much the same survival occurred in 7 on MMC microsphere chemoembolization and 3 on continuous infusion.

Effects of intra-arterially infused biodegradable microspheres containing mitomycin C

We prepared biodegradable microspheres containing about 5% mitomycin C (MMC) and of 45 ± 8 μm in diameter. These preparations were infused into the rat hepatic artery as a preclinical model of intra‐arterial infusion treatment for patients with inoperable hepatic tumor. The leaked MMC levels in the hepatic vein decreased below the assay limitation 2 hours after conventional MMC injection, whereas in the case of MMC microsphere the leaked drug levels were maintained at almost the same concentration for over 2 hours after infusion. The entrapped period of MMC microspheres within the hepatic artery was at least 2 weeks, and the necrobiotic foci due to antitumor effects of the condensed MMC released from the microspheres were observed in the area fed by these entrapped arterioles. This phenomenon was never observed in the case of conventional MMC and placebo microspheres. Intra‐arterial infusion of MMC microspheres may be a promising clinical treatment for patients with malignant hepatic tumor.

A clinical pilot study combining surgery with intraoperative pelvic hyperthermochemotherapy to prevent the local recurrence of rectal cancer

Intraoperative pelvic hyperthermochemotherapy (IOPHC) with mitomycin C (MMC) was prescribed for 14 patients with resectable advanced rectal cancer in an attempt to prevent a postoperative local recurrence. Immediately after rectal amputation and extended lymphadenectomy, IOPHC was performed using physiologic saline containing 40 micrograms/mL of MMC at 45.5 +/- 0.6 C for 90 minutes, with an apparatus devised for IOPHC. At the end of IOPHC, the esophageal temperature was 37.2 +/- 0.8 C and cooling was not required. Antitumor efficacy and complications in the IOPHC group were compared with findings in 12 rectal cancer patients who underwent surgery only within the same period of time. Operation time was not prolonged with IOPHC treatment. In cytologic examinations of the pelvic lavage just before IOPHC treatment, viable cancer cells were detected in 6 of the 14 patients but were never detected in the postoperative exudate drained from the pelvic cavity. Of the 12 patients in the control group, 2 had a local recurrence, while in the IOPHC group there was no local recurrence for 16.9 +/- 9.7 months at this writing. Postoperative complications did not differ between the groups. This IOPHC treatment is a favorable method in eradicating cancer cells for postoperative local recurrence of rectal cancer.

Stapled or manual suturing in esophagojejunostomy after total gastrectomy: A comparison of outcome in 379 patients

From January 1983 to December 1989, we performed esophagojejunostomy on 379 patients who underwent total gastrectomy for gastric cancer. A mechanical EEA stapler or conventional manual suturing was used. The clinical outcomes of 199 patients in whom stapling was used (stapler group) and 180 patients in whom manual suturing was done (manual group) were compared. Two of the 199 patients in the stapler group and 3 of the 180 patients in the manual group died of causes directly related to the anastomosis. In the stapler group, 16 stapled anastomoses were formed supradiaphragmatically, and manual suturing was done for 6 patients. The highly placed anastomosis was formed without left thoracotomy or with median sternotomy in 8 of the 16 patients in whom the stapling device was used and in 1 of the 6 patients in whom manual suturing was used. The incidence of anastomotic leakage and stenosis did not differ between the groups. Thus, the mechanical stapler facilitated the construction of a rapid, reliable esophagojejunostomic anastomosis.

Continued in vitro and in vivo release of an antitumor drug from albumin microspheres

Heated albumin microspheres with an average diameter of 45±8 μm and containing mitomycin C, released, in vitro, about 20% of this antibiotic over a 3-day period. VX-2 tumors were implanted into the hind leg of rabbits and the drug-containing microspheres were injected into the femoral artery of these animals. High levels of the drug were maintained for several hours in the tumor and growth of the tumor was inhibited considerably, compared to findings in control rabbits given the conventional mitomycin C. Half the number of the rabbits treated with our new method are alive with no evidence of tumor.

A chronic contained rupture of an abdominal aortic aneurysm complicated with severe back pain

Chronic contained rupture of an abdominal aortic aneurysm is an uncommon occurrence with the aneurysms usually small-to-moderate in size. Diagnosis may be difficult because patients present with both atypical and chronic symptoms. Pressure erosion of the lumbar spine is presumably a highly significant associated disorder, but an enhanced computed tomographic scan is the most reliable method for the correct diagnosis. We report on a 46-year-old man who developed severe back pain which was initially thought to result from spinal disease. Retrospective review of computed tomographic scans taken two years before admission revealed the beginning of the leakage of the aneurysm. Remarkably, the patient remained stable two years after the rupture.