Three-Dimensional Study of the Terminal Portion in Sprague-Dawley Rat Ejaculatory Ducts.

In mammals, a pair of ejaculatory ducts exists in the urethra at the seminal colliculus. The detailed anatomical structures of the distal end of the ejaculatory ducts of Sprague-Dawley rats were investigated by the computer-assisted three-dimensional reconstruction analysis using light-microscopic serial sections. A three-dimensional reconstruction revealed that in adult rats, the ejaculatory sinus pair consists of two parts: the cranial section - a compartment region composed of a fusion of the ampullary gland duct and the seminal vesicle duct, and the caudal section - a grooved region composed of a long slitlike ejaculatory ostium that extends into the urethra on both sides of the seminal colliculus. But the sphincter structure was not observed. The long axis of the compartment region was approximately 58 µm in length, and that of the groove region was approximately 495 µm. Although many epithelial glands ducts were distributed throughout the ejaculatory sinuses, the prostate and coagulation gland ducts did not open in these sinuses. The urethra was composed of transitional epithelium, while the ejaculatory sinuses were composed of single to stratified cuboidal epithelium. The ejaculatory ducts continued to the ejaculatory ostium in male adult Sprague-Dawley rat were composed of the seminal vesicle ducts received the ampullary gland ducts.

Clinical pilot studies on pre-operative hyperthermic tumour ablation for advanced breast carcinoma using an 8 MHz radiofrequency heating device.

The multimodality treatment approach for advanced breast cancer provides survival advantages with decreased locoregional and distant recurrences, but these intensive anti-tumour treatments cause severe myelosuppression. Thus, in this study, the usefulness of pre-operative anti-tumour treatment without myelosuppression was investigated. Nine patients with advanced breast carcinoma underwent pre-operative hyperthermic tumour ablation (HTA) using an 8 MHz radiofrequency (RF) heating device (Thermotron RF-8) combined with a grounded needle electrode. The patients had a mean age of 58.3+/-13.9 years and included four patients with stage IIIA, two with stage IIIB and three with stage IV cancer. The target temperature was over 50 degrees C. They tolerated pre-operative HTA therapy well with no early or late complications. The initial mean tumour size was 122.1+/-71.5 cm3 and the post-HTA tumour size was 82.2+/-63.4 cm3; the reduction rate was significant (p = 0.000 293). After the pre-operative HTA, all patients underwent surgery with Level III nodal extirpation. Post-operatively, no locoregional recurrence was observed. Microscopic examination of the primary focus showed complete coagulation necrosis expanding for a diameter of 3.5-5.0 cm. Taken together, the pre-operative HTA was a safe, well-tolerated and effective treatment, achieving tumour reduction as well as complete coagulation necrosis that resulted in a large volume of destruction in breast cancer tissue.

Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma.

BACKGROUND: The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence, even when a curative gastrectomy is performed, because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal-invaded focus. In an attempt to prevent peritoneal recurrence, intraperitoneal hyperthermic chemoperfusion (IHCP) treatment was combined with aggressive surgery. METHODS: Between March 1987 and December 1996, 141 gastric carcinoma patients with macroscopic serosal invasion were allocated randomly to 2 groups. Seventy-one patients underwent IHCP combined with surgery (IHCP group) and the remaining 70 patients underwent surgery alone (control group). IHCP was performed just after gastric resection and alimentary tract reconstruction under general anesthesia along with systemic hyperthermia. RESULTS: Postoperative complications were reported in 2 of the 71 patients in the IHCP group and in 2 of the 70 patients in the control group. The peritoneal recurrence rate in the IHCP group was significantly decreased (P = 0.0000847) compared with that in the control group. The 2-year, 4-year, and 8-year survival rates for the IHCP group were 88%, 76%, and 62%, respectively, whereas those for the control group were 77%, 58%, and 49%, respectively. The IHCP group thus reaped a significant survival benefit (P = 0.0362) compared with the control group. CONCLUSIONS: Although this study was conducted randomly for a small number of patients, compared with the control group, the IHCP group had a high survival rate and better prognosis.

Histologic evaluation of preventive measures for scald injury on the peritoneo-serosal surface due to intraoperative hyperthermic chemoperfusion for patients with gastric cancer and peritoneal metastasis.

To histologically assess the preventive efficacy of cimetidine against scald injury on the peritoneo-serosal surface during intraperitoneal hyperthermic chemoperfusion (IHCP) for advanced gastric cancer, a randomized histologic study using cimetidine, a histamine H2-receptor antagonist, was performed for 20 patients with advanced or recurrent gastric cancer and peritoneal metastasis. Cimetidine 50 mg/kg was administered intravenously to 10 patients just prior to the IHCP (cimetidine group), and the remaining 10 patients underwent the IHCP without cimetidine (control group). The background factors and IHCP treatments of these two groups were nearly the same. Although the antitumour efficacy of the IHCP was not histologically different between the two groups, the histological analysis revealed that the peritoneo-serosal surface in the cimetidine group was protected against scald injury, compared with the control group. This finding suggests that pre-IHCP cimetidine is of great benefit for protecting the peritoneo-serosal surface from scald injury due to IHCP.

Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery.

BACKGROUND: Peritoneal carcinomatosis from gastric carcinoma has a very poor prognosis. The purpose of this study was to evaluate the efficacy of intraperitoneal hyperthermic chemoperfusion (IHCP) in advanced gastric carcinoma patients with peritoneal carcinomatosis. METHODS: IHCP combined with aggressive surgery was performed in 48 gastric carcinoma patients with peritoneal carcinomatosis; 18 gastric carcinoma patients with peritoneal carcinomatosis serving as controls were treated with surgery alone. RESULTS: The survival period was extended for the 48 patients who underwent surgery plus IHCP compared with the control patients (P = 0.00167). Of the 29 patients with peritoneal carcinomatosis in the upper abdominal cavity, the 21 patients treated with IHCP and surgery had survival periods superior to those of the 8 patients treated by surgery alone (P = 0.000817). The 5-year survival rate of the 18 IHCP patients with countable metastases in the entire cavity was 41.6%, whereas the 50% survival duration of the control group was 110 days. Nineteen patients with numerous metastases in the entire cavity died within 673 days, regardless of whether or not IHCP was used. CONCLUSIONS: Peritoneal carcinomatosis is not a disease beyond treatment. IHCP treatment combined with extensive surgery provides an effective and practical method of treating this disease entity.

Clinicopathologic characteristics of gastric cancer patients with cancer infiltration at surgical margin at gastrectomy.

Although curative surgery is desirable in patients with gastric cancer, tumors adjacent to the esophagogastric and/or gastroduodenal junctions present surgeons with some difficulty in estimating whether or not the lesion has infiltrated beyond the surgical margin. We report herein a retrospective analysis with respect to the clinicopathologic features of the primary lesion and margin positivity for tumor cells. Between 1982 and 1993, 861 gastric cancer patients underwent gastrectomy in our clinics. Of these, 340 had early cancer and the remaining 521 advanced cancer. Cancer infiltration at the surgical margin was determined macroscopically in the fresh resected specimen; re-resection was carried out immediately for positive cases and, subsequently, a rapid histologic examination at the newly-incised edge was carried out intraoperatively. Of the 340 patients with early cancer. 15 (4.4%) had a positive surgical margin which was directly resected successfully. Of the 521 patients with advanced cancer, 73 (14%) had a positive surgical margin and 28 of them had a microscopically negative surgical edge after re-resection; however, 8 others had a positive result at the newly-excised edge after re-resection, and the remaining 37 could not undergo re-resection because of their poor general condition and/or because the tumor had spread to other sites. The positive rate for the final surgical margin was 5.2% (45/861 patients). All of the patients with a positive margin and early cancer had a superficial or excavative type lesion, and 76.7% (56/73 patients) of those with advanced cancer had Borrmann's III or IV type lesion. These findings suggest that in such patients with a tumor adjacent to the esophagogastric and/or gastroduodenal junctions, particular attention should be paid to Borrmann's III or IV lesions in advanced cancer and to superficial or excavated type lesions in early cancer in order to reduce the frequency of positive surgical margin. Additionally, an immediate histologic examination after re-resection is extremely important.

Survival time and prevention of side effects of intraperitoneal hyperthermic perfusion with mitomycin C combined with surgery for patients with advanced gastric cancer.

In an attempt to prevent postoperative intraperitoneal recurrence in patients with advanced gastric cancer and consequently to improve survival time, we treated patients with intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C (MMC) combined with surgery. There were 60 patients with advanced gastric cancer who were treated with IPHP (long-term study) group, and the survival of this group was compared with the outcome in 52 patients with advanced gastric cancer treated with surgery alone (control group). To avoid or diminish side effects derived from scald injury of the peritoneal surface due to IPHP, 50 mg/kg of cimetidine was given intravenously just before administration of IPHP. For prophylaxis of anastomotic leakage, duodenostomy using a Foley catheter was performed. The 60 patients who were treated with IPHP lived longer than the 52 patients in the control group (p = 0.000610). The 3 year survival rate was 45 percent for the former compared with 16 percent for the latter. The intravenous administration of cimetidine just prior to IPHP protected the peritoneoserosal surface from scald injury, even though the heated perfusate exposure was at 44.3-46.3 degrees C for 2 hours. Because the intraabdominal pressure within the duodenum and jejunum was decompressed postoperatively through catheter duodenostomy and the peritoneoserosal surface was protected from scald injury caused by IPHP, anastomotic leakage in the study group was nil. Therefore, IPHP treatment plus aggressive surgery combined with pre-IPHP cimetidine administration are indicated for patients with advanced gastric cancer. The side effects of IPHP and postoperative morbidity can thus be reduced and a favorable outcome obtained.

Clinical outcome of intraoperative pelvic hyperthermochemotherapy for patients with Dukes' C rectal cancer.

In attempts to prevent local recurrence after curative resection for rectal cancer, intraoperative pelvic hyperthermochemotherapy (IOPHC) was prescribed for 27 patients with Dukes' C cancer. The procedures used were as follows: immediately after amputation or resection of the rectum with extended lymphadenectomy, the pelvic cavity was filled with physiological saline containing 40 micrograms/ml mitomycin C, which was warmed at 45 degrees C for 90 min with an apparatus devised for IOPHC. Thirty-five patients who underwent surgery alone for Dukes' C rectal cancer within the same period served as controls. There was a local recurrence in three patients in the IOPHC group (11.1%), and in 13 in the control group (37.1%). With regard to hepatic or pulmonary metastasis, there was no difference between the two groups. There was no morbidity in the IOPHC treatment except for a large volume of exudate from the pelvic cavity. Thus, IOPHC can be considered as one option for limiting local recurrence after surgical resection of an advanced rectal cancer.

[Pelvic hyperthermochemotherapy combined with surgery for rectal cancer].

In an attempt to prevent local recurrence, intraoperative pelvic hyperthermochemotherapy (IOPHC) was performed in combination with curative surgery for rectal cancer. One hundred twenty-three patients were divided into four groups: A, 8 patients without nodal involvement (n0) and given IOPHC; B, 22 with nodal involvement (n+) and given IOPHC; C, 47 n0 and no IOPHC; D, 46 n (+) and no IOPHC. Local recurrence developed in one patient in group A (12.5%), 3 in group B (13.6%), 5 in Group C (10.6%), and 16 in Group D (34.8%), respectively. Thus, the rate of local recurrence in group B was low compared to that of Group D, even through there was no statistical difference (p = 0.11). IOPHC may be one option for limiting local recurrence after surgical resection of rectal cancer.

Clinicopathologic characteristics and survival of elderly patients with gastric cancer.

From 1980 to 1991, Japanese patients aged over 49 years with gastric cancer underwent gastric resection in our hospitals. For various studies, two groups, 35 patients over 79 years (advanced age group) and 884 patients aged 50-79 years (mature age group) were prepared. A retrospective study was done with special reference to clinicopathological features and the prognosis. There were no differences in clinicopathological characteristics between the two groups, except for operative procedures and the size, histology and vascular involvement of the primary tumor. The survival rate for the advanced age group was higher than that for the mature age group, with a significant difference at p = 0.00556. However, the postoperative morbidity rate was 48.6% in the advanced age group compared with 5.1% in the mature age group. The most frequent complications were respiratory-related, that is, atelectasis, pneumonia or aspiration pneumonia. Based on these data, advanced age is not a contraindication for resection of a gastric cancer, but patients with serious pulmonary and/or cardiac diseases would not be candidates.

Comparative clinicopathologic features of early gastric cancer in young and older patients.

BACKGROUND: The clinicopathologic features of advanced gastric cancer have been analyzed in young or older patients; however, with regard to early gastric cancer, it remains unknown whether the features differ between young and older patients. Reported here is an analysis of clinicopathologic characteristics in young and in older patients. METHODS: This study is based on a retrospective review of 25 patients less than 40 years of age with early gastric cancer and of 64 patients more than 70 years of age with early gastric cancer. These patients were treated from 1977 through 1991. RESULTS: Because in the older group there were early double cancers in three patients and quadruple cancers in one, 70 early cancers were present in these 64 patients. Although the young group included a larger percentage of women, the ratio of mucosal cancer to submucosal and the incidence of nodal metastasis did not differ between the groups. Poorly differentiated adenocarcinoma was detected in 13 (52%) of the 25 younger patients, whereas in the older group it was present in 6 cancers (8.6%) alone. The number of metastatic nodes and extent of nodal metastasis were more severe in the young group, but survival rates did not differ between the groups. The depressed type of lesion was present in all patients in the young group, whereas it was only 41 of 70 cancers in the older group. CONCLUSIONS: These findings suggest that early gastric cancer in young adults has aggressive features as based on the histologic pattern, in particular with cancer invasion into the submucosal layer. For these patients nodal extirpation and postoperative adjuvant chemotherapy should be performed in an attempt to prevent lymphatic or hematogenic metastases.

Hyperthermia-induced antitumor activity in human gastric cancer cells serially transplanted into nude mice.

Hyperthermia-induced antitumor activity was assessed histopathologically and findings related to transplantation of human gastric cancer into nude mice were examined. Fragments of human gastric cancer were incubated at 37 degrees C to 47 degrees C for various durations of time, then were evaluated either histologically or with regard to delay in tumor growth and the rates of transplantation into nude mice. Fragments exposed to 39 degrees C for 30 min to 120 min and 41 degrees C for 30 min did not differ from findings in the controls concerning tumor growth and transplantability. In the case of 41 degrees C for 60 min or more, the rates of transplantation decreased significantly and there was a delay in tumor growth. At 43 degrees C for 120 min, 45 degrees C for 30 and 60 min, and 47 degrees C for 15 to 60 min, transplantability was nil. In the groups with a delay in tumor growth, there were irreversible changes in nucleic and cytoplasmic components, and in 6 groups with no evidence of transplantability, complete destruction of the glandular structure, pyknosis and karyorrhexis as well as disappearance of the cytoplasm occurred in almost all cases. Thus, the thermal dose of 43 degrees C for 120 min seems to be the minimally effective one for hyperthermia-induced tumoricidal activity.

Relation between clinical and histologic outcome of intraperitoneal hyperthermic perfusion for patients with gastric cancer and peritoneal metastasis.

In 15 patients with refractory gastric cancer and peritoneal metastasis, the relationship among histologic outcome of intraperitoneal hyperthermic perfusion (IPHP), extent of peritoneal metastasis, and cause of death was studied. The IPHP treatment did not kill all the gastric cancer cells which had penetrated deeply into subperitoneal layers. In contrast, gastric cancer cells in the abdominal effusion and/or lavage vanished. Three patients with peritoneal metastasis, deeply invaded and spread all over the peritoneum, died of peritoneal recurrence and 1 died of pericardial metastasis. In the remaining 11 patients with a lesser extent of peritoneal metastasis, 5 are living without recurrence and among the other 6, 4 died of recurrence of the disease and 1 died of other causes.