Influence of differences in tumor vascularity upon the effects of hyperthermia

Summary Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.     

Mechanism of testicular atrophy induced by di-n-butyl phthalate in rats. Part 1

Repeated oral doses of di-n-butyl phthalate (DBP) to male rats caused a decrease in testicular fructose and glucose and a sloughing of the germ cells on the first day of treatment. On day 2, more severe sloughing was seen and was accompanied by decreases in testicular iron and zinc levels and increases in the level of inositol and cholesterols. The sloughing was followed by atrophy, accompanied by dissociation of the germ cells from the Sertoli cells and reduction of triglycerides, cholesterols and phospholipids containing choline and ethanolamine residues in the testis.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

A new method for monitoring the cerebrovascular response to acetazolamide using 99mTc-DTPA-HSA.

We developed a new method for monitoring the cerebrovascular response to acetazolamide using technetium-99m diethylenetriaminepentaacetic acid human serum albumin (99mTc-DTPA-HSA). We infused 740 M Bq (20 mCi) of 99mTc-DTPA-HSA intravenously and carried out dynamic scanning of the anterior view of the head for 50 minutes. Ten minutes after the start of scanning, 1,000 mg of acetazolamide was injected intravenously. In three normal volunteers, the radioactivity in brain increased for an average of 8 minutes after the injection of acetazolamide and then remained relatively stable. The average of dilatation index [(peak count/the count just before acetazolamide injection-1)x 100] was 16.1. Our method enabled us to observe vasodilation caused by acetazolamide straight, and may be of value in assessing cerebral perfusion reserve easily and quantitatively.     

Phase I study of a recombinant gamma interferon (S-6810)

A phase I study of a recombinant gamma interferon (S-6810) was conducted in a cooperative study involving 11 institutions. S-6810 was administered at doses of 2, 4, 8, 12, 32 and 64 X 10(6) U/m2 by one-hour infusion for 5 consecutive days. A total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills occurred in about 80% of patients. The incidences of other toxicities were fatigue in 50%, gastrointestinal toxicities in 30-40%, and changes in hepatic enzymes and hematologic toxicities in 20-30%. Dose-limiting factors were judged to be hypotension, leukopenia and central nervous toxicity. Maximum tolerated dose was 64 X 10(6) U/m2 and an optimal dose for phase II study was considered to be 6 X 10(6) U/m2 by daily chronic schedule. Blood concentration was highest at the end of infusion, and then decreased rapidly with a biphasic curve. The peak concentrations were elevated by escalation of doses. A partial response was observed in a patient with mycosis fungoides.     

Objective definition and measurement method of ground-glass opacity for planning limited resection in patients with clinical stage IA adenocarcinoma of the lung

Objective: The standard operation for patients with stage IA lung adenocarcinoma is considered to be a lobectomy. Recently, some researchers have reported that patients with tumors showing greater proportions of ground-glass opacity (GGO) at computed tomography (CT) could be candidates for limited resection, because of its less aggressive nature. However, the lack of a precise definition or standard measuring method of GGO prevents its general use as an index for planning limited resection. Therefore, we attempted to define GGO based on CT number and measured it more objectively. Methods: Between 1998 and 2001, 90 patients with clinical stage IA adenocarcinoma, who underwent standard or intentional limited resection and whose images of chest high-resolution CT were preserved in Digital Imaging and Communications in Medicine (DICOM) format, constituted the study population. The tumor shadow seen on the solid window (WL, −160 HU; WW, 2 HU) was regarded as the central solid area of the tumor seen on the lung window, and GGO was defined as the whole tumor area with the exception of the central solid area. Each area was measured using Scion Image (Scion Corp., Frederick, MD). We analyzed the relationship between the proportion of GGO and both of pathologic findings and recurrence. Results: Among the 90 tumors, 31 (34.4%) were calculated to have a GGO area greater than or equal to 50%. Of these, 27 (87%) tumors were bronchioloalveolar carcinoma. Lymphatic and vascular invasions, or nodal involvement were found only in patients with a smaller proportion of GGO (<50%) (P<0.05). During the follow-up period (median 36 months), recurrences occurred in eight patients who were diagnosed as having tumors showing smaller proportion of GGO (<50%). Conclusions: Tumors with a greater proportion of GGO measured by our method are thought to have a less invasive nature. Our objective measuring method of GGO could be useful for future multicenter trials to elucidate the value of limited resection for clinical stage IA adenocarcinoma based on the proportion of GGO.     

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION METHOD FOR LARGE COLORECTAL TUMORS

The goal of endoscopic mucosal resection (EMR) is to allow the endoscopist to obtain tissue or resect lesions not previously amenable to standard biopsy or excisional techniques and to remove malignant lesions without open surgery. In this article, we describe the results of conventional EMR and EMR using an insulation‐tipped (IT) electrosurgical knife (submucosal dissection method) for large colorectal mucosal neoplasms and discuss the problems and future prospects of these procedures. At present, conventional EMR is much more feasible than EMR using IT‐knife from the perspectives of time, money, complication, and organ preservation. However, larger lesions tend to be resected in a piecemeal fashion; and it is difficult to confirm whether EMR has been complete. For accurate histopathological assessment of the resected specimen en bloc EMR is desirable although further experience is needed to establish its safety and efficacy. Further improvements of in EMR with special knife techniques are required to simply and safely remove large colorectal neoplasms.     

The male reproductive function in patients with spinal cord injury

Seminal findings and blood hormone levels were studied for evaluating the male reproductive function in patients with spinal cord injury. The patients were divided into 3 groups, namely, 18 patients with complete injury, 5 patients with incomplete injury and 3 patients with dyspermatism. The number of sperms, the rate of movement and rate of deformation were measured for semen obtained by forced ejaculation. The number of sperms was kept at a relatively high level in the three groups, while the rate of movement fell off in all of the three groups. The rate of deformation was highest in the patients with complete injury and lowest in the patients with dyspermatism. As for blood hormone levels, LH, FSH and Testosterone (hereinafter referred to as TES) were determined by the RIA. The cases were classified into those in the acute stage and those in the chronic stage 3 months after sustaining injury for a comparative study. The subjects consisted of 27 cases in the acute stage and 47 cases in the chronic stage. For 8 patients in the acute stage, the blood hormone levels were determined even in the chronic stage and follow-up observations were made on the changes in the levels. The FSH level was low in both stages, while LH and TES tended to increase in the chronic stage. Particularly, the TES level was elevated in all the cases in the follow-up observations made in 8 patients. From the results mentioned above, transient disturbance of the interstitial function is suggested as the mechanism of male gonadal disturbance due to spinal cord injury.     

Reduced-intensity unrelated cord blood transplantation for patients with advanced malignant lymphoma.

We report the results of reduced-intensity unrelated cord blood transplantation (RI-UCBT) in patients with advanced malignant lymphoma. Twenty patients (median age, 46.5 years; range, 27-66 years) underwent RI-UCBT with a preparative regimen consisting of fludarabine 125 mg/m2 , melphalan 80 mg/m 2 , and 4 Gy of total body irradiation. The median infused total cell dose was 2.75 x 10(7)/kg (range, 2.3-3.4 x 10(7)/kg). Graft-versus-host disease (GVHD) prophylaxis was composed of cyclosporine or tacrolimus alone. Fifteen patients achieved primary neutrophil engraftment after a median of 20 days. Eight patients developed grade II to IV acute GVHD, and 2 developed chronic GVHD. Of the 16 patients with evaluable disease, 10 achieved a complete response. Primary disease recurred in 1 patient, and transplant-related mortality within 100 days occurred in 8 of 20 patients. The estimated 1-year probability of progression-free survival was 50%. These data suggest that RI-UCBT is a feasible option for patients with refractory lymphoma who lack an HLA-matched donor.     

Catalase, a Specific Antigen in the Feces of Human Subjects Infected with Helicobacter pylori

Recently, we reported the production of three new monoclonal antibodies with high specificity for a Helicobacter pylori antigen suitable for diagnosis of H. pylori infection. The aim of the present study was to identify the antigen recognized by these monoclonal antibodies concerning both H. pylori and the feces of human subjects infected with H. pylori. The cellular antigen was purified from an H. pylori cell extract by immunoaffinity column chromatography with the monoclonal antibody as a ligand. The amino-terminal amino acid sequences (eight residues) of the purified antigen and H. pylori catalase were the same. The molecular weights of native and subunit, specific catalase activity, and UV and visible spectra of the purified antigen were in good agreement with those of H. pylori catalase. The human fecal antigens were purified from two fecal samples of two H. pylori-positive subjects by ammonium sulfate precipitation, CM-Sephadex C₅₀ chromatography, and the same immunoaffinity chromatography used for the H. pylori cellular antigen. The fecal antigens had catalase activity. The amino-terminal amino acid sequences (five residues) of the human fecal antigen and H. pylori catalase were the same. The monoclonal antibodies reacted with the native cellular antigen, but did not react with the denatured antigen, human catalase, and bovine catalase. The results show that the target antigen of the monoclonal antibodies is native H. pylori catalase and that the monoclonal antibodies are able to specifically detect the antigen, which exists in an intact form, retaining the catalase activity in human feces.