Antitumor efficacy of a human interleukin-12 expression plasmid demonstrated in a human peripheral blood leukocyte/human lung tumor xenograft SCID mouse model.

Genes encoding the p35 and p40 subunits of human interleukin-12 (IL-12) and the bacterial aminoglycoside phosphotransferase were cloned into a mammalian expression plasmid. The resultant plasmid, pCMVIL-12neo, was used to transfect human lung tumor cell lines in vitro. Stably transfected subclones were generated and found to secrete human IL-12 for at least 10 days following a lethal dose of gamma-radiation. The ability of the IL-12--producing tumor cells to promote an antitumor response in vivo was evaluated in SCID mice co-engrafted subcutaneously with human peripheral blood lymphocytes (PBLs) and viable human lung tumor cells (SCID-Winn assay). Using this model system, it was established that IL-12 released locally into tumors by irradiated IL-12--transfected cells activated the human PBL and promoted their ability to suppress tumor development in a dose-dependent fashion. PBL subset depletion studies revealed that the antitumor effect promoted by the IL-12--modified cells was dependent on the presence of human CD8(+) T cells and, to a lesser extent, human CD56(+) natural killer cells within the xenograft. We conclude that (a) irradiated human lung tumor cells genetically modified with pCMVIL-12neo secrete bioactive human IL-12 at concentrations sufficient to promote a human lymphocyte-mediated antitumor response in the microenvironment of the xenograft, and (b) that the SCID-Winn assay provides a useful model for the preclinical evaluation of cytokine-based human immunotherapy protocols.

Spontaneous healing of pancreatic abscess after fistulization to the duodenal bulb.

A 70-year-old man was admitted to the hospital because of sudden, upper abdominal and back pain. Laboratory and image data indicated acute pancreatitis. Shortly after the admission, pancreatic and liver abscess with bacteremia developed. Antibiotic therapy seemed effective. A month later, spontaneous fistulization of the pancreatic abscess to the duodenal bulb was found by gastroduodenal fiberscopy. Injection of contrast medium into the duodenal orifice showed that the fistula was draining the abscess and that no other fistula formed from the abscess. Endoscopic retrograde cholangiopancreatogram indicated no fistula formation to the pancreatic duct. The pancreatic abscess became smaller and was not visible using computerized tomography and ultrasonography 3 months later and thereafter. Closure of the duodenal orifice was ascertained by the endoscopy. It is suggested that retrograde infection from the fistula was prevented by the single fistulization to the acidic duodenal bulb, which is not supposed to allow most bacterial growth. Pancreatic abscess usually necessitates operative treatment, even with fistulization to the alimentary tract. It seems likely that the single, small fistulization to the bulb, in addition to the lack of underlying disease and medical and nutritional support, facilitated the spontaneous healing process.

An alpha-fetoprotein producing pancreatic cystadenocarcinoma.

An autopsy case of an 83-year-old Japanese woman with pancreatic cancer with significantly elevated serum alpha-fetoprotein levels is reported. The pancreatic tumor was a mucinous cystadenocarcinoma with multiple metastasis to the liver. The immunohistochemistry for alpha-fetoprotein revealed positive reactivity in the cytoplasm of cancer cells in the primary and liver metastatic lesions. The current case is the first reported in which mucinous cystadenocarcinoma of the pancreas produced alpha-fetoprotein.

A case of polypoid cavernous hemangioma of the sigmoid colon excised by colonoscopic polypectomy.

A 28-year-old Japanese man was admitted to our institute because of sharp anal pain and a mass that prolapsed from the anus after defecation. After spinal anesthesia for emergency operation, the mass spontaneously withdrew into the anus and the pain disappeared. Surgery was postponed. Barium enema and colonoscopy revealed a pedunculated polyp in the sigmoid colon, which was removed by snare polypectomy with electrocautery. The resected polyp was granular and reddish, and measured 33 x 22 x 14 mm. Histological examination of the polyp revealed a cavernous hemangioma. Hemangioma of the colon is rare; only 52 cases have been reported in Japan. Of these patients, eight underwent endoscopic polypectomy. The present lesion is the largest thus treated that has been documented. Endoscopic polypectomy seems to be a safe and preferable procedure for the diagnosis and treatment of small, solitary polypoid hemangiomas of the colon.

Case report: silent thyroiditis developed during alpha-interferon therapy.

Alpha-interferon (IFN-alpha) was used for the treatment of chronic active hepatitis C in a 30-year-old woman who was euthyroid but had low titers of antithyroid antibodies before treatment. Two months after the initiation of IFN-alpha therapy she became thyrotoxic. She had nontender diffuse goiter. A laboratory examination revealed elevated levels of serum free thyroid hormones and a suppressed concentration of serum thyrotropin. Titers of antimicrosomal antibodies increased. The anti-thyrotropin receptor antibody was negative. A 99mTcO- scintigram of the thyroid showed reduced uptake. During the IFN therapy free thyroid-hormone levels started to decline. The IFN-alpha therapy was completed 1 month after the onset of thyrotoxicosis. Two months after the completion of the therapy the patient became euthyroid and 99mTcO- uptake was normalized. It is likely that preexisting chronic thyroiditis was exacerbated to cause silent thyroiditis during IFN-alpha therapy. None of the other 11 patients with chronic hepatitis C who had had no anti-thyroid antibodies and were treated with IFN-alpha showed anti-thyroid antibodies and thyroid dysfunction after the therapy. It is advisable to assess anti-thyroid antibodies and thyroid function in patients who are going to receive IFN-alpha treatment.

Two cases of endoscopically identified esophageal cancer of the superficial-slightly depressed type.

We experienced two cases of superficial type esophageal cancer. Case 1 was a 72-year-old man in whom endoscopic examination revealed a slightly protruded, partially reddened and faded area of irregular shape corresponding to 0-IIa + IIc (slightly depressed type) of the endoscopic classification of esophageal cancers. Macroscopically, it was a superficial, ill-defined and non-cicatrized solitary tumor measuring 2.5 x 2.4 cm in size. Histologically it was a monofocal semidifferentiated squamous cell carcinoma of a swelling type of stage 0. Case 2 was 55-year-old man. Endoscopic examination disclosed an almost roundish, smooth-surfaced, flat and dull red area corresponding to IIc (slightly depressed type). Macroscopically it was a superficial, semidefined and non-cicatrized solitary tumor measuring 1.0 x 1.0 cm in size. Histologically it was a monofocal, semidifferentiated squamous cell carcinoma of stage 0. To detect esophageal cancer at an early stage, the endoscopist needs to inspect the mucosa carefully. In case of males aged over 50, the endoscopist would be well advised to employ the dye-spraying method (Lugol staining method) at the endoscopic examination.