[Multilocular thymic cyst].

We describe a case of multilocular thymic cyst with severe acute inflammation. A 23-year-old man was admitted to our hospital with a sudden onset of chest pain and high fever. A computed tomography scan showed multilocular cystic lesion at anterior mediastinum. We resected the tumor with the thymus by median sternotomy. Macroscopically, the mediastinal mass showed thick-walled multiloculated cavities filled with turbid yellow fluid. Histological examination revealed that the tumor was a multilocular thymic cyst which is reported by Suster.

[Tension hemothorax associated with congenital pulmonary arteriovenous fistula].

We describe a case of intrapleural rupture of pulmonary arteriovenous fistula A 37-year-old woman was admitted to our hospital with a sudden onset of right chest pain. A computed tomography scan showed massive pleural effusion and tension hemothorax. Subsequently the patient went into shock. Partial resection of the lung was performed emergently. Pulmonary arteriovenous fistula is often associated with Rendu-Osler-Weber disease (ROW). Because of her brain arteriovenous malformation and family history, we could not exclude the possibility of ROW.

Regulation of mast cell differentiation studied using the diffusion chamber technique.

A homogeneous population of mast cells was obtained by culturing bone marrow cells of WBB6F1(-)+/+ mice. The proliferation of the cultured mast cells in diffusion chambers was investigated to examine whether the diffusion chamber technique was applicable for study of the regulation of mast cell proliferation. WBB6F1-W/Wv mice are genetically deficient in mast cells. When cultured mast cells of WBB6F1(-)+/+ mouse origin were directly injected into the peritoneal cavity of WBB6F1-W/Wv mice, the mast cells survived. In contrast, WBB6F1(-)+/+ mouse-derived cultured mast cells did not survive in diffusion chambers implanted in the peritoneal cavity of either WBB6F1-W/Wv or WBB6F1(-)+/+ mice. Because the coinoculation of NIH/3T3 cells supported the proliferation of mast cells in diffusion chambers, a certain type of cells in the peritoneal cavity appeared to have the same mast cell-supporting activity as NIH/3T3 cells. The magnitude of either interleukin 3-dependent or NIH/3T3 cell-dependent proliferation of mast cells in diffusion chambers was not significantly influenced by the genotype of chambers recipients (i.e., WBB6F1(-)+/+ or WBB6F1-W/Wv mice), suggesting that the previously reported inhibitory effect of mast cells on differentiation of mast cells may be mediated by direct contact between mast cells.

Inhibition of attachment between cultured mast cells and fibroblasts by phorbol 12-myristate 13-acetate and stem cell factor.

Cultured mast cells (CMC) derived from the bone marrow of mice express the receptor encoded by the W (c-kit) locus (W receptor), and the WCB6F1(+/+)-3T3 fibroblasts express the ligand encoded by the Sl locus (stem cell factor [SCF]). CMC attach to the fibroblasts through the W receptors and cell-bound SCF. We investigated the effect of phorbol 12-myristate 13-acetate (PMA) and recombinant murine SCF (rmSCF) on the attachment. PMA induced both the internalization and shedding of W receptors, whereas rmSCF induced only the internalization. Moreover, both PMA and rmSCF reduced the expression of c-kit mRNA levels in CMC. Addition of either PMA or rmSCF to the coculture of CMC and fibroblasts resulted in the inhibition of attachment. Since the magnitude of the attachment between CMC and fibroblasts may be manipulated by changing the doses of either PMA or rmSCF, the present experimental system may be useful as a model for the attachment between blood cells and stromal cells.

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction.

Recent studies have disclosed the presence of a second estrogen receptor (ER; ER-beta) in addition to a classical ER-alpha. ER-beta mRNA expression has yet to be studied in pancreatic cancers. Thus, we studied the expression of ER-alpha and ER-beta mRNA in pancreatic cancers (n=29) by real-time quantitative reverse transcriptase-polymerase chain reaction, and compared the expression levels in pancreatic cancers with those in breast cancers (n=116) which are typical estrogen-dependent tumors. Breast cancers were divided into two groups, ER-positive and ER-negative, according to the ER status determined by enzyme immunoassay. ER-alpha mRNA levels were significantly (P<0.01) higher in ER-positive (679.4+/-74.7 fmol/microg RNA) than ER-negative (159.7+/-33.4) breast cancers, and pancreatic cancers showed significantly (P<0.01) lower ER-alpha mRNA levels (17.5+/-10.0) than ER-negative breast cancers. On the other hand, ER-beta mRNA levels were significantly (P<0.01) higher in ER-negative (14.1+/-1.6) than ER-positive breast cancers (7.9+/-1.0), and pancreatic cancers showed significantly (P<0.01) higher ER-beta mRNA levels (28.1+/-5.1) than ER-negative breast cancers. Accordingly, ER-alpha/ER-beta mRNA ratios were significantly (P<0.01) lower in pancreatic cancers (0.94+/-053) than in ER-positive (203.9+/-34.5) and ER-negative (21.9+/-5.2) breast cancers. ER-beta2 mRNA variant expression was significantly (P<0.05) higher in pancreatic cancers than in ER-positive and ER-negative breast cancers, and, on the contrary, ER-beta1 mRNA variant expression was significantly (P<0.01) lower in pancreatic cancers than in ER-positive and ER-negative breast cancers. These results suggest a possibility that ER-beta (ER-beta2) plays a more important role than ER-alpha in pancreatic cancers.

Human stomach-specific gene, CA11, is down-regulated in gastric cancer.

To reveal the implication in gastric cancer pathogenesis of the novel human gene referred to as CA11, which was recently isolated by a differential display technique using normal gastric mucosa and gastric cancer tissue, we examined CA11 expression in 50 primary gastric cancers and also introduced the CA11 gene into gastric cancer cells. RNA dot blot analysis against various human organs and developmental stages demonstrated that CA11 was intensively expressed especially in normal stomach tissue. Northern blot analysis showed that expression of the CA11 gene in cancer tissue was down-regulated compared with normal tissue. Semi-quantitative RT-PCR also demonstrated that CA11 gene expression was decreased in 41 out of 50 (82%) of the gastric cancer tissues, when compared with normal stomach tissues, while no relationship was found between CA11 expression and various clinicopathological characteristics including histological type, depth of invasion, lymph node metastasis, and clinical stage. Immunohistochemical analysis with anti CA11 antibody showed that CA11-positive staining was observed in the surface regions of normal gastric epithelium, but was found faintly or not at all in cancer tissues. CA11 transfected MKN28 cells also displayed a marked decrease in the number of colony formations when compared to double normal controls. These findings suggest that the loss of CA11 expression in gastric tissues may play an important role in gastric carcinogenesis.

Practical grouping of positive lymph nodes in pancreatic head cancer treated by an extended pancreatectomy.

BACKGROUND: Until recently long-term survival has not been expected when at least one positive node was detected at any site in pancreatic head cancer treated by conventional pancreatectomy. However, even when nodal involvement is seen, there has been an increasing number of long-term survivors after extended pancreatectomy in which a wide range of lymphatic and connective tissues were cleared. Thus the purpose of the present study was to establish a practical rational grouping of positive lymph nodes in pancreatic head cancer treated by extended pancreatectomy. METHODS: In 81 patients who tolerated extended pancreatectomy for cancer of the pancreatic head, a mean of 56 +/- 23 (range, 28 to 89) lymph nodes in each patient were examined under a microscope to determine the presence or absence of cancer. They were classified anatomically into 14 lymph node groups, and the incidence, distribution, and number of positive nodes were examined. A simplified grouping was made on the basis of the histologic findings and was checked against long-term survival rates. RESULTS: Nodal involvement was detected in 59 (73%) of 81 patients, and positive nodes were more commonly observed in the posterior pancreaticoduodenal (PPD), superior mesenteric (SM), and anterior pancreaticoduodenal (APD) groups than in the 11 other groups (p < 0.05). The PPD, APD, and SM groups offered the sole sites of nodal involvement with incidence levels of 23%, 17%, and 6%, respectively, whereas none of the 11 other groups did. Thus patients were classified into four groups: (a), negative in all 14 lymph node groups (n = 22); (b), positive but limited to the PPD/APD groups (n = 14); (c), also positive in the SM group, but negative in the 11 other groups (n = 13); and (d), also positive in at least one of the 11 other groups (n = 32). This classification was associated well with the 5-year survival rate: 59% in group (a), 53% in group (b), 15% in group (c), and 0% in group (d) [p < 0.05; group (b) versus group (c)]. Also this grouping associated well with the total number of positive nodes (p < 0.05). The 5-year survival rate in patients with one to three positive nodes was 47% and was more than 6% in patients with four to seven positive nodes (p < 0.05). CONCLUSIONS: In the clinicopathologic staging of the lymphatic spread from carcinoma of the pancreatic head, the PPD and APD groups were considered the first stations of lymphatic metastasis, whereas the 12 other groups-including the SM group-were categorized as second or more distant stations.

K-ras point mutation in the nerve plexuses around the superior mesenteric artery in resectable adenocarcinoma of the pancreatic head: distribution pattern and related factors.

BACKGROUND: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer. HYPOTHESIS: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA. DESIGN: Prospective consecutive series. SETTING: Cancer center hospital. PATIENTS AND METHODS: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method. RESULTS: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification. CONCLUSIONS: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.

Characterization of c-kit-positive neurons in the dorsal root ganglion of mouse.

Previously, we showed that c-kit receptor tyrosine kinase is expressed by a subpopulation of dorsal root ganglion (DRG) neurons, and that the ligand for the c-kit receptor, stem cell factor (SCF), induces the neurite outgrowth and supports the survival of these neurons in culture [16]. However, it is unknown which class of DRG neurons express c-kit receptor and which factor regulates differentiation and survival of c-kit-positive neurons. In the present study, we attempted to characterize c-kit positive neurons in the mouse DRG. The c-kit-positive neurons were small or medium in size, and 44% of these neurons contained substance P. Central fibers of the c-kit-positive neurons terminated in laminae I and II of the gray matter of the spinal cord. These results suggest that c-kit-positive neurons in the DRG belong to a functional subpopulation. The c-kit receptor protein was presented on the membrane of processes and growth cones in neurons. When DRG cells of embryonic day 15.5 or 17.5 were cultured, the survival of c-kit-positive neurons was supported by SCF, nerve growth factor (NGF) or leukemia inhibitory factor. SCF and NGF synergistically supported the survival of c-kit-positive neurons at submaximal concentrations. c-kit-positive DRG neurons from neonatal mice survived without addition of any factor in culture, suggesting that the requirement for trophic support in c-kit-positive neurons changes during development.

Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients.

AIM: The purpose of the present study was to evaluate the usefulness of gamma probe and ultrasonographically-guided fine-needle aspiration biopsy (FNAB) in the pre-operative detection of sentinel node (SN) metastasis in breast cancer patients. METHODS: Sentinel node biopsy (SNB) was performed in patients with stage I or II breast cancer with clinically negative nodes using dye and radio-isotope. Axillas of 60 patients in whom a hot spot was detected by gamma probe were examined by ultrasonography. Pre-operative diagnosis of SN metastasis by gamma probe and ultrasonographically-guided FNAB was compared with the histological results of SN. RESULTS: The sensitivity, specificity and overall accuracy of ultrasonography in the diagnosis of SN metastasis were 50.0%, 92.1% and 76.7%, respectively. SNs were visualized by ultrasonography in 29 of 60 patients. Of 14 patients with positive results by ultrasonography, four had positive and two had negative cytology. The combination of ultrasonography and ultrasonographically-guided FNAB for visualized nodes had a sensitivity of 78.5%, specificity of 93.3% and overall accuracy of 86.2%. Blind FNAB in the hot spot was not useful in the detection of SN metastasis in patients whose SNs failed to be detected by ultrasonography. CONCLUSIONS: Gamma probe and ultrasonographically-guided FNAB is a potentially useful method for pre-operative detection of SN metastasis. In patients with positive SNs, SNB is not indicated and complete axillary lymph-node dissection can be performed as a primary procedure.

Intraoperative cytodiagnosis for detecting a minute invasion of the portal vein during pancreatoduodenectomy for adenocarcinoma of the pancreatic head.

During pancreatoduodenectomy for adenocarcinoma of the pancreatic head, we frequently encountered cases in which the superior mesenteric-portal venous confluence (SMPVC) was involved with cancer. With regard to the indication of the concomitant SMPVC resection, as suggested by recent papers, a better long-term outcome would be expected if the cancer invasions were limited to the tunica adventitia or media of the SMPVC wall. Since this raised fears whether such a small SMPVC invasion was always detectable by macroscopic inspection alone, we have performed an intraoperative cytology on the touch smear of the exposed SMPVC wall for 23 patients with pancreatic head cancer. All of their SMPVCs were separated from the pancreatic head and appeared to be intact at a macroscopic level. As a result of the cytologic examination, however, 7 patients (30%) were newly diagnosed as having cancer cells on the SMPVC wall, and they received an additional resection of the SMPVC. Postoperative histology indicated that cancer invasion into the SMPVC wall was present in 6 of the 7 patients, and that the cancer invasions were limited in the tunica adventitia in 5 patients and to the tunica media in 1 patient. Thus, in order not to miss the chance of cure by SMPVC resection, our intraoperative cytology on the touch smear of the SMPVC is worth performing more actively on the macroscopically intact-looking SMPVC during resection of pancreatic cancer.

Development of mast cells and basophils: processes and regulation mechanisms.

Mast cells and basophils are offspring of the multipotential hematopoietic stem cell. Although mast cells sometimes are misunderstood as basophils that have invaded connective or mucosal tissue, these two kinds of basophilic cells are distinguishable by morphology and surface antigenicity. Developmental processes of mast cells and basophils are different. Basophils complete their differentiation within the bone marrow, but precursors of mast cells leave the bone marrow, invade connective or mucosal tissue, proliferate, and differentiate into mast cells. The mechanisms regulating development are different between mast cells and basophils. Both T cell-dependent and fibroblast-dependent mechanisms are involved in the development of rodent mast cells, but only the fibroblast-dependent mechanism is known for development of human mast cells and only the T cell-dependent mechanism for the development of basophils of both rodents and humans. The most important cytokine for the T cell-dependent mechanism appears to be interleukin-3, whereas for the fibroblast-dependent mechanism it appears to be the ligand for the c-kit receptor (ie, stem cell factor).

Crystalline light-chain deposition and amyloidosis in the thyroid gland and kidneys of a patient with myeloma.

A 48-year-old Japanese woman died of multiple myeloma (lambda light-chain type) with chronic renal failure. Histological examination revealed deposition of a homogeneous substance and crystals in the kidneys and thyroid gland. The homogeneous substance was stained with Congo red after permanganate treatment but did not stain with antibody to amyloid A protein, and it was recognized as AL-type amyloid. Crystals were not stained with Congo red, but crystals were stained with antibody to the lambda light chain. Since AL-type amyloid is considered to be derived from a myeloma light chain, the present case showed two different types of deposition, both of which were derived from the same myeloma protein.

Comparison of computed tomography and pathologic examination for evaluation of response of primary lung cancer to neoadjuvant therapy.

Twenty-four patients (nine with squamous cell carcinoma, 14 with adenocarcinoma, and one with large cell carcinoma) underwent neoadjuvant therapy followed by surgical resection. The authors studied changes in tumor size, shape, and contrast enhancement on computed tomography (CT), and compared them with results of pathologic examination of surgical specimens. The size of tumors on CT was evaluated according to the criteria of the World Health Organization. Surgical specimens were evaluated histologically on the basis of the area of viable cancer cells. Of 14 patients considered to have a partial response on the basis of World Health Organization criteria, five had pathologic changes of complete response. After therapy, the residual tumors in these five patients showed irregular shapes with concave tumor margins on CT images and no enhancement. The authors found that CT size criteria tended to underestimate the therapeutic effect demonstrated by pathologic examination. On the basis of these results, the authors propose three CT criteria for complete response: 1) more than 50% size reduction, 2) a change in tumor morphologic features from round or oval to irregular after neoadjuvant therapy, and 3) disappearance of contrast enhancement.

Brushing cytology for the diagnosis of gastric cancer involving the cardia or the lower esophagus.

In 173 patients with gastric cancer involving the cardia or the lower esophagus, endoscopic biopsy and/or brushing cytology were utilized in establishing the diagnosis microscopically. Biopsy was positive in 132 of 170 patients (77.0%) while brushing was positive in 78 of 93 patients (83.8%). However, a combined use of biopsy and brushing yielded a higher diagnostic accuracy of 88.0 per cent. Further, endoscopic findings of the lower esophagus or the cardial orifice and diagnostic yields of the two methods were correlated. In patients with mucosal elevation, thick fold or a tight cardial stenosis as a pattern of esophageal involvement by gastric cancer on esophagoscopy, supplementary application of brushing increased diagnostic accuracy approximately 20 per cent compared to that of biopsy alone. It is concluded that brushing cytology should be utilized more frequently in gastric cancer involving the cardia to the lower esophagus, especially in the three types of esophageal involvement mentioned above.

Endoscopic cytology of the esophagus, stomach and pancreas.

Cytology and biopsy under direct vision using a fiberscope as microscopic diagnostic procedures for carcinoma of the esophagus and stomach were described, and results of cytology were evaluated as compared with the results of biopsy. The diagnostic accuracy of brushing cytology under direct vision using a fiberscope was 97% in 116 cases of esophageal carcinoma and 78% both in 119 patients with carcinoma of the gastric cardia and in 63 patients with gastric carcinoma exclusive of the cardia. The diagnostic accuracy for cytology of pancreatic juice collected by cannulation in 36 patients with carcinoma of the pancreas was 56%: 79% for carcinoma of the head of the pancreas, but only 35% for carcinoma of the body and/or tail. For the esophagus and stomach, the diagnostic accuracy of direct vision biopsy has become almost as high as with cytology. As such biopsies are easily performed, esophagogastric cytology has become in our clinics a supplementary routine to the biopsy, and is done in a limited number of cases in which the biopsy failed or was not appropriate. However, cytology of the pancreas, in which biopsy is difficult, is important as the only microscopic diagnostic procedure. There, the development of newer instruments and the improvement of techniques of cell collecting are required, as is the development of expertise in the interpretation of cells from pancreatic carcinoma, in which the diagnostic accuracy is still relatively low.

The diagnosis of pancreatic cancer by pancreatic juice cytology.

Cytologic examination of pancreatic juice collected during cannulation was performed on 105 patients. Positive results were obtained in 23 of 44 cases (52.3%) of carcinoma of the pancreas. Cytologic specimens were collected by direct suction, washing with saline, aspiration after secretin stimulation and brushing. Washing with saline (63.2%) and aspiration after secretin stimulation (51.3%) gave higher positive results than did the other two methods. Positive results when obtained in carcinoma of the head in 12 of 17 cases (70.6%) and in carcinoma of the body and tail in 9 of 24 cases (37.5%). The results were better in carcinoma of the head, and it is necessary to further improve the method of collection in carcinoma of the body and tail.

Strial dysfunction in a melanocyte deficient mutant rat (Ws/Ws rat).

A homozygous mutant rat at the white spotting (Ws) locus showing a deficiency of melanocytes has recently been found (4, 5). The function and morphology of the inner ear of the Ws/Ws rat were examined by auditory brainstem response (ABR), endocochlear DC potential (EP), and electron microscopy. The mean ABR threshold of the Ws/Ws rat was significantly higher than that of the control +/+ rat. Most Ws/Ws rats showed no or very little EP. In electron microscopy, the stria vascularis of the Ws/Ws rat proved to be very thin and flat with poor interdigitation of marginal cells, and absence of intermediate cells. The organ of Corti appeared to be intact in both the +/+ rat and the Ws/Ws rat. These electrophysiological and morphological findings suggest that the Ws/Ws rat suffered from severe hearing loss caused by strial dysfunction.

Use of endoscopic laser in gastroenterology.

In this presentation we report the current use of endoscopic laser in gastroenterology in Japan with the results of a nation-wide survey and our own experience with more than 100 cases. Nd:YAG laser (photocoagulative therapy) and argon dye laser with hematoporphyrin derivative (photodynamic therapy) were most commonly used in digestive endoscopy, and were investigated as new modalities of cancer therapy and detection. By November 1985, 1588 of gastrointestinal (GI) cancers had been treated in Japan by endoscopic lasers, either as curative or palliative treatment in Japan. Endoscopic laser therapy is "used for" pre-cancerous lesions and early gastric cancer in high risk surgical patients. The Nd:YAG laser at high energy provides a new approach to the palliative treatment, such as relief of neoplastic obstruction in the advanced stage of GI cancers.

[A case of recurrent esophageal cavernous hemangioma increasing rapidly after surgery].

A 40-year-old female was referred to our hospital for dysphagia. A hemangioma measuring 5 x 2.5 x 2.5 cm was revealed as a round defect by esophagography and was partially cystic on CT and MRI. Through a neck incision, the esophageal wall on the tumor side was initially opened. The tumor partially adhered to the esophageal wall, but was dissected from the esophageal wall and then resected easily. Microscopic examination of tumor revealed cavernous hemagioma. Thirty days after the initial surgery, the recurrent tumor was detected in the pharynx and increased rapidly. Then a second operation was performed. The tumor was completely resected by mucosectomy including normal esophageal mucosa. Recurrence was caused by residual cystic wall of the hemangioma adhering to the esophageal mucosa after the first procedure.