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A 26-year-old man was admitted to our hospital with dyspnea, fever, and weight loss. A chest X-ray showed multiple tumor shadows, and a computed tomography (CT) scan showed swelling of the mediastinal and hilar lymph nodes, a mass in the retroperitoneum, and an embolus in the inferior vena cava. A biopsy from the left cervical lymph node revealeda poorly differentiated adenocarcinoma. Metastatic lung cancer was suspected, but in spite of the examinations, its primary site was unknown. Serum alfa-fetoprotein(AFP)was slightly elevated, but an AFP stain of the tumor was negative. The patient's respiratory failure rapidly worsened, and therefore, additional examinations could not be performed. The patient received chemotherapy with carboplatin and paclitaxel. His condition improved, but the tumor increased in size after 5 courses of chemotherapy. He received chemotherapy with docetaxel as second-line treatment, but it was not effective. The third-line chemotherapy regimen with carboplatin and gemcitabine was effective. In total, he received 7 lines of chemotherapy, and he lived for approximately 12 months since receiving the first chemotherapy regimen. After he died, we were able to perform OCT-4 immunohistochemistry on a tumor biopsy specimen from the lymph node, which came back positive for OCT-4. Therefore, we made a final diagnosis of extragonadal germ cell cancer syndrome.

We report patients with advanced Stage IV gastric cancer responding to chemotherapy with S-1 or UFT. Case 1: The patient was a 59-year-old man with Stage IV gastric cancer because of CY 1. After surgery, chemotherapy with S-1 (100 mg/body/day) was performed for one year and 11 months. At present, 5 years and 5 months after surgery, this patient shows no signs of tumor recurrence. Case 2: The patient was a 68-year-old woman with Stage IV gastric cancer because of P 1. She was treated with 200 mg/day of UFT for one year and 9 months. At present, 5 years after surgery, she shows no signs of tumor recurrence. We considered that the longterm survival of such patients is attributable to chemotherapy with S-1 or UFT. The OPRT activity of the two cases was high, so chemotherapy with S-1 or UFT was thought to be effective for them.

We report a patient with advanced stage IV gastric cancer treated by chemotherapy for over two years. The patient was a 69-year-old man with paraaortic lymph node metastasis of gastric cancer. He underwent a distal gastrectomy in non-curative resection. After surgery, chemotherapy with TS-1 (100 mg/body/day) was performed. At 7 months after surgery, progression of lymph node metastasis in porta hepatis was recognized, and paclitaxel was administered at a weekly dose of 80 mg/m(2) for 3 weeks followed by one week rest. He remained stable for 12 months under paclitaxel treatment. At 26 months after surgery, progression of lymph node metastasis in porta hepatis was recognized again, and CPT-11 was administered at a bi-weekly dose of 80 mg/m(2). Although the patient died two years seven months after surgery, the chemotherapy with sequential administration of TS-1, paclitaxel and CPT-11 was thought to be effective for advanced gastric cancer.

Background: In the West, the incidence of adenocarcinoma of the cardia or esophagogastric junction (EGJ) is increasing. This carcinoma is variously defined, however, and it contains heterogeneous tumors. In Japan, the frequency of this carcinoma is low, and little is known about it. We studied small esophagogastric junctional adenocarcinoma to determine its characteristics in Japanese patients., Methods: Fifty-four patients with Siewert type II junctional adenocarcinoma (with tumors <<4 cm in maximum diameter) were studied. The carcinomas were classified into two types: tumors straddling the EGJ (EGJ-type) and tumors occurring entirely below the EGJ (bEGJ-type). Characteristics of the tumors and surrounding mucosae were evaluated. Phenotypic expression of mucin, p53 overexpression, and Helicobacter pylori infection were investigated histologically and immunohistochemically., Results: Twenty-three (43%) patients had EGJ-type and 31 (57%) had bEGJ-type carcinomas. The ratio of advanced cancers was significantly higher in EGJ-type. Some between-group similarities and differences existed in histological type, mucin phenotype, and p53 protein overexpression, but they were not statistically significant. In the mucosa surrounding EGJ-type tumors vs bEGJ-type tumors, oxyntic glands were significantly better preserved, gastric intestinal metaplasia occurred significantly less frequently, and the H. pylori infection rate was lower. Barrett's metaplasia was seen in only 2 patients, with the EGJ-type., Conclusion: EGJ-type and bEGJ-type adenocarcinomas have different background mucosa of the stomach. EGJ-type has less atrophy of the oxyntic glands and less intestinal metaplasia in the stomach. This type appears to be the Western-type junctional adenocarcinoma that is still rare in Japan. Many cases of advanced junctional adenocarcinoma in Japan are of subjunctional origin.

Objective: To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer., Summary Background Data: The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy., Methods: This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence., Results: Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence., Conclusions: Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Objectives: To analyze the lung-nodule interfaces on small peripheral pulmonary nodules (<2 cm) in thin-section CT (HRCT) images with fractal analysis., Methods: Thin-section CT images from 70 patients with bronchogenic carcinomas (61 adenocarcinomas and 9 squamous cell carcinomas) and 47 patients with benign pulmonary nodules (23 hamartomas, 13 organizing pneumonias, and 11 tuberculomas) were used. For calculation of fractal dimensions (FDs), the authors used a box-counting method for binary- and gray-scale images of nodules. FD(two-dimensional [2D]) was an FD obtained from the binary image, and FD(three-dimensional [3D]) was an FD obtained from the gray-scale image., Results: The FD(2D)s of hamartomas were smaller than those of other nodules ( < 0.05). The FD(3D)s obtained from the gray-scale images of organizing pneumonias and tuberculomas were greater than those of bronchogenic carcinomas ( < 0.0001) and hamartomas ( < 0.0001). In bronchogenic carcinomas, FD(3D)s of adenocarcinomas were greater than those of squamous cell carcinomas ( < 0.05)., Conclusions: Fractal dimensions reflect the characteristics of the lung-nodule interfaces of small peripheral pulmonary nodules. The FD(2D)s revealed the irregularities of the contours. On the other hand, FD(3D)s revealed the complexities of the heterogeneous textures. With use of FD(2D) and FD(3D), it may be possible to distinguish bronchogenic carcinomas from benign pulmonary nodules. Moreover, FD(3D) may make it possible to distinguish between adenocarcinomas and squamous cell carcinomas.

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.

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.

Objective: The purpose of this study was to determine whether thin-section CT could be used to differentiate small localized bronchioloalveolar carcinoma from peripheral adenocarcinoma having a bronchioloalveolar (replacement) growth pattern of alveolar lining cells and from adenocarcinoma not having a replacement growth pattern on the basis of the extent of ground-glass opacity revealed by thin-section CT., Materials and Methods: One hundred twenty-four small, surgically resected, peripheral adenocarcinomas from 119 patients (67 men and 52 women; mean age, 60 years) were studied. Lesion diameters were 0.4-2.0 cm (median, 1.5 cm). The extent of ground-glass opacity within lesions on preoperative thin-section CT was reviewed retrospectively by three thoracic radiologists. On the basis of replacement growth of alveolar lining cells, small adenocarcinomas were classified histologically as localized bronchioloalveolar carcinomas (n = 42) or as adenocarcinomas with (n = 53) or without (n = 29) a replacement growth pattern of alveolar lining cells., Results: The percentage of lesions that had ground-glass opacity was significantly greater in localized bronchioloalveolar carcinomas (mean, 56.7%+/-33.0%) than in adenocarcinomas with a replacement growth pattern (mean, 26.3%+/-25.3%, p < .001) or in adenocarcinomas without a replacement growth pattern (mean, 8.3%+/-4.7%, p < .001)., Conclusion: Determination of the ground-glass opacity area in each tumor as revealed on thin-section CT was useful for differentiating small localized bronchioloalveolar carcinomas from small adenocarcinomas not having a replacement growth pattern.

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.

Background: Cathepsin D, an aspartic lysosomal proteinase, has been described to be closely associated with tumor progression and prognosis in some human malignancies. The purpose of this study was to determine clinicopathological and prognostic significance of cathepsin D expression in lung adenocarcinoma., Methods: Expression of cathepsin D in 152 lung adenocarcinoma patients was immunohistochemically studied using the antihuman cathepsin D antibody., Results: Eighty patients (53%) showed negative immunoreactivities in tumor cells. The cathepsin D-positive patients (72 patients, 47%) were divided into two subgroups; granular type expression (48 patients, 31%) with its polarized expression mainly in the luminal side of the cytoplasm of tumor cells and basal type expression (24 patients, 16%) with its polarized expression mainly in the basal or infranuclear side of the cytoplasm. Patients with basal type expression showed significantly more marked scar formation (P = 0.042), and especially among the patients with stage I disease, those with basal type tended to show poorer prognosis (P = 0.071) than the others. Cathepsin D was also expressed in stromal cells within the tumor tissues, and 86 patients (57%) with moderate to massively infiltrating cathepsin D-positive stromal cells showed a lower grade of differentiation (P = 0.005) and higher scar grade (P = 0.0003) than those with few cathepsin D-positive stromal cells. Cathepsin D status in stromal cells was significantly associated with prognosis (P = 0.014), and in a multivariate analysis, its expression status in stomal cells was marginally an independent prognostic factor only among the stage I patients., Conclusions: In determining significance of cathepsin D expression in this disease, it is important to consider separately its expression cell type and its polarization pattern in tumor cells within the tumor tissue. How ever, only cathepsin D status in stromal cells within the tumor tissue is a marginal marker influencing prognosis among stage I patients.

A 58-year-old woman who was inoperable because of S3 (pancreas and colon) and P1 at the initial operation was treated with UFT, ADM and MMC at a dosage of 242.7 g, 418 mg and 166 mg, respectively. After the chemotherapy (2 years and 6 months from initial operation), a second look operation revealed that a tumor was localized in the submucosal layer and there were no lymph node metastases. Thus, it could be resected radically. Until now, various methods of chemotherapy for unresectable gastric cancer have been reported, and many cases of CR contained fluoropyrimidine derivates. In the case under study, combination chemotherapy containing UFT was performed with good results.

This report describes the case of a 74-year-old female, who had been admitted to hospital because of epigastralgia and appetite loss. An ultrasonogram and a CT scan of the abdomen revealed a remarkable lymph node metastasis. Through an upper gastrointestinal tract (UGI) X-ray, a Borrmann III type gastric carcinoma was detected. Under endoscopic guidance, a gastric and a lymph node specimen were taken and biopsied, revealing a keratinous, well-differentiated squamous cell carcinoma and a poorly differentiated adenocarcinoma, leading to a diagnosis of a primary gastric adenosquamous carcinoma with a remarkable lymphnode metastasis. After chemotherapy, a CT scan, a UGI X-ray, and an endoscopic examination revealed distinct tumor reduction.