Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Previously, we identified human α1,4-N-acetylglucosaminyltransferase (α4GnT), which is responsible for the O-glycan biosynthesis and characterized αGlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt -/-mice to better understand its role in vivo. A4gnt -/-mice showed complete lack of αGlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt -/-mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced αGlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of αGlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, αGlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.
In conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.
BackgroundSolitary metastasis of a malignancy to the spleen is rare, particularly for gastric cancer. Only a few case reports have documented isolated splenic metastasis from early gastric cancer. We describe a case of splenic metastasis from early gastric cancer.Case presentationA 60-year-old man underwent a distal gastrectomy for early gastric cancer. It infiltrated the submucosa with pathological nodal involvement (pT1bN2M0, stage IIB). One year after the gastrectomy, an abdominal computed tomography scan showed a low-density lesion, 17 mm in diameter, at the upper pole of the spleen. Positron emission tomography/computed tomography showed focal accumulation of fluorine-18 fluorodeoxyglucose in the spleen without extrasplenic tumor dissemination or metastasis. We diagnosed splenic metastasis of gastric cancer, and performed a splenectomy. Histological examination confirmed moderately differentiated tubular adenocarcinoma and poorly differentiated adenocarcinoma (solid type) that was consistent with the features of the primary gastric cancer. The splenic tumor was pathologically and immunohistochemically diagnosed as a metastasis from the gastric carcinoma. More than 18 months after the splenectomy, the patient has had no evidence of recurrent gastric cancer.ConclusionWhen solitary metastasis to the spleen is suspected during the postoperative follow-up of a patient with gastric cancer, a splenectomy is a potentially effective treatment.
Oxaliplatin in combination with 5-fluorouuacil and leucovorin (FOLFOX) is one of the most commonly used first-line chemotherapies for patients with advanced or metastatic colorectal cancer. Pulmonary toxicity, including interstitial pneumonia (IP)/peumonitis, is a very rare complication. We report a case of fatal IP associated with FOLFOX therapy in a patient with metastatic rectal cancer. A 74-year-old man with rectal adenocarcinoma and associated liver metastases underwent palliative surgery and 21 cycles of modified FOLFOX6 therapy. After starting the 22nd therapy cycle, the patient developed a high fever with non-productive cough. Chest X-ray demonstrated diffuse ground-glass opacities in both lungs, and computed tomography showed severe disorder of the bilateral lung architecture. On the basis of a lymphocyte stimulation test (DLST), oxaliplatin-induced IP was diagnosed. Intravenous administration of high-dose methylprednisolone was started, but the symptoms and radiological findings were not improved. The patient died of respiratory failure 16 days after the last administration of oxaliplatin. Although IP is a rare but potentially fatal complication of oxaliplatin-based treatment in colorectal cancer patients, clinicians should pay careful attention to the clinical respiratory symptoms and radiographic findings in colorectal cancer patients receiving FOLFOX therapy.
BackgroundIt is a big topic for general thoracic surgery whether still curability can be obtained by limited resection for peripheral small-sized nodules of non-small cell lung cancer (NSCLC) in the current era of frequent computed tomography (CT) use. Accumulation of information on problematic cases would be meaningful for surgeons to select better surgical procedures.Case presentationA 69-year-old man was pointed out an enlarged 2.1-cm solid nodule on the edge of staple line of the residual right upper lobe by chest CT. He had past history of the lung cancer surgery, wedge resection of the same right upper lobe 13 years ago. The pathological findings were 1.1-cm, p-TlbN0M0, p-stage IA2-adenocarcinoma. Thereafter, he received no adjuvant therapy. This time, the trans-bronchial lung biopsy revealed adenocarcinoma. After the completion lobectomy of the residual right upper lobe, the tumor was diagnosed as adenocarcinoma consistent with recurrence of small-sized adenocarcinoma in the lung periphery developed from the cut-end because of similarities between present and previous tumors on histopathology and p53-positivity.ConclusionsWhen limited resection has been performed for small-sized NSCLC presenting solid nodule on thin-slice CT images, long-term postoperative follow-up time will be necessary for monitoring, considering the possibility of cut-end recurrence.
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