Lumbar posterolateral fusion inhibits sensory nerve ingrowth into punctured lumbar intervertebral discs and upregulation of CGRP immunoreactive DRG neuron innervating punctured discs in rats

Degeneration of lumbar intervertebral discs is thought to be a cause of low back pain. Studies have found that a cause of discogenic low back pain is intervertebral disc inflammation and axonal growth of afferent fibers innervating the disc. Lumbar spine fusion for chronic discogenic low back pain is considered an effective procedure. However, no study has investigated the mechanism of pain relief. We did this by applying Fluoro-Gold (FG) to the ventral aspect of the L4–L5 intervertebral discs of 40 rats. We exposed the nucleus pulposus to the annulus fibrosus in a disc punctured model. Rats were divided into 4 groups. Group A: Punctured intervertebral disc with sham posterolateral fusion (PLF) (n = 10), Group B: Punctured intervertebral disc with PLF (n = 15), Group C: Normal intervertebral disc (no puncture) with PLF (n = 10), and Group D: Normal disc (no disc puncture) with sham PLF (n = 5). Four weeks after surgery, bilateral L1–L5 dorsal root ganglia (DRGs) were stained with growth-associated protein 43 (GAP43), a marker of axonal growth, and calcitonin gene-related peptide (CGRP), a neuropeptide marker of pain. Bone union was evaluated using X-ray imaging. Of the FG-labeled neurons, the proportions of GAP43- and CGRP-immunoreactive (IR) neurons in Group A were significantly higher than in Group D (P < 0.05). The proportions of GAP43- and CGRP-IR neurons in bone union rats in Group B were significantly lower than in nonunion rats in Group B and in the rats in Group A (P < 0.05). No significant differences in GAP43- and CGRP-IR neurons were observed between bone union and nonunion rats in Group C and the rats in Group D (P > 0.05). PLF is strongly related to the downregulation of GAP43 and CGRP expression. Therefore, PLF may suppress the increase of inflammatory neuropeptides and the process of axonal growth. Moreover, these results may explain, in part, the mechanism of pain relief following lumbar spinal fusion for chronic discogenic low back pain in humans.     

Intrahepatic micrometastases around liver metastases from gastric cancer

Background/Purpose  We aimed to clarify the association between the presence of micrometastases around liver metastases from gastric cancer and the results of hepatic resection. In addition, we investigated the influence of E-cadherin and matrix metalloproteinase (MMP)-7 expression on the development of micrometastases. Methods  Micrometastases around liver metastases were examined microscopically in 31 metastatic liver tumor specimens resected from 17 patients who had undergone hepatic resection for liver metastases from gastric cancer. E-cadherin and MMP-7 expression in the primary gastric tumor, the liver metastases, and the micrometastases were examined immunohistochemically. Results  Hepatic micrometastases were present in around 48% of the liver metastases, accounting for 59% of the patients. The tumor recurrence rate in the remnant liver after hepatic resection was significantly higher, and survival significantly poorer, in patients with such micrometastases than in those without. Micrometastases tended to appear around the liver metastases that had reduced E-cadherin expression. Most of the micrometastases in the lymph ducts and sinusoids showed reduced E-cadherin expression. MMP-7 expression was not correlated with the presence of micrometastases. Conclusions  About half of the hepatic metastases from gastric cancer had seeded off micrometastases, and the presence of these micrometastases was associated with a poorer result of hepatic resection. Reduced E-cadherin expression in metastatic liver tumors may be associated with the development of micrometastases.     

Prognostic role of angiogenesis and its correlations with thymidine phosphorylase and p53 expression in ductal adenocarcinoma of the pancreas

BACKGROUND/AIMS: Currently, little information is available regarding the prognostic role of angiogenesis and its correlation with Thymidine phosphorylase (dThdPase) in ductal adenocarcinoma of the pancreas. In the present study, we aimed to evaluate whether tumor angiogenesis, dThdPase expression correlates with prognosis in patients after radical surgical treatment for ductal adenocarcinoma of the pancreas and to investigate the correlation between tumor angiogenesis and dThdPase expression. Furthermore, the role of p53 expression in tumor neovascularization was also examined in this study. METHODOLOGY: Tissue samples were taken from 32 patients with ductal adenocarcinoma of the pancreas after radical surgical treatment. Intratumoral microvessel density (IMVD) and dThdPase, p53 expression were examined immunohistochemically. RESULTS: Increased IMVD significantly correlated with the tumor size, lymph node metastasis and advanced TNM stage (p < 0.05, respectively). Furthermore, increased IMVD correlated withpoorer survival curve (p < 0.05). A significant correlation was present between IMVD and dThdPase expression (p < 0.001), while dThdPase expression did not correlate with prognosis. p53 expression correlated with prognosis, whereas no significant correlation was shown between p53 expression and IMVD in ductal adenocarcinoma of the pancreas. CONCLUSIONS: Tumor angiogenesis is associated with clinicopathological factors regarding tumor progression and may be an important prognostic factor in ductal adenocarcinoma of the pancreas. dThdPase plays an important role in tumor angiogenesis in ductal adenocarcinoma of the pancreas. Mutant p53 expression may not involve in tumor angiogenesis in ductal adenocarcinoma of the pancreas.     

Neuroendocrine carcinoma of the stomach with peripancreatic lymph node metastases successfully treated with pancreaticoduodenectomy

Neuroendocrine carcinoma of the stomach is an uncommon tumor, usually associated with highly malignant biological behavior and extremely poor prognosis. In this report, we described a case of advanced neuroendocrine carcinoma of the stomach with the peripancreatic lymph node metastases which was treated with pancreaticoduodenectomy with extended lymphadenectomy. The patient was admitted to our hospital for anemia. An upper gastrointestinal endoscopy revealed a 4x4-cm fungating tumor with its fundus locating mainly in the duodenal bulbus and extending to the gastric antrum, and tumor biopsy revealed the histological findings of adenocarcinoma. Computed tomography (CT) showed a large mass in the duodenal bulbus with regional lymph node metastases. The patient's disease was diagnosed as primary duodenal cancer with regional lymph node metastases preoperatively. During the operation, an obviously swollen lymph node on the anterior surface of the head of the pancreas 4.0 x 3.5 cm in size was found growing into the parenchyma of the pancreas head and could not be separated from the pancreas, and the swollen lymph node along the superior mesenteric vein was also hard and suspected to be a metastatic node. A pancreaticoduodenectomy with extended lymphadenectomy was performed to achieve a radical resection. Histopathologically, the origin of the primary tumor was considered as a gastric origin, and the tumor was composed of diffused small cells with a moderate mitotic index and occasional rosette formation. Immunohistochemical investigations of the neoplastic cells confirmed the tumor to be neuroendocrine carcinoma. The obvious swollen lymph node on the anterior surface of the head of the pancreas and the swollen lymph node along the superior mesenteric vein were also identified as metastatic lymph nodes. Adjuvant chemotherapy with TS-1 was administered on an out-patient basis 6 weeks after the operation. The patient is well and has now been free of symptoms of recurrence and metastasis for 8 months.     

Case of sarcomatoid carcinoma of the urinary bladder

A 57-year-old man was referred to our hospital for bladder tumor. The computed tomographic scan demonstrated an 8 cm solid mass in the posterior wall of the bladder. Cystoscopy revealed a non-papillary large bulky tumor and a necrotic tumor surface. The tumor was transurethrally resected and its histology showed sarcomatoid carcinoma composed of a urothelial cell carcinoma. Total cystectomy was performed and an ileal neobladder was constructed. He now shows no evidence of disease 43 months after the operation.