Background and Objectives: Gastrectomy causes vitamin B-12 deficiency since vitamin B-12 requires gastric acid and intrinsic factor for its absorption. Vitamin B-12 deficiency is considered to ...develop years after gastrec- tomy because of large hepatic storage. However, most gastric cancer develops after long-standing atrophic gastri- tis with vitamin B-12 malabsorption. Methods and Study Design: We have investigated vitamin B-12 status in 22 patients before gastrectomy and 53 patients after gastrectomy due to gastric cancer, also with consideration on post-gastrectomy anemia. Results: Blood vitamin B-12, folic acid, homocysteine concentrations, parameters of anemia, and dietary intake were evaluated. Percentage of patients with severe vitamin B-12 deficiency (serum vitamin B-12 < 150 pmol/L), vitamin B-12 deficiency (150 pmol/L to < 258 pmol/L) was 19.0 %, and 52.4 % re- spectively in patients gastrectomized within three years. Before gastrectomy, three and seven patients exhibited severe deficiency and deficiency, respectively. In gastrectomized patients, plasma homocysteine concentration was inversely associated with serum vitamin B-12 concentration, and vitamin B-12 deficiency- and iron deficien- cy- anemia coexisted with their mean corpuscular volume within the reference range. Conclusions: Vitamin B-12 deficiency is prevalent in patients early after and before gastrectomy. Coexistence of vitamin B-12 and iron deficiency obscures the diagnosis of post-gastrectomy anemia, and necessitates the blood vitamin B-12 measurement.
Functioning pancreaticoduodenal neuroendocrine tumors (PD-NETs) are popular in a textbook, but they are still unfamiliar to a general clinician, and delay of diagnosis or misdiagnosis has been ...reported even today. It is a consensus that sporadic functioning PD-NET is cured only by surgical resection. So, early detection and early resection is the gold standard for the treatment of functioning PD-NET. Functioning PD-NETs in patients with multiple endocrine neoplasia type 1 (MEN 1) are often multiple. You should check about MEN 1 whenever you encountered multiple PD-NET. They are diagnosed in younger age than sporadic cases. In most cases they are accompanied with numerous microscopic or macroscopic nonfunctioning P-NETs, which are potentially metastatic and the most common cause of death in MEN 1 patients.
AIM： To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS： Sixteen patients with genetically ...confirmed multiple endocrine neoplasia type 1 （MEN 1） and Zollinger-Ellison syndrome （ZES） underwent resection of both gastrinomas and duodenopancreatic neuroendocrine tumors （NETs） between 1991 and 2009. For localization of gastrinoma, selective arterial secretagogue injection test （SASI test） with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy （SRS） and other imaging methods such as computed tomography （CT） or magnetic resonance imaging （MRI）. The modus of surgery for gastrinoma has been changed over time, searching for the optimal surgery： pancreaticoduodenectomy （PD） was first performed guided by localization with the SAST test, then local resection of duodenal gastrinomas with dissection of regional lymph nodes （LR）, and recently pancreas-preserving total duodenectomy （PPTD） has been performed for multiple duodenal gastrinomas. RESULTS： Among various types of preoperative localizing methods for gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of gastrinoma was achieved in 14 of 16 patients （87.5%）; that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR （although in 2 patients （33.3%） second LR was performed for recurrence of duodenal gastri- noma）, and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic gastrinoma with duodenal gastrinoma in 2 of 16 patients （13%）, and G cell hyperplasia and/or microgastrinoma in the duodenal Brunner＇s gland was revealed in all of 7 duodenal specimens after PPTD. CONCLUSION： Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of gastrinoma in patients with MEN 1.Imamura Metal. Curative resection of gastrinoma in MEN-1
Objectives: The aim of this study was to use magnetic resonance imaging (MRI) to elucidate the site and depth of the primary abscesses associated with deep posterior anal fistulas and their extension ...patterns. Methods: We analyzed 176 consecutive patients with deep posterior anal fistulas and classified the fistulas according to whether the MRI-detected site of the primary abscess was at a superficial or a deep external anal sphincter (EAS) level. Results: The distance between the anal center and the primary abscess center was significantly shorter than the length of the EAS and radius at an angle of 45°. In addition, deep posterior anal fistulas with primary abscesses located at the deep EAS level penetrated the EAS significantly more laterally and made external openings at a significantly more lateral site than when the primary abscess was located at a superficial EAS level. Conclusions: Primary abscesses associated with deep posterior anal fistulas are located in the posterior intersphincteric space or in the EAS muscle itself, not in Courtney's space, as had previously been claimed.
In gastric cancer, lymph node metastasis is one of the major prognostic factors and forms the basis for surgical removal of local lymph nodes. Recently, several studies have demonstrated that ...overexpression of lymphangiogenic growth factor VEGF‐C or VEGF‐D induces tumor lymphangiogenesis and promotes lymphatic metastasis in mouse tumor models. We examined whether these processes could be inhibited in naturally metastatic tumors by blocking of their cognate receptor VEGFR‐3 signaling pathway. Using a mouse orthotopic gastric cancer model which has a high frequency of lymph node metastasis, we estimated lymphatic vessels in gastric cancers by immunostaining for VEGFR‐3 and other specific lymphatic markers, LYVE‐1 and prox‐1. Then we systemically administered anti‐VEGFR‐3 blocking antibodies. This treatment resulted in the inhibition of regional lymph node metastasis and reduction of lymphatic vessel density in the primary tumors. In addition, increased density of LYVE‐1‐positive lymphatic vessels of primary tumors was closely correlated with lymph node metastasis in human samples of gastric cancer. Antilymphangiogenesis by inhibiting VEGFR‐3 signaling could provide a potential strategy for the prevention of lymph node metastasis in gastric cancer.
Vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis. VEGF-C, however, is thought to stimulate the growth of lymphatic vessels because an expression of its specific ...receptor, VEGF receptor-3 (VEGFR-3), was demonstrated to be restricted to lymphatic vessels. Here we demonstrate that the inactivation of VEGFR-3 by a novel blocking monoclonal antibody (mAb) suppresses tumor growth by inhibiting the neo-angiogenesis of tumor-bearing tissues. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of the tumor-bearing tissues. Hence, VEGFR-3 is another receptor tyrosine kinase involved in tumor-induced angiogenesis. Micro-hemorrhage in the tumor-bearing tissue was the most conspicuous histologic finding specific to AFL4 mAb-treated mice. Scanning microscopy demonstrated disruptions of the endothelial lining of the postcapillary venule, probably the cause of micro-hemorrhage and the subsequent collapse of the proximal vessels. These findings suggest the involvement of VEGFR-3 in maintaining the integrity of the endothelial lining during angiogenesis. Moreover, our results suggest that the VEGF-C/VEGFR-3 pathway may serve another candidate target for cancer therapy. (Blood. 2000;96:546-553)
Background and Aim
Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes ...of palliative chemotherapy for advanced biliary tract cancer in elderly patients.
Methods
We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non‐elderly group (< 75 years old; n = 309).
Results
Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non‐elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89–1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non‐elderly group (4.3% vs 0%, P < 0.01).
Conclusions
In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non‐elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.
Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease ...has not been well studied because of a small number of patients with recurrent BTC in previous studies.
This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors.
The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels.
The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC.
We have shown that Peyer's patch (PP) first develops as a simple and even cell aggregation during embryogenesis. To investigate when and how such a simple cell aggregation forms the complex PP ...architecture, we analyzed the distribution of cells expressing IL-7R alpha (PP inducer cells), VCAM-1 (mesenchymal cells), CD11c (dendritic cells), and mature lymphocytes by whole-mount immunostaining of 17.5 days post coitus to 2 days postpartum mouse gut. Our results show that compartmentalization of PP anlagen commences at day 18.5 of gestation by clustering and subsequent follicle formation of IL-7R alpha(+), VCAM-1(+), and CD11c(+) cells. This process adds the primitive architecture of PP anlage with several follicles in which IL-7R alpha(+) cells localize in the center, while VCAM-1(+) and CD11c(+) cells localize at the fringe. This follicle formation is accompanied by the establishment of PP-specific vascular network expressing mucosal addressin cellular adhesion molecule-1. Mature B and T lymphocytes entering in the PP anlage are distributed promptly to their own target zones; B cells to the follicle and T cells to nonfollicular zones. Our analysis of scid/scid mouse indicate that the initial processes including formation of PP-specific vascular network occur in the absence of lymphocytes. These observations indicate that the basic architecture of PP is formed by a set of cell lineages assembled during the initial phase of induction of PP anlagen before entry of mature lymphocytes.
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