The atrophy and changes in the cellular compositions of the thymus and spleen observed in mice subjected to short-term exposure to perfluorooctanesulfonate are high-dose phenomena mediated in part by peroxisome proliferator-activated receptor-alpha (PPARα)

We have previously shown that short-term, high-dose exposure of mice to the environmentally persistent perfluorooctanoate (PFOA) results in thymic and splenic atrophy and the attenuation of specific humoral immune responses. Here we characterize the effects of a 10-day treatment with different dietary doses (1–0.001%, w/w) of perfluorooctanesulfonate (PFOS), a similar fluorochemical, on the immune system of male C57BL/6 mice. At doses greater than 0.02%, PFOS induced clinical signs of toxicity in the animals, whereas at the concentration of 0.02%, this compound caused weight loss, hepatomegaly and atrophy of the thymus, spleen and adipose tissue without toxicity. With this latter dose, histopathological and flow-cytometric analysis revealed that (i) the thymic cortex was virtually depleted of cells; (ii) the total numbers of thymocytes and splenocytes were reduced by 84 and 43%, respectively; (iii) although all populations of thymocytes and splenocytes were smaller, the thymic CD4⁺CD8⁺ cells and the splenic B-lymphocytes were most decreased. These alterations resembled those evoked by analogous exposure to PFOA, but were less pronounced. At lower doses (less than 0.02%), PFOS induced hepatomegaly without affecting the thymus or spleen. Finally, comparison of male wild-type 129/Sv mice and the corresponding knock-outs lacking peroxisome proliferator-activated receptor-alpha (PPARα) indicated that these effects of PFOS are not strain-dependent. More importantly, hepatomegaly is independent of PPARα, the thymic changes are partially dependent on this receptor, and splenic responses are largely eliminated in its absence. Thus, immunomodulation caused by PFOS is a high-dose phenomenon partially dependent on PPARα.     

贲门癌术后存活10年以上病例分析

目的探讨影响贲门癌切除术后长期生活的因素。方法对584例贲门癌切除术后生存10年以上的病例进行回顾性分析。结果本组10年生存率为17．1％。肿瘤的病理分期、分化程度、大体类型、瘤体大小对10年生存率的影响均有统计学意义（P〈0．05）。有无淋巴结转移对10年生存率的影响有统计学意义（P〈0．01）。伴有切端癌残留、癌栓形成、肿瘤浸润浆膜、手术切除性质,以及性别、年龄、病程等对10年生存率影响无统计学意义（P〉0．05）。结论贲门癌的早期发现、早期诊断、早期切除治疗仍是提高其10年生存率的关键。切端癌残留、癌栓形成、手术切除性质等因素对10年生存率的影响尚待进一步探讨。     

原发性脾脏肿瘤25例临床分析

目的探讨原发性脾脏肿瘤的诊断和治疗。方法对我院25例原发性脾脏肿瘤患者的临床资料进行回顾性分析。结果本组除4例失访外,其余21例术后随访15个月～4年。其中良性肿瘤患者随访7例均存活;恶性肿瘤患者随访14例,生存期〈1年5例,生存期1～3年6例,生存期〉3年3例。结论B超、CT等检查是诊断原发性脾脏肿瘤的主要手段,治疗方法首选手术。     

Entirely laparoscopic radical gastrectomy for adenocarcinoma: lymph node yield and resection margins

Background  Laparoscopic assisted distal gastrectomy for adenocarcinoma has been widely reported from Japan and Korea but there are sparse data for Western patients. This study aimed to describe and compare the perioperative outcomes and pathological staging for consecutive patients who underwent laparoscopic or open gastrectomy by a single surgeon in the UK. Methods  During the period from April 2005 to May, 2007, patients with gastric adenocarcinoma were selected for open or laparoscopic resection at the discretion of the surgeon. Gastric resections for gastrointestinal stromal tumour (GIST) or benign disease were excluded. Laparoscopic gastrectomy was performed entirely laparoscopically with intracorporeal anastomosis, followed by specimen retrieval via a suprapubic incision. Results  There were 21 men and 8 women, median age 75 years (range 45–88 years), with American Anaesthesiology Association scores of 3 or 4 in 19 patients. Gastrectomy was performed laparoscopically in 18 patients (62%; total gastrectomy, 6 patients) or open in 11 patients (total gastrectomy, 7). Five laparoscopic gastrectomies were converted to open procedures, three patients had re-laparoscopy and one patient had subsequent laparotomy. As compared with open gastrectomy, laparoscopic resection had longer operation time and similar length of hospital stay. There was one postoperative mortality in each group. There was similar lymph node retrieval for laparoscopic or open resection [23 (range 10–44) versus 26 (8–95), respectively; p = 0.40], with inadequate lymphadenectomy (<15 nodes) in two laparoscopic cases and one open case. R1 resection was limited to patients with pT3 disease (laparoscopic, 4; open, 2). Conclusions  Perioperative outcomes were similar for laparoscopic or open gastrectomy. Lymphadenectomy was adequate in 89% of laparoscopic gastrectomies. pT3 tumours were at risk of noncurative resection, as described in large Western series of open gastrectomy.     

Central nervous system administration of interleukin-6 produces splenic sympathoexcitation

Interleukin-6 (IL-6) is a multifunctional cytokine that has been shown to play a pivotal role in centrally-mediated physiological responses including activation of the hypothalamic-pituitary-adrenal axis. Cerebral spinal fluid (CSF) concentrations of IL-6 are elevated in multiple pathophysiological conditions including Alzheimer's disease, autoimmune disease, and meningitis. Despite this, the effect of IL-6 on central regulation of sympathetic nerve discharge (SND) remains unknown which limits understanding of sympathetic-immune interactions in health and disease. In the present study we determined the effect of intracerebroventricular (i.c.v, lateral ventricle) administration of IL-6 on splenic SND in urethane-chloralose-anesthetized rats. A second goal was to determine if icv injected IL-6 enters the brain parenchyma and acts as a volume transmission signal to access areas of the brain involved in regulation of sympathetic nerve outflow. i.c.v administration of IL-6 (10 ng, 100 ng, and 400 ng) significantly and progressively increased splenic SND from control levels in baroreceptor-denervated Sprague-Dawley rats. Administration of 100-ng and 400-ng IL-6 resulted in significantly higher SND responses when compared to those elicited with a 10-ng dose. Sixty minutes following icv administration, fluorescently labeled IL-6 was not distributed throughout the parenchyma of the brain but was localized to the periventricular areas of the ventricular system. Brain sections counter-stained for the IL-6 receptor (IL-6R) revealed that IL-6 and the IL-6R were co-localized in periventricular areas adjoining the third ventricle. These results demonstrate that icv IL-6 administration increases splenic SND, an effect likely achieved via signaling mechanisms originating in the periventricular cells.     

The spleen's role in transplantation immunology

While graft rejection has been studied for many years, recent investigations have focused on the generation and maintenance of transplantation tolerance. This review examines the role of secondary lymphoid organs, especially the spleen, characterizes the maintenance mechanism that is key to the development of tolerance and explores the implications of new strategies for inducing tolerance in transplantation.     

Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG)

Background The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer. Patients and methods Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks. Results The median number of cycles delivered per patient was 2 (range 1–6). Two patients (9%) had ≥ 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55–9.39). Conclusions Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.     

Gastrointestinal stromal tumor of the stomach: preliminary results of preoperative evaluation with CT gastrography

Background To determine whether CT gastrography can be used as a comprehensive imaging modality for the evaluation of gastrointestinal stromal tumor (GIST) of the stomach. Methods Thirty patients with gastric GISTs were included. Using CT gastrography, two radiologists determined the morphology, location, size of the tumor, and the nearest distance from the tumor to the gastroesophageal junction or pylorus in consensus. The ability of 3D CT gastrography in dealing with surface-shaded/transparent images and virtual endoscopic images was also evaluated and compared with the results of barium study and gastroscopy, respectively. Results In regard to lesion morphology and location, almost perfect agreements (κ = 0.87 ∼ 1.00) were achieved between CT gastrography and surgery, and the difference in lesion size between CT and surgery was not statistically significant (P = 0.824). In terms of the distance from the tumor to the gastroesophageal junction or pylorus, a statistically significant difference was found between the laparoscopic and open gastric surgery groups (P < 0.001). Findings on CT gastrography were mostly similar or superior to those seen on barium study and gastroscopy. Conclusions CT gastrography can serve as a comprehensive imaging test for the preoperative evaluation of gastric GIST.     

Recurrence after laparoscopic excision of nonparasitic splenic cysts

Background

Minimally invasive treatments for nonparasitic splenic cysts are well described. Recent evidence suggests that laparoscopic splenic cystectomy is associated with high recurrence rates in children. Because these cysts are uncommon, no large series is available. We reviewed our clinical data focusing on cyst recurrences and their management.

Methods

All children who underwent laparoscopic excision of a nonparasitic splenic cyst from January 2002 to December 2006 were identified. Medical and surgical records were reviewed for perioperative details, hospital course, and outcome.

Results

Eight children (median age, 13 years; range, 7-16 years) who underwent laparoscopic splenic cystectomy were identified. The most common presenting complaint was left upper quadrant pain or mass (n = 6; 75%). Median cyst size was 13 cm (range, 4-20 cm). There were no conversions to an open technique, completion splenectomies, or perioperative complications. Cysts were identified pathologically as epidermoid (n = 6) or posttraumatic (n = 2). Median hospital stay was 1.5 days. One child required partial splenectomy because of cyst anatomy and remains recurrence-free at 12 months. Cyst recurrence occurred in 7 patients (88%) at a median of 9.4 months (range, 3-18 months) after initial surgery. Median recurrent cyst size was 5.6 cm (range, 3-11 cm). Of 7 recurrences, 4 (57%) were symptomatic. Percutaneous ultrasound-guided cyst drainage and sclerosis were performed in 2 children with symptomatic recurrences, one of whom required 4 separate interventions. There were no complications during management of cyst recurrences. Five children with recurrence (71%) have been followed conservatively and are free of morbidity at a median of 23 months (range, 8-55 months).

Conclusions

Laparoscopic excision of nonparasitic splenic cysts in children is associated with a high recurrence rate and may be insufficient treatment. Partial splenectomy may decrease recurrence rates. Conservative management of splenic cyst recurrence after laparoscopic excision is associated with good short-term outcomes. If necessary, image-guided management of symptomatic recurrences can be performed safely.