Pharmacokinetics of intraperitoneally instilled aminophylline, terbutaline and tobramycin in pigs

Introduction: Venous catheters are sometimes difficult or even impossible to insert and may also be associated with serious complications. This study was carried out to investigate whether intraperitoneal administration of drugs may be an alternative to the intravenous route in patients with limited vascular access.
Materials and methods: Three drugs commonly in use in clinical practise, aminophylline, terbutaline and tobramycin, were administered to pigs intravenously and intraperitoneally in small volumes. Serum concentrations were analysed over a period of 6 h and pharmacokinetic key variables for each drug were calculated.
Results: Aminophylline (theophylline), terbutaline and tobramycin were absorbed from the peritoneal space and into systemic circulation. For theophylline, the concentration/time profiles after intraperitoneal and after intravenous administration were almost identical, and the intraperitoneal bioavailability was calculated to 0.94. For terbutaline and tobramycin, the intraperitoneal absorption was delayed without any initial peak. Moreover, the intraperitoneal bioavailability was lower than for theophylline (0.71 and 0.65, respectively).
Conclusion: The pharmacokinetic properties after intraperitoneal administration differed among the three drugs, but the results are encouraging and provide a basis for further investigation in humans.     

Ovarian and peritoneal psammocarcinoma: Results of a multicenter study on 25 patients

PurposePsammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers.Patients and methodsAll consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed.ResultsTwenty-five patients were identified. The median age was 53 years [range 17–78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (n = 13) and 56% postoperatively (n = 14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0–33]. Eighty-four percent had a complete cytoreductive surgery through digestive (n = 7), spleen (n = 3), pancreas (n = 1) resections and/or multiple peritonectomies (n = 11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2–194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (n = 16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis.ConclusionComplete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.     

Meconium peritonitis,intraperitoneal calcifications and cystic fibrosis

Twelve cases of meconium peritonitis were retrospectively reviewed in this study. Five of these patients had cystic fibrosis. Of the patients with cystic fibrosis, intraperitoneal calcifications were present in three (60%) and two (40%) had none. All seven patients (100%) who had abconium peritonitis without cystic fibrosis had abdominal calcifications. There results indicate that the presence of intraperitoneal calcification does not exclude the diagnosis of cystic fibrosis and that the absence of calcification favors cystic fibrosis. However, a review of the literature indicates the absence of calcification is merely of clue and not definitive as to the etiology of the meconium peritonitis.     

Pharmacokinetics of recombinant human erythropoietin in children treated with continuous ambulatory peritoneal dialysis

In children treated by continuous ambulatory peritoneal dialysis (CAPD) renal anaemia is preferably treated by intraperitoneal administration of erythropoietin, since subcutaneous administration is painful and frightening for the child. Pharmacokinetics of erythropoietin were studied in three groups of children treated by CAPD. In group subcutaneous (SC) (n=5) erythropoietin was administered subcutaneously, whereas in group intraperitoneal 1 (IP1) (n=8) and intraperitoneal 2 (IP2) (n=8) erythropoietin was given intraperitoneally during a 12-h dwell. Group IP1 received erythropoietin in 20 ml/kg of dialysis fluid, while in group IP2 the hormone was added to only 50 ml of dialysate, irrespective of body weight. The median area under the curve (AUC) was 4064 mU·h/ml (range 2647–24357) in group SC, 1698 (570–5514) in group IP1 and 3577 (1225–6555) in group IP2. In comparison to group SC the AUC was significantly lower in group IP1 (Wilcoxon;P=0.02). The difference between group SC and group IP2 was not statistically significant.In children on CAPD the resorption of erythropoietin after intraperitoneal administration, measured as AUC, is similar to subcutaneous administration, when erythropoietin is administered in 50 ml of dialysate. The dose needed to treat renal anaemia with erythropoietin administered intraperitoneally this way will have to be established in a therapeutic study.     

Intraperitoneal Cytokine Productions and Their Relationship to Peritoneal Sepsis and Systemic Inflammatory Markers in Patients With Inflammatory Bowel Disease

PURPOSE This prospective, blinded study was designed to assess intraperitoneal cytokine productions and their relationship to clinical presentations and systemic inflammatory markers in patients with inflammatory bowel disease.METHODS Fifty patients who required abdominal surgery for active inflammatory bowel disease (ulcerative colitis, 27; and Crohns disease, 23) were investigated. Interleukin-1, interleukin-6, and tumor necrosis factor- levels in intraperitoneal fluid (obtained by intraoperative lavage) and plasma were measured by enzyme-linked immunosorbent assay. To compare intraperitoneal cytokine productions between diseases with a different degree of inflammation, intraperitoneal cytokine measurement also was performed for patients who required surgery for colorectal cancer (n = 25) and acute appendicitis (n = 25).RESULTS The median intraperitoneal cytokine (interleukin-1, interleukin-6, and tumor necrosis factor-) levels were significantly higher in patients with inflammatory bowel disease than in patients with colorectal cancer and acute appendicitis. In patients with inflammatory bowel disease, intraperitoneal cytokine levels were significantly higher in patients with intraperitoneal sepsis (abscess/fistula) than in patients without intraperitoneal sepsis at laparotomy. Intraperitoneal cytokine levels did not correlate with type of disease (ulcerative colitis/Crohns disease), age, gender, duration of disease before surgery, preoperative medical treatment, and the extent or site of disease. There were no significant correlations between intraperitoneal cytokine levels and the following systemic inflammatory markers: plasma cytokine levels, white blood cell count, platelet count, erythrocyte sedimentation rate, and C-reactive protein levels. Postoperative intraperitoneal septic complications (anastomotic leak/abscess/enterocutaneous fistula) more frequently occurred in patients with higher intraperitoneal cytokine levels.CONCLUSIONS Intraperitoneal cytokine productions were greatly elevated in patients with inflammatory bowel disease, and their levels correlated with the presence of intraperitoneal sepsis at laparotomy and development of postoperative intraperitoneal septic complications. Intraperitoneal cytokine levels showed no correlations with systemic inflammatory markers.     

术后腹腔化疗对老年结直肠癌患者生存质量的影响

目的评价老年结直肠癌患者手术后腹腔化疗对生存质量的影响。方法调查1998年1月至2002年12月期间52例60岁以上进行术后腹腔化疗的患者的生存质量GLQI指数,并与同期、同年龄段44例静脉化疗患者和40名健康老年对照组进行比较。所有病人于术前和术后6个月期间调查患者的生存质量。结果老年结直肠癌患者手术前的生存质量GLQI指数明显低于正常老年人群(P<0.05)。而两组患者手术前的生存质量GLQI指数无显著差异(P>0.05)。腹腔化疗组患者手术后6个月期间的生存质量GLQI指数高于静脉化疗组患者,其差异存在统计学意义(P<0.05)。腹腔化疗组患者手术后3月、4月、5月和6月的生存质量GLQI指数与正常老年人群无显著差异(P>0.05);而静脉化疗组患者手术后3月、4月、5月和6月的生存质量GLQI指数仍低于正常老年人群(P<0.05)。结论针对老年结直肠癌患者的生理特点,手术后采用腹腔化疗,不仅有利于提高手术后的生存期;而且有助于提高患者的生存质量,是老年结直肠癌患者手术后首选的理想化疗方式。     

利多卡因腹腔内麻醉用于腹腔镜术后镇痛的临床研究

目的 :评价腹腔内注射利多卡因用于腹腔镜术后镇痛的临床疗效。方法 :选择行胆囊切除术的患者12 0例 ,随机分成两组。利多卡因组 (A组 ,n =6 0例 )于术毕在膈下注射 5 0毫升 0 2 5 %的利多卡因 ;生理盐水组 (B组 ,n =6 0例 )于术毕在膈下注射 5 0毫升的生理盐水。于术后 2小时、 6小时、 8小时、 12小时和 2 4小时视觉模拟评分法 (visualanologuescale,VAS)记录VAS评分、镇痛药用量。结果 :利多卡因组 (A组 )于术后 2小时、 6小时、 8小时、 12小时和 2 4小时的VAS评分明显小于生理盐水组 (B组 ) (P <0 0 1) ,镇痛药用量也明显减少。结论 :利多卡因腹腔内注射可用于腹腔镜术后的镇痛 ,可明显减少术后镇痛药的用量 ,疗效确切。     

超声检查对原发性肝癌腹腔转移的初步研究

目的探讨超声在原发性肝癌腹腔转移诊断中的临床应用价值。方法回顾性分析28例原发性肝癌腹腔转移患者的超声表现、手术所见及甲胎蛋白(AFP)、糖类抗原19-9等临床资料。结果超声诊断腹腔转移21例,漏诊7例。16例腹腔转移患者表现为腹腔内孤立或散在多发结节,余5例表现为腹腔内巨大实性结节。单发结节11例,多发结节10例,CDFI探及17例患者结节内有血流信号。结论结合肝癌原发病灶的情况和AFP、糖类抗原19-9血清学资料,对于高度可疑发生腹腔转移的患者在超声检查时应注意全面扫查,重点扫查中上腹网膜区;对于腹腔内肠气干扰明显的患者可结合CT等其他影像学检查。     

Peritoneal surface oncology: review of a personal experience with colorectal and appendiceal malignancy

Peritoneal surface malignancy usually results from implantation of gastrointestinal cancer. In the past, this clinical situation was treated with palliative intent. A definitive approach to peritoneal surface malignancy involves peritonectomy procedures, visceral resections, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The quantitative prognostic indicators necessary for valid clinical judgements include the cancer histopathology (invasive vs. expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long–term survival in selected patients. Carcinomatosis from colon cancer had an overall 5–year survival of 45% with selected patients. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. The definitive prognostic indicator was the complete cytoreduction. Oncologists must seek new knowledge regarding the management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies; in contrast all historical controls show 0% long–term survival. Additional adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.     

胃癌腹腔化疗毒副反应的观察和处理

目的 评价胃癌腹腔化疗的毒副反应，并探讨其处理方法。方法 将156例胃癌病人进行随机分组。分为术中即时低渗温热腹腔化疗联合术后早期腹腔化疗组（治疗组），单纯术中即时低渗温热腹腔化疗组（对照组1），未行腹腔化疗组（对照组2），共三组，观察化疗的安全性和毒副反应。结果 治疗组化学性腹膜炎、消化道反应、骨髓抑制和肝功能异常的发生率明显高于两个对照组。结论 应用术中即时，低渗温热腹腔化疗联合术后早期腹腔化疗时化学性腹膜炎的防治不容忽视。