早期腹腔化疗与胃肠吻合口的愈合

治愈性手术联合早期腹腔化疗有益于提高结直肠癌患者的长期生存率,但化疗药物干扰成纤维细胞的DNA、RNA,阻碍胶原纤维的生物合成,延迟吻合口的愈合。因此,在临床中必须考虑这种疗法对胃肠愈合的潜在影响。近年的实验研究发现有效预防措施可避免不利影响,从而充分发挥早期腹腔化疗的优势。     

早期腹腔化疗与胃肠吻合口的愈合

治愈性手术联合早期腹腔化疗有益于提高结直肠癌患者的长期生存率,但化疗药物干扰成纤维细胞的DNA、RNA,阻碍胶原纤维的生物合成,延迟吻合口的愈合。因此,在临床中必须考虑这种疗法对胃肠愈合的潜在影响。近年的实验研究发现有效预防措施可避免不利影响,从而充分发挥早期腹腔化疗的优势。     

谷氨酰胺对术后早期腹腔化疗的结肠吻合口愈合的影响

目的研究应用谷氨酰胺(glutamine)对术后早期腹腔化疗条件下结肠吻合口愈合的影响。方法 Wistar大鼠60只, 随机分为3组:对照组, 单纯行肠切除吻合;术后早期腹腔化疗组(5-Fu组), 术后连续3天腹腔内注射氟尿嘧啶(5-Fu)(20mg/kg·d);glutamine组, 术后给予谷氨酰胺(1g/kg·d)7天及术后早期腹腔化疗。术后8天处死各组大鼠, 剖腹切取吻合口测量吻合口评分(评分越高提示吻合口与周围组织的黏连越重)和测量吻合口破裂压力及进行吻合口组织学评分。结果 谷氨酰胺组的吻合口评分2.00, 低于对照组(2.60), 显著低于5-Fu组的2.90, P＜0.05;差异有统计学意义。谷氨酰胺组的吻合口破裂压力229.95mmHg, 高于对照组(199.75mmHg), P＜0.05;显著高于5-Fu组(171.79mmHg), P＜0.01。谷氨酰胺组的吻合口组织学评分(2.9), 高于对照组(2.1)及5-Fu组(1.7), P＜0.05。结论 应用谷氨酰胺能提高吻合口愈合强度, 促进术后早期腹腔化疗条件下结肠吻合口愈合。     

The effect of dacarbazine on wound healing

The effects of dacarbazine on wound healing were studied in an animal model. Sixty rats were divided into four groups. Each animal received a standard dorsal midline wound on day 0. Group 1 was injected with normal saline and acted as control; group 2 received 4 mg/kg of dacarbazine daily on days -3, -2, -1 (preoperative); group 3 received dacarbazine on days +1, +2, +3 (perioperatively); and group 4 received dacarbazine on days +5, +6, +7 (postoperatively). Wound bursting strength (WBS) was measured on days +7, +14, and +21. There was a significant decrease in WBS in experimental animals in groups 3 and 4 (perioperative and postoperative administration) compared to control animals, but no significant effect of preoperative dacarbazine on WBS in experimental animals (group 2). It is suggested that these effects are mediated through the late inflammatory phase of wound healing.     

Effect of intraperitoneal chemotherapy and fibrinolytic therapy on tumor implantation in wound sites

Failure of surgical treatment for gastrointestinal cancers is often caused by recurrence of the tumor in traumatized peritoneal surfaces. This study examined the effect of intraperitoneal administration of doxorubicin and recombinant tissue plasminogen activator (rt-PA), a fibrinolytic agent, on incidence and volume of postoperative tumor implants in peritoneal wounds. Prior to randomization, a surgical wound was created on the right parietal peritoneum of 110 BDIX rats and 6 × 10⁵ DHD/K12 colon cancer cells were inoculated intraperitoneally (ip). The control group was given an intraperitoneal injection of saline. Five groups received 1 mg/kg of ip doxorubicin at different times postoperatively: at the end of surgery (DO), 3 hr after surgery (D + 3), postoperative day 1 (Dl), postoperative day 3 (D3), and postoperative day 7(D7). In a second set of experiments, five groups of rats received, in addition to postoperative doxorubicin, 5 mg/kg of intraoperative ip rt-PA. Incidence and volume of tumor implants in peritoneal wounds were assessed for each group 20 days after the tumor inoculation. All rats of the control group (incidence = 100%) developed tumor implants in peritoneal wounds. Mean (SD) volume was 16.2 (4.7) mm³. When administered at DO, D + 3, and Dl intraperitoneal doxorubicin reduced significantly the incidence and volume of tumor implants in wounds. Postoperative administration of doxorubicin at D3 and D7 did not affect significantly the incidence and the volume of tumor implants in peritoneal wounds. When rt-PA was administered intraoperatively, ip injection of doxorubicin at any postoperative timing decreased significantly the incidence and volume of tumor implants. In conclusion, ip doxorubicin administered before postoperative D3 may act on tumor cell implanted in peritoneal wounds. Delayed (D3, D7) ip administration of doxorubicin does not prevent the development of tumor implants in peritoneal wounds. Intraoperative administration of rt-PA may significantly increase the efficacy of delayed ip chemotherapy. © 1996 Wiley-Liss, Inc.     

The effects of doxorubicin and mitoxantrone on wound healing

Summary The goal of the present study was to determine whether mitoxantrone would impair wound healing to a similar degree as doxorubicin when given in equally cytotoxic doses. On day 0, male Fischer rats were wounded and treated with 5% dextrose (control), 6 mg/kg doxorubicin, or 1.2 or 2.4 mg/kg mitoxantrone. On day 5, WBCs for the doxorubicin group and the group that had been treated with 1.2 mg/kg mitoxantrone were 33% and 43% lower than control values, respectively. All rats that had been given 2.4 mg/kg mitoxantrone died within 1 week of being wounded due to drug toxicity. On day 21, wound-breaking strength (WBS) analysis was performed: two skin specimens were taken from each dorsal skin incision perpendicular to the scar axis and were subjected to wound disruption (grams of force) by uniaxial extension. The WBS analysis indicated significant differences between the doxorubicin treated group (1183±96 g) and the control group (2422±247 g). However, no significant difference was found between the group that had been given 1.2 mg/kg mitoxantrone (2140±191 g) and control animals. Thus, mitoxantrone seems to exert myelosuppressive effects similar to those displayed by doxorubicin, but the former drug results in significantly less impairment of wound healing in the rat model.     

Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.     

The stimulation of postdermabrasion wound healing with stabilized aloe vera gel-polyethylene oxide dressing

Full-face dermabrasion provided an ideal opportunity to document the effects of dressings on wound healing management. Following the procedure, the abraded face was divided in half. One side was treated with the standard polyethylene oxide gel wound dressings. The other side was treated with a polyethylene oxide gel dressing saturated with stabilized aloe vera. The polyethylene oxide dressing provided an excellent matrix for the release of aloe vera gel during the initial 5 days of wound healing. By 24-48 hours there was dramatic vasoconstriction and accompanying reduction in edema on the aloe-treated side. By the third to fourth day there was less exudate and crusting at the aloe site, and by the fifth to sixth day the reepithelialization at the aloe site was complete. Overall, wound healing was approximately 72 hours faster at the aloe site. This acceleration in wound healing is important to reduce bacterial contamination, subsequent keloid formation, and/or pigmentary changes. The exact mechanism of acceleration of wound healing by aloe vera is unknown.     

The impact of postoperative complications following cytoreductive surgery combined with oxaliplatin based heated intraperitoneal chemotherapy

IntroductionCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) has become the mainstream treatment for peritoneal metastases of colorectal origin. This extensive treatment is known for its increased morbidity rate.In this study, the impact of postoperative complications on survival was evaluated in a high-volume centre.Patients and methodBetween November 2016 through October 2018, all 106 patients with peritoneal metastases of colorectal origin treated with CRS + HIPEC with oxaliplatin were evaluated. Data on patient characteristics, Peritoneal Carcinomatosis Index (PCI), operative procedure, post-operative complications (Clavien-Dindo classification grade III or higher) and survival were collected. In-hospital postoperative complications were analysed for their association with patient characteristics, tumour load (PCI), and operative procedure with logistic regression analyses. Survival was analysed with the Cox regression analysis.ResultsOf 106 patients, 78% had an un-eventful in-hospital recovery. Of those patients who experienced complications, 52% patients had one complication and 48% had more than one.The median follow-up time was 33.8 months. Median survival was 22.4 months (95% CI 12.2–NR) for patients who experienced complications and not reached for those who did not. Survival was significantly associated with complications (HR 2.2, 95% CI 1.2–4.0) as well as with PCI (HR 1.1, 95% CI 1.1–1.2) in univariate analyses. A stepwise Cox regression analysis showed both PCI and complications had an independent negative impact on survival.ConclusionPostoperative complications, independently of tumour load, led to reduced survival in patients with peritoneal metastases of colorectal origin when treated with CRS + HIPEC with oxaliplatin.     

The role of intraperitoneal therapy in advanced ovarian cancer

Intraperitoneal (i.p.) chemotherapy is a preferred treatment option that should be offered to all women for front-line treatment of stage III optimally debulked ovarian cancer. Patients should be provided with information on the survival and toxicity for both i.p. and intravenous (i.v.) therapies, as well as practical information about the administration of each regimen, so that they may play an active role in the decision-making process. When making a decision between i.p. and i.v. therapeutic options, the experience and preference of the oncologist are critical factors in determining appropriate therapy for each woman.     

The quantitative and qualitative impairment of wound healing by adriamycin.

Clinical impression suggests that Adriamycin (ADR) interferes with wound healing. To examine the effects of ADR on wound healing, male Fischer rats were subjected to a dorsal, midline, full-thickness longitudinal incision (day 0). Wound clips were removed on day +7. Twenty animals per group were given intravenous ADR on day -7, day 0, day +3 and day +7. Twenty animals served as non-treated, wounded controls (C). Five animals/group were sacrificed on days +7, +14 and +21, at which time two 9.5 mm wide strips were taken from each animal perpendicular to the wound axis and submitted for wound breaking strength (WBS) measurements and load-extension curve analysis. WBS differed most markedly at Day 21 between C(1671 +/- 59g) and ADR day -7(1360 + 71 g) p less than 0.01; C and ADR day 0 (1051 +/- 108 g) p less than 0.001; C and ADR day + 3(1134 +/- 176 g) p less than 0.02. No difference existed between C and day +7 (1790 +/- 153 g). A point of inflection always occurred between 55-60% elongation in ADR treated animals only. This portion of the curve has been previously shown to represent collagen content. It is concluded that perioperative ADR administration (day -7 through day +3) significantly and substantially impairs skin wound healing in the rat. A form of collagen yielding underlies and may contribute to this defect.     

The effect of 13-cis-retinoic acid on wound healing in dogs

13-cis-retinoic acid is currently accepted as a valuable treatment for patients with severe nodulocystic acne. Many of these individuals express interest in surgical scar-correcting procedures. To ascertain the effect of 13-cis-retinoic acid on wound healing, sequential biopsies were examined from partial and full-thickness wounds in dogs following a 2-month course of retinoids. No significant difference was histologically observed from the control animal.     

Emerging approaches of wound healing in experimental models of high-grade oral mucositis induced by anticancer therapy

Clinical guidelines for oral mucositis (OM) still consist in palliative care. Herein, we summarize cellular and molecular mechanisms of OM ulceration in response to chemical therapies in animal models. We discuss evidenced anti-inflammatory and anti-oxidant drugs which have not been ever used for OM, such as synthetic peptides as well as cell therapy with mesenchymal stem cells; amniotic membranes, mucoadhesive polymers loaded with anti-inflammatory agents and natural or synthetic electrospun. These approaches have been promising to allow the production of drug-loaded membranes, scaffolds for cells encapsulation or guided tissue regeneration.     

耳穴贴压联合时间疗法对肝癌患者术后疼痛的影响

目的探讨耳穴贴压联合时间疗法对肝癌患者术后疼痛的影响。方法选取2016年10月至2019年1月间陕西省延安大学附属医院收治的108例原发性肝癌患者,采用随机数表法分为观察组和对照组,每组54例。两组患者术后均采用经静脉自控镇痛泵常规疼痛控制方法,观察组患者在此基础上施行耳穴贴压结合时间疗法。术后24h和48h,采用视觉模拟评分(VAS)法对疼痛程度进行评估。统计两组患者术后3d内睡眠时长和对镇痛疗效的满意程度。结果术后第1天和第2天,观察组患者疼痛程度均低于对照组患者,差异均有统计学意义(均P <0. 05)。术后1～3天,观察组患者睡眠时长均高于对照组,差异均有统计学意义(均P <0. 05)。观察组患者对镇痛疗效总体满意率为98. 1%,高于对照组的87. 0%,差异有统计学意义(P <0. 05)。结论耳穴贴压结合时间疗法有助于缓解肝癌患者术后疼痛程度,改善睡眠,提高患者对镇痛效果的满意度。     

胃癌术后腹腔热灌注联合全身化疗的临床应用

为研究胃癌术后腹腔热灌注化疗联合全身化疗的治疗效果。对140例胃癌根治术后患者随机分为腹腔热灌注化疗组(n=72)和全身化疗组(n=68)。腹腔热灌注化疗组患者在全身化疗同时应用腹腔热灌注化疗,观察两组术后并发症、不良反应、术后生存率及腹腔复发率。两组在术后并发症及不良反应差异无统计学意义。腹腔热灌注化疗组和全身化疗组术后3、5年生存率分别为86.1%(62/72)、60.2%(41/68)和58.3%(42/72)、29.4%(20/68)(P<0.05)。腹腔热灌注化疗组和全身化疗组术后3、5年腹腔复发率分别为5.6%(4/72)、27.8%(19/68)和20.6%(15/72)、53%(36/68),差异有统计学意义,P<0.05。初步研究结果提示,胃癌术后腹腔热灌注联合全身化疗可有效控制肿瘤的复发和转移,提高胃癌术后患者的生存率。     

进展期胃癌术后腹腔化疗的临床疗效分析

目的:观察分析进展期胃癌术后早期连续腹腔化疗的疗效及毒副反应。方法:对2002-03-2007-03胃癌根治术后的69例进展期患者,早期用腹腔化疗的病例进行回顾性分析,并以同期行静脉化疗的61例患者作对照。分析比较两组患者生存率、复发率和不良反应的差异。结果:腹腔化疗组1、2和3年生存率分别为89.86%、79.71%和65.22%,静脉化疗组1、2和3年生存率分别为77.05%、68.85%和59.01%。而连续腹腔化疗组不良反应(除腹痛、腹胀外)及复发率均低于静脉化疗组。结论:进展期胃癌术后早期腹腔化疗简单实用、安全、全身毒副反应小,可有效预防腹腔内复发和转移,提高术后生存质量和生存率。     

After thirty years of experience with early postoperative intraperitoneal 5-fluorouracil now saying goodbye

In the management of colorectal and appendiceal peritoneal metastases, intraperitoneal 5-fluorouracil (5-FU) has been used in 3 different ways. It has been used as part of an early postoperative intraperitoneal chemotherapy (EPIC) regimen along with EPIC mitomycin C. This EPIC mitomycin C plus EPIC 5-FU has been shown to be equivalent or inferior to HIPEC. Because it is more work intensive than HIPEC and not superior, its use should be abandoned if HIPEC is available. A second way to use intraperitoneal 5-FU is along with HIPEC. Several studies suggest a survival advantage for the combination of HIPEC with EPIC 5-FU. However, patient ineligibility for EPIC 5-FU in high-risk CRS is more likely the cause for the alleged survival advantage attributed to the combination. A third use of intraperitoneal 5-FU is long-term through a peritoneal access device. This plan for 5-FU use has shown favorable results in three randomized controlled studies. Normothermic intraperitoneal chemotherapy (NIPEC) with 5-FU should be considered as a regional chemotherapy component of a randomized trial for prevention or treatment of peritoneal metastases from colorectal or appendiceal cancer. Intravenous oxaliplatin combined with NIPEC 5-FU has been suggested as a bidirectional adjuvant regimen.     

Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer

Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.