8-Year Follow-up of Randomized Trial: Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy in Patients with Peritoneal Carcinomatosis of Colorectal Cancer

Introduction  The treatment of peritoneal carcinomatosis is based on cytoreduction followed by hyperthermic intraperitoneal chemotherapy and combined with adjuvant chemotherapy. In 2003, a randomized trial was finished comparing systemic chemotherapy alone with cytoreduction followed by hyperthermic intraperitoneal chemotherapy and systemic chemotherapy. This trial showed a positive result favoring the studied treatment. This trial has now been updated to a minimal follow-up of 6 years to show long-term results. Patients and Methods  For all patients still alive, the follow-up was updated until 2007. In the original study, four patients were excluded—two because of no eligible histology/pathology and two because of major protocol violations. After randomization, four patients in the HIPEC arm and six in the control arm were not treated using the intended therapy, one patient because of withdrawal, one because of a life-threatening other malignant disease and the others because of progressive disease before initiation of the treatment. During the follow-up, one patient was crossed over from the control arm and underwent cytoreduction and HIPEC for recurrent disease, after the assigned treatment was completed. The data from these patients were censored at the moment of the cross-over. Progression-free and disease-specific survival were analyzed using the Kaplan Meyer test and compared using the log rank method. The long-term results were studied in more detail to evaluate efficacy and toxicity. Results  At the time of this update, the median follow-up was almost 8 years (range 72–115 months). In the standard arm, 4 patients were still alive, 2 with and 2 without disease; in the “HIPEC’ arm, 5 patients were still alive, 2 with and 3 without disease. The median progression-free survival was 7.7 months in the control arm and 12.6 months in the HIPEC arm (P = 0.020). The median disease-specific survival was 12.6 months in the control arm and 22.2 months in the HIPEC arm (P = 0.028). The 5-year survival was 45% for those patients in whom a R1 resection was achieved. Conclusion  With 90% of all events having taken place up to this time, this randomized trial shows that cytoreduction followed by HIPEC does significantly add survival time to patients affected by peritoneal carcinomatosis of colorectal origin. For a selected group, there is a possibility of long-term survival.     

Treatment of Peritoneal Carcinomatosis From Colorectal Cancer: Impact of Complete Cytoreductive Surgery and Difficulties in Conducting Randomized Trials

Background Colorectal peritoneal carcinomatosis (PC) is a frequent and very lethal event. However, cure may be possible with maximal cytoreductive surgery associated with early postoperative intraperitoneal chemotherapy (EPIC).Methods Between 1996 and 2000, we conducted a two-center prospective randomized trial comparing EPIC plus systemic chemotherapy with systemic chemotherapy alone, both after complete cytoreductive surgery of colorectal PC. Only 35 patients could be included among the 90 who were theoretically required, mainly because of patient dissatisfaction with the inclusion criteria. For this reason, the trial was stopped prematurely.Results Analysis of these 35 patients showed that complete resection of PC resulted in a 2-year survival rate of 60%—far above the classic 10% survival rate among patients with colorectal PC treated with systemic chemotherapy and symptomatic surgery. In this small series, EPIC did not demonstrate any advantage for survival.Conclusions This supports the use of complete cytoreductive surgery in selected patients and calls for a prospective randomized trial comparing adjuvant systemic chemotherapy with intraperitoneal chemohyperthermia after complete resection.     

胸内食管吻合口隐匿瘘的诊断与治疗

目的探讨胸内食管吻合口隐匿瘘的诊断治疗方法。方法回顾性分析2006年1月至2010年12月青岛大学医学院附属医院32例食管、贲门癌患者行胸内胃食管吻合术后出现脓毒血症表现,并先后行水溶性造影剂食管X线造影+胸部CT扫描患者的临床资料。32例均无造影剂渗漏,但CT显示吻合口周围出现小气泡、包裹性积液。其中15例按"隐匿瘘"处理,给予禁食、广谱抗生素、延长胃肠减压时间、鼻肠管肠内营养等治疗;另17例按非吻合口瘘相关感染处理,仅应用高效广谱抗生素。结果 32例患者中按吻合口瘘处理的15例患者口服水溶性造影剂食管X线造影+胸部CT扫描显示均未发展为吻合口瘘(0%,0/15);而未按吻合口瘘处理的17例患者中有14例发展为吻合口瘘(82.4%,14/17),其中2例发生吻合口主动脉瘘死亡,3例并发多器官功能衰竭死亡。结论口服水溶性造影剂食管X线造影+胸部CT扫描显示吻合口周围有小气泡、不规则包裹性积液为"隐匿瘘"的特异性征象,应按吻合口瘘处理。     

直肠癌前切除术后吻合口漏原因的多因素分析

目的探讨直肠癌前切除术后发生吻合口漏的相关因素。方法 2001年1月～2009年3月,行开放（504例）或腹腔镜（65例）直肠癌前切除术569例,术后发生吻合口漏39例,发生率为6.8%（39/569）。33例（84.6%）经保守治疗,6例行横结肠造瘘术。对不同医院,术者,患者年龄（≥55岁或〈55岁）、性别、吻合方式（手工或吻合器）、手术方式（腹腔镜或开放）、是否近端肠管预防性造瘘、肿瘤位置（腹膜反折以下或以上）、Duke分期的吻合口漏的发生率进行单因素分析和多因素非条件Logistic回归分析。结果 39例吻合口漏均治愈。肿瘤位置、Duke分期与吻合口漏的发生密切相关。肿瘤位于腹膜反折以下的患者吻合口漏的发生率（8.9%,28/313）是肿瘤位于腹膜反折以上者（4.3%,11/256）的2.1倍（OR=2.38,95%CI=1.13～7.12,P=0.004）。Duke分期A期吻合口漏发生率2.9%（3/104）,B期6.2%（17/274）,C期11.6%（16/138）,D期21.4%（3/14）（OR=2.54,95%CI=1.08～6.68,P=0.011）。结论直肠癌前切除术后吻合口漏的发生与肿瘤分期及肿瘤部位密切相关。     

经肛双管冲洗引流在防治低位结直肠吻合口漏中的应用

为探讨防治低位结直肠吻合口漏的方法．回顾性分析应用经肛内吻合口上下双管引流法防治低位结直肠吻合口漏71例的资料。结果显示,发生吻合口漏2例,创口感染3例,1例自动出院,其余患者均一期愈合出院。结果表明,应用经肛双管冲洗引流防治低位结直肠吻合口漏是安全可行的。     

Prophylactic intra-abdominal drainage following colorectal anastomoses. A systematic review and meta-analysis of randomized controlled trials

BackgroundClinically evident Anastomotic Leakage (AL) remains one of the most feared complications after colorectal resections with primary anastomosis. The primary aim of this systematic review and meta-analysis was to determine whether Prophylactic Drainage (PD) after colorectal anastomoses confers any advantage in the prevention and management of AL.MethodsSystematic literature search was performed using MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE databases for randomized studies comparing clinical outcomes of patients with Drained (D) or Undrained (UD) colorectal anastomoses performed for any cause.ResultsFour randomized controlled trials comparing D and UD patients undergoing colorectal resections with primary anastomosis were included for quantitative synthesis. In total, 1120 patients were allocated to group D (n = 566) or group UD (n = 554). The clinical AL rate was 8.5% in the D group and 7.6% in the UD group, with no statistically significant difference (P = 0.57). Rates of radiological AL (D: 4.2% versus UD: 5.6%; P = 0.42), mortality (D: 3.6% versus UD: 4.4%; P = 0.63), overall morbidity (D: 16.6% versus UD: 18.6%, P = 0.38), wound infection (D: 5.4% versus UD: 5.3%, P = 0.95), pelvic sepsis (D: 9.7% versus UD: 10.5%, P = 0.75), postoperative bowel obstruction (D: 9.9% versus UD: 6.9%, P = 0.07), and reintervention for abdominal complication (D: 9.1% versus UD: 7.9%, P = 0.48) were equivalent between the two groups.ConclusionsThe present meta-analysis of randomized controlled trials investigating the value of PD following colorectal anastomoses does not support the routine use of prophylactic drains.     

Prevention of leakage by sealing colon anastomosis: experimental study in a mouse model

Background

In colorectal surgery, anastomotic leakage (AL) is the most significant complication. Sealants applied around the colon anastomosis may help prevent AL by giving the anastomosis time to heal by mechanically supporting the anastomosis and preventing bacteria leaking into the peritoneal cavity. The aim of this study is to compare commercially available sealants on their efficacy of preventing leakage in a validated mouse model for AL.

Methods

Six sealants (Evicel, Omnex, VascuSeal, PleuraSeal, BioGlue, and Colle Chirurgicale Cardial) were applied around an anastomosis constructed with five interrupted sutures in mice, and compared with a control group without sealant. Outcome measures were AL, anastomotic bursting pressure, and death.

Results

In the control group there was a 40% death rate with a 50% rate of AL. None of the sealants were able to diminish the rate of AL. Furthermore, use of the majority of sealants resulted in failure to thrive, increased rates of ileus, and higher mortality rates.

Conclusions

If sealing of a colorectal anastomosis could achieve a reduction of incidence of clinical AL, this would be a promising tool for prevention of leakage in colorectal surgery. In this study, we found no evidence that sealants reduce leakage rates in a mouse model for AL. However, the negative results of this study make us emphasize the need of systemic research, investigating histologic tissue reaction of the bowel to different sealants, the capacity of sealants to form a watertight barrier, their time of degradation, and finally their results in large animal models for AL.     

直肠充气试验＋美蓝试验在直肠癌TME术中的应用研究

目的探讨直肠充气试验十美蓝试验在直肠癌全直肠系膜切除（TME）术中检测吻合口漏的作用。方法2010年3月至2013年3月期间笔者所在医院科室收治直肠癌患者132例,将其随机分为直肠充气试验组（充气组）65例和直肠充气试验＋美蓝试验组（充气＋美蓝组）67例,2组均遵循TME原则行Dixon术。充气组在行TME术及肠吻合完毕后,用肠钳在吻合口上端2cm处钳夹肠管,于盆腔内倒人蒸馏水500mL;经肛门置入24#Foley尿管,向尿管球囊注水使球囊膨胀封闭肛门,使吻合肠段处于相对封闭状态;再经尿管注入气体50mL,观察水面有无气泡出现,若有气泡则表示存在吻合口漏,并予以修补,至无气泡出现。充气＋美蓝组患者则在充气组的基础上加行美蓝试验,吸出盆腔内的蒸馏水和直肠内气体后,经尿管注入美蓝1支（20mg）和生理盐水50mL,观察吻合口有无美蓝漏出。结果充气组术中发现吻合口漏3例（4．62％）,均给予了修补;术后发生吻合口漏9例（13．85％）,5例经充分引流、禁食及对症治疗后治愈,3例经肛门缝合修补后治愈,1例经横结肠造口、局部引流后治愈。充气＋美蓝组经充气试验发现吻合口漏2例,后经美蓝试验发现13例存在吻合口漏,共发现吻合口漏15例（22．39％）,均给予修补;术后无一例患者发生吻合口漏。与充气组比较,充气＋美蓝组术中吻合口漏的检出率较高（P〈0．05）,术后吻合口漏的发生率较低（P〈0．05）。结论充气试验可发现较大的吻合口漏,而美蓝试验可发现小的吻合口漏和隐性漏,两种试验联合应用可发现吻合口缺陷与漏;直视下修补可有效防止TME术后吻合口漏的发生。     

Peritoneal Dissemination of Early Gastric Cancer: Report of a Case

Recurrence of early gastric cancer is rare, with an incidence of less than 10% in Japan. Using peritoneal lavage cytological examination, we detected tumor cells in the peritoneal cavity of a 73-year-old man undergoing surgery for early gastric cancer. Peritoneal dissemination of early gastric cancer is rare. Thus, we summarized the clinicopathological findings of the total 15 cases of peritoneal dissemination of early gastric cancer documented in the English medical literature, including this case. All of the patients had a tumor size >2 cm, submucosal invasion, differentiated adenocarcinoma, lymph node metastasis, and a shorter disease-free interval (average 33.1 months) than patients with other types of recurrent early gastric cancer, and the involvement of both recurrent lymph nodes and peritoneal dissemination. Based on this analysis, we conclude that patients with early gastric cancer, especially if the tumor is >2 cm with submucosal invasion, should be examined carefully for any form of recurrence.     

Early and late anastomotic leak after colorectal surgery: A systematic review of the literature

The aim of this study was to review and to assess the quality of the scientific articles regarding early and late anastomotic leak (AL) after colorectal surgery and their risk factors.An electronic systematic search for articles on Colorectal Surgery, AL and its timing was undertaken using the MEDLINE database via PubMed, Cochrane and Embase. The selected articles were thoroughly reviewed and assessed for methodological quality using a validated methodology quality score (MINCIR score). This review was registered in the PROSPERO registry under ID: CRD42022303012. 9 articles were finally reviewed in relation to the topic of early and late anastomotic leak.There is a lack of consensus regarding the exact cut-off in time to define early and late anastomotic leak, but it is clear that they are two differentiated entities. The first, occurring in relation to technical factors; whereas the latter, is related to impaired healing.     

Aggressive Surgical Management of Peritoneal Carcinomatosis With Low Mortality in a High-Volume Tertiary Cancer Center

Background Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for treatment of peritoneal carcinomatosis (PC) traditionally involves high perioperative morbidity and mortality. We report our experience performing CS-HIPEC in a high-volume regional perfusion program designed to limit morbidity and mortality. Methods A total of 122 patients underwent 124 CS-HIPEC procedures. Common tumors treated with CS-HIPEC included appendiceal (38.5%), colorectal (24.6%), and ovarian cancers (13.1%), and peritoneal mesothelioma (12.3%). Complete cytoreduction was performed in all patients, with organ resections performed as necessary. Results R0 resection was achieved in 28.7% of cases, R1 in 54.9%, and R2 in 16.4%. Median operative time was 460 minutes (range, 250–840 minutes), and median blood loss was 1150 mL (range, 10–14,000 mL). Median hospital and intensive care unit stays were 12 days (range, 6–50 days) and 3 days (range, 0–41 days), respectively. Grade 3 or 4 morbidity by National Cancer Institute criteria (major morbidity) was seen in 29.8% of cases, with overall morbidity 56.5%. Independent prognostic variables for major morbidity included number of anastomoses and degree of cytoreduction. In-hospital and 30-day mortality rates were 0% and 1.6%, respectively. The most favorable diagnosis was appendiceal cancer, for which 2-year survival was 66.7%, with lower-grade histologic subtypes of appendiceal cancer reaching 85.7% 2-year survival. Colorectal cancer had 2-year survival of 36.7%. Conclusions In a high-volume center with extensive experience treating peritoneal malignancies, perioperative mortality can be lowered to nearly zero, although morbidity remains high. CS-HIPEC procedures should be studied further in a controlled manner to help define their important role in the care of patients with PC.     

Mechanical Bowel Preparation for Elective Colorectal Surgery with Primary Intraperitoneal Anastomosis by a Single Surgeon: Interim Analysis of a Prospective Single-Blinded Randomized Trial

We report an interim analysis of a prospective single-blinded randomized trial designed to investigate whether preoperative mechanical bowel preparation influences the rate of surgical-site infection and anastomotic failure after elective colorectal surgery with primary intraperitoneal anastomosis performed by a single surgeon. Patients scheduled to undergo an elective colorectal procedure with a primary intraperitoneal anastomosis were randomized to receive either oral polyethylene glycol lavage solution and enemas (group A) or no preparation (group B). Surgical-site infection and anastomotic failure were investigated. Of 97 patients included, 48 were assigned to group A and 49 to group B. Twelve (12.4%) developed wound infections, six in each group (12.5 vs. 12.2%; NS). Intra-abdominal sepsis was only seen in group A (n = 3, 6.3%). Anastomotic failure occurred in four patients in group A (8.3%) vs. two patients in group B (4.1%) (NS). The overall complication rate in group A was 27.1%, vs. 16.3% in group B. The number needed to harm was 9.3. Our interim analysis of a prospective single-blinded randomized trial suggests that a surgeon may have the same or even worse outcomes when mechanical bowel preparation is routinely used for colorectal surgery with primary intraperitoneal anastomosis. This work was presented in abstract form at the 47th Meeting of the Society of Surgery of The Alimentary Tract.     

胰腺癌的内镜诊治进展

目的介绍胰腺癌的内镜诊治进展。方法查阅国内、外近几年有关胰腺癌内镜诊治的文献并做综述。结果近年来,随着消化内镜的发展,特别是超声内镜,超声内镜下细针穿刺技术,逆行性胰胆管造影,内镜下胰管活检、胰液中脱落细胞检测、肿瘤标志物检测、经口胰管镜、光学相干体层摄影等技术的发展,胰腺癌的早期诊断率逐渐提高;而且对于晚期胰腺癌,内镜下可开展支架置入、放射性粒子植入、神经阻滞等多种治疗。结论消化内镜提高了胰腺癌的早期诊断率,同时为晚期胰腺癌的治疗提供了新的选择。     

原发性胆囊癌的早期诊断进展

目的介绍原发性胆囊癌早期诊断的各种方法及进展,以期提高原发性胆囊癌的早期诊断率。方法复习相关文献资料并作一综述。结果原发性胆囊癌早期诊断困难,预后差。通过详细了解病史及详细查体,再辅以现代多种影像学检查方法及分子生物学技术,可以提高原发性胆囊癌的早期诊断率。结论了解和掌握各种原发性胆囊癌早期诊断方法对提高原发性胆囊癌的早期诊断率和选择合理的临床诊治方法有积极的意义。     

胱抑素C早期诊断造影剂肾病的临床研究

目的：探讨血浆胱抑素C（Cys C）在造影剂肾病（CI N）早期诊断中的临床意义。方法：选择使用非离子型低渗造影剂进行血管造影的130例患者为研究对象,所有患者分别于造影前24 h内、造影后8 h、24 h和48 h抽血检测Cys C、肌酐（Scr）、尿素氮（BUN）、尿酸（UA）以及根据公式推算的肾小球滤过率（eGFR）,根据患者在造影后48 h内是否发生造影剂肾病（CI N）,分为CI N组和非CI N组。结果：（1）CI N的发生率为12.3%。（2）CI N组血浆Cys C浓度造影后8 h明显升高,24 h达最高峰,48 h有所降低,但均明显高于造影前以及非CI N组相应时间点的水平,差异均有统计学意义（P〈0.05）。而CI N组Scr造影后8 h无明显变化,24 h开始升高,48 h达最高值,只有48 h的值明显高于造影前以及非CI N组相应时间点的水平,差异有统计学意义（P〈0.05）。非CI N组造影前后各时间点Cys C、Scr等各项指标比较差异无统计学意义（P〉0.05）。（3）患者造影前Cys C与Scr（r=0.431）呈明显正相关,与eGFR（r=-0.392）呈明显负相关。（4）若以造影后8 h和24 h内血浆Cys C浓度较造影前基础值上升25%作为诊断CI N的标准,其敏感性分别为83.2%和89.2%,特异性分别为74.1%和80.5%。阳性预测值分别为45.6%和51.3%,阴性预测值分别为92.5%和94.2%。结论：造影后8 h和24 h的血浆Cys C浓度对CI N的早期诊断有一定的价值,能较Scr更早反映肾功能的变化。     

创伤性上颈椎不稳的早期诊断和治疗（附56例报告）

目的　回顾创伤性上颈椎不稳病例 5 6例 ,强调早期诊断的重要性及治疗原则。方法　对未合并横韧带断裂病例采用保守治疗 ;合并横韧带断裂者应早期外科干预。结果　 47例经治疗后上颈椎获满意稳定性 ,优良率达 86 8%。结论　全面体检 ,影像学检查早期可作出诊断。横韧带是否断裂是保守及手术治疗的重要依据之一     

The added value of systematic biopsy in men with suspicion of prostate cancer undergoing multiparametric MRI-targeted biopsy

Purpose

Incorporation of multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TBx) in the diagnostic pathway for prostate cancer (CaP) is rapidly becoming common practice. In men with a prebiopsy positive mpMRI a TBx only approach, thereby omitting transrectal ultrasound-guided systematic biopsy (SBx), has been postulated. In this study we evaluated the additional clinical relevance of SBx in men with a positive prebiopsy mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥ 3) undergoing TBx for CaP detection, Gleason grading and CaP localization.