Min-Chi Chang

Oxaliplatin-induced severe anaphylactic reactions in metastatic colorectal cancer: Case series analysis

AIM To investigate oxaliplatin-induced severe anaphylactic reactions (SAR) in metastatic colorectal cancer in a retrospective case series analysis and to conduct a systemic literature review. METHODS During a 6-year period from 2006 to 2011 at Kaohsiung Veterans General Hospital, a total of 412 patients exposed to oxaliplatin-related chemotherapy were retrospectively reviewed. Relevant English-language studies regarding life-threatening SAR following oxaliplatin were also reviewed in MEDLINE® and PubMed® search. RESULTS Eight patients (1.9%, 8 of 412 cases) were identified. Seven patients were successful resuscitated without any sequelae and one patient expired. We changed the chemotherapy regimen in five patients and rechallenged oxaliplatin use in patient 3. Twenty-three relevant English-language studies with 66 patients were reported. Patients received a median of 10 cycles of oxaliplatin (range, 2 to 29). Most common symptoms were respiratory distress (60%), fever (55%), and hypotension (54%). Three fatal events were reported (4.5%). Eleven patients (16%) of the 66 cases were rechallenged by oxaliplatin. CONCLUSION SAR must be considered in patients receiving oxaliplatin-related chemotherapy, especially in heavily pretreated patients. Further studies on the mechanism, predictors, preventive methods and management of oxaliplatin-related SAR are recommended.

Factors that influence survival in colorectal cancer with synchronous distant metastasis

Background: Treatments for the purposes of curing or more effectively managing metastatic colorectal cancer (CRC) are evolving. Our study focused on patients with primary CRC with synchronous distant metastasis, and we analyzed the factors influencing patient survival. Methods: Data review was conducted retrospectively. Clinicopathological parameters included age, sex, site of primary cancer, tumor cell differentiation, number of liver metastasis, presence of extrahepatic metastasis, treatment of liver metastasis, pre‐treatment carcinoembryonic antigen (CEA) level, status of treatment response, salvage treatment and survival. Results: A total of 420 patients were identified and considered for our study. Of those, 275 patients (65.4%) had liver‐only metastasis, 100 patients (23.8%) had concomitant lung metastasis, and 40 patients (9.5%) had other metastases. Additionally, 145 patients (34.5%) had liver‐directed treatment including surgical resection (28.5%), radiofrequency ablation (RFA) (10.6%) and transcatheter arterial chemoembolization (TAE) (1.2%). There were 80 patients (19%) with CEA levels < 10, 135 patients (32.1%) with CEA 10–100, and 165 patients (39.2%) with CEA > 100. There were 200 patients (47.6%) who had received chemotherapy, 130 patients (30.9%) with target therapy, and 40 patients (9.5%) who had not undergone any salvage treatment. Three significant factors were identified, including treatment of liver metastasis (p = 0.027), pre‐treatment CEA (p = 0.04), and salvage treatment (p = 0.005). Conclusion: We demonstrated three factors influencing patient survival including treatment of liver metastasis, pre‐treatment CEA level, and salvage treatment. Aggressive treatment of liver metastasis including surgical resection or RFA combined with chemotherapeutic agents appear to provide an increased rate of survival to patients.

Measurement of peritoneal fluid urea nitrogen and creatinine levels is useful to detect iatrogenic urinary tract leakage in colorectal surgery

Background Increased peritoneal drainage after colorectal surgery is a common problem. Measurement of peritoneal fluid urea nitrogen (UN) and creatinine (Cr) is a diagnostic tool to detect the urinary tract leakage (UTL). We evaluated its application in colorectal surgery. Methods We conducted a retrospective chart review study. We enrolled patients with iatrogenic UTL, and measured their UN and Cr levels in peritoneal fluid and compared them with those in blood and urine. Meanwhile, we assigned patients without UTL to a control group and compared clinical parameters of both groups. Results Twenty‐three patients with iatrogenic UTL were recruited. The overall incidence was 0.5%. UN level in peritoneal fluid (322 ± 56 mg/dL) was significantly higher than that in blood (18.7 ± 4.0 mg/dL, p < 0.001); Cr level in peritoneal fluid (69.7 ± 14.3 mg/dL) was also significantly higher than that in blood (1.5 ± 0.5 mg/dL, p < 0.001). UN level in peritoneal fluid was significantly higher in the iatrogenic UTL group than in the control group (322 mL/dL vs. 9.3 mL/dL, p < 0.001); Cr level in peritoneal fluid was also significantly higher (69.7 mg/dL vs. 0.98 mg/dL, p < 0.001). Conclusion When increased peritoneal drainage is found postoperatively in colorectal surgery, measurement of UN and Cr levels in peritoneal fluid can be a useful diagnostic tool to determine intraperitoneal iatrogenic UTL.

Comparison of laparoscopic versus open surgery in a three-stage operation for obstructive left-sided colorectal cancer.

Background Treatment for obstructive left‐sided colorectal cancer (OLCC) typically consists of a three‐staged procedure. During the first stage, the obstruction is managed with diversion colostomy. Traditionally in the second stage, we perform open resection for the primary tumor. In this study, we evaluated the feasibility of laparoscopic resection of OLCC with diversion colostomy in terms of operative results and short‐term outcomes. Methods A total of 20 patients underwent laparoscopic resection for OLCC (study group), 48 patients underwent open resection for OLCC (control group 1), and 53 patients underwent laparoscopic resection for non‐OLCC (control group 2). Afterwards, results from the procedures were obtained and clinical data were analyzed. Results The operative time was significantly longer in the study group than in the control group 1 (153 minutes vs. 126 minutes, p = 0.041), and the length of hospitalization was shorter in the study group than in the control group 1 (5.3 days vs. 7.6 days, p = 0.032). Regarding the operative results and short‐term outcomes, there were no significant differences between the study group and control group 2. Colostomy retraction was a specific morbidity which occurred in two patients of the study group. Conclusion Laparoscopic resection of OLCC with diversion colostomy is feasible. Abdominal cavity adhesion is only limited. We strongly recommend that laparoscopic resection should be performed at least 2 weeks after diversion colostomy, and the plastic rod should be left in place during the pneumoperitoneum to reduce the risk of colostomy retraction.

Life-threatening severe anaphylactic reactions in patients receiving oxaliplatin chemotherapy

Dear Editor: Oxaliplatin is a third-generation platinum compound frequently used in the treatment of stage III colorectal cancer (CRC) adjuvant chemotherapy and stage IV advanced CRC. Among the common reasons for its withdrawal are frequent peripheral neuropathy, a delayed hypersensitivity reaction, and, most troublesome, anaphylaxis when patients receive accumulated doses of oxaliplatin. Life-threatening severe anaphylactic reactions (SAR) had been reported but without a systemic review. We performed a retrospective analysis of our patients who had oxaliplatin exposure and selected those who developed SAR. During a 6-year period from 2006 to 2011 at Kaohsiung Veterans General Hospital, a total of 412 patients exposed to oxaliplatin-related chemotherapy (FOLFOX) were retrospectively reviewed. Life-threatening SAR was defined as side effects including symptomatic bronchospasm, allergyrelated edema/angioedema, hypotension or anaphylaxis (grade III/IV anaphylactic reactions reference by NIH common Toxicity Criteria v3.0) requiring hospitalization and medical interventions. Relevant English language studies regarding life-threatening SAR following oxaliplatin were also reviewed in MEDLINE® and PubMed® search. Seven patients (1.7 %, 7 of 412 cases) were identified who developed life-threatening SAR in this duration, which occurred after infusion of oxaliplatin-related chemotherapy. Six patients were successfully resuscitated with oxygen support and medical interventions and fully recovered without any sequelae. However, one patient suffered from SAR and went into shock status 20 min after infusion of oxaliplatin. Despite cardiopulmonary resuscitation and inotropic agent use, this patient expired 50 min later. We changed the chemotherapy regimen in five patients and rechallenged oxaliplatin use in patient 3. Because the patient 3’s disease manifestations responded well to FOLFOX chemotherapy regimen, continuation was felt to be desirable. We have thus decided to attempt rechallenge of oxaliplatin by prolongating the infusion rate and using premedications with additional 100 mg hydrocortisone plus diphenhydramine before the next treatment course. Fortunately, no anaphylactic reactions developed thereafter. Twenty-three relevant English language studies, published from 1997 to 2011, were reviewed. We found 59 reported cases that fitted the definition of life-threatening SAR. Together with this seven cases we presented, the median cycles of oxaliplatin given before was 10 (ranged from 2 to 29). The most common symptoms were respiratory distress (60 %), fever (55 %), and hypotension (54 %). Three fatal events were reported (4.5 %). Eleven patients of the 66 cases were rechallenged by oxaliplatin. The estimated incidence of oxaliplatin-induced SAR in most other series was less than 2 %. Multiple mechanisms of actions have been proposed but still unknown. In literature reviews, SAR developed after several cycles of oxaliplatin chemotherapy (median cycles before SAR is 10), suggesting a sensitization process of type I hypersensitivity due to the rapid appearance of symptoms. C.-W. Hsu : T.-M. King :M.-C. Chang : J.-H. Wang (*) Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veteran General Hospital, 386 Ta-Chung 1st RD, Kaohsiung, Taiwan 81346, Republic of China e-mail: ss851124@yahoo.com.tw

Using a Simple Surgical Skill to Forecast a Safe Distal Resection Margin for Low Anterior Resection of Rectal Cancer

Purpose. This study was designed to forecast a safe distal resection margin while performing low anterior resection of rectal cancer. Methods. We included patients with stage I to VI rectal cancer who had been operated on by a single surgeon at Kaohsiung Veterans General hospital between October 2012 and June 2013.We created a mark at the lower border of the tumor. Then, we measured the length (for the upper rectum, 3 cm; for the mid-low rectum, 2 cm) from the lower border in anatomical position as a resection mark. We cut the rectum from the resection mark and then removed the specimen. We measured the distal resection margin of the specimen.We followed the distal resection margin of specimens in pathology reports. We compared the difference between these distal resection margins. Results. Low anterior resection was performed for 70 patients during the study. Other surgeons treated 38 patients who were excluded. Two patients were excluded because they had received neoadjuvant chemoradiation therapy. Totally, 30 patients were included in the study (25 men and 5 women). Seventeen tumors were located in the upper rectum and 13 tumors in the mid-low rectum. The mean distal resection margin (in vivo) was 36.3 ± 8.50 mm. The mean distal resection margin (pathology) was 21.0 ± 9.37 mm. The rate of specimen shrinkage was 44.1%. Conclusion. By measuring the distal resection margin of low anterior resection, we can obtain R0 resection and forecast at least a 1-cm safe pathologic distal resection margin.

Early Enteral Feeding after Colorectal Surgery: Preliminary Hospital Experience

Purpose. The aim of this study was to determinate whether early postoperative enteral feeding is suitable for patients undergoing colorectal surgery in our hospital. Methods. A retrospective review was performed of a prospectively collated database of patients undergoing colorectal surgery in our hospital between March 2014 and March 2015. Patients were divided into two groups, early enteral feeding and traditional ＂nil by mouth＂. The early feeding group was treated by a modified fast track protocol and the traditional group was treated as per usual practice. Primary end point was time to first defecation; secondary end point was anastomosis leakage. Results. Of the 200 enrolled patients, 190 patients were analyzed (95/ group). Mean time to flatus was 2.76 (1 to 10) days in the modified fast track group and 4.07 (3 to 7) days in the traditional group; mean time to first defecation was 4.04 (2 to 13) days and 6.05 (3 to 19) days, respectively. These results were statistically significant (p ＜ 0.05). Time to solid diet in the modified fast track group was 4.44 (3 to 17) days compared with 6.72 (4 to 21) days in the traditional group (p ＜ 0.05). There was one case of anastomic leakage in the traditional group (p=0.316). Conclusion. Early enteral feeding plays an important role in the recovery of patients after colorectal surgery and can improve gastrointestinal function without increasing postoperative complications. More aggressive patient treatment protocols with strict application should be considered in the future.

Horizontal Tumor Size is Inversely Related to Prognosis in Nodal-Positive Stage III Colorectal Cancer

Purpose. Vertical tumor growth, reflected by the T classification, is the most important prognostic variable in colorectal cancer. However, the data regarding the prognostic impact of horizontal tumor size are limited and contradictory. In the present study, we aimed to investigate the effect of maximal horizontal tumor size on patient outcome in patients with nodal-positive stage III colorectal cancer. Methods. We retrospectively reviewed the medical records from 1996 to 2009. We included individuals diagnosed with nodal-positive stage III colorectal cancer who underwent surgical resection, and for whom complete medical records were available. In our analysis, the cut-off values for tumor size were set at 1.0 cm and 0.5 cm. A Kaplan-Meier survival analysis and the Cox proportional hazard model were applied to the data for further analysis. Results. In total, 939 nodal-positive stage III colorectal cancer specimens were reviewed retrospectively. We classified the patients into two groups: those with a maximum horizontal tumor size of ＜ 1.0 cm (57 patients; 6%) and those with a maximum horizontal tumor size of ＞ 1.0 cm (887 patients; 94%).With regard to the TNM classification, the group of patients with tumors ＜ 1.0 cm in size had a greater number of T1-2 stage tumors compared to the group with tumors ＞ 1.0 cm in size (42.1% vs. 27%, p = 0.02).With regard to the primary tumor site, the group of patients with tumors ＜ 1.0 cm in size had a greater number of rectal tumors compared to the group with tumors ＞ 1.0 cm in size (61.7% vs. 45%, p = 0.01). The median disease-free-survival was shorter in patients with tumors ＜ 1.0 cm in size than in patients with tumors ＞ 1.0 cm in size (6.96 months vs. 17.64 months, p = 0.003). Survival was significantly different between these two groups of patients as well (p = 0.008). Using a Cox proportional hazard model, the hazard ratio was found to be 2.29 for patients with tumors ＜ 0.5 cm in size and 1.224 for those whose tumor measured 0.5-1.0 cm in size. Further multivariate analysis also demonstrated that small tumor size is a significant risk factor for a negative prognosis (p = 0.01). Conclusion. In nodal-positive stage III colorectal cancer, tumor size is inversely related to prognosis. We postulated that smaller nodal-positive tumors would display significantly more aggressive tumor behavior as compared to larger tumors. However, these interesting findings require further investigation to corroborate the results.

A Transanal Technique for Accurately Measuring Distal Resection Margin in Rectal Cancer

Purpose. Adequate distal resection margin (DRM) is an important factor determining the outcome of rectal cancer surgery. Traditionally, DRM is measured intra-abdominally after mesorectal excision. We proposed a new method to achieve sufficient DRM and avoid tumor cell exfoliation-caused bysurgical over-manipulation of the rectum involved with tumor. Material and Methods. Between October 2013 and February 2014, 17 patients (seven males, 10 females; median age: 71.1 yrs (range: 44-85 yrs) with rectal cancer who underwent low anterior resection (15 patients) or colo-anal anastomosis (two patients) received our intra-operative trans-anal technique. We used a plastic anoscopeto expand the anal canal and allow the use of a plastic ruler to measure the distal tumor margin. We then performed purse string suture ligation of the distal margin with 3-O vicryl leaving a sufficient length to use as a guide during surgery. During the colectomy, we performed the resection below the suture site. Results. The average ＂in vivo＂ DRM was 43.8 mm +/- SD of 12.7 mm (range: 20-80 mm). Average ＂ex-vivo＂ DRM was 32.7 mm +/- SD of 8.85 mm (range: 20-60 mm). The shrinkage rate, comparing ＂in vivo＂ with ＂ex vivo＂, was 25.3%. The average DRM, as measured by the pathologist (i.e., ＂in vitro＂), was 24.9 mm (range: 15-53 mm). The average shrinkage rate at pathology was 41.9%. Conclusions. Our transanal suture ligation method offers an optimal method to avoid insufficient DRM and tumor cell exfoliation caused by surgical over-manipulation of the rectum involved with tumor.

Drainage placement through the extraperitoneal tunnel can prevent its postoperative dislodgement effectively in laparoscopic rectal surgery.

Background: Drainage placement is frequently used in laparoscopic rectal surgery, and dislodgement is common in conventional transperitoneal drainage placement. We proposed that extraperitoneal tunnel for drainage placement is useful to prevent the dislodgement. Methods: We conducted an observational case-matched control study. In study group, a total of 40 patients undergoing laparoscopic rectal surgery with drainage through the extraperitoneal tunnel were enrolled. In control group, a total of 35 matched patients with drainage through the transperitoneal route were enrolled. Clinical data, tumor features, and intraoperative and postoperative characteristics were analyzed. Results: Ten patients had drainage dislodgement in the transperitoneal group (28%) and 4 patients in the extraperitoneal group (10%). The P value was 0.039. Postoperative recovery was faster in the extraperitoneal group than in the transperitoneal group, as reflected by a shorter time to diet (P=0.049) and postoperative length of stay (P=0.032). In a multivariate analysis, drain dislodgement had a significant impact on the time to diet (P=0.023) and the postoperative length of stay (P=0.037). Drain placement influenced the time to diet (P=0.055) and the postoperative length of stay (P=0.079). Conclusions: In laparoscopic rectal surgery, drainage placement through the extraperitoneal tunnel can prevent its postoperative dislodgement effectively and is associated with better postoperative recovery.