Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group's Comparative Survey Study.

PURPOSE: Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. MATERIALS AND METHODS: A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. RESULTS: The radiation oncologists chose "bone" more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored "peritoneal seeding" (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that "irrelevant, if all metastatic lesions are amendable to local therapy", while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. CONCLUSION: This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy.

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist's and surgeon's perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.

Long-term oncologic outcome of D3 lymph node dissection for clinical stage 2/3 right-sided colon cancer.

PURPOSE: To investigate oncologic outcomes including overall survival and disease-free survival depending on the extent of lymphadenectomy (D3 versus D2) by comparing D3 and D2 lymphadenectomy in patients with clinical stage 2/3 right colon cancer. METHODS: Consecutive series of patients who underwent radical resection for right colon cancer at our three hospitals between January 2015 and June 2018 were retrospectively analyzed. Study cohorts were divided into two groups: D3 group and D2 group. Oncologic, pathologic, and perioperative outcomes of the two groups were compared. RESULTS: A total of 295 patients (167 in the D2 group and 128 in the D3 group) were included in this study. Patients' characteristics showed no significant difference between the two groups. The median number of harvested lymph nodes was significantly higher in the D3 group than in the D2 group. The rate of complications was not significantly different between the two groups except for chyle leakage, which was more frequent in the D3 group. Five-year disease-free survival was 90.2% (95% CI: 84.8-95.9%) in the D3 group, which was significantly (p = 0.028) higher than that (80.5%, 95% CI: 74-87.5%) in the D2 group. There was no significant difference in overall survival between the two groups. CONCLUSION: Our results indicate that D3 lymphadenectomy is associated with more favorable 5-year disease-free survival than D2 lymphadenectomy for patients with stage 2/3 right-sided colon cancer. D3 lymphadenectomy might improve oncologic outcomes in consideration of the recurrence rate.

Clinical outcomes of surgical management for recurrent rectal prolapse: a multicenter retrospective study.

Purpose: There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. Methods: We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. Results: A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2-129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. Conclusion: For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

Oxaliplatin-based adjuvant chemotherapy rather than fluorouracil-based chemotherapy in rectal cancer is more efficient to decrease distant metastasis and increase survival after preoperative chemoradiotherapy and surgery: a meta-analysis.

PURPOSE: The standard treatment of stage II-III rectal cancer is preoperative chemoradiotherapy (CRT), followed by total mesorectal excision (TME). However, the rate of metastasis is still high following this treatment. Therefore, several adjuvant chemotherapy studies have been conducted on reducing subsequent metastases and increasing survival, although there are still no definite conclusions. METHODS: We searched for published prospective randomized controlled trials comparing adjuvant chemotherapy regimens following standard preoperative CRT and curative surgery in stage II-III rectal cancer. We systematically searched Medline, Embase, and the Cochrane Library for relevant trials done from January 2004 to January 2021. Review Manager (RevMan, version 5.3) was used to analyze the data. RESULTS: We initially searched 1955 studies. We screened and carefully selected four randomized controlled trials with 2897 patients. Compared to the 5-FU-based regimen group, the oxaliplatin-added regimen group attained a higher 3-year locoregional control rate (relative risk [RR] of 0.64, 95% confidence interval [CI], 0.48-0.86; p = 0.003) and 3-year distant metastasis control rate (RR of 0.82, 95% CI, 0.71-0.95; p = 0.007). The oxaliplatin-added regimen group had significantly increased 3-year disease-free survival with a hazard ratio (HR) of 0.85 (95% CI: 0.74-0.97, p = 0.020), but not overall survival (p = 0.740). Grade 3 or higher acute toxicity rates did not differ between the two groups (p = 0.190). CONCLUSION: The addition of oxaliplatin to adjuvant therapy for stage II-III rectal cancer following preoperative CRT and TME may increase disease-free survival without significant increases in toxicity, but not overall survival.

Impact of D3 lymph node dissection on upstaging and short-term survival in clinical stage I right-sided colon cancer.

BACKGROUND: D3 lymph node dissection is becoming the standard procedure for the treatment of advanced right colon cancer and has shown increasing evidence of its oncologic benefit. However, a clear indication for its application is lacking and data on this topic is unsatisfactory. Thus, the necessity for D3 lymph node dissection in clinical stage I right colon cancer remains controversial. METHODS: We retrospectively analyzed data from clinical stage I right colon cancer patients who underwent radical surgery at three hospitals of Korea university medical center between January 2015 and June 2018. We compared surgical complications and short-term oncologic outcomes between D2 and D3 lymph node dissections in these patients. RESULTS: Among 512 patients, 122 (23.8%) were clinical stage I. Of these, 88 and 34 patients received D2 and D3 lymph node dissection, respectively. There were no statistically significant differences in clinicopathologic variables and surgical outcomes between the two groups. Upstaging occurred in 16 patients (47.1%) in the D3 group and 23 patients (26.1%) in the D2 group. There were four recurrences in the D2 group but no recurrence in the D3 group. Log-rank tests showed no statistically significant difference in disease-free survival rates between the two groups (p = 0.210). CONCLUSION: There was no significant difference in disease-free survival rates between D2 and D3 lymph node dissection in clinical stage I right colon cancer patients. However, recurrence occurred in the D2 group. Efforts to improve the accuracy of clinical staging are required and more studies with better quality are needed.

Laparoscopic surgery: an effective and safe surgical method of pediatric inguinal hernia repair.

Purpose: Inguinal hernia (IH) repair is very commonly performed in children. While open repair (OR) is the standard approach, laparoscopic repair is increasingly used. This study was aimed to investigate safety and feasibility of laparoscopic repair of pediatric IH compared to OR. Methods: We retrospectively enrolled 105 pediatric patients with IH repair between January 2011 and October 2019. The laparoscopic procedures performed were laparoscopic percutaneous extraperitoneal closure (LPEC), and three-port mini-laparoscopic repair (TLR). The OR was performed as per usual technique. Results: Thirty-nine patients underwent OR, 16 LPEC, and 50 TLR. The preoperative laterality of IH was 45 patients (42.9%) on the right side, 50 (47.6%) on the left side, and 10 (9.5%) on both sides. It was, however, diagnosed postoperatively in 27 patients (25.7%) on the right side, 38 (36.2%) on the left side, and 40 (38.1%) on both sides. Of the 63 patients who presented with unilateral IH in the laparoscopic groups, 32 (50.8%) had synchronous contralateral patent process vaginalis (PPV) which were simultaneously repaired. This was significantly more common in children under 3 years of age. Operative time in unilateral or bilateral repair was significantly shorter in the laparoscopic repair groups (p < 0.001). Ipsilateral recurrence was not observed in any group. Metachronous contralateral IH occurrence was not significantly different between groups. Conclusion: Laparoscopic IH repair may have benefit in terms of shorter operation time and diagnosis of unpredicted contralateral PPV compared to OR.

Anti-metastatic effect of metformin via repression of interleukin 6-induced epithelial-mesenchymal transition in human colon cancer cells.

Metformin, a first-line drug used to treat type 2 diabetes, has also been shown to have anticancer effects against a variety of malignancies, including colorectal cancer. Although inhibition of the mTOR pathway is known to be the most important mechanism for the antitumor effects of metformin, other mechanisms remain unclear. The purpose of this study was to identify the antitumor mechanism of metformin in colorectal cancer using high-throughput data, and then test the mechanism experimentally. We identified the gene signature of metformin-treated colon cancer cells. This signature was processed for prediction using colon adenocarcinoma patient data from the Cancer Genome Atlas to classify the patients showing a gene expression pattern similar to that in metformin-treated cells. This patient group showed better overall and disease-free survival. Furthermore, pathway analysis revealed that the metformin-predicted group was characterized by decreased interleukin (IL)-6 pathway signaling, epithelial-mesenchymal transition, and colon cancer metastatic signaling. We induced epithelial-mesenchymal transition in colon cancer cell lines via IL-6 treatment, which increased cell motility and promoted invasion. However, these effects were blocked by metformin. These findings suggest that blockade of IL-6-induced epithelial-mesenchymal transition is an antitumor mechanism of metformin.

Korean physicians' policies for postoperative surveillance of colorectal cancer.

Background/Aims: We explored Korean physicians' policies for surveillance of colorectal cancer (CRC) after curative surgery. METHODS: Web-based self-report questionnaires were developed. Invitations to participate were emailed to physicians who diagnosed and treated CRC from October 1 to November 15, 2015. The questionnaire consisted of the role doctors played in the surveillance, examination of surveillance, and duration of postoperative surveillance according to CRC stage or primary site of the cancer. RESULTS: Ninety-one physicians participated in the online survey, and 78 completed the survey. Sixty-seven participants (13%) answered "up to 5 years" for stage I surveillance duration; and 11 (13%) responded with a duration of > 5 years for stage I. A total of 61 (75%) responded with a surveillance duration of up to 5 years for stage II; and 19 (24%) responded with a duration of > 5 years for stage II. Sixty-seven (97%) and 61 (91%) physicians monitored patients with stage II/III every 3 or 6 months by laboratory examination and by abdominopelvic computed tomography scan for the first year, respectively. A total of 43 (53%) responded with a surveillance duration of up to 5 years for stage IV; and 46 (46%) responded with a duration of > 5 years for stage IV after curative resection. Conclusions: Korean physicians mostly followed up CRC using intensive postoperative surveillance. In preference to monitoring over a comparatively shorter period of time, the physicians tended to prefer monitoring patients post-operatively over a > 5 year period, particularly in cases of advanced-stage CRC.

Effect of a Shortened Duration of FOLFOX Chemotherapy on the Survival Rate of Patients with Stage II and III Colon Cancer.

BACKGROUND: FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. METHODS: Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. RESULTS: Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). CONCLUSIONS: Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates.

Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II-III resectable rectal cancer: a meta-analysis of randomized controlled trials.

PURPOSE: Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II-III rectal cancer. MATERIALS AND METHODS: We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. RESULTS: Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41-0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). CONCLUSIONS: As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

Clinical Significance of 5-Fluorouracil Chemosensitivity Testing in Patients with Colorectal Cancer.

AIM: To evaluate whether the results of chemosensitivity testing were associated with prognosis of colorectal cancer patients after adjuvant 5-fluorouracil (FU)/ leucovorin chemotherapy. PATIENTS AND METHODS: Eighty-nine patients who received 5-FU/leucovorin adjuvant chemotherapy for colorectal cancer were enrolled. Chemosensitivity tests were performed and tumor growth inhibition rate was calculated using the MTT (3-(4,5-dimethylthiazol-2-yl)02,5-diphenyl-2H tetrazolium bromide) assay. RESULTS: Fifty-one patients (57.3%) were sensitive to 5-FU according to the chemosensitivity test. After a median follow-up of 64 months, there was a significant difference between the 5-year disease-free survival rates of the chemo-sensitive and chemo-resistant groups. However, there was no significant difference in the overall 5-year survival between the chemo-sensitive and chemo-resistant groups. CONCLUSION: A positive 5-FU sensitivity test with in vitro histoculture drug response assay (HDRA) was associated with better disease-free survival. Chemosensitivity may be a prognostic factor for colorectal cancer patients undergoing adjuvant 5-FU/leucovorin chemotherapy.

Lymph Node Micrometastasis Cannot Be Considered as Positive Lymph Node in Nonmetastatic Colorectal Cancer.

The prognostic value of micrometastasis in colorectal cancer (CRC) remains controversial. The study investigated whether lymph node (LN) micrometastasis can have prognostic value in CRC as compared with macrometastasis. The study included 488 patients with curatively resected stage I, II, or III CRC treated between 2004 and 2011. Immuohistochemical staining with monoclonal antibody CAM 5.2 was performed on negative LNs by hematoxylin-eosin staining. The prognostic value of LN micrometastasis was investigated in multivariate analysis. Regression analysis was performed to identify a causal relationship between micro- and macrometastasis. Survival differences were compared between conventional N staging and hypothetic N staging taking micrometastasis in the positive node. A total of 93 patients (19.1%) showed LN micrometastasis. Patients with micrometastasis had more advanced tumor characteristics in terms of tumor size, grade, T stage, N stage, lymphatic invasion, and vascular invasion. In multivariate analysis, micrometastasis was not related with recurrence. Preoperative carcinoembryonic antigen level, neural invasion, and macrometastasis were independent risk factors in the analysis. Regression analysis showed that there was not a causal relationship between micro- and macrometastasis (R2 = 0.004, P = 0.153). When the cumulative numbers of micro- and macrometastatic LNs were calculated together, the discriminative power of survival difference between each node stage became less prominent, compared with conventional N staging. LN micrometastasis is related with advanced tumor characteristics, but does not reflect poor prognosis in nonmetastatic CRC. Micrometastasis cannot be considered as positive LN to predict poor prognosis.

Clinical benefits and oncologic equivalence of self-expandable metallic stent insertion for right-sided malignant colonic obstruction.

BACKGROUND: The efficacy of stenting for right-sided malignant colonic obstruction is unknown. This study aimed to evaluate the safety, feasibility, and clinical benefits of self-expandable metallic stent insertion for right-sided malignant colonic obstruction. METHODS: Clinical data from patients who underwent right hemicolectomy for right colon cancer from January 2006 to July 2014 at three Korea University hospitals were retrospectively reviewed. A total of 39 patients who developed malignant obstruction in the right-sided colon were identified, and their data were analyzed. RESULTS: Stent insertion was attempted in 16 patients, and initial technical success was achieved in 14 patients (87.5 %). No stent-related immediate complications were reported. Complete relief from obstruction was achieved in all 14 patients. Twenty-five patients, including two patients who failed stenting, underwent emergency surgery. In the stent group, 93 % (13/14) of patients underwent elective laparoscopic surgery, and only one surgery was converted to an open procedure. All patients in the emergency group underwent emergency surgery within 24 h of admission. In the emergency group, only 12 % (3/25) of patients underwent laparoscopic surgery, with one surgery converted to an open procedure. All patients in both groups underwent either laparoscopy-assisted or open right/extended right hemicolectomy with primary anastomoses as the first operation. The operative times, retrieved lymph nodes, and pathologic stage did not differ between the two groups. Postoperative hospital stay (9.4 ± 3.4 days in the stent group vs. 12.4 ± 5.9 in the emergency group, p = 0.089) and time to resume oral food intake (3.2 ± 2.1 days in the stent group vs. 5.7 ± 3.4 in the emergency group, p = 0.019) were shorter in the stent group. And there were no significant differences in disease-free survival and overall survival between the two groups. CONCLUSIONS: Stent insertion appears to be safe and feasible in patients with right-sided colonic malignant obstruction. It facilitates minimally invasive surgery and may result in better short-term surgical outcomes.

Risk factors causing structural sequelae after anastomotic leakage in mid to low rectal cancer.

AIM: To investigate the risk factors causing structural sequelae after anastomotic leakage in patients with mid to low rectal cancer. METHODS: Prospectively collected data of consecutive subjects who had anastomotic leakage after surgical resection for rectal cancer from March 2006 to May 2013 at Korea University Anam Hospital were retrospectively analyzed. Two subgroup analyses were performed. The patients were initially divided into the sequelae (stricture, fistula, or sinus) and no sequelae groups and then divided into the permanent stoma (PS) and no PS groups. Univariate and multivariate analyses were performed to identify the risk factors of structural sequelae after anastomotic leakage. RESULTS: Structural sequelae after anastomotic leakage were identified in 29 patients (39.7%). Multivariate analysis revealed that diversion ileostomy at the first operation increases the risk of structural sequelae [odds ratio (OR) = 6.741; P = 0.017]. Fourteen patients (17.7%) had permanent stoma during the follow-up period (median, 37 mo). Multivariate analysis showed that the tumor level from the dentate line was associated with the risk of permanent stoma (OR = 0.751; P = 0.045). CONCLUSION: Diversion ileostomy at the first operation increased the risk of structural sequelae of the anastomosis, while lower tumor location was associated with the risk of permanent stoma in the management of anastomotic leakage.

Endoscopic obstruction in rectal cancers: survival and recurrence patterns following curative surgery.

BACKGROUND: It is controversial whether preoperative obstruction in rectal cancers can affect prognosis or influence recurrence patterns. We investigated the association between endoscopic obstruction with survival and recurrence patterns in patients with locally advanced rectal cancers. MATERIALS AND METHODS: An observational study and multivariate analysis were conducted to identify determinants of survival and to compare recurrence patterns between patients with obstructive or nonobstructive tumors after curative resection. Endoscopic obstruction was defined as a luminal obstruction of the rectum severe enough to prevent the colonoscope from passing beyond the tumor. RESULTS: Cancer was obstructive in 91 patients (16.8%) and nonobstructive in 452 (83.2%). Median follow-up was 50 (range, 3-161) months. Local recurrence occurred in 17 patients (14 nonobstructed [5.4%] and 3obstructed [5.5%]; P=1.0) and systemic recurrence in 83 (62 nonobstructed [23.8%] and 21 obstructed [38.2%]; P=.042]). Endoscopic obstruction was a significant prognostic factor in stage III rectal cancers (P=.001) but not in stage II tumors. The multivariate analysis showed that endoscopic obstruction was an independent prognostic factor for overall survival, but not for disease-free survival, in patients with stage III rectal cancers. Endoscopic obstruction was associated with multiple-site systemic recurrence that was unsalvageable (salvageable surgery, 24 nonobstructed [40%] and 2 obstructed [10%]; P=.014). CONCLUSIONS: Endoscopic obstruction in patients with stage III rectal cancer predicted worse overall survival and was associated with multiple-site systemic recurrence.

Tracheal metastasis from rectal cancer: a case report and review of the literature.

The trachea is an uncommon site of metastasis from colorectal carcinoma. A few cases have been reported in the literature, but these focused mostly on the clinical aspects without detailing radiologic and histologic findings. The authors describe a 70-year-old woman who was diagnosed with tracheal metastasis from a primary rectal cancer. We present the contrast-enhanced chest computed temography (CT), including volume-rendered image, as well as bronchoscopic findings.

Transanal rectal foreign body removal using a SILS port.

Rectal foreign bodies are being detected more frequently, and their textures, sizes, shapes, and locations are critical considerations when removal and deciding on management plans. Many removal techniques have been described and various theories have been put forward to explain procedural mechanics. Here the authors report a case in which a transanal technique using a SILS port was successfully used.

Can immunohistochemistry of multidrug-resistant proteins replace the histoculture drug response assay in colorectal adenocarcinomas?

BACKGROUND/AIMS: To investigate 1) whether immunohistochemistry of multidrug-resistant (MDR) proteins (MDR1, MRP1, MRP2 and BCRP) in colorectal adenocarcinomas can substitute for histoculture drug response assays (HDRA) and 2) whether chemosensitivity as indicated by HDRA and MDR protein expression is related to prognostic parameters in colorectal cancers. METHODOLOGY: Chemosensitivity of cancer tissues to 5-FU, irinotecan and oxaliplatin was assessed by HDRA. Immunohistochemical staining of MDR proteins was quantified by image analysis in 76 colorectal adenocarcinoma patients. RESULTS: Inhibition rates (IRs) of the anticancer drugs by HDRA were not related to MDR protein expression. However, the IR of 5-FU was significantly decreased with lymph node metastasis (p=0.03) and advanced clinical stages (p=0.047). The IRs of irinotecan and oxaliplatin were not associated with clinicopathological parameters. Immunohistochemically, positive scores for MRP2 and BCRP protein were paradoxically related to lower clinical stages (p=0.043) and male gender (p=0.019), respectively. CONCLUSIONS: Immunohistochemical staining of MDR proteins can not predict tumor responses to anticancer drugs in colorectal cancers. Chemoresistance to 5-FU as indicated by HDRA was highly associated with aggressive prognostic factors.