A case report of anal fistula-associated mucinous adenocarcinoma developing 3 years after treatment of perianal abscess.

BACKGROUND: A long-standing (over 10 years) anal fistula is considered a fundamental cause of fistula-associated mucinous adenocarcinoma (FAMC). Perianal abscesses and anal fistulas are two sequential phases of the same anorectal infectious process. We experienced a case of FAMC which developed 3 years after the treatment of a perianal abscess. CASE PRESENTATION: A 68-year-old woman was admitted to our hospital because of progressive anal pain and a palpable tumor. She had a history of undergoing a drainage operation for a perianal abscess 3 years previously. A 15 × 15-mm tumor at the former drainage site was identified; transanal ultrasonography showed an intersphincteric fistula connecting to the tumor. A biopsy taken from the tumor demonstrated mucinous adenocarcinoma; the tumor was diagnosed as FAMC. Laparoscopic abdominoperineal resection was performed. Histopathology showed highly dysplastic cells lining the lumen of the anal fistula and poorly differentiated mucinous adenocarcinoma proliferating in the dermis and epidermis in the distal aspect of the fistula. CONCLUSIONS: FAMC can develop within fewer than 3 years after the development of a perianal abscess and anal fistula.

Subcutaneous incision of the fistula tract and internal sphincterotomy (SIFT-IS): a novel surgical procedure for transsphincteric anal fistula.

AIM: The aetiology of anal fistula has not been fully clarified. One of the causes of anal fistulas may be the markedly deep crypts that characterize the primary openings. We developed subcutaneous incision of the fistula tract and internal sphincterotomy (SIFT-IS) to eradicate these deep crypts. The aim of this study was to evaluate outcomes in patients with anal fistula treated with SIFT-IS. METHOD: A retrospective study was performed over a 2-year period. Patients with transsphincteric anal fistula who underwent SIFT-IS were enrolled. The primary endpoint was the anal fistula healing rate at 16 weeks postoperatively. The secondary endpoints were healing time, postoperative complications and clinical continence status. RESULTS: One hundred and fifty one patients were enrolled. Primary healing was accomplished in 129 patients (85%). There were 17 patients (11%) with a remnant fistula and five (3%) with a recurrence. The remnant fistulas healed spontaneously at more than 16 weeks postoperatively in seven patients. The median healing time was 6 (3-96) weeks. Surgical intervention was required in seven patients with a remnant fistula and four with recurrence. At the final follow-up, the wounds had healed in 148 patients (98%). No significant postoperative complications or incontinence were observed. CONCLUSION: Subcutaneous incision of the fistula tract and internal sphincterotomy is a promising surgical option for transsphincteric anal fistulas, with a satisfactory healing rate.

Even a partial pathological response is associated with lower relapse rates in patients with operable rectal cancer undergoing neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy to treat locally advanced rectal cancer is an effective therapeutic strategy for the prevention of local recurrence and distant organ metastasis after surgery. OBJECTIVES: To assess the prognostic significance of histopathological tumor response in rectal cancer patients undergoing neoadjuvant chemotherapy. METHODS: This study included patients with operable rectal cancer who received neoadjuvant chemotherapy using the FOLFOX regimen (5-fluorouracil, l-leucovorin, and oxaliplatin) in a hospital between February 2012 and November 2017. The main outcome measure was disease-free survival with respect to histopathological response to neoadjuvant chemotherapy in resected specimens. RESULTS: The median follow-up was 32 months. Of 48 patients treated with neoadjuvant FOLFOX, 24 (50%) were classified as responders, which included two patients with pathological complete response and 22 patients with partial response. The remaining 24 patients (50%) were classified as nonresponders. Responders had a significantly better 3-year disease-free survival than nonresponders (86% vs. 62%, p = .02). CONCLUSIONS: Patients whose surgical specimens show a pathological complete response or partial response have good oncologic outcomes.

Emerging RAS, BRAF, and EGFR mutations in cell-free DNA of metastatic colorectal patients are associated with both primary and secondary resistance to first-line anti-EGFR therapy.

Oncogenic RAS mutations are negative biomarkers of response to epidermal growth factor receptor (EGFR) blockade. RAS mutations are usually detected in biopsies of primary colorectal tumors. However, the genomic profiles of primary tumors and metastases are not always concordant, and chemotherapeutic agents can alter the tumor molecular landscape. Cell-free DNA (cfDNA) is a novel tool to detect molecular heterogeneity. This study evaluated the clinical utility of cfDNA to predict primary or secondary resistance to EGFR blockade in patients with metastatic colorectal cancer. Thirty metastatic colorectal cancer patients without RAS and BRAF mutations were prospectively enrolled and treated with cytotoxic agents and EGFR blockade as first-line therapy. cfDNA was analyzed for the presence of RAS, BRAF, and EGFR (S492R) point mutations before initiating chemotherapy and every 2 months during chemotherapy. The analysis was performed in 223 plasma samples from all 30 patients. Of the 30 patients, five had RAS mutations in their cfDNA before starting chemotherapy and did not respond. Twenty-four of the remaining 25 patients without cfDNA RAS mutations had a response. Twenty of the 24 responders developed secondary resistance and cfDNA RAS mutations were found in 17 of the 20. cfDNA BRAF mutations were found in seven, and EGFR mutations were found in eight of the 20 patients. Emerging RAS, BRAF, and EGFR mutations occurred in patients with primary and secondary resistance to EGFR blockade. The detection of these mutations in cfDNA is a promising approach to predict treatment response and secondary resistance.

Development of transomental hernia shortly after laparoscopic colonic surgery: a case report.

BACKGROUND: A transomental hernia is defined as bowel invagination into an abnormal hiatus of the omentum. It is a rare type of internal hernia that is sometimes lethal. We herein report a case of a transomental hernia developing shortly after laparoscopic sigmoidectomy. CASE PRESENTATION: A 71-year-old man underwent laparoscopic sigmoidectomy. He was admitted to our hospital because of abdominal pain and nausea on postoperative day 12. Laboratory investigation showed increased levels of inflammatory markers. Abdominal computed tomography showed a closed loop and mesenteric edema of the small intestine with ascites. We performed an emergency operation under the diagnosis of strangulated bowel obstruction. Operative findings showed internal herniation of strangulated ileal loops through a defect of the omentum with hemorrhagic ascites. The incarcerated small bowel was resected and reconstructed because the ischemic change was irreversible after the reduction. We partially resected the omentum that had formed the defect. The patient's postoperative progress was good, and he was discharged on postoperative day 8. CONCLUSIONS: Almost all internal hernias after intestinal surgery are mesenteric hernias; however, we should bear in mind that the more lethal transomental hernia is also possible. Therefore, immediate surgical exploration should be performed in a timely manner for internal hernias, especially for patients with early-onset symptoms after laparoscopic intestinal surgery.

Circulating cell-free long DNA fragments predict post-hepatectomy recurrence of colorectal liver metastases.

INTRODUCTION: Most patients with colorectal liver metastases, who undergo hepatectomy, experience recurrence. Although the prognosis is poorer for patients with early recurrence (within 6 months after hepatectomy) compared with later recurrence, no biomarker has been identified to predict early recurrence. Minimal residual disease (MRD) in patients who undergo curative surgery is the main cause of recurrence. In cancer patients, long fragment cell-free DNA is detected, and the presence of long fragments of cell-free DNA after surgery can indicate MRD. In this study, we developed a novel biomarker to predict early recurrence of colorectal liver metastases using cell-free DNA. MATERIALS AND METHODS: Forty-one patients with colorectal liver metastases were enrolled. Peripheral blood samples were collected before and at 1 month after hepatectomy. Cell-free DNA was extracted from 1 ml plasma, and the long fragment/ß-globin ratio, which can indicate MRD, was measured by real-time polymerase chain reaction. RESULTS: Three of 21 patients (14.3%) with decreases in the long cell-free DNA fragment/ß-globin ratio after hepatectomy developed early recurrence compared with twelve of 20 patients (60.0%) with an increased ratio (P = 0.002). Patients with a decreased long fragment/ß-globin ratio after hepatectomy had significantly longer recurrence-free survival compared with patients with an increased ratio (366 vs 102 days, P < 0.001). CONCLUSION: The cell-free DNA long fragment/ß-globin ratio may serve as an effective biomarker of early recurrence in patients with colorectal liver metastases, who undergo hepatectomy.

Establishment and characterization of a novel neuroendocrine carcinoma cell line derived from a human ascending colon tumor.

The incidence of rare neuroendocrine tumors (NET) is rapidly increasing. Neuroendocrine carcinoma (NEC) is a NET with poorly differentiated histological features, high proliferative properties and associated poor prognoses. As these carcinomas are so rare and, thus, affect only a small number of patients allowing for few cell lines to be derived from patient biopsies, the histological, immunohistochemical, and clinical characteristics associated with colorectal NEC and NEC in other organs have yet to be clearly defined. Herein, we describe the establishment of a novel NEC cell line (SS-2) derived from a tumor resection of the ascending colon from a 59-year-old Japanese woman. The histological, electron microscopic and immunohistochemical features of chromogranin A (CgA) as well as confirmation of synaptophysin positivity in this tumor were typical of those commonly observed in surgically resected colorectal NEC. Further, the Ki-67 labeling index of the resected tumor was >20% and, thus, the tumor was diagnosed as an NEC of the ascending colon. The SS-2 cell line maintained characteristic features to those of the resected tumor, which were further retained following implantation into subcutaneous tissues of nude mice. Additionally, when SS-2 cells were seeded into ultra-low attachment plates, they formed spheres that expressed higher levels of the cancer stem cell (CSC) marker CD133 compared to SS-2 cells cultured under adherent conditions. SS-2 cells may, therefore, contribute to the current knowledge on midgut NEC biological function while providing a novel platform for examining the effects of colorectal NEC drugs, including CSC.

In vitro and in vivo studies on the association of long non­coding RNAs H19 and urothelial cancer associated 1 with the susceptibility to 5­fluorouracil in rectal cancer.

There is no predictive biomarker for response to 5­fluorouracil (5FU)­based neoadjuvant chemotherapy (NAC) in rectal cancer. In the present study, we examined potential long non­coding RNAs (lncRNAs) linked to the susceptibility to 5FU in cultured colorectal cancer cells, and in biopsy and resected tissues of 31 human rectal cancer cases treated with NAC. Candidate lncRNAs for the prediction of susceptibility to 5FU were investigated by comprehensive analysis of expression profiles of 84 lncRNAs in cultured cells using PCR array. Bioinformatic analysis identified H19 and urothelial cancer associated 1 (UCA1) as candidate biomarkers for 5FU susceptibility. Quantitative PCR of H19 and UCA1 in cultures of colorectal cancer cells demonstrated the notable variation in expression. The ratios of changes of H19 and UCA1 expression in response to 5FU were low in cells resistant to 5FU, whereas ratios were high in cells susceptible to 5FU. In 5FU­susceptible cells, cell proliferation was inhibited by 5FU. Upregulation of H19 and UCA1 were associated with the reduction in target molecule expression, including retinoblastoma and p27kip1. In 31 cases of rectal cancer, H19 and UCA1 expression levels in biopsy and resected tissue were comparable. The ratios of H19 and UCA1 expression in resected tissue compared with biopsy samples were low in 17 cases, whereas the ratios were high in 14 cases; 11 of the 17 cases (65%) with low ratios exhibited poor response to NAC, whereas 4 of the 14 cases (29%) with high ratios showed poor response (P=0.045). The increase in H19 and UCA1 expression may represent the response to impaired cell cycle in cells susceptible to 5FU. Our results indicate that changes in H19 and UCA1 expression may be considered for predicting the susceptibility to 5FU­based NAC in rectal cancer.

Analysis of colorectal cancer-related mutations by liquid biopsy: Utility of circulating cell-free DNA and circulating tumor cells.

We recruited 56 colorectal cancer patients and compared the mutational spectrum of tumor tissue DNA, circulating cell-free DNA (ccfDNA) and circulating tumor cell (CTC) DNA (ctcDNA) to evaluate the potential of liquid biopsy to detect heterogeneity of cancer. Tumor tissue DNA, ccfDNA, and ctcDNA were extracted from each patient and analyzed using next-generation sequencing (NGS) and digital PCR. To maximize yields of CTC, three antibodies were used in the capture process. From 34 untreated patients, 53 mutations were detected in tumor tissue DNA using NGS. Forty-seven mutations were detected in ccfDNA, including 20 not detected in tissues. Sixteen mutations were detected in ctcDNA, including five not detected in tissues. In 12 patients (35.3%), mutations not found in tumor tissues were detected by liquid biopsy: nine (26.5%) in ccfDNA only and three (8.8%) in ctcDNA only. Combination analysis of the two liquid biopsy samples increased the sensitivity to detect heterogeneity. From 22 stage IV patients with RAS mutations in their primary tumors, RAS mutations were detected in 14 (63.6%) ccfDNA and in eight (36.4%) ctcDNA using digital PCR. Mutations not detected in primary tumors can be identified in ccfDNA and in ctcDNA, indicating the potential of liquid biopsy in complementing gene analysis. Combination analysis improves sensitivity. Sensitivity to detect cancer-specific mutations is higher in ccfDNA compared with ctcDNA.

Liquid Biopsy for the Management of Patients with Colorectal Cancer.

BACKGROUND: Liquid biopsy is a collective term that refers to the analysis of tumor-derived biomarkers isolated from biological fluids of cancer patients. Recently, many authors reported the usefulness of liquid biopsy for the management of malignancy. Summary and Key Messages: The peripheral blood of cancer patients is a pool of cells and/or cell products derived from the primary or metastatic tumor, including circulating tumor cells (CTCs), circulating free (cf) DNA or RNA, and exosomes containing proteins, nucleic acids, and lipids. CTCs are tumor cells that can be isolated from peripheral blood. Free circulating DNA with a tumor-specific mutation is called circulating tumor DNA (ctDNA). Some patients who undergo curative surgery experience recurrent disease, which can be due to the presence of minimal residual disease (MRD). Thus, MRD indicates a high risk of relapse. Detection of ctDNA or CTC after surgery is a direct proof of MRD. Molecular volume (e.g., the number of CTCs and level of ctDNA) might reflect tumor burden, thus high molecular volume may indicate poor prognosis. The most notable application of liquid biopsy in cancer is to understand spatial and temporal heterogeneities. Heterogeneity is one of the causes of refractoriness and hampers prediction of chemotherapeutic effect. Emerging mutations that are not present in primary tumors but are found in their metastases can be detected in ctDNA. Some colorectal cancer patients with wild-type RAS do not respond to epidermal growth factor receptor blockade. In a subset of these patients, RAS mutation is detected in ctDNA, indicating heterogeneity.

[Effectiveness of Chemoradiotherapy for the Treatment of Local Recurrence in Rectal Cancer-A Case Report].

Chemoradiotherapy(CRT)for locally recurrent rectal cancer can shrink the tumor and permit R0 resection; however, its effectiveness and safety have not been established. Herein, we report a case of a 60s man with locally recurrent rectal cancer invading the surrounding organs who was administered CRT followed by R0 laparoscopic-assisted abdominoperineal resection( APR). Local recurrence was detected 11 months after laparoscopic-assisted low anterior resection(pT3N0M0, pStage Ⅱ). After tumor shrinkage by CRT(capecitabine 3,000mg/day plus 45 Gy/25 Fr), laparoscopic-assisted APR was performed. The pathological findings showed a pathological complete response(pCR). The patient had not experienced recurrent disease at 6 months after the second surgery. CRT may improve the prognosis of patients with locally recurrent rectal cancer, especially those with possibly unresectable tumors.

[Consideration for Prognostic Indicators of Ovarian Metastasis of Colorectal Cancer].

Ovarian metastasis of colorectal cancer is associated with poor prognosis. Recent advances in chemotherapy may improve this prognosis. In this retrospective study, we evaluated indicators of poor prognosis for ovarian metastasis of colorectal cancer. Twenty patients, who were diagnosed with ovarian metastasis of colorectal cancer from April 2000 to December 2017, were enrolled. Oophorectomy was performed in 18 of the 20 patients. Postoperative chemotherapy was provided to 13 patients, and molecular targeting agents were administered in 5 patients. Metastases to other organs besides the ovaries, premenopausal condition, undifferentiated histologic type of the primary tumor, and no resection of ovarian metastases were identified as indicators of poor prognosis. The 3-year survival rate was 15%, and the 5-year survival rate was 0%. In conclusion, oophorectomy can improve the prognosis of patients with ovarian metastasis of colorectal cancer. However, prognostic improvement due to molecular target agents was not shown.

Male sex and history of ischemic heart disease are major risk factors for anastomotic leakage after laparoscopic anterior resection in patients with rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is the most serious and common complication of surgery for rectal cancer, and associated risk factors remain unknown despite developments in laparoscopic surgery. The present study aimed to determine risk factors for AL after laparoscopic anterior resection (AR) of rectal cancer. METHODS: This retrospective cohort study extracted information from a prospective database of all consecutive colorectal resections that proceeded at Nippon Medical School Hospital between January 2011 and December 2015 (n = 865). We identified 154 patients with rectal cancer treated by elective laparoscopic AR with anastomosis using primary double-stapling. Clinical variables and comorbidity, habits, and surgery-related variables were assessed by univariate and multivariate analyses to determine preoperative risk factors for clinical AL. RESULTS: The overall rate of clinical AL was 11.7% (18 of 154 patients), and 5 (27.8%) of 18 patients required revised laparotomy. Data from males were analyzed because AL occurred only in males. Univariate analysis of male patients (n = 100) significantly associated preoperative creatinine values (p = 0.03) and a history of ischemic heart disease (IHD) (p = 0.012) with AL. The frequency of AL tended to increase (p = 0.06) when patients had low AR (p = 0.06) and transanal drainage. Having AL significantly prolonged hospital stays compared with patients without leakage (36.2 vs. 11.1 days; p <  0.01). Multivariate analysis identified a history of IHD (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.27-17.5; p = 0.025] as an independent risk factor for AL. CONCLUSIONS: Male sex and a history of IHD are possible risk factors for AL after elective laparoscopic rectal cancer surgery.

Feasibility of Neoadjuvant FOLFOX Therapy Without Radiotherapy for Baseline Resectable Rectal Cancer.

BACKGROUND/AIM: The combination of oxaliplatin, leucovorin and fluorouracil (FOLFOX) has been established as postoperative adjuvant chemotherapy for stage III colon cancer. However, the safety and efficacy of neoadjuvant FOLFOX in patients with rectal cancer are still controversial. This prospective pilot study aimed to evaluate the feasibility of neoadjuvant FOLFOX therapy without radiation for baseline resectable rectal cancer (RC). PATIENTS AND METHODS: The study included 30 patients with clinical stage II/III RC between February 2012 and December 2015. The patients were treated with six cycles of FOLFOX followed by elective surgery. The primary endpoint was the R0 resection rate. The secondary endpoints were the scheduled treatment completion rate, adverse events, pathological response and the disease-free survival (DFS) rate. RESULTS: All the patients underwent elective R0 resection after neoadjuvant FOLFOX therapy. The completion rate of the 6-cycle regimen was 93.3% (28/30 patients). Grade 3-4 adverse events occurred in seven patients (23.3%). Pathological complete response was noted in two patients (6.7%). The 3-year DFS rate was 77.5% (95% confidence interval, 61.4%-93.7%). CONCLUSION: Neoadjuvant FOLFOX therapy without radiation is a feasible therapeutic strategy for baseline resectable RC.

Evaluation of liquid biopsies for detection of emerging mutated genes in metastatic colorectal cancer.

BACKGROUND: Detection of gene mutations is important for planning molecular targeted therapy. Although most gene mutations are concordant between primary colon cancers and their liver metastases, new mutations can emerge in metastases. The liquid biopsy is a newly developed, gene analytic method to detect mutations in metastatic tumors. In this prospective study, we evaluated the applicability of liquid biopsies in the detection of mutations in primary and metastatic tumors. METHODS: We included 22 patients with liver metastases from colorectal cancer and extracted DNA from primary colorectal tumors, metastatic liver tumors, and peripheral blood (liquid biopsy). Next-generation sequencing (NGS) and digital PCR were performed to detect mutations in these three sample types. RESULTS: We found a total of 36 different mutations in samples from primary tumors, liver metastases, and liquid biopsies using NGS. Twenty-eight of these mutations were found in all three types of samples, whereas liquid biopsy did not identify four mutations that had been found in both primary tumors and liver metastases, but did identify four mutations that were found in liver tumors but not in primary tumors. The sensitivity of liquid biopsies for detecting mutations in liver metastases was 64% (23/36) using NGS and 89% (32/36, P = 0.02) using dPCR. The specificities of NGS and dPCR were 100% (23/23) and 100% (32/32), respectively. CONCLUSIONS: Emerging mutations, which are not found in primary tumors, can be detected in their metastases and liquid biopsies.

Combined use of preoperative lymphocyte counts and the post/preoperative lymphocyte count ratio as a prognostic marker of recurrence after curative resection of stage II colon cancer.

PURPOSE: Diagnostic markers for recurrence of colorectal cancer have not been established. The aim of the present study was to identify new diagnostic markers for recurrence after curative surgery of stage II colon cancer. MATERIALS AND METHODS: In this study, the prognostic values of the preoperative lymphocyte count and the post/preoperative lymphocyte count ratio (PPLR) were evaluated in 142 patients with localized colon cancer treated with surgery at a single medical center. The associations of patient demographics, blood chemistry, and serum biochemical indices with recurrence-free survival (RFS) and cancer-specific survival (CSS) were examined by univariate and multivariate analyses. RESULTS: Receiver operating characteristic (ROC) curve analysis showed that the optimal cut-off values of the lymphocyte count and PPLR were, respectively, 1555.2/µl and 1.151 for RFS. On univariate analysis, tumor depth of invasion, carbohydrate antigen 19-9 (CA19-9), and preoperative low lymphocyte count (≤1555.2/µl) were all correlated with poorer RFS (p < 0.05). On multivariate analysis, T4, low lymphocyte count, and low PPLR were independent predictors of poor RFS. Furthermore, the patients were categorized into four categories based on preoperative lymphocyte count high/low and PPLR high/low. Patients with a low preoperative lymphocyte count and low PPLR had the poorest RFS and CSS compared to the other patients. CONCLUSION: The combination of the preoperative lymphocyte count and the PPLR appears to be a potential marker for predicting recurrence of stage II colon cancer.

Primary small intestinal volvulus after laparoscopic rectopexy for rectal prolapse.

Primary small intestinal volvulus is defined as torsion in the absence of congenital malrotation, band, or postoperative adhesions. Its occurrence as an early postoperative complication is rare. A 40-year-old woman presented with rectal prolapse, and laparoscopic rectopexy was uneventfully performed. She could not have food on the day after surgery. She started oral intake on postoperative day 3 but developed abdominal pain after the meal. Contrast-enhanced CT revealed torsion of the small intestinal mesentery. An emergent laparotomy showed small intestinal volvulus, without congenital malformation or intestinal adhesions. We diagnosed it as primary small intestinal volvulus. The strangulated intestine was resected, and reconstruction was performed. The patient recovered uneventfully after the second surgery. To the best of our knowledge, this is the first report of primary small intestinal volvulus occurring after rectopexy for rectal prolapse. Primary small intestinal volvulus could be a postoperative complication after laparoscopy.

Oncological Assessment of Stent Placement for Obstructive Colorectal Cancer from Circulating Cell-Free DNA and Circulating Tumor DNA Dynamics.

BACKGROUND: The self-expanding metallic stent (SEMS) provides effective decompression for patients with malignant large bowel obstruction (MLBO); however, mechanical damage to malignant cells from insertion may negatively affect prognosis, similar to surgical manipulation, and its oncological safety is unclear. We examined mechanical damage from SEMS placement using circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA). METHODS: Between 1 November 2014 and 30 June 2017, 35 MLBO patients were analyzed, comprising 25 SEMS patients and 10 transanal decompression tube (TDT) patients (control). Blood samples were collected before and after decompression on days 0, 1, 3, and 7. cfDNA, ctDNA, white blood cells, C-reactive protein, and lactate dehydrogenase were analyzed. RESULTS: The clinical success rates of SEMS and TDT were 88 and 90%, respectively (p = 1.0). The cfDNA concentration on day 7 was significantly higher in the SEMS group than in the TDT group (992 vs. 308 ng/mL; p = 0.005). A significant increase in ctDNA was observed in the SEMS group compared with the TDT group (83% vs. 22%; p = 0.002). The cfDNA concentration showed strong positive correlations with ctDNA and lactate dehydrogenase (R 2 = 0.838 and 0.593, respectively), and a weak positive correlation with C-reactive protein (R 2 = 0.263). CONCLUSIONS: Despite equivalent clinical success rates, SEMS placement increased plasma levels of cfDNA and ctDNA by tumor manipulation, but TDT did not. Colonic stenting showed oncological risk in terms of molecular analysis.

Oxaliplatin-induced increase in splenic volume; irreversible change after adjuvant FOLFOX.

BACKGROUND AND OBJECTIVES: Oxaliplatin can cause hepatic sinusoidal obstruction syndrome (SOS). SOS can cause chemotherapy-related adverse effects or morbidity after liver resection. Conventionally, SOS is diagnosed using liver biopsy. Recently, it was reported that increased splenic volume (SV) can be used to detect SOS. In this study, we evaluated the changes in SV during adjuvant chemotherapy. METHODS: We enrolled 103 consecutive patients with stage III and high-risk stage II colorectal cancer treated with mFOLFOX6 (n = 37) or oral fluorouracil and leucovorin (n = 66) after curative surgery. SV was measured three times; pre-operatively, after chemotherapy, and 1 year after chemotherapy. RESULTS: SV was higher after mFOLFOX6 (median 135.89 mL) than pre-operatively (105.75 mL) (P < 0.001); SV at 1-year after finishing mFOLFOX6 (114.16 mL) returned to the same level as before surgery (P = 0.0015). SV increased in 28 patients (75.7%) treated with mFOLFOX6 (95%CI, 61.8-89.5), but had not recovered in 12 of these cases (42.9%) 1 year after finishing treatment (95%CI, 17.3-47.5). In contrast, oral fluorouracil and leucovorin did not change SV. CONCLUSIONS: SV increased after adjuvant mFOLFOX6, and had not recovered in almost half of cases 1-year after finishing chemotherapy. This increase may indicate continuous SOS, which can adversely affect treatment after recurrence.