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Abstract Identification of an early biomarker and effective testing device to differentiate dry eye disease secondary to autoimmune disease (Sjögren’s syndrome dry eye disease) from non-Sjögren’s dry eye disease are prerequisites for appropriate treatment. We aimed to demonstrate the capacity of a new photo-detection device to evaluate tear lactoferrin levels as a tool for differentiating systemic conditions associated with dry eye disease. Patients with non-Sjögren’s and Sjögren’s syndrome dry eye disease (n = 54 and n = 52, respectively) and controls (n = 11) were enrolled. All participants completed the Ocular Surface Disease Index questionnaire. Tear collection was performed with Schirmer test, and tear break-up time was examined using a slit lamp. Tear lactoferrin was evaluated using our newly developed photo-detection device. The average lactoferrin concentration was significantly lower in samples from patients with non-Sjögren’s dry eye disease (0.337 ± 0.227 mg/mL, n = 54) and Sjögren’s syndrome dry eye disease (0.087 ± 0.010 mg/mL, n = 52) than in control samples (1.272 ± 0.54 mg/mL, n = 11) (p

Abstract Background Intussusception, a common cause of abdominal pain in children, often lacks clear underlying causes and is mostly idiopathic. Recurrence, though rare, raises clinical concerns, with rates escalating after each episode. Factors like pathological lead points and Henoch-Schönlein purpura (HSP) are associated with recurrent cases. On the other hand, the prevalence of Helicobacter pylori (H. pylori), often asymptomatic, in children has been declining. Although its infection is reported to be linked with HSP, its role in recurrent intussusception remains unexplored. Further research is needed to understand the interplay among H. pylori (culprit pathogen), HSP (trigger), and intractable intussusception so as to develop effective management strategies. Case presentation A two-year-old girl experienced four atypical episodes of intussusception at distinct locations, which later coincided with HSP. Despite treatment with steroids, recurrent intussusception persisted, suggesting that HSP itself was not a major cause for intractable presentations. Subsequent identification of H. pylori infection and treatment with triple therapy resulted in complete resolution of her recalcitrant intussusception. Conclusion This instructive case underscored a sequence wherein H. pylori infection triggered HSP, subsequently resulting in recurrent intussusception. While H. pylori infection is not common in young children, the coexistence of intractable intussusception and steroid-resistant recurrent HSP necessitates consideration of H. pylori infection as a potential underlying pathogen.

Abstract Background Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. Materials We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. Results In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. Conclusion The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P

Background and Objectives: Approximately 5–10% of all patients with metastatic colorectal cancer (mCRC) harbor a BRAFV600E mutation. These patients exhibit distinct metastatic patterns, poor prognosis, and heterogenous survival outcomes. The findings from the TRIBE study indicated that the administration of FOLFOXIRI plus bevacizumab as first-line treatment extended the median duration of overall survival (OS). In this study, we explored the effects of UGT1A1 polymorphism on the outcomes of irinotecan dose escalation versus FOLFOXIRI plus bevacizumab in patients with BRAFV600E-mutant mCRC. Materials and Methods: We retrospectively reviewed the medical records of 25 patients who had received a diagnosis of BRAFV600E-mutant mCRC between October 2015 and August 2022. All patients underwent UGT1A1 genotyping before receiving bevacizumab plus FOLFIRI. The primary end point was progression-free survival (PFS), and secondary endpoints were OS and adverse events (AEs). The two treatment arms were compared in terms of 6-month PFS and 12-month OS. Results: Over a median follow-up duration of 15.0 (interquartile range, 10.0–30.5) months, no significant differences were noted between the treatment arms in severe AEs (SAEs), 6-month PFS, or 12-month OS (all p < 0.05). Regarding AEs, the FOLFIRI plus bevacizumab regimen was associated with a lower incidence of anorexia than was the FOLFOXIRI plus bevacizumab regimen (p = 0.042). Conclusions: Our findings indicate that FOLFIRI plus bevacizumab with irinotecan dose escalation is an effective first-line treatment regimen for patients with BRAFV600E-mutant mCRC. This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.

BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy.MethodsWe retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy.ResultsTreatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075).ConclusionsIn the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.

Personalized treatments based on the genetic profiles of tumors can simultaneously optimize efficacy and minimize toxicity, which is beneficial for improving patient outcomes. This study aimed to integrate gene alterations associated with predictive and prognostic outcomes in patients with metastatic colorectal cancer (mCRC) with polymerase chain reaction (PCR) and in-house next-generation sequencing (NGS) to detect KRAS, NRAS, and BRAF mutations. In the present study, 41 patients with mCRC were assessed between August 2017 and June 2019 at a single institution. The overall concordance between NGS and PCR results for detecting KRAS, NRAS, and BRAF mutations was considerably high (87.8–92.7%), with only 15 discrepant results between PCR and NGS. Our companion diagnostic test analyzes KRAS, NRAS, and BRAF as a panel of CRC molecular targets; therefore, it has the advantages of requiring fewer specimens and being more time and cost efficient than conventional testing for separate analyses, allowing for the simultaneous analysis of multiple genes.

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.

Abstract To investigate the structure–function correlation analysed by full-field electroretinography (ffERG) and optical coherence tomography (OCT) in typical and pericentral subtypes of retinitis pigmentosa (RP). A retrospective, cross-sectional, observational study of right eyes was conducted. The primary analysis used ffERG data to compare the RP subtypes. The subgroup analysis was used to correlate the structure, analysed by OCT, and function, determined by ffERG. Linear regressions explored the relationship between best-corrected visual acuity (BCVA) and multiple parameters. A total of 188 eyes were included. Amplitudes of responses of rod, rod-cone, cone, and 30 Hz flicker of typical type were lower than those of pericentral and other types. In the subgroup analysis, 41 and 21 eyes of the typical and pericentral types were studied, respectively. The correlation between the estimated preserved photoreceptor area and all ffERG amplitude parameters were significant in the typical type, but not in pericentral type. Old age, decreased intact ellipsoid zone length, typical type, and thin central retinal thickness were negatively correlated with BCVA. Typical type RP developed more extensive degeneration and poorer BCVA compared to others. Strong structure–function correlation was found in typical type while not in pericentral type. OCT may be a useful tool for monitoring RP status in typical type, providing useful parameters for the prediction of BCVA.

Aims: This study analyzed the oncological outcomes of robotic-assisted total mesorectal excision (TME) in patients with rectal cancer after neoadjuvant concurrent chemoradiotherapy (CCRT). Methods: We enrolled 109 consecutive patients with stage II–III rectal cancer who underwent robotic-assisted TME after neoadjuvant CCRT at one hospital between July 2013 and June 2018. Results: All 109 patients underwent preoperative CCRT. Of them, 37 (33.9%) achieved a pathologic complete response, and 29 (26.6%) experienced relapse, with local recurrence in 9 (8.3%) and distant metastasis in 20 (18.3%). R0 resection was performed in 104 (95.7%) patients; however, 7 (6.7%) of them developed local recurrence and 17 (16.3%) developed distant metastasis. Over a median follow-up of 42 months, the 3-year disease-free survival and overall survival rates were 73.4% and 87.2%, respectively. Conclusions: Robotic-assisted TME after neoadjuvant CCRT is safe and effective for treating patients with stage II–III rectal cancer in one institution with acceptable short-term oncological outcomes. It may be a therapeutic alternative to salvage surgery for T4 tumors invading adjacent organs, such as the bladder, prostate, and uterus.

Colorectal cancer (CRC) is a global public health concern because of its high prevalence and mortality. Although radiotherapy is a key method for treating CRC, radioresistance is an obstacle to radiotherapy use. The molecular mechanisms underlying the radioresistance of CRC remain unclear. Increasing evidence has revealed the multiple regulatory functions of non-coding RNAs (ncRNAs) in numerous malignancies, including CRC. Several ncRNAs have been reported to be involved in the determination of radiosensitivity of CRC cells, and some have excellent potential to be prognostic biomarkers or therapeutic targets in CRC treatment. The present review discusses the biological functions and underlying mechanisms of ncRNAs (primarily lncRNA, miRNA, and circRNA) in the regulation of the radiosensitivity of CRC. We also evaluate studies that examined ncRNAs as biomarkers of response to radiation and as therapeutic targets for enhancing radiosensitivity.

Objective The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. Methods We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m 2 . Results Six of the seven patients tolerated 120 mg/m 2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. Conclusions mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m 2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.

Background: Although surgical resection is the main treatment for rectal cancer, the optimal surgical protocol for elderly patients with rectal cancer remains controversial. This study evaluated the feasibility of robot-assisted surgery in elderly patients with rectal cancer. Patients and Methods: This retrospective study enrolled 156 patients aged 28–93 years diagnosed with Stage I–III rectal cancer, who underwent robot-assisted surgery between May 2013 and December 2018 at a single institution. Results: In total, 156 patients with rectal cancer, including 126 non-elderly (aged < 70 years) and 30 elderly (aged ≥70 years) patients, who underwent robot-assisted surgery were recruited. Between the patient groups, the post-operative length of hospital stay did not differ statistically significantly (P = 0.084). The incidence of overall post-operative complications was statistically significantly lower in the elderly group (P = 0.002). The disease-free and overall survival did not differ statistically significantly between the two groups (P = 0.719 and 0.390, respectively). Conclusions: Robot-assisted surgery for rectal cancer was well tolerated by elderly patients, with similar results to the non-elderly patients. Oncological outcomes and survival did not depend on patient age, suggesting that robot-assisted surgery is a feasible surgical modality for treating operable rectal cancer and leads to age-independent post-operative outcomes in elderly patients.

ObjectivePatients with metastatic colorectal cancer (mCRC) had oncological benefits with irinotecan dose escalation of FOLFIRI regimen combined with bevacizumab according to UGT1A1 genotypes in our previous study. In the current study, we performed a quality of life (QOL) outcome evaluation and cost-utility analysis of different irinotecan dose regimens in patients with mCRC.Materials and MethodsWith inverse probability-of-treatment weighting (IPTW) matching on all covariates, 75 patients with dose escalation of irinotecan (study group) and 121 patients with the recommended dose of irinotecan (control group) were recruited between October 2015 and December 2019. The QOL outcome measures were Functional Assessment of Cancer Therapy-Colorectal, Beck Anxiety Inventory, Beck Depression Inventory, and SF-36; cost-utility outcome measures were medical direct costs, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs).ResultsAll mCRC patients exhibited a significant decrease in both emotional wellbeing and depression from pretherapeutic period to posttherapeutic 6th month (P < 0.05); however, from the posttherapeutic 1st year to the 2nd year, improvement in most QOL measures was significantly better in the study group than in the control group (P < 0.05). Over a 2-year time period, the study group had higher total medical direct costs than the control group (US$ 54,742 ± 14,013 vs. US$ 54,608 ± 9,673) and higher average QALYs gained (1.88 vs. 1.65), with an ICUR of US$ 583 per QALY gained.ConclusionFor patients with mCRC, irinotecan dose escalation appeared cost-effective with considerable QOL improvements during the study period. Further randomized, multi-institutional controlled trials are warranted to corroborate these results.

Abstract Introduction Post-operative pain control remains unsatisfactory in patients after laparotomy. This study aimed to evaluate the efficacy, safety, and quality of life with a single dose of extended-release dinalbuphine sebacate (ERDS) pre-operatively to intravenous patient-controlled analgesia (PCA) with fentanyl in patients undergoing laparotomy. Methods This was a prospective, open-label, randomized controlled study. Of 110 randomized patients, 107 completed all assessments. The area under the curve (AUC) of visual analogue scale (VAS) from baseline to 48 h after surgery, VAS throughout 7 days after surgery, post-operative analgesics use, quality of life, satisfaction, and safety were evaluated. Results The AUC of VAS from baseline to 48 h after surgery were 118.6 [97.5% confidence interval (CI) 95.6–141.6] in ERDS group and 176.13 (97.5% CI 150.8–201.4) in PCA group, which showed the non-inferiority because the upper limit of the 97.5% CIs of ERDS group was lower than the lower limit of PCA group (P

Abstract Colorectal cancer is a major public health problem worldwide, and locally advanced rectal cancer (LARC) is known for its poor prognosis. A multimodal treatment approach is the only method to achieve satisfactory local recurrence and survival rates in LARC. Determining which therapeutic modality for LARC has the most satisfactory influence on quality of life and disease outcome is still controversial. LARC treatment is subject to continuous advancement due to the development of new and better diagnostic tools, radiotherapy techniques, and chemotherapeutic agents. Herein, we review various therapeutic modalities for LARC from several aspects. In addition to radiotherapy techniques such as neoadjuvant chemoradiotherapy (NCRT), we discuss the progress of chemotherapy, appropriate time interval between NCRT and surgery, relationship between tumor location and NCRT efficacy/safety, wait‐and‐watch policy, and predictors of treatment response following NCRT. Because of the controversies and unanswered questions regarding NCRT treatments for LARC, additional investigations are required to determine which therapeutic approach is the most feasible for LARC patients.

Abstract Background Total mesorectal excision (TME) with or without neoadjuvant concurrent chemoradiotherapy (CCRT) is the treatment for rectal cancer (RC). Recently, the use of conventional laparoscopic surgery (LS) or robotic-assisted surgery (RS) has been on a steady increase cases. However, various oncological outcomes from different surgical approaches are still under investigation. Methods This is a retrospective observational study comprising 300 consecutive RC patients who underwent various techniques of TME (RS, n = 88; LS, n = 37; Open surgery, n = 175) at a single center of real world data to compare the pathological and oncological outcomes, with a median follow-up of 48 months. Results Upon multivariate analysis, histologic grade (P = 0.016), and stage (P

Abstract Background Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC. Methods A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded. Discussion Dose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC. Trial registration ClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019.

BackgroundWhether high or low ligation of the inferior mesenteric artery (IMA) is superior in surgery for rectal and sigmoid colon cancers remains controversial. Although several meta-analyses have been conducted, the level of lymph node clearance was poorly defined. We performed a meta-analysis comparing high and low ligation of the IMA for sigmoid colon and rectal cancers, with emphasis on high dissection of the lymph node at the IMA root in all the included studies.MethodsPubMed, MEDLINE, and EMBASE databases were searched to identify relevant articles published until 2020. The patient’s perioperative and oncologic outcomes were analyzed. Statistical analysis was performed using the statistical software RevMan version 5.4.ResultsA total of 17 studies, including four randomized controlled trials, published between 2011 and 2020 were selected. In total, 1,846 patients received low ligation of the IMA plus high dissection of lymph nodes (LL+HD), and 2,648 patients received high ligation of the IMA (HL). LL+HD was associated with low incidence of anastomotic leakage (p < 0.001), borderline long operative time (p = 0.06), and less yields of total lymph nodes (p = 0.03) but equivalent IMA root lymph nodes (p = 0.07); moreover, LL+HD exhibited non-inferior long-term oncological outcomes.ConclusionIn comparison with HL, LL+HD was an effective and safe oncological procedure for sigmoid colon and rectal cancers. Therefore, to ligate the IMA below the level of the left colic artery with D3 high dissection for sigmoid colon and rectal cancers might be suggested once the surgeons are familiar with this technique.Systematic Review RegistrationINPLASY.com, identifier 202190029.

Therapeutic options for metastatic CRC (mCRC) have changed significantly in recent years, greatly increasing the complexity of therapeutic decision-making. Although oncology guidelines have helped improve the care process, guidelines may also limit the flexibility to individualize in-clinic decision-making. This consensus paper addresses specific gaps in the current international guidelines to assist Taiwanese colon and rectal experts make specific therapeutic choices. Over 3 years and three meetings with selected experts on “real-world” Taiwanese practice patterns for mCRC, consensus was achieved. The experts also discussed specific questions during in-depth one-on-one consultation. Outcomes of the discussion were then correlated with published evidence by an independent medical writer. The final consensus includes clinically implementable recommendations to provide guidance in treating Taiwanese mCRC patients. The consensus includes criteria for defining fit and unfit intensive treatment patients, treatment goals, treatment considerations of molecular profiles, treatment consideration, and optimal treatment choices between different patient archetypes, including optimal treatment options based on RAS, BRAF, and microsatellite instability (MSI) status. This consensus paper is the second in the Taiwan Society of Colon and Rectal Surgeons (TSCRS) Consensus series to address unmet gaps in guideline recommendations in lieu of Taiwanese mCRC management. Meticulous discussions with experts, the multidisciplinary nature of the working group, and the final drafting of the consensus by independent medical professionals have contributed to the strong scientific value of this consensus.

Perivascular epithelioid cell tumour (PEComa) is an extremely rare neoplasm with distinctive morphology and specific expression of immunohistochemical markers. The lesion is typically diagnosed in middle-aged women, with few reports of paediatric cases, and there is no standardized treatment for the tumour type. Here, the case of a 17-year-old female, who presented with painless haematochezia for 2 days and was diagnosed with gastrointestinal PEComa of the sigmoid colon with regional lymph node metastasis after serial examination, is presented. She was treated by surgical resection of the tumour and cytotoxic chemotherapy comprising 900 mg/m 2 gemcitabine and 100 mg/m 2 docetaxel every 3 weeks for six cycles. Haematochezia did not recur, and complete response was achieved, with progression-free survival at the 24-month follow-up examination. Surgical resection with adjuvant conventional cytotoxic chemotherapy may be considered as an option for treating gastrointestinal PEComa.

Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

Anorectal malignant melanoma is a very rare but aggressive cancer which carries poor prognosis. Surgical intervention is the main management but whether wide local excision or abdominoperineal resection has better survival benefit remains controversial. However, robotic-assisted restorative proctectomy with coloanal anastomosis with intersphincteric resection (ISR) has not been reported yet. Hence, we presented a case with anorectal malignant melanoma treated with robotic-assisted ISR with coloanal anastomosis. The patient has satisfied post-operative life quality, and no local recurrence was noted after 3-year follow-up.

Gastric ectopic pancreas presenting as a submucosal tumour accounts for approximately 11% of all endoscopic ultrasonography (EUS) examinations. Definitive diagnosis through endoscopy is difficult, even with EUS-guided fine-needle aspiration biopsy for histological examination. For symptomatic patients or those with uncertain diagnosis, complete surgical resection is the primary strategy for treatment and diagnosis. Herein, we report a case of gastric ectopic pancreas treated using robotic surgery.

Abstract Background Neurovascular unit restoration is crucial for nerve regeneration, especially in critical gaps of injured peripheral nerve. Multipotent vascular stem cells (MVSCs) harvested from an adult blood vessel are involved in vascular remodeling; however, the therapeutic benefit for nerve regeneration is not clear. Methods MVSCs were isolated from rats expressing green fluorescence protein (GFP), expanded, mixed with Matrigel matrix, and loaded into the nerve conduits. A nerve autograft or a nerve conduit (with acellular matrigel or MVSCs in matrigel) was used to bridge a transected sciatic nerve (10-mm critical gap) in rats. The functional motor recovery and cell fate in the regenerated nerve were investigated to understand the therapeutic benefit. Results MVSCs expressed markers such as Sox 17 and Sox10 and could differentiate into neural cells in vitro. One month following MVSC transplantation, the compound muscle action potential (CMAP) significantly increased as compared to the acellular group. MVSCs facilitated the recruitment of Schwann cell to regenerated axons. The transplanted cells, traced by GFP, differentiated into perineurial cells around the bundles of regenerated myelinated axons. In addition, MVSCs enhanced tight junction formation as a part of the blood-nerve barrier (BNB). Furthermore, MVSCs differentiated into perivascular cells and enhanced microvessel formation within regenerated neurovascular bundles. Conclusions In rats with peripheral nerve injuries, the transplantation of MVSCs into the nerve conduits improved the recovery of neuromuscular function; MVSCs differentiated into perineural cells and perivascular cells and enhanced the formation of tight junctions in perineural BNB. This study demonstrates the in vivo therapeutic benefit of adult MVSCs for peripheral nerve regeneration and provides insight into the role of MVSCs in BNB regeneration.

Abstract Background In the management of patients with RAS wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) therapies have demonstrated a clinical benefit, with longer survival. However, the correlation between the emergence of circulating RAS mutations and secondary resistance to anti-EGFR therapies requires further elucidation. In this study, we aim to examine evolutionary changes in RAS mutations through liquid biopsy in patients with mCRC during and after anti-EGFR therapy. Methods A total of 120 patients diagnosed with RAS wild-type mCRC will be enrolled in this study. Patients will receive a cetuximab-based infusional 5-fluorouracil regimen as first-line treatment. Cetuximab-based treatment is expected to continue until disease progression, intolerable toxic effects, or withdrawal of consent. Blood samples from enrolled patients will be collected before and then every 3 months during cetuximab-based treatment and also at disease progression. These blood samples will be evaluated for RAS resistance mutations by using the MassARRAY platform. The primary endpoint is the percentage of RAS mutations detected in circulating DNA from patients during cetuximab treatment. The correlation between the tumor response and survival outcomes of these patients and the emergence of circulating RAS mutations will be further analyzed. Discussion Liquid biopsy is a powerful technology that can represent tumor heterogeneity in a relatively noninvasive manner. Because RAS mutations play a major role in resistance to anti-EGFR therapy for mCRC, examining evolutionary changes in these mutations during such treatment through liquid biopsy would be useful. After comprehensively analyzing the emergence of circulating RAS mutations and its clinical relevance in this study, our results should provide practical guidance on anti-EGFR therapy for mCRC. Trial registration The date of trial registration (NCT03401957) in this study was January 17, 2018.

BACKGROUND: To evaluate the efficacy and toxicities of regorafenib plus irinotecan, dose-escalated on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping, in previously heavily treated metastatic colorectal cancer (mCRC) and the prognostic values of EGFR expression, KRAS mutations, and tumor sidedness. METHODS: Forty-one patients with mCRC with disease progression after treatment with fluoropyrimidines, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR MoAbs were subjected to UGT1A1 genotyping and received regorafenib combined with FOLFIRI with dose-escalated irinotecan. RESULTS: The median follow-up period was 10.0 months (1.3-23.5 months). The overall disease control rate was 58.5%, whereas the median progression-free survival (PFS) and overall survival (OS) were 6.0 months and 12.0 months, respectively. KRAS mutations were significantly associated with positive EGFR expression (P = .026). KRAS mutations significantly correlated with a shorter OS than KRAS wild-type (6.0 vs. 14.4 months, P = .014) but had no significant association with PFS. Positive EGFR expression had an inverse correlation with PFS (2.5 vs. 14.0 months, P = .039) and OS (9.6 vs. 19.7 months, P = .044). Moreover, left-sided tumors associated with superior PFS (2.0 vs. 7.0 months, P

Abstract Background A long-acting prodrug of nalbuphine, nalbuphine sebacate, has been developed for meeting the unmet medical need of long-acting analgesics. Naldebain® (nalbuphine sebacate) has been developed as a new premedication for postoperative pain management. The primary objective of this study is to determine the efficacy and safety of a single dose of intramuscular Naldebain® in patients scheduled to undergo elective laparotomy. Methods/design A total of 110 patients will be recruited and randomized into two treatment groups. Group 1 receives a single dose of Naldebain® intramuscularly 24 ± 12 h prior to surgery. Group 2 receives intravenous patient-controlled analgesia (PCA) with fentanyl through 48 h postsurgery. Both groups will have follow-up observations until the final visit (day of discharge, day 6–30). The primary efficacy endpoint is to assess time-specific pain intensity calculated as the area under the curve (AUC) of a visual analog scale at individual time points and by using total AUC. Safety endpoints—including incidence of treatment, emergent adverse events, and percentage of abnormality from baseline to final visit—in vital signs, laboratory tests, and injection site evaluations will also be analyzed. Statistical analyses will be performed on the data to compare the two groups. Discussion Post-laparotomy pain can have a harmful effect on patient recovery; therefore, a slow-release formulation that can cover at least 7 days of analgesic effect is required. This study will demonstrate whether a single use of Naldebain® is not less efficacious than PCA with fentanyl for pain management as a non-inferior trial. Trial registration NCT03296488.

Summary: Background: In colorectal cancer (CRC) patients, pulmonary nodules are usually considered lung metastases (LM). However, approximately 10% of LM is presented as a solitary pulmonary nodule which mimics primary lung cancer (PLC). This study aims to determine the distinguishing characteristics of the two pulmonary nodule types during postoperative surveillance of CRC patients. Methods: Between March 2009 and February 2018, 47 CRC patients with pulmonary nodules from a single institution were retrospectively analyzed. They were divided into two groups, namely CRC with second PLC (CSPLC) and CRC with LM (CRCLM), and their demographic data and clinicopathological features were analyzed. Results: When pulmonary nodules are presented, multiple lesions and serum carcinoembryonic antigen (CEA) level >5 ng/mL indicated a higher probability of CRCLM (p 5 ng/mL when an isolated pulmonary nodule detected, and initial TNM stage IV CRC are more likely related to LM rather than SPLC. Image-guided needle biopsy and IHC stain can reduce the probability of misdiagnosis and rule out LM. CSPLC may have a favorable prognosis owing to early detection and receiving appropriate treatment. Keywords: Colorectal cancer, Lung metastasis, Lung nodules, Postoperative surveillance, Second primary lung cancer

Background: Enhanced recovery after surgery (ERAS) is valuable in perioperative care for its ability to improve short-term surgical outcomes and facilitate patient recuperation after major surgery. Early postoperative mobilization is a vital component of the integrated care pathway and is a factor strongly associated with successful outcomes. However, early mobilization still has various definitions and lacks specific strategies.Methods: Patients who underwent minimally invasive surgery for colorectal cancer followed our perioperative ERAS program, including mobilization from the first postoperative day. After perioperative care skills were improved in our well-established program, compliance, inpatient surgical outcomes, and complications associated with adding smartband use were evaluated and compared with the outcomes for standard protocol. Quality of recovery was evaluated using patient-rated QoR-40 questionnaires the day before surgery, on postoperative days 1 and 3, and on the day of discharge.Results: Smartband use after minimally invasive colorectal surgery failed to increase compliance with early mobilization or reduce the occurrence of postoperative complications significantly compared with standard ERAS protocol. However, when smartbands were utilized, quality of recovery was optimized and patients returned to their preoperative status earlier, at postoperative day 3. The length of hospital stay, as defined by discharge criteria, and hospital stay of patients without complications was reduced by 1.1 and 0.9 days, respectively (P = 0.009 and 0.049, respectively).Conclusions: Smartbands enable enhanced communication between patients and surgical teams and strengthen self-management in patients undergoing minimally invasive colorectal resection surgery. Accelerated recovery to preoperative functional status can be facilitated by integrating smartbands into the process of early mobilization during ERAS.

Background Locally advanced colon cancer (LACC) is associated with surgical challenges during R0 resection, increased postoperative complications, and unfavorable treatment outcomes. Neoadjuvant concurrent chemoradiotherapy followed by surgical resection is an effective treatment strategy that can increase the complete surgical resection rate and improve the patient survival rate. This study investigated the efficacy and toxicity of concurrent chemoradiotherapy in patients with LACC as well as the prognosis and long-term clinical outcomes of these patients. Materials From January 2012 to July 2020, we retrospectively reviewed the real-world data of 75 patients with LACC who received neoadjuvant concurrent chemoradiotherapy. The chemotherapy regimen consisted of folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX). The following data were obtained from medical records: patients’ characteristics, pathologic results, toxicity, and long-term oncologic outcome. Results Of the 75 patients, 13 (17.3%) had pathologic complete responses. Hematologic adverse effects were the most common (grade 1 anemia: 80.0% and leukopenia: 82.7%). Conversely, grade 2 or 3 adverse effects were relatively uncommon (Conclusion The long-term oncologic outcome of patients with LACC following concurrent chemoradiotherapy is acceptable, and the adverse effects seem to be tolerable. Pathologic N downstaging was an independent prognostic factor for patients’ overall survival. However, a large prospective, randomized control study is required to confirm the current results.

Studies have demonstrated that metformin has antitumor effects in addition to therapeutic effects on hyperglycemia; however, few studies have explored the effects of metformin in chemotherapy. Therefore, we hypothesized that the administration of metformin would enhance the therapeutic effects of 5-fluorouracil and oxaliplatin (FuOx) to inhibit the growth of colorectal cancer (CRC) cells in vitro and in vivo. The results of our in vitro experiments demonstrated that metformin significantly increased the effects of FuOx with respect to cell proliferation (p < 0.05), colony formation (p < 0.05), and migration (p < 0.01) and induced cell cycle arrest in the G0/G1 phase in HT29 cells and the S phase in SW480 and SW620 cells (p < 0.05). Flow cytometry analysis revealed that metformin combined with FuOx induced late apoptosis (p < 0.05) by mediating mitochondria-related Mcl-1 and Bim protein expression. Furthermore, in vivo, metformin combined with FuOx more notably reduced tumor volume than FuOx or metformin alone did in BALB/c mice (p < 0.05). These findings demonstrate that metformin may act as an adjunctive agent to enhance the chemosensitivity of CRC cells to FuOx. However, further clinical trials are warranted to validate the clinical implications of the findings.

Background: Curative resection of sigmoid colon and rectal cancer includes “high tie” of the inferior mesenteric artery (IMA). However, IMA ligation compromises blood flow to the anastomosis, which may increase the complication rate. We present preliminary experiences of operative and oncologic outcomes of patients with rectal or sigmoid colon cancer who underwent robotic surgery employing the high dissection and selective ligation technique.Methods: Over May 2013 to April 2017, 113 stage I–III rectal or sigmoid colon cancer patients underwent robotic surgery with the single-docking technique at one institution. We performed D3 lymph node dissection and low-tie ligation of the IMA (i.e., high dissection and selective ligation technique). Clinicopathological features, perioperative parameters, and postoperative outcomes were retrospectively analyzed. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan–Meier method.Results: Sphincter preservation rate was 96.3% in rectal cancer patients. Median number of harvested lymph nodes was 12. Apical nodes were pathologically harvested in 84 (82.4%) patients. R0 resection was performed in 108 (95.6%) patients. Overall complication rate was 17.7%; but most complications were mild and the patients recovered uneventfully. Estimated 5-year OS was 86.1% and 3-year DFS was 79.6% after median follow-up periods of 49.1 months (range, 5.3–85.3).Conclusions: High dissection of the IMA and selective ligation of the major feeding vessel to the sigmoid colon or rectum can be safely performed using da Vinci Surgical System,yielding favorable clinical, and oncologic outcomes in rectal or sigmoid colon cancer treatment.

BackgroundThis aim of this study was to evaluate the effects of time interval between the completion of radiotherapy and robotic-assisted surgery on the outcomes among patients with rectal cancer undergoing preoperative concurrent chemoradiotherapy (CCRT).MethodsIn total, 116 patients with stage I-III rectal cancer who underwent preoperative CCRT and robotic-assisted surgery between September 2013 and February 2019 were enrolled. Patients were categorized into two groups based on the time interval: group A (10-12 weeks) and group B (≥ 12 weeks).ResultsAmong the 116 enrolled patients, 98 (84.5%) had middle and lower rectal cancers. Two (1.7%) patients underwent abdominoperineal resection with a sphincter preservation rate of 98.3%. Thirty-seven (31.9%) patients had a pathologic complete response (pCR). The circumferential resection margin and distal resection margin were positive in 2 (1.7%) and 1 (0.9%) patients, respectively. Therefore, the R0 resection rate was 97.4%. A total of 24 (22.4%) patients experienced postoperative relapse and 12 (10.3%) patients died; these were slightly more common in group B than in group A (28.8% vs 15.8% and 15.3% vs 5.3%, respectively; both P > 0.05); however, this difference was nonsignificant. Three-year disease-free survival (DFS) and overall survival (OS) were 75% and 89%, respectively, among all patients. Non-significant trend of favorable 3-year DFS, 3-year OS, 3-year locoregional control rate and 3-year distant metastasis control rate were observed in group A compared with group B (all P > 0.05).ConclusionRobotic-assisted surgery after a longer interval is safe and feasible for patients with rectal cancer undergoing preoperative CCRT. The present study's results suggested that the time interval of 10-12 weeks can be considered because comparable clinical and perioperative outcomes and preferable oncological outcomes were observed for interval of this length. However, future prospective randomized clinical trials are required to verify the present finding.

Colorectal cancer (CRC) is the third most common cancer worldwide. The incidence and mortality rates of CRC are significantly higher in Taiwan than in other developed countries. Genes involved in CRC tumorigenesis differ depending on whether the tumor occurs on the left or right side of the colon, and genomic analysis is a keystone in the study and treatment of CRC subtypes. However, few studies have focused on the genetic landscape of Taiwanese patients with CRC. This study comprehensively analyzed the genomes of 141 Taiwanese patients with CRC through whole-exome sequencing. Significant genomic differences related to the site of CRC development were observed. Blood metabolomic profiling and polygenic risk score analysis were performed to identify potential biomarkers for the early identification and prevention of CRC in the Taiwanese population. Our findings provide vital clues for establishing population-specific treatments and health policies for CRC prevention in Taiwan.

BACKGROUND: Increasing bodies of evidence suggest that metformin may be beneficial in the primary prevention of colorectal cancer (CRC), and a dose–response relationship has been reported. However, long-term epidemiological observations between the treatment period, cumulative dose, and intensity of metformin and CRC are rarely reported. The aim of this study was to identify the association between the effect of metformin and CRC development in a nationwide cohort study. METHODS: This nationwide population-based study examined a cohort of 1,000,000 patients randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. Patients with newly diagnosed type 2 diabetes mellitus (DM) between 1997 and 2007 were enrolled. A statistical variables, including the demographic data, treatment period, cumulative dose, and intensity of metformin use, was compared between patients developing CRC and those without CRC. RESULTS: This study included 47,597 patients. The mean follow-time was 7.17 ± 3.21 years. After adjustment, metformin use was an independent protective factor against CRC development (P < .001). Although the protective ability of metformin against CRC development was reduced during long-term therapy, the risk of CRC decreased progressively with a higher cumulative dose or higher intensity of metformin use (both P < .001). CONCLUSION: This study revealed that metformin use significantly reduced the risk of CRC in a dose-dependent manner in patients with type 2 DM in the Taiwanese population. However, a gradual decline in medication adherence may reduce the protective ability of metformin against CRC development during long-term therapy.

Abstract Background We aimed to explore the efficacy and safety profile of preoperative neoadjuvant chemoradiation (NACRT) in locally advanced rectal cancer (LARC) in upper rectum versus middle/lower rectum. Methods The study included 173 patients with stage II or III (T2-4b, N0-2b) LARC who underwent NACRT followed by total mesorectal excision (TME) between January 2011 and October 2016. Cox regression, log-rank test, and Kaplan–Meier curves were calculated. Results Among the 173 patients, 58 had lesions in the upper rectum and 115 patients had lesions in middle/lower rectum. In a median follow-up of 35 months (range, 6–73 months), the 5-year disease-free survival (DFS) and overall survival (OS) were 84% and 88% for the patients with upper rectal cancer and 77% and 68% for those with middle/lower rectal cancer (P = 0.251 and P = 0.058, respectively). The 5-year DFS (P = 0.012) and OS (P = 0.003) were better in the NACRT responders [tumor regression grade (TRG) 0 or 1] compared with nonresponders (TRG 2 or 3). The independent prognostic factor of favorable response to NACRT was the FOLFOX regimen (P = 0.004). Conclusions Patients with LARC in the upper rectum who underwent NACRT followed by TME had similar DFS and a trend toward longer OS, compared with those who had middle/lower rectal lesions. Furthermore, FOLFOX may yield superior results than fluoropyrimidine based regimen during NACRT. NACRT might be an alternative option for patients with LARC in the upper rectum as it has a favorable pathological complete response rate and comparable clinical outcomes when compared with patients with LARC in middle/lower rectum.

Background: Three operative techniques have been used for colorectal cancer (CRC) resection: Conventional laparotomy (CL) and the mini-invasive techniques (MITs)– laparoscopic-assisted surgery (LAS) and mini-laparotomy (ML). The aim of the study was to compare the short- and long-term outcomes of patients undergoing the three surgical approaches for Stage I–III CRC resection. Patients and Methods: This study enrolled 688 patients with Stage I–III CRC undergoing curative resection. The primary endpoints were perioperative quality and outcomes. The secondary endpoints were oncological outcomes including disease-free survival (DFS), overall survival (OS) and local recurrence (LR). Results: Patients undergoing LAS had significantly less blood loss (P < 0.001), earlier first flatus (P = 0.002) and earlier resumption of normal diet (P = 0.025). Although post-operative complication rates were remarkably higher in patients undergoing CL than in those undergoing MITs (P = 0.002), no difference was observed in the post-operative mortality rate (P = 0.099) or 60-day re-intervention rate (P = 0.062). The quality of operation as assessed by the number of lymph nodes harvested and rates of R0 resection did not differ among the groups (all P > 0.05). During a median follow-up of 5.42 years, no significant difference was observed among the treatment groups in the rates of 3-year late morbidity, 3-year LR, 5-year LR, 5-year OS or 5-year DFS (all P > 0.05). Conclusions: Patients undergoing CL had higher post-operative morbidities. Moreover, the study findings confirm the favourable short-term and comparable long-term outcomes of LAS and ML for curative CRC resection. Therefore, both MITs may be feasible and safe alternatives to CL for Stage I-III CRC resection.

Backgroundand objectives: Patients with BRAF-mutated metastatic colorectal cancer have considerably poorer responses to conventional systemic treatment. The real-world effects of triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in Asia have not been well-reported. Materials and Methods: This single-center case series included patients with BRAF-mutated metastatic colorectal cancer undergoing triplet therapy after failure of prior systemic treatment from 2016 to 2020. The primary outcome was progression-free survival, and secondary outcomes were overall survival, response rate, disease control rate, and adverse events. Results: Nine eligible patients with BRAF-mutated metastatic colorectal cancer receiving triplet therapy were enrolled, with a median follow-up time of 14.5 months (range, 1–26). Most patients (88.8%) had two or more prior systemic treatments, and the triplet regimen was mainly dabrafenib, trametinib, and panitumumab. The overall response rate and disease control rate were 11.1% and 33.3%, respectively. Median progression-free survival and overall survival were 2.9 and 7.4 months, respectively, and a trend toward better overall survival was found with left-sided metastatic colorectal cancer compared with right-sided disease (9.2 vs. 6.9 months, p = 0.093). Adverse events were mostly Grade 1–2, including nausea, hypertension, gastrointestinal symptoms, and skin disorders. Conclusions: In this single-center case series, triplet therapy with BRAF, mitogen-activated protein kinase kinase, and epidermal growth factor receptor inhibitors in BRAF-mutated metastatic colorectal cancer had an acceptable safety profile and reasonable efficacy.

Abstract Background Colorectal carcinoma (CRC) is one of the most common causes of cancer-related deaths. The mean age of patients with CRC ranges from 49 to 60 years. Pediatric CRC is unusual, which often escapes early diagnosis because of a lack of awareness of its occurrence in children. The association between the mutation of APC and the occurrence of CRC in the first decade of life remains unknown. Case presentation We report a 10-year-old child with CRC; he was diagnosed with stage IIIB advanced transverse colon cancer without distal metastases. We detected a heterozygous germline mutation at c.5465 T > A in both blood and tissue samples and a heterozygous somatic mutation at c.7397C > T in the tissue sample. Both of these mutations can cause CRC tumorigenesis in the first decade of life. Conclusions The rare genetic features of this 10-year-old patient might be the predisposing cause of pediatric CRC. Therefore, screening patients with early-onset CRC through clinical and genetic characterizations is suggested.

Abstract Background The robotic system has advantages of high-definition three-dimensional vision and articular instruments with high dexterity, allowing more precise dissection in the deep and narrow pelvic cavity. Methods We enrolled 95 patients with stage I-III rectal cancer (adenocarcinoma) who underwent totally robotic-assisted total mesorectal excision (TME) with single-docking technique at a single institution between September 2013 and December 2016. Results Of the 95 patients, 48 (50.5%) and 30 (31.6%) patients had lower and middle rectal cancers, respectively. Of the 75 (78.9%) patients undergoing preoperative concurrent chemoradiotherapy (CCRT), 27 (28.4%) exhibited pathologic complete response (pCR). Only four (4.2%) patients underwent abdominoperineal resection and the sphincter preservation rate was 95.8%. R0 resection was performed in 92 (96.8%) patients. Circumferential resection margin (CRM) and distal resection margin (DRM) were positive in 2 (2.1%) and 1 (1.1%) patients, respectively. The anastomotic leakage rate was 5.4% (5/95 patients). The overall complication rate was 17.9% (17/95 patients); most of them were mild. No 30-day hospital mortality occurred, and no patients required conversion to open surgery. In 92 patients undergoing R0 resection, 2-year overall survival was 94% and 2-year disease-free survival was 83%. Conclusions The results demonstrated that totally robotic-assisted TME with the single-docking technique is safe and feasible for patients with rectal cancer, with or without preoperative CCRT. Moreover, favorable pCR rate, R0 resection rate, CRM, DRM, sphincter preservation rate, and short-term oncological outcomes can be achieved by combining this approach with appropriate preoperative CCRT.

Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray to compare the miRNA profiles of patients with LARC who achieved pCR (pCR group, n = 5) with those who did not (non-pCR group, n = 5). The validation set confirmed that miRNA-148a was overexpressed in the pCR group (n = 11) compared with the non-pCR group (n = 40). Cell proliferation and clonogenic assays revealed that miRNA-148a overexpression radio-sensitized cancer cells and inhibited cellular proliferation, before and after irradiation (p < 0.01). Apoptosis assays demonstrated that miRNA-148a enhanced apoptosis before and after irradiation. Reporter assays revealed that c-Met was the direct target gene of miRNA-148a. An in vivo study indicated that miRNA-148a enhanced the irradiation-induced suppression of xenograft tumor growth (p < 0.01). miRNA-148a may be a biomarker of pCR following NACRT and can promote apoptosis and inhibit proliferation in CRC cells by directly targeting c-Met in vitro and enhancing tumor response to irradiation in vivo.

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-–5FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the (1) induction of cell cycle arrest in the S phase and (2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both the c-mesenchymal–epithelial transition (MET)/Kirsten rat sarcoma virus (KRAS)/extracellular signal-regulated kinase (ERK) and the c-MET/phosphatidyl-inositol 3-kinases (PI3K)/protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required in order to validate the results of the present study.

Abstract Background After a low anterior resection, creating a defunctioning stoma is vital for securing the anastomosis in low-lying rectal cancer patients receiving concurrent chemoradiotherapy. Although it decreases the complication and reoperation rates associated with anastomotic leakage, the complications that arise before and after stoma closure should be carefully evaluated and managed. Methods This study enrolled 95 rectal cancer patients who received neoadjuvant concurrent chemoradiotherapy and low anterior resection with anastomosis of the bowel between July 2010 and November 2012. A defunctioning stoma was created in 63 patients during low anterior resection and in another three patients after anastomotic leakage. Results The total complication rate from stoma creation to closure was 36.4%. Ileostomy led to greater renal insufficiency than colostomy did and significantly increased the readmission rate (all p