Efficacy of ramucirumab and subsequent nivolumab therapy in patients with advanced gastric cancer: A retrospective study.

Nivolumab monotherapy is a standard treatment of metastatic gastric cancer, and this type of cancer involves vascular endothelial growth factor (VEGF) signaling in the tumor immunological environment. The subgroup analysis of the ATTRACTION-2 trial revealed that prior treatment with ramucirumab (RAM), a VEGF inhibitor, affected the therapeutic effect of nivolumab. The present retrospective study aimed to review patients with metastatic gastric cancer who were treated with paclitaxel (PTX) and RAM followed by nivolumab. A total of 29 patients with metastatic gastric cancer were treated with PTX + RAM as second-line treatment, followed by nivolumab monotherapy as third-line treatment. The therapeutic efficacy of nivolumab was compared in 13 patients with progression-free survival (PFS) of <5 months and 16 patients with PFS ≥5 months after PTX + RAM therapy. The present study included 22 male and seven female patients, with a median age of 68 years (range, 45-82 years). Human epidermal growth factor receptor 2 positivity was observed in six patients. The disease control rate was 62.1%. The PFS and overall survival (OS) were 4.4 and 11.9 months, respectively. Patients with PFS ≥5 months after PTX + RAM therapy showed better outcome in both PFS (5.3 months vs. 2.8 months, P=0.039) and OS (6.9 months vs. 15.2 months, P=0.066) after nivolumab treatment than patients with PFS of <5 months after PTX + RAM therapy. However, no significant relationship was observed between the outcome of first-line treatment and nivolumab. The therapeutic effect of nivolumab was associated with prior PTX + RAM treatment in advanced gastric cancer.

Clinical features and distribution of the APC variant in duodenal and ampullary polyps in patients with familial adenomatous polyposis: a multicenter retrospective cohort study in Japan.

BACKGROUND: Management of duodenal or ampullary adenomas in patients with familial adenomatous polyposis (FAP) is a major challenge for clinicians. Insufficient data are available to evaluate the clinical manifestations and distribution of adenomatous polyposis coli (APC) variants in these patients. METHODS: We enrolled 451 patients with data regarding duodenal or ampullary polyps from 632 patients with FAP retrospectively registered in a nationwide Japanese multicenter study. Clinicopathological features and distribution of APC variants were compared between patients with and without duodenal or ampullary polyps. RESULTS: Duodenal and ampullary polyps were found in 59% and 18% of patients with FAP, respectively. The incidence of duodenal cancer was 4.7% in patients with duodenal polyps, and that of ampullary cancer was 18% in patients with ampullary polyps. Duodenal polyps were significantly associated with the presence of ampullary polyps and jejunal/ileal polyps. Duodenal polyps progressed in 35% of patients with a median follow-up of 776 days, mostly in those with early Spigelman stage lesions. Ampullary polyps progressed in 50% of patients with a follow-up of 1484 days. However, only one patient developed a malignancy. The proportion of patients with duodenal polyps was significantly higher among those with intermediate- or profuse-type APC variants than attenuated-type APC variants. The presence of duodenal polyps was significantly associated with ampullary and jejunal/ileal polyps in patients with intermediate- or profuse-type APC variants. CONCLUSIONS: Periodic endoscopic surveillance of the papilla of Vater and small intestine should be planned for patients with FAP with duodenal polyps.

A postoperative body weight increase is a novel risk factor for incisional hernia of midline abdominal incision after elective gastroenterological surgery.

PURPOSE: Midline abdominal incisions (MAIs) are widely used in both open and minimally invasive surgery. Incisional hernia (IH) accounts for most long-term postoperative wound complications. This study explored the risk factors for IH due to MAI in patients with clean-contaminated wounds after elective gastroenterological surgery. METHODS: The present study targeted patients enrolled in 2 randomized controlled trials to evaluate the efficacy of intraoperative interventions for incisional SSI prevention after gastroenterological surgery for clean-contaminated wounds. The patients were reassessed, and pre- and intraoperative variables and postoperative outcomes were collected. IH was defined as any abdominal wall gap, regardless of bulge, in the area of a postoperative scar that was perceptible or palpable on clinical examination or computed tomography according to the European Hernia Society guidelines. The risk factors for IH were identified using univariate and multivariate analyses. RESULTS: The study population included 1,281 patients, of whom 273 (21.3%) developed IH. Seventy-four (5.8%) patients developed incisional SSI. Multivariate logistic regression analysis revealed that female sex (odds ratio [OR], 1.39; 95% confidence interval [CI] 1.03-1.86, p = 0.031), high preoperative body mass index (OR, 1.81; 95% CI 1.19-2.77, p = 0.006), incisional SSI (OR, 2.29; 95% CI 1.34-3.93, p = 0.003), and postoperative body weight increase (OR, 1.49; 95% CI 1.09-2.04, p = 0.012) were independent risk factors for IH due to MAI in patients who underwent elective gastroenterological surgery. CONCLUSION: We identified postoperative body weight increase at one year as a novel risk factor for IH in patients with MAI after elective gastroenterological surgery.

Enhancement of DNA hypomethylation alterations by gastric and bile acids promotes chromosomal instability in Barrett's epithelial cell line.

Gastric and bile acid reflux leads to chronic inflammation, resulting in methylation alterations in Barrett's esophagus (BE) together with chromosomal instability (CIN). We investigated DNA hypomethylation following acid exposure and confirmed its significance in BE-related carcinogenesis by inducing CIN in vitro. OACP4C, an esophageal cancer cell line, and CP-A, a non-dysplastic cell line originating from BE, were exposed to acidic conditions using deoxycholic acid. CP-A exhibited substantially increased DNA hypomethylation of alpha satellite sequences in the centromere region, as well as increased levels of alpha satellite transcripts, but no changes were observed in the long interspersed nucleotide element-1 sequences distributed throughout the entire genome. These changes were not clearly found in OACP4C. Copy number changes at specific chromosomes were identified in CP-A, along with an increased number of cells exhibiting abnormal segregations, whereas these changes were rarely observed in OACP4C. The changes were maintained after several cell divisions. These findings suggest that alpha satellites are likely targets of DNA hypomethylation induced by acid exposure. CP-A was more sensitive to acid exposure than OACP4C, indicating that acid-induced DNA hypomethylation is involved in cancer development rather than progression, which could be involved in the underlying mechanism of esophagogastric junction carcinoma development.

Indications and Outcomes of a Hybrid Method Combining Laparoscopic and Anterior Approaches for Inguinal Hernia Repair.

Introduction Surgery for complex inguinal hernia (IH) (recurrent IH or IH after radical prostatectomy (RP)) may be difficult because of the presumed scar or adhesion in the retropubic space. A hybrid method combining the laparoscopic and anterior approaches (HLAA) in a bidirectional surgical technique may be an option in complex IH cases. Methods Patients at our institution who underwent IH repair for complex IH using HLAA from April 2018 to November 2019 were included. We retrospectively evaluated the patient characteristics, IH diagnosis, intraoperative variables, complications, and hernia recurrence during the follow-up period. Results Twenty patients were involved in this study. Seven patients underwent hLAA for recurrent IH, whereas the remaining 13 underwent hLAA for IH after RP. Five patients had bilateral IH, all of whom had IH after RP. The type of IH was lateral in 21 patients, medial in six patients, and lateral and medial in two patients. Hernia repair was performed using a patch alone in two patients and a plug and patch in 18 patients. Seroma or hematoma was observed in five patients, and one patient experienced chronic pain. No hernia recurrence was observed during the median follow-up period of 24 months. Conclusion hLAA could facilitate precise diagnosis and intraoperative confirmation of repair for recurrent IH and IH after RP. The intraoperative findings and the cause of recurrence can be easily shared among surgeons in hLAA. Further investigations are necessary to determine the long-term efficacy of hLAA in a larger cohort.

Mid-term Efficacy of Local Repair Using Modified Altemeier Technique for Stomal Prolapse: A Case Series.

INTRODUCTION:  Stomal prolapse (SP) is characterized by full-thickness protrusion of the bowel through the stoma site. The surgical procedures for SP include local repair, abdominal wall fixation, and stoma relocation. However, previous reports were mostly case reports or case series with a small number of patients and lacked long-term results. A modified Altemeier technique (MAT) has been used for the local repair of SP in our institution, and this study aimed to evaluate its mid-term efficacy. METHODS:  We reviewed patients who underwent MAT for SP between August 2013 and December 2020. The variables included patient characteristics, type of stoma, indications of stoma creation, the time interval from stoma creation to prolapse, site of prolapse, reasons for SP surgery, perioperative variables, complications during SP surgery, and length of follow-up. Recurrence of SP was defined as the need for change in stoma care or re-protrusion of the stoma by more than 5 cm in length. RESULTS:  Ten patients were included in this study. The median age at the time of SP surgery was 71.5 years. The indications of stoma creation included unresectable or recurrent intra-abdominal malignancies in four patients, diverting ileostomy with rectal cancer surgery in two, transverse colon cancer in one, gastric and rectal cancer in one, rectovaginal fistula in one, and non-occlusive mesenteric ischemia in one. The median interval from stoma creation to prolapse was 2.5 months. Six patients underwent elective SP surgery, and four patients underwent emergency surgery for incarcerated prolapse. The median operative time was 75.5 min. Postoperative complications that included transient mucosal ischemia and subcutaneous abscess occurred in one patient. There were four recurrences (40%), and the median time interval from surgery to recurrence was 4.5 months. Two patients underwent repeated MAT, one of whom underwent stomal reversal with laparotomy for re-recurrence. The median follow-up duration was 19 months. CONCLUSION:  MAT for SP is associated with a high recurrence rate in mid-term follow-up.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability and reflects drug sensitivity in mouse cancer cells.

Overexpression of satellite RNAs in heterochromatin induces chromosomal instability (CIN) through the DNA damage response and cell cycle checkpoint activation. Although satellite RNAs may be therapeutic targets, the associated mechanisms underlying drug sensitivity are unknown. Here, we determined whether satellite RNAs reflect drug sensitivity to the topoisomerase I inhibitor camptothecin (CPT) via CIN induction. We constructed retroviral vectors expressing major satellite and control viruses, infected microsatellite stable mouse colon cancer cells (CT26) and MC38 cells harboring microsatellite instability, and assessed drug sensitivity after 48 h. Cells overexpressing satellite RNAs showed clear features of abnormal segregation, including micronuclei and anaphase bridging, and elevated levels of the DNA damage marker γH2AX relative to controls. Additionally, overexpression of satellite RNAs enhanced MC38 cell susceptibility to CPT [half-maximal inhibitory concentration: 0.814 µM (control) vs. 0.332 µM (MC38 cells with a major satellite), p = 0.003] but not that of CT26. These findings imply that MC38 cells, which are unlikely to harbor CIN, are more susceptible to CIN-induced CPT sensitivity than CT26 cells, which are characterized by CIN. Furthermore, CPT administration upregulated p53 levels but not those of p21, indicating that overexpression of major satellite transcripts likely induces CPT-responsive cell death rather than cellular senescence.

Prophylactic use of pegfilgrastim enables the management of severe neutropenia without dose delays in patients with metastatic colorectal cancer treated with TAS-102 plus bevacizumab.

Combined treatment with bevacizumab and trifluridine/tipiracil (TAS-102) leads to an increased chance of survival in patients with refractory metastatic colorectal cancer (mCRC); however, this treatment is associated with an increased frequency of severe neutropenia (number of neutrophils <1,000), which should ideally be managed without dose delays. The present study provided a retrospective review of 35 patients with mCRC, and aimed to elucidate the benefits of prophylactic pegfilgrastim for the treatment of severe neutropenia. Patients received TAS-102 (35 mg/m2) orally twice daily on days 1-5 and 8-12 of each 28-day treatment cycle, along with intravenous bevacizumab (5 mg/kg) on days 1 and 15. Moreover, the patients received 3.6 mg pegfilgrastim on day 15 of each cycle. The incidence of adverse events (AEs), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were assessed. In the first and subsequent cycles, 23 and 12 patients, respectively, received pegfilgrastim. The most common AE experienced was grade 3/4 neutropenia (8 patients; 22.9%). Among these 8 patients, 6 (17.1%) and 3 (8.6%) exhibited neutropenia prior to receiving pegfilgrastim or following discontinuation of pegfilgrastim administration, respectively. Moreover, 1 individual among these 8 patients (2.9%) demonstrated grade 3 neutropenia both prior to receiving pegfilgrastim and following discontinuation of pegfilgrastim. A total of 2 patients (5.7%) exhibited grade 3 bone pain, which prevented sustainable administration of pegfilgrastim and resulted in grade 3 neutropenia. Dose delays and dose reduction of TAS-102 due to neutropenia were required in 5 (14.3%) and 2 (5.7%) patients, respectively, during the treatment period. None of the patients exhibited severe neutropenia during chemotherapy after pegfilgrastim administration, thereby preventing dose delays and dose reduction of TAS-102. The relative dose intensity was 96.8% (65.0-100.0%), and the DCR was 54.3%. The median PFS and median OS were 4.4 and 14.9 months, respectively. In conclusion, prophylactic pegfilgrastim may facilitate the management of severe neutropenia without dose delays in patients with mCRC treated with TAS-102 plus bevacizumab.

Genome­wide DNA hypomethylation drives a more invasive pancreatic cancer phenotype and has predictive occult distant metastasis and prognosis potential.

Genome­wide DNA hypomethylation is the most common molecular feature in human cancers associated with chromosomal instability (CIN), which is involved in the mechanisms that regulate pancreatic cancer (PC) metastasis. It was investigated whether genome­wide DNA hypomethylation affects the phenotype in PC via CIN in vitro, and its significance on the biological behavior of PC was verified. The relative demethylation level (RDL) of long interspersed nucleotide element­1 (LINE­1) in human PC cell lines was used to characterize DNA hypomethylation using methylation­specific quantitative (q)PCR. CIN was estimated by changes in chromosomal copy number using comparative genomic hybridization analysis. Abnormal segregation of chromosomes was assessed by immunocytochemistry, and the DNA damage response was evaluated using the number of anti­Î³H2AX positive cells. Invasion ability was assessed using a Matrigel invasion assay. Clinical specimens from 49 patients with PC who underwent curative surgery were evaluated for a correlation of DNA hypomethylation with clinical outcome. Successful induction of genome­wide DNA hypomethylation in PC cells led to copy number changes in specific chromosomal regions. The number of cells with abnormal segregation of chromosomes significantly increased with the number of anti­Î³H2AX positive cells. The invasive potential of these cells also significantly increased. The occurrence of occult distant metastasis in the clinical specimens and receiver operating characteristic analysis clearly identified those who were and were not likely to have occult distant metastasis, with high LINE­1 RDL significantly correlated with the presence of occult distant metastasis (P=0.035) and poor prognosis (P=0.048). The significance of genome­wide DNA hypomethylation on the biological behavior of PC, which promotes a more invasive phenotype via CIN in vitro and predicts the susceptibility to occult distant metastasis and poor prognosis in patients with PC was revealed.

Impact of sarcopenia on surgical and oncologic outcomes of laparoscopic surgery for colorectal cancer.

BACKGROUND: The study aimed to evaluate the impact of sarcopenia on short- and long-term outcomes for laparoscopic colorectal cancer surgery. METHODS: Study participants were 209 patients who underwent laparoscopic surgery for any stage of colorectal cancer between 2016 and 2017. Skeletal muscle indices were calculated with preoperative computed tomography. Patients were divided into sarcopenic and non-sarcopenic groups based on index cut-off values and variables were compared. RESULTS: The prevalence of sarcopenia was 41.1%. Sarcopenic patients experienced shorter operative times and a lower incidence of surgical site infections; however, the incidence of severe postoperative complications and readmission were increased for this group. Although the 3-year disease-free survival rate was not statistically different between groups, sarcopenic patients had a significantly worse 3-year overall survival rate compared with than the non-sarcopenic group. CONCLUSION: Sarcopenia has both favorable and unfavorable effects on patients who underwent laparoscopic colorectal cancer surgery.

Optimal value of CA19-9 determined by KRAS-mutated circulating tumor DNA contributes to the prediction of prognosis in pancreatic cancer patients.

Despite the acceptance of carbohydrate antigen 19-9 (CA19-9) as a valuable predictor for the prognosis of pancreatic ductal adenocarcinoma (PDAC), its cutoff value remains controversial. Our previous study showed a significant correlation between CA19-9 levels and the presence of KRAS-mutated ctDNA in the blood of patients with PDAC. Based on this correlation, we investigated the optimal cutoff value of CA19-9 before surgery. Continuous CA19-9 values and KRAS-mutated ctDNAs were monitored in 22 patients with unresectable PDAC who underwent chemotherapy between 2015 and 2017. Receiver operating characteristic curve analysis identified 949.7 U/mL of CA19-9 as the cutoff value corresponding to the presence of KRAS-mutated ctDNA. The median value of CA19-9 was 221.1 U/mL. Subsequently, these values were verified for their prognostic values of recurrence-free survival (RFS) and overall survival (OS) in 60 patients who underwent surgery between 2005 and 2013. Multivariate analysis revealed that 949.7 U/mL of CA19-9 was an independent risk factor for OS and RFS in these patients (P = 0.001 and P = 0.010, respectively), along with lymph node metastasis (P = 0.008 and P = 0.017), unlike the median CA19-9 level (P = 0.150 and P = 0.210). The optimal CA19-9 level contributes to the prediction of prognosis in patients with PDAC before surgery.

Superiority trial comparing intraoperative wound irrigation with aqueous 10% povidone-iodine to saline for the purpose of reducing surgical site infection after elective gastrointestinal surgery: study protocol for a randomised controlled trial.

INTRODUCTION: Surgical site infection (SSI) is one of the most common complications after gastrointestinal surgery, with a reported incidence of approximately 10%-25%, which is higher than the rates after other types of surgery. Intraoperative wound irrigation (IOWI) is a simple intervention for SSI prevention, and recent studies have reported that IOWI with aqueous povidone-iodine (PVP-I) is significantly more effective at reducing the incidence of SSI than saline. However, the evidence level of previous trials evaluating the efficacy of aqueous PVP-I solution for preventing SSI has been low. METHODS AND ANALYSES: We propose a single-institute, prospective, randomised, blinded-endpoint trial to assess the superiority of IOWI with aqueous 10% PVP-I solution compared with normal saline for reducing SSI in clean-contaminated wounds after elective gastrointestinal surgery. In the study group, IOWI with 40 mL of aqueous 10% PVP-I solution is performed for 1 min before skin suture, and in the control group, IOWI with 100 mL of saline is performed for 1 min before skin suture. We hypothesise that IOWI with aqueous 10% PVP-I solution will achieve a 50% reduction in the incidence of SSIs. The target number of cases is set at 950. The primary outcome is the incidence of incisional SSI up to postoperative day 30 and will be analysed in the modified intention-to-treat set. ETHICS AND DISSEMINATION: This trial was designed and is being conducted by Saitama Medical Center, Jichi Medical University, with approval from the Bioethics Committee for Clinical Research, Saitama Medical Center, Jichi Medical University. Participant recruitment began in June 2019. The final results will be reported in international peer-reviewed journals immediately after trial completion. TRIAL REGISTRATION NUMBER: UMIN000036889.

Effect of Antithrombotic Therapy on Secondary Bleeding After Proctological Surgery.

Introduction Surgery for patients taking antithrombotic drugs for the prevention and treatment of cardiovascular disease, including anticoagulants and antiplatelet drugs, is increasing because of the aging society. In patients with moderate to high risk for cardiovascular events, receiving antiplatelet therapy, and requiring noncardiac surgery continuing antiplatelet drugs perioperatively is recommended. To date, there have been limited reports on the risk of secondary bleeding after proctological surgery in patients who are administered antithrombotic drugs. The purpose of this study was to identify the incidence and severity of secondary bleeding after proctological surgery for patients with or without antithrombotic therapy. Methods We retrospectively identified 113 patients who underwent proctological surgery in our hospital from March 2009 to February 2019. In general, antiplatelet drugs were continued and anticoagulant drugs were either substituted or withdrawn prior to surgery. The severity of secondary bleeding was classified as mild, moderate, or severe. Results Eighteen patients underwent antithrombotic therapy (A group) and 95 patients did not undergo antithrombotic therapy (N group). Secondary bleeding was observed in nine patients (8.0%) and patients in the A group exhibited a significantly higher rate of secondary bleeding than those in the N group (39% vs. 2.4%, P < 0.01). The median interval from surgery to the onset of secondary bleeding was five days (range: 0-11). The severity of bleeding was the highest in patients administered direct oral anticoagulants (DOAC) and was the lowest in those administered aspirin. There was no mortality or cardiovascular event. Conclusion Antithrombotic therapy carries a high risk of secondary bleeding after proctological surgery. Delaying the postoperative resumption of anticoagulants is considered while balancing the risk of postoperative thromboembolic complications against secondary bleeding.

Risk factors and management of stoma-related obstruction after laparoscopic colorectal surgery with diverting ileostomy.

BACKGROUND: Stoma-related obstruction (SRO) is defined as small bowel obstruction occurring around the limbs of diverting ileostomy (DI). This study was aimed to investigate the incidence, risk factors, and management of SRO after laparoscopic colorectal surgery with DI creation. METHODS: This study included 155 patients who underwent laparoscopic colorectal surgery with DI creation for rectal cancer (n = 138), ulcerative colitis (UC) (n = 14), and familial adenomatous polyposis (FAP) (n = 3) between 2011 and 2019. Univariate and multivariate analyses were performed to identify the risk factors of SRO. RESULTS: The incidence of SRO was 7.7% (n = 12), and it was significantly lower (P < 0.01) in patients with lower anterior resection or intersphincteric resection (4.3%) than in those with ileal-pouch anal anastomosis (IPAA) (35.2%). The multivariate analysis revealed that IPAA was independently associated with the development of SRO (P = 0.001; odds ratio, 9.4; 95% confidence interval, 2.5-35.4). Eleven of 12 patients (92%) with SRO required trans-stomal tube decompression, and 8 of those (67%) underwent early stoma closure. CONCLUSION: IPAA was an independent risk factor of SRO in laparoscopic colorectal surgery with DI creation. Early stoma closure was needed in most cases of SRO.

Intra-abdominal desmoid tumor after laparoscopic low anterior resection for rectal cancer: A case report.

Desmoid tumors are monoclonal fibroblastic proliferations arising from soft tissue classified as intra-abdominal, extra-abdominal and abdominal wall types. We present a patient with an intra-abdominal desmoid tumor diagnosed 20 months after laparoscopic resection of rectal cancer. A 70-year-old woman with hematochezia was diagnosed with advanced rectal cancer. Preoperative chemoradiotherapy followed by laparoscopic low anterior resection was performed. During follow-up, a nodular soft-tissue density measuring 28 mm was detected in the presacral region. Metastasis from rectal cancer was diagnosed and four courses of chemotherapy were given, including capecitabine, oxaliplatin and bevacizumab. Computed tomography scan showed that the mass slightly decreased in size and surgical resection was performed. Histopathological examination revealed a proliferation of spindle-shaped cells and collagenous stroma diagnosed as a desmoid tumor. This report highlights the possibility of a desmoid tumor in the differential diagnosis of an intra-abdominal mass found during follow-up after resection of colorectal cancer including following laparoscopic resection.

Idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy: A case report.

Idiopathic mesenteric phlebosclerosis is a rare entity characterized by chronic intestinal ischemia due to calcification and obstruction of the mesenteric veins. Here, we report a patient with idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy after evaluation by imaging studies. The patient was a 68-year-old Japanese woman with recurrent abdominal pain who had taken a Chinese herbal medicine for more than 20 years. Abdominal CT showed wall thickening of the right colon with calcification of branches of the superior mesenteric vein. Colonoscopy showed cyanotic mucosa from the cecum to the sigmoid colon. The affected area seen on colonoscopy extended to the distal colon. Despite discontinuation of the herbal medicine, her symptoms did not improve. Laparoscopic subtotal colectomy was performed. This report highlights the importance of appropriately evaluating the extent of the affected preoperatively area based on findings from colonoscopy, CT, and contrast enema.

Temporary loss of consciousness during cetuximab treatment of a patient with metastatic colon cancer: a case report.

BACKGROUND: Anti-epidermal growth factor receptor (EGFR) antibody is widely used for the treatment of patients with metastatic colorectal cancer. Hypomagnesemia is a comparatively frequent adverse event of this drug, which is likely overlooked because it occurs later in treatment without symptoms. Furthermore, hypomagnesemia and hypomagnesemia-induced corrected QT (QTc) prolongation may lead to loss of consciousness (LOC), the onset of which is not generally considered associated with the treatment of anti-EGFR antibody because of its rare occurrence. Here, we present a colorectal cancer patient treated with anti-EGFR antibody, who suffered LOC during treatment while severe hypomagnesemia or QTc prolongation was not observed. CASE PRESENTATION: A 69-year-old man with metastatic colon cancer was treated with cetuximab (anti-EGFR antibody) plus irinotecan as third-line chemotherapy. His serum magnesium level gradually decreased, and grade 2 hypomagnesemia (a serum magnesium level of 0.9 mg/dL) was observed at the 12th administration of cetuximab. In light of this development, intravenous supplementation of 20 mEq magnesium sulfate began with careful blood monitoring despite the lack of clinical symptoms. Electrocardiogram (ECG) showed prolonged QT or corrected QT (QTc) intervals (grade 1). His serum magnesium level remained at 0.9 mg/dL, and no hypomagnesemia symptoms were observed by the 17th administration of cetuximab. After the treatment, however, he suddenly lost consciousness without symptoms related to infusion or allergic reactions. Circulatory collapse following dermatological reactions and respiratory events were not evident. Intravenous supplementation of magnesium sulfate was administered again. He awakened 2 min after the onset of temporary LOC without any other symptoms related to hypomagnesemia, such as lethargy, tremor, tetany, and seizures. No other etiology outside of the low level of serum magnesium was confirmed in further examinations. Cetuximab was discontinued, and his serum magnesium level returned to a level within the normal range after 6 weeks. Because of tumor progression, regorafenib and TAS-102 (trifluridine tipiracil hydrochloride) were introduced sequentially for 6 months. Five months after the final treatment of TAS-102, he died of his primary disease, which reflected a survival period of 4 years and 6 months since the beginning of treatment. CONCLUSIONS: This case report reminds clinicians that LOC can be induced without severe hypomagnesemia or QTc prolongation, during anti-EGFR antibody treatment for metastatic colorectal cancer even while under carefully monitored magnesium supplementation.

High relative levels of satellite alpha transcripts predict increased risk of bilateral breast cancer and multiple primary cancer in patients with breast cancer and lacking BRCA­related clinical features.

Patients with breast cancer who undergo surgery have a risk of developing multiple cancers in the contralateral breast and other organs. We previously reported that overexpression of satellite alpha transcripts (SAT) facilitates chromosomal instability, which is involved in the development of multiple tumors in patients with colorectal and gastric cancer. In this study, we elucidated the significance of SAT in the development of multiple tumors in patients with breast cancer. Relative expression of SAT (rSAT) was calculated in normal and tumor tissues from 167 patients. In total, 27 patients developed bilateral breast cancer (BBC) and 27 patients showed multiple primary cancer (MPC), with patients with BBC and MPC showing higher rSAT levels in tumor tissues than those in patients with single breast cancer (SBC) (P=0.0312 and P=0.0420, respectively). Additionally, higher rSAT levels in tumor tissues from patients with BBC were a significant factor according to univariate analysis, and multivariate analysis showed that rSAT >1.5 was a significant predictor of MPC [hazard ratio (HR): 2.96; P=0.0243); however, we did not clarify the involvement of SAT in normal tissues. Excluding 71 patients with BRCA­related clinical features, rSAT levels were higher in patients with BBC and MPC than in patients with SBC in tumor tissues and normal tissues (P<0.05). Significant predictors according to univariate analysis included rSAT >1.5 in tumor tissues, rSAT >2.4 in normal tissues, and T <2, whereas those for multivariate analysis included rSAT >2.4 in normal tissues for BBC (HR: 22.7; P=0.00120) and MPC (HR: 13.0; P=0.00601). Our data indicated that patients with breast cancer and high rSAT levels in their breast tissues exhibit a 10­ to 20­fold increased risk for the development of multiple cancers when harboring no BRCA­related clinical features.

Successful mesh plug repair using a hybrid method for recurrent inguinal hernia after laparoscopic transabdominal preperitoneal approach: A case report.

INTRODUCTION: The HerniaSurge Group and the European Hernia Society guidelines recommend an anterior approach to treat recurrent inguinal hernias after a failed posterior approach. The hybrid method combining explorative laparoscopy and anterior open approach can provide the benefits of both approaches. PRESENTATION OF CASE: A 79-year-old man presented with a recurrent inguinal hernia after primary repair for an indirect hernia using the laparoscopic transabdominal preperitoneal approach (TAPP) 5 years ago. The indirect hernia formed inferior to the lower edge of the previous mesh was diagnosed under laparoscopy. The hernia defect (2 cm) was fixed using a mesh plug via the anterior approach. Appropriate mesh overlap was confirmed using laparoscopy. DISCUSSION: This minimally invasive method enabled us to choose the best treatment for recurrent hernia and prevent chronic pain due to possible nerve damage caused by extended dissection of the scar tissue. Furthermore, the final confirmation step using laparoscopy assures complete coverage of all defects within the myopectineal orifice. CONCLUSION: This hybrid method facilitates the choice of an optimal approach for the treatment of recurrent hernia and may reduce surgical complications and re-recurrence rate.

Efficacy of Neoadjuvant Chemotherapy with Capecitabine plus Oxaliplatin in the Treatment of Locally Advanced Sigmoid Colon Cancer Invading the Urinary Bladder: A Report of Three Cases.

INTRODUCTION: We herein present three cases of locally advanced colon cancer (LACC) invading the urinary bladder, in whom combined neoadjuvant chemotherapy with surgical intervention was effective in disease control and preserving urinary function. CASE PRESENTATION: Before neoadjuvant chemotherapy, all three cases underwent loop transverse colostomy for symptomatic colonic obstruction. Case 1: after 6 courses of capecitabine plus oxaliplatin (CAPOX), we performed sigmoid colectomy and partial resection of the bladder. The histological examination revealed pathological complete response (pCR). The final diagnosis was ypStage 0 (ypT0ypN0M0). Case 2: after 13 courses of CAPOX plus bevacizumab, we performed Hartmann's operation with partial resection of the bladder. The histological examination revealed pCR. The final diagnosis was ypStage 0 (ypT0ypN0M0). Case 3: after 6 courses of chemotherapy with CAPOX plus bevacizumab, we performed sigmoid colectomy and partial resection of the bladder. The pathological response was grade 1a according to the Japanese Classification of Colorectal Carcinoma. The final diagnosis was ypStage IIC (ypT4bypN0M0). All three cases underwent capecitabine-based adjuvant chemotherapy after radical surgery and patients are alive without recurrence. CONCLUSION: Neoadjuvant chemotherapy with CAPOX with or without bevacizumab followed by radical surgery could be an effective treatment option for LACC invading the urinary bladder.