A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer.

BACKGROUND: This study aimed to elucidate the clinicopathological and molecular features of HER2-amplified and HER2-low colorectal cancers (CRCs). We also characterised HER2 expression statuses in CRCs focusing on their intratumoral heterogeneity and alterations in metastatic lesions to establish practical HER2 status assessment. METHODS: We evaluated 1009 CRCs for HER2 expression and HER2 amplification by immunohistochemistry and FISH, respectively, and correlated the results to clinicopathological and molecular data. For HER2-positive tumours, HER2 expression in metastatic lesions was also assessed. RESULTS: Twenty-five HER2-amplified (2.5%) and 46 HER2-low tumours (4.6%) were identified. HER2-amplified tumours consistently lacked a mucinous component and HER2-low tumours tended to be in the right colon, but no other clinicopathological features were noted. KRAS, NRAS or BRAF mutations were detected in only two HER2-amplified tumours (8%), whereas 23 HER2-low tumours (50%) had one of these mutations. Most HER2-amplified and HER2-low tumours showed a homogeneous or mosaic HER2 expression pattern and a clustered heterogeneous expression pattern was rather rare. HER2 expression was maintained in most metastatic lesions in both HER2-amplified (93%) and HER2-low tumours (81%). CONCLUSIONS: These results suggest that biopsy-based assessment of primary lesions is appropriate for the identification of CRC patients eligible for systemic HER2-targeted therapy.

Aqueous Povidone-Iodine Versus Normal Saline For Intraoperative Wound Irrigation on The Incidence of Surgical Site Infection in Clean-Contaminated Wounds After Gastroenterological Surgery: A Single-Institute, Prospective, Blinded-Endpoint, Randomized Controlled Trial.

OBJECTIVE: This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared with that with saline for reducing the incidence of surgical site infection (SSI). BACKGROUND: IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and the Centers for Disease Control and Prevention, although the evidence level is low. METHODS: This single institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison with IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients 20 years or older were assessed for eligibility, and the eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for 1 minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set. RESULTS: Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P =0.154). CONCLUSION: The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

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.

Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.

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.

Early peritoneal metastasis after laparoscopic incisional hernia repair secondary to colon cancer resection: A case report.

INTRODUCTION: and importance: We report a case of a patient who developed early peritoneal metastasis after laparoscopic incisional hernia repair secondary to curative colon cancer resection. CASE PRESENTATION: A 77-year-old woman underwent ileocecal resection with open laparotomy for locally advanced cecal cancer. The pathological diagnosis was adenocarcinoma with T3N2aM0. Three months after the surgery, she developed incisional hernia at the midline incision site. After the completion of adjuvant chemotherapy, surveillance computed tomography (CT) showed no cancer recurrence. Her abdominal discomfort persisted because of incisional hernia, and thus we performed laparoscopic incisional hernia repair using the intraperitoneal onlay mesh technique at 11 months after the initial surgery.Five months after incisional hernia repair, CT showed multiple liver and peritoneal metastases. She was started on systemic chemotherapy. Two days after the first therapeutic infusion, she developed small bowel obstruction. We decided to perform palliative surgery with intestinal bypass. Exploratory laparoscopy revealed that the implanted mesh for incisional hernia repair was completely covered with multiple nodules of peritoneal metastasis. Two months after the bypass surgery, she resumed her chemotherapy, but CT showed significant progression of all recurrent lesions. She did not wish to continue further chemotherapy and decided to receive the best supportive care. CLINICAL DISCUSSION: This case may raise important clinical questions regarding the indication and timing of incisional hernia repair for patients who are at high risk of cancer recurrence. CONCLUSION: Incisional hernia repair must be performed in the absence of any possibility of cancer recurrence, particularly in the earlier follow-up period.

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.

Tolerability and Adverse Events of Adjuvant Chemotherapy for Rectal Cancer in Patients With Diverting Ileostomy.

BACKGROUND/AIM: The impact of diverting ileostomy on the feasibility of adjuvant chemotherapy (ACT) remains unclear. We retrospectively investigated the tolerability and adverse events of ACT for rectal cancer in patients with diverting ileostomy. PATIENTS AND METHODS: Thirty-three patients who received ACT after curative resection with ileostomy construction for rectal cancer were analyzed. We assessed completion rate, the mean relative dose intensities, and the factors affecting the tolerability of ACT. RESULTS: The completion rate of each chemotherapy regimen was 10 out of 16 patients in oral uracil-tegafur plus leucovorin (UFT/LV), 1 out of 3 patients in oral capecitabine (Capecitabine) and 2 out of 14 patients in capecitabine plus oxaliplatin (CAPOX). The mean relative dose intensities were 77% in UFT/LV, 48% in Capecitabine, and 57% of capecitabine and 42% of oxaliplatin in CAPOX. In multivariate analysis, laparoscopic surgery (Odds ratio=11.6, p=0.021) and receiving preoperative chemoradiotherapy (Odds ratio=32.4, p=0.021) were associated with treatment completion. CONCLUSION: Completion rate of ACT in patients with diverting ileostomy was lower than that of colorectal cancer patients in the previous studies. UFT/LV may be a more tolerable regimen than Capecitabine or CAPOX in colorectal cancer patients with diverting ileostomy.

A case of corrosive esophagitis causing extensive cicatricial esophageal stenosis treated by esophageal bypass with supercharged pedicled jejunal pull-up.

INTRODUCTION: Swallowing a corrosive substance causes delayed gastrointestinal stenosis due to scar formation. Here, we report on our use of esophageal bypass using a supercharged pedicled jejunal flap to treat cicatricial esophageal stenosis caused by corrosive esophagitis. PRESENTATION OF CASE: Nineteen years before presentation, a 57-year-old man had swallowed a chemical cleaning agent, which caused extensive corrosive cicatricial stenosis from the thoracic upper esophagus to the gastric fornix. An enterostomy had been created, and the patient had since been subsisting on enteral nutrition. However, he wanted to be able to eat through his mouth again and was referred to our department for treatment. With the exception of the cervical esophagus, circumferential cicatricial stenosis was present throughout the esophagus and gastric fornix, with severe adhesions to the surrounding tissue. It was decided not to perform esophagectomy but to perform esophageal bypass surgery using a supercharged pedicled jejunal flap. DISCUSSION: Despite the extremely high risk of cancer in the stenotic esophagus due by corrosive esophagitis, indicating that esophagectomy should be performed if possible, we chose to perform bypass surgery because the severe adhesions posed a high risk of early injury to the surrounding organs. CONCLUSION: We suggest that esophageal bypass using pedicled jejunal pull-up "supercharging" by creating anastomoses between the jejunal and internal thoracic vessels is the optimal procedure for patients with extensive cicatricial esophageal stenosis caused by corrosive esophagitis.

Bevacizumab is associated with delayed anastomotic leak after low anterior resection with preoperative radiotherapy for rectal cancer: a case report.

BACKGROUND: Bevacizumab is an anti-angiogenesis agent used to treat patients with metastatic colorectal cancer and is associated with a variety of complications. We present a patient with rectal cancer who developed a delayed anastomotic leak more than 5 years after undergoing low anterior resection. CASE REPORT: A 78-year-old man with hematochezia was diagnosed with two synchronous rectal cancers 7 years prior to presentation. Preoperative chemo-radiotherapy was given followed by a very low anterior resection. During follow-up, multiple lymph node metastases developed, which were treated with chemotherapy. First-line chemotherapy, capecitabine, oxizaliplatin, and bevacizumab, was given over 3 years, and second-line chemotherapy, capecitabine, irinotecan, and bevacizumab, was administered over a 3-month period. After the last treatment, the patient presented with pneumaturia and fecaluria. Computed tomography scan revealed extraluminal air between the prostate and rectum, adjacent to the anastomotic site. Ulceration and fistula formation were observed on colonoscopy, and contrast radiography demonstrated a fistula at the anastomotic site. An anastomotic-urethral fistula was diagnosed and transverse colostomy was performed. CONCLUSIONS: This patient highlights a rare late adverse event at the anastomotic site associated with bevacizumab treatment and preoperative chemo-radiotherapy. Signs and symptoms suggesting anastomotic complications should be thoroughly evaluated during bevacizumab treatment, even long after surgical resection.

Surgical Resection with Neoadjuvant Chemotherapy for Locoregionally Recurrent Appendiceal Cancer Invading the External Iliac Vessels.

Recent advancements in multimodal therapy can provide oncologic benefits for patients with recurrent colorectal cancer. This report presents a case of locoregionally recurrent appendiceal cancer treated with neoadjuvant chemotherapy followed by surgical resection with vascular reconstruction. A 68-year-old Japanese woman was diagnosed with appendiceal cancer and underwent ileocecal resection. The pathological evaluation revealed KRAS-mutant adenocarcinoma with the final stage of T4bN1M0. She received oral fluorouracil-based adjuvant chemotherapy. One year later, she was found to have peritoneal dissemination in the pelvic cavity and vaginal metastasis. She received an oxaliplatin-based chemotherapy followed by surgical resection. One year after the second surgery, she developed a locoregional recurrence involving the right external iliac vessels and small intestine. She received an irinotecan-based regimen with bevacizumab as neoadjuvant chemotherapy, followed by surgical resection. At first, a femoro-femoral bypass was made to secure the blood supply to the right lower extremities. Subsequently, an en bloc resection including the recurrent tumor and the external iliac vessels was completed. Surgical resection for recurrent colorectal cancer is often technically challenging because of the tumor location and invasion to adjacent organs. In this case, a surgical approach with persistent chemotherapy achieved oncologic resection of locoregionally recurrent appendiceal cancer.