Short-term outcomes of laparoscopic and robotic distal gastrectomy for gastric cancer: Real-world evidence from a large-scale inpatient database in Japan.

BACKGROUND AND OBJECTIVES: Robotic distal gastrectomy (RDG) has been widely performed throughout Japan since it became insured in 2018. This study aimed to evaluate the short-term outcomes of RDG and laparoscopic distal gastrectomy (LDG) for gastric cancer using real-world data. METHODS: A total of 4161 patients who underwent LDG (n = 3173) or RDG (n = 988) for gastric cancer between April 2018 and October 2022 were identified through the Japanese Diagnosis Procedure Combination Database, which covers 42 national university hospitals. The primary outcome was postoperative in-hospital mortality rate. The secondary outcomes were postoperative complication rates, time to diet resumption, and postoperative length of stay (LOS). RESULTS: In-hospital mortality and postoperative complication rates in the RDG group were comparable with those in the LDG group (0.1% vs. 0.0%, p = 1.000, and 8.7% vs. 8.2%, p = 0.693, respectively). RDG was associated with a longer duration of anesthesia (325 vs. 262 min, p < 0.001), similar time to diet resumption (3 vs. 3 days, p < 0.001), and shorter postoperative LOS (10 vs. 11 days, p < 0.001) compared with LDG. CONCLUSIONS: RDG was performed safely and provided shorter postoperative LOS, since it became covered by insurance in Japan.

Cetuximab Enhances the Efficacy of MRTX1133, a Novel KRASG12D Inhibitor, in Colorectal Cancer Treatment.

BACKGROUND/AIM: Kirsten Rat Sarcoma viral oncogene homolog (KRAS) has remained undruggable for decades. KRAS has predominantly been used to evaluate the applicability of anti-Epidermal Growth Factor Receptor (EGFR) antibody drugs. However, various KRAS inhibitors have recently emerged. Unfortunately, KRAS inhibitors have not been effective against colorectal cancer. Therefore, this study aimed to determine the effects of MRTX1133, a novel KRASG12D inhibitor, in combination with an anti-EGFR antibody, cetuximab, on signal transduction and cell proliferation. MATERIALS AND METHODS: The KRASG12D-mutated LS513 and KRAS wild-type CACO-2 human colon cancer cell lines were utilized. The KRASG12D mutation was stably transduced into the CACO-2 cells using a retrovirus. We evaluated the effects of the drugs using the CCK-8 assay and assessed the activity of proteins related to the MAPK pathway using western blotting. RESULTS: We demonstrated that the administration of MRTX1133, a novel KRASG12D inhibitor, to KRASG12D-mutated colorectal cancer cells led to feedback activation of the ERK pathway via EGFR activation, inducing drug resistance. Intriguingly, when MRTX1133 was used in combination with cetuximab, KRASG12D-mutant colorectal cancer growth was effectively inhibited, both in vitro and in vivo. CONCLUSION: The combination of MRTX1133 and cetuximab serves as a potential and promising therapeutic approach for colorectal cancer with KRASG12D mutation. KRASG12D is a frequent genetic mutation not only in colorectal cancer, but also in pancreatic and lung cancer, and the results of this study open new avenues for potential treatment of many cancer patients.

Comparison of Short-term Outcomes Between Esophageal Bypass Surgery and Self-expanding Stent Insertion in Esophageal Cancer: A Propensity Score-matched Analysis Using a Large-scale Inpatient Database.

BACKGROUND: Advanced esophageal cancer is occasionally accompanied by difficulty swallowing owing to esophageal stenosis or tracheoesophageal fistula formation. Esophageal bypass surgery and stent insertion are considered feasible palliative management options. The aim of this study was to evaluate the short-term outcomes of these palliative treatments. MATERIALS AND METHODS: Patient data were obtained from a large-scale inpatient database of 42 National University Hospitals in Japan. Patients with advanced esophageal cancer who underwent esophageal bypass surgery or stent insertion between April 2016 and March 2021 were included in this study. One-to-one propensity score matching of patients who underwent bypass surgery or stent insertion was performed. The primary outcomes were time to diet resumption and length of hospital stay after surgery. The secondary outcome was the incidence of postoperative complications. RESULTS: In 43 propensity score-matched pairs, the incidence of postoperative respiratory complications was significantly higher in the bypass group than in the stent group (32.6% vs. 9.3%, P = 0.008). Postoperative length of hospital stay was longer in the bypass group than in the stent group (24 vs. 10 d, P < 0.001). Logistic regression analysis revealed that stent insertion was associated with a decreased risk of respiratory complications (odds ratio 0.077, P < 0.007). Among patients who underwent the interventions (bypass surgery or stent insertion) and subsequently underwent anticancer therapy (chemotherapy/radiotherapy) during hospitalization, the interval between the intervention and anticancer therapy was longer in the bypass group than in the stent group (25 vs. 7 d, P = 0.003). CONCLUSIONS: Esophageal stent insertion provides better short-term outcomes than bypass surgery in patients with advanced unresectable esophageal cancer.

MEK inhibitor and anti-EGFR antibody overcome sotorasib resistance signals and enhance its antitumor effect in colorectal cancer cells.

The Kirsten rat sarcoma (KRAS) oncogene was "undruggable" until sotorasib, a KRASG12C selective inhibitor, was developed with promising efficacy. However, inhibition of mutant KRAS in colorectal cancer cells (CRC) is ineffective due to feedback activation of MEK/ERK downstream of KRAS. In this study, we screened for combination therapies of simultaneous inhibition to overcome sotorasib resistance using our previously developed Mix Culture Assay. We evaluated whether there was an additive effect of sotorasib administered alone and in combination with two or three drugs: trametinib, a MEK inhibitor, and cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody. The MAPK pathway was reactivated in KRASG12C-mutated cell lines treated with sotorasib alone. Treatment with KRAS and MEK inhibitors suppressed the reactivation of the MAPK pathway, but upregulated EGFR expression. However, the addition of cetuximab to this combination suppressed EGFR reactivation. This three-drug combination therapy resulted in significant growth inhibition in vitro and in vivo. Our data suggest that reactive feedback may play a key role in the resistance signal in CRC. Simultaneously inhibiting KRAS, MEK, and EGFR is a potentially promising strategy for patients with KRASG12C-mutated CRC.

Clinical impact of C-reactive protein to albumin ratio of the 7th postoperative day on prognosis after laparoscopic colorectal cancer surgery.

PURPOSE: C-reactive protein to albumin ratio (CAR) has been utilized as a prognostic factor in various carcinomas. We investigated the relationship between preoperative, postoperative day (POD) 1, and POD 7 CARs and the prognosis of patients with colorectal cancer (CRC). METHODS: Three hundred twenty patients with CRC who underwent laparoscopic radical resection between May 2011 and December 2016 were enrolled. Patients were selected into 2 groups, high CAR and low CAR (n=72/group), based on preoperative, POD 1, and POD 7 CARs. The relapse-free survival (RFS) and overall survival (OS) were compared between groups using propensity score matching. RESULTS: The high CAR group had a significantly worse RFS (P<0.001) and OS (P=0.002) at POD 7 than those in the low CAR group. However, in preoperative and POD 1 analysis, no differences were observed. CONCLUSION: In patients with CRC, CAR of POD 7 was a significant prognostic factor.

Resection of solitary abdominal wall metastasis of ascending colon cancer along the ventriculoperitoneal shunt: A case report.

INTRODUCTION: Ventriculoperitoneal (VP) shunt is often placed as a treatment for hydrocephalus. Additionally, it is also not uncommon to perform laparoscopic surgery for colon cancer with a VP shunt in place. It is very rare for colorectal cancer to metastasize to an implanted VP shunt. We report a case of VP shunt-related metastasis of the ascending colon that was successfully resected. PRESENTATION OF CASE: A 79-year-old man who had a VP shunt for hydrocephalus two years earlier underwent laparoscopic right colectomy for ascending colon cancer. Six months after the colectomy, imaging examinations showed mass formation in the subcutaneous tissue of the abdominal wall along the VP shunt. Because of the possible metastasis of colorectal cancer and the fact that it was a solitary lesion, a tumor resection with replacement of the VP shunt was performed. Histopathological examination revealed that the mass was a metastasis of colon cancer. DISCUSSION: This case involves the metastasis of colorectal cancer in the subcutaneous tissue of the abdominal wall after laparoscopic surgery, and since the tumor had reached the serosa, the possibility of metastasis by pneumoperitoneum was considered. Careful intraoperative manipulation is considered to be important for prevention. CONCLUSION: Metastasis of colorectal cancer to the VP shunt is extremely rare, but possible. In such cases, intraoperative prevention and careful postoperative follow-up are required.

The first single-incision plus one-port transverse colon resection using Senhance Digital Laparoscopy System: a case report.

BACKGROUND: We have introduced the Senhance Digital Laparoscopy System and actively use for colorectal cancer surgery. Recently, we also try to perform surgery by reduce port as less invasive method. For the first time, we report a case of single-incision plus one-port transverse colectomy using Senhance system. CASE PRESENTATION: The case was a 57-year-old woman, diagnosed with transverse colon cancer referred to our department. The preoperative diagnosis was cT1bN0M0, Stage I. We performed single-incision plus one-port transverse colon resection using Senhance system without any problems. The operative time was 203 min and the blood loss was 35 ml. CONCLUSION: We report the first case of single-incision plus one-port transverse colectomy using Senhance system. We trust this approach will find increasing use, enabling a safer means of minimally invasive robotic surgery.

Impact of Lymphovascular Invasion in Patients With Stage II Colorectal Cancer: A Propensity Score-matched Study.

BACKGROUND/AIM: Whether lymphovascular invasion (LVI) is a high-degree risk factor in stage II colorectal cancer has not been fully clarified, as different results have been reported in the literature. If LVI is a risk factor, postoperative chemotherapy may be recommended. The purpose of this study was to evaluate the impact of lymphovascular invasion on disease recurrence and patient prognosis in conjunction with stage II colorectal cancer (CRC). PATIENTS AND METHODS: A total of 636 patients with stage II CRC, each undergoing radical resection between April 2007 and December 2015, were selected for the study. Subjects with or without venous or lymphatic invasion were assigned to positive and negative groups, respectively. We then compared overall survival (OS) and disease-free survival (DFS) using propensity score matching. RESULTS: After matching (n=226, each group), OS and DFS were found to be significantly lower (OS: p=0.047; DFS: p=0.004) in patients positive (vs. negative) for venous invasion. However, the same was not true of lymphatic invasion. After matching, positive and negative groups (n=92, each) did not significantly differ in terms of OS (p=0.951) or DFS (p=0.258). CONCLUSION: In patients with stage II CRC, venous invasion proved to be a significant high-degree risk factor that may warrant adjuvant chemotherapy.

Prognostic Utility of Geriatric Nutritional Risk Index After Curative Resection of Colorectal Cancer: A Propensity Score-matched Study.

Background/Aim: The geriatric nutrition risk index (GNRI) is a presumptive prognosticator in a variety of carcinomas. We investigated whether it similarly predicts outcomes of elderly patients with colorectal cancer (CRC). Patients and Methods: A total of 904 older adults (≥65 years) undergoing radical resections of CRC between April 2011 and December 2015 proved eligible for study. Each was grouped by preoperative status (cut-off point, 98) as low-level or normal GNRI, using propensity score matching to compare rates of complications, disease-free survival (DFS), and overall survival (OS). Results: After matching (n=127, each group), those with low-level (vs. normal) GNRI values experienced significantly more complications (p=0.001), and 5-year survival was significantly poorer (DFS: p=0.006; OS: p=0.002). Conclusion: In elderly patients with resected CRC, preoperative GNRI may have significant prognostic merit.

Right hemicolectomy with D3 lymph node dissection for right-sided transverse colon cancer using the Senhance robotic system: a case report.

BACKGROUND: The evolution of remote systems and artificial intelligence technology has led to increase in robotic surgeries. One system used in this case report is the Senhance robotic system. The most important premise for using robotic surgery in cancer therapeutics is to ensure oncological safety. Similar to conventional laparoscopic surgery, robotic surgery needs to be a reliable and secure surgical procedure, such as complete mesocolic excisions with central vascular ligations in Western countries or D3 lymph node dissections (dissection of the lymph nodes that locates from the origin to the terminal branch of the main feeding artery of cancer) in Japan. CASE PRESENTATION: A 76-year-old man underwent clinical examination for severe anemia. He was diagnosed with transverse colon cancer of tumor (T)3, node (N)1a, metastasis (M)0 cancer stage IIIA. A right hemicolectomy with D3 lymph node dissection using the Senhance surgical system was performed. The operative time was 313 min and the estimated blood loss was 5 ml. He was discharged from our hospital 12 days after the surgery without any complications. What is the remarkable of this report, not only mobilization of right colon but also D3 lymph node dissection and vascular ligation were performed intraperitoneally by using Senhance robotic system as conventional laparoscopic surgery. We tried using fourth robotic arm to accomplish lymphadenectomies and middle colic artery dissection. A right hemicolectomy with D3 dissection using the Da Vinci surgical system was reported. Another report of a right hemicolectomy performed with the Senhance robotic system was identified; however, in that study, lymph node dissections were not performed intraperitoneally. CONCLUSIONS: Therefore, to our knowledge, this is the first report using the Senhance robotic system for right hemicolectomy with D3 dissection. We hope that our case report will assist in the establishment of this robotic procedure in surgical practice.

Laparoscopic right hemicolectomy for metastatic renal cell carcinoma in the ascending colon: A case report.

INTRODUCTION: Renal cell carcinoma (RCC) arises from the renal parenchyma and is the most common primary malignancy of the kidney. RCC frequently metastasizes to the lung, bone, lymph nodes, and other locations, but rarely to the colon. We report a case of metastatic RCC of the ascending colon that was successfully resected with laparoscopic right hemicolectomy. PRESENTATION OF CASE: The patient is a 65-year-old man who developed hip joint pain and was diagnosed with polymyalgia rheumatica during the first year after laparoscopic right nephrectomy for right RCC. A screening colonoscopy was performed and a tumor was found in the ascending colon. Biopsy strongly suggested metastatic RCC. No other distant metastases were found, and laparoscopic right hemicolectomy was performed. The tumor extended from the mucosa to the subserosa and was diagnosed histopathologically as colonic metastasis of RCC. There were no lymph node metastases in the simultaneously resected mesentery, but venous invasion was observed. DISCUSSION: RCC can metastasize to various organs, but metastasis to the colon is extremely rare. In cases of colon metastasis, abdominal symptoms, hematochezia, or anemia may occur, and their occurrence should be checked during follow-up. Based on past reports, resection of metastatic lesion is considered the most appropriate treatment. CONCLUSION: Although it is rare for RCC to metastasize to the colon, it is possible. Resection can be recommended for colon metastasis with no other metastases, and colectomy with R0, including the regional mesocolon, may provide a favorable long-term prognosis.

Stability and aromaticity of the cyclopenta-fused pyrene congeners.

The aromaticity of all possible cyclopenta-fused pyrene congeners has been investigated at various levels of theory. On the basis of the calculated resonance energies and magnetic properties (delta(1)H data, magnetic susceptibility anisotropies, and NICS values), the overall aromaticity of these compounds is found to decrease gradually with increasing number of externally fused five-membered rings. The relatively small differences (<5 kcal/mol) in thermodynamic stability of the isomeric dicyclopentapyrenes (E(tot): dicyclopenta[cd,fg]- > dicyclopenta[cd,jk]- > dicyclopenta[cd,mn]pyrene), which differs from the aromaticity order based on the magnetic criteria (dicyclopenta[cd,mn]- > dicyclopenta[cd,fg]- > dicyclopenta[cd,jk]pyrene), is shown by model calculations to be dominated by sigma-strain imposed on the pyrene skeleton by sequential cyclopenta-fusion. This is supported by the computed homodesmotic reaction energies and aromatic stabilization energy (ASE(isom)) from isodesmic aromatic-nonaromatic isomerization, and by the model calculations on "distorted" cyclopenta[cd]pyrenes. The elusive tetracyclopenta[cd,fg,jk,mn]pyrene is computed to be bowl-shaped; its corresponding planar geometry is the transition state for bowl-bowl interconversion.