[Tolerability and Outcome of Neoadjuvant GS Therapy for Resectable Pancreatic Cancer].

INTRODUCTION: Neoadjuvant chemotherapy with gemcitabine plus S-1(NAC GS)has been reported to prolong the prognosis of resectable pancreatic cancer, and is now being used in daily practice. In this study, we investigated the tolerability and outcome of neoadjuvant GS therapy for resectable pancreatic cancer in our hospital. PATIENTS: Fifty-two patients who underwent NAC GS for resectable pancreatic cancer between November 2019 and March 2023 were included in this study. RESULTS: The mean age of all 52 patients was 75 years, 28 were male and 24 were female. Tumor site was pancreatic head cancer in 32 patients, pancreatic body cancer in 13 patients, and pancreatic tail cancer in 8 patients. Only 2 patients of the 52 patients completed 2 cycles of GS therapy with full dose, and dose reduction and treatment deferral were performed in remaining 50 patients. The dose intensity was 78.4% for gemcitabine and 66.7% for S-1. Grade 3 or higher adverse events included neutropenia in 21 patients(40.4%), biliary tract infection in 6 patients(11.5%), fatigue, anorexia, hepatic dysfunction, and constipation in 1 patient each(1.9%). 47 patients(90.4%)underwent R0 resection. 4 patients had pancreatic fistula, which was classified as Grade Ⅲ by Clavien-Dindo, and one of them died in the hospital due to bleeding from a pseudoaneurysm. CONCLUSION: NAC GS therapy for resectable pancreatic cancer was considered feasible with appropriate management of adverse events.

PLXND1/SEMA3E Promotes Epithelial-Mesenchymal Transition Partly via the PI3K/AKT-Signaling Pathway and Induces Heterogenity in Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of cancer-related deaths. Metastasis is enhanced through epithelial-mesenchymal transition (EMT), a process primarily induced by the transforming growth factor beta (TGF-ß)-mediated canonical Smad pathway. This study focused on plexin D1 (PLXND1), a chemoreceptor for the ligand SEMA3E to mechanosensory, showing that PLXND1 induces EMT via activation of the PI3K/AKT pathway in CRC cells. The findings showed that PLXND1-knockdown decreases cell migration and invasion significantly, and that the binding of p61-SEMA3E to the PLXND1 enhances the invasiveness and migration through EMT. Furin inhibitor suppresses EMT, decreasing cell migration and invasion. Furin cleaves full-length SEMA3E and converts it to p61-SEMA3E, suggesting that furin inhibitors block PLXND1 and p61-SEMA3E binding. Furin is a potential therapeutic target for the purpose of suppressing EMT by inhibiting the binding of p61-SEMA3E to PLXND1. In vivo experiments have shown that PLXND1-knockdown suppresses EMT. Mesenchymal cells labeled with ZEB1 showed heterogeneity depending on PLXND1 expression status. The high-expression group of PLXND1 in 182 CRC samples was significantly associated with poor overall survival compared with the low-expression group (P = 0.0352, median follow-up period of 60.7 months) using quantitative real-time polymerase chain reaction analysis. Further research is needed to determine whether cell fractions with a different expression of PLXND1 have different functions.

Administration Method of Adjuvant Tegafur-Uracil and Leucovorin Calcium in Patients with Resected Colorectal Cancer: A Phase III Study.

LESSONS LEARNED: The 3-year disease-free survival rate of the twice-daily regimen was not inferior to that of the conventional three-times-daily regimen, and the twice-daily regimen did not lead to an increase in adverse events. The effectiveness of the twice-daily regimen highlights an increased number of treatment options for patients. This will facilitate personalized medicine, particularly for elderly or frail patients who may experience more severe side effects from the combination therapy. BACKGROUND: Tegafur-uracil (UFT)/leucovorin calcium (LV) is an adjuvant chemotherapy treatment for colorectal cancer. We conducted a multicenter randomized trial to assess the noninferiority of a twice-daily compared with a three-times-daily UFT/LV regimen for stage II/III colorectal cancer in an adjuvant setting. METHODS: Patients were randomly assigned to group A (three doses of UFT [300 mg/m2 per day]/LV [75 mg per day]) or B (two doses of UFT [300 mg/m2 per day]/LV [50 mg per day]). The primary endpoint was 3-year disease-free survival. RESULTS: In total, 386 patients were enrolled between July 28, 2011, and September 27, 2013. The 3-year disease-free survival rates of group A (n = 194) and B (n = 192) were 79.4% and 81.4% (95% confidence interval, 72.6-84.4-74.5-85.9), respectively. The most common grade 3/4 adverse events in group A and B were diarrhea (3.9% vs. 7.3%), neutropenia (2.9% vs. 1.6%), increase in aspartate aminotransferase (4.0% vs. 3.9%), increase in alanine aminotransferase (6.2% vs. 6.8%), nausea (1.7% vs. 3.4%), and fatigue (1.1% vs. 2.3%). CONCLUSION: Group B outcomes were not inferior to group A outcomes, and adverse events did not increase.

[A Case of Primary Jejunal Cancer Treated with Laparoscopic Jejunectomy with Appearance of Ileus].

An 83-year-old man visited our hospital for vomiting. Chest-abdominal computed tomography(CT)revealed that a tumor whose inside was imaged in the jejunum about 15 cm after leaving the Treitz ligament was pointed out, and dilation of the oral intestinal tract of the tumor was observed. Upper gastrointestinal endoscopy showed a type 3 circumferential tumor at the jejunum. He was diagnosed with obstructive ileus due to jejunal cancer. Laparoscopic-assisted partial jejunal resection was performed. Although the patient was followed up without chemotherapy, CT showed multiple lung and liver metastases and a mass lesion was found in the right entire chest, and a biopsy revealed skin metastasis 6 months after the operation. The patient is being followed up 10 months after surgery, there is no progression of liver, lung, and skin metastasis.

[Locally Advanced Breast Cancer Successfully Treated with Abemaciclib and Fulvestrant-A Case Report].

A 78-year-old woman visited our hospital for a tumor in her left breast with discharge. The 10 cm tumor had ulceration and foul smell. Scirrhous breast carcinoma was diagnosed based on core-needle biopsy findings. Chest and abdominal computed tomography( CT) revealed the tumor invading the pectoralis major muscle and a large number of swollen lymph nodes from the left axilla to the subclavian region, but no distant metastases. After 6 months of locally advanced breast cancer treatment with abemaciclib and fulvestrant, ulceration improved. CT revealed that the tumor and lymph nodes tended to shrink. Left mastectomy with axillary lymph node dissection and combined resection of pectoralis major muscle was performed. Postoperative pathological histology revealed ypT2, ypN0, ypM0, ypStage ⅡA. Subsequently, abemaciclib plus fulvestrant therapy was continued as an adjuvant therapy. The patient has survived without recurrence 6 months after the operation. We report a case of locally advanced breast cancer in which abemaciclib and fulvestrant were effective.

[A Case of Pulmonary Embolism Developed during Combination Chemotherapy with S-1 and Cisplatin in a Young Female Patient with Type 4Gastric Cancer].

We report a case of a 23-year-old womanwho developed pulmonary embolism(PE)during chemotherapy for advanced gastric cancer following total gastrectomy(R1). She presented with type 4 gastric cancer with peritoneal dissemination and positive washing cytology. Palliative total gastrectomy was performed(R1)and first-line chemotherapy with S-1(80mg/m2, days 1 to 21) plus CDDP(60mg/m2, day 8)(SP; every 35 days)was administered. PE occurred on day 15 of the 3rd courses of SP. Computed tomography(CT)revealed massive PE in both the pulmonary arteries, and ultrasonography indicated an increase in right-sided pressure. Thrombolysis using urokinase and heparin was performed immediately, and she recovered after 10 days in intensive care. Dehydration caused by the adverse event, as well as nausea and the anticancer drug itself, are risk factors for DVT and PE. Risk stratification, prevention, and early treatment are very important for PE.

[Effectiveness of Irinotecan, S-1, and Bevacizumab for Rectal Cancer with Lung and Skin Metastases after Adjuvant Chemotherapy].

A 50-year-old woman with a chief complaint of bloody stools was diagnosed with rectal cancer via colonoscopy. Laparoscopic rectal anterior resection with D3 lymph node dissection was performed in June 2014. The pathological diagnosis was pStage III a(Ra, pT3, N1)cancer, and the patient received 8 courses of XELOX as postoperative adjuvant chemotherapy. During follow-up at 12 months after surgery, chest computed tomography revealed a mass in the left lingular segment measuring 25mm in diameter and multiple small nodules in both the lungs, indicating lung metastases. We found several subcutaneous nodules with a maximum diameter of 10mm in her abdomen and the back of head. We removed 3 subcutaneous nodules for the purpose of diagnosis and treatment in June of 2015. The pathological findings were consistent with cutaneous metastases of rectal cancer. The patient received a 1 course of IRIS and 5 courses of IRIS plus bevacizumab. Subsequently, the lung metastases disappeared and no new skin lesions were detected. We suggest that this case could be a good reference in determining the appropriate treatment for rectal cancer having lung or cutaneous metastases.

[A Case of Lateral Lymph Node Recurrence Five-Years after Curative Surgery for Rectal Cancer].

A 62-year-old woman had undergone laparoscopic abdominoperineal resection for rectal cancer in February 2008. The pathological diagnosis was pT2, pN0, M0, pStageⅠ. At her request, she took UFT for 5 years as adjuvant chemotherapy. A CT examination revealed lateral lymph node swelling in January 2014. She was referred to our hospital after a diagnosis of lateral lymph node recurrence. She was administered 6 courses of FOLFIRI plus Cmab as neoadjuvant chemotherapy, after which the tumor size reduced by 62%. The treatment effect was rated as a PR. Laparoscopic right intrapelvic lymph node dissection was performed in July 2014, and the pathological diagnosis was recurrence of rectal cancer in the lateral lymph nodes. We report a case of dissection of lymph node recurrence 5 years after curative surgery for rectal cancer, along with a literature review.

Single-incision Laparoscopic Colonic Surgery: A Systemic Review, Meta-analysis, and Future Prospect.

Although single-incision laparoscopic surgery (SILS) has gained some attention as a feasible alternative to conventional multiport laparoscopic surgery (MPLS) in colonic surgery, it became less prevalent than expected. Hence, we conducted this systematic review to evaluate the feasibility, safety, and oncological outcomes of single-incision laparoscopic colectomy (SILC) with meta-analysis and discussion of the future prospect of SILS. The search was conducted from September to October 2023 using PubMed and the Cochrane Central Register of Controlled Trials. Articles on colorectal cancer comparing SILC with multiport laparoscopic colectomy (MPLC) from all randomized controlled trials and comparative studies with 50 patients or more per arm were examined. The primary outcomes were the intra- and postoperative complication rates, and the secondary outcomes were the perioperative and oncological outcomes. The trends of the SILS number in Japan and the trends of the number of articles on SILS in PubMed were also reviewed. There were no significant differences in perioperative complication rates, operative factors, and oncological outcomes between SILC and MPLC, although heterogeneity was observed mainly in operative factors and the total length of the skin incision was significantly shorter in SILC. Therefore, SILC is technically and oncologically feasible and safe when performed by experienced laparoscopic surgeons. The case number of SILS was gradually increasing but the rate of SILS was decreasing in Japan. The number of articles on SILS was also decreasing. SILS has gained foothold to some extent but has plateaued. The emerging new robotic platform may reappraise the concept of SILS.

Defecation Function After Laparo-Assisted Restorative Proctocolectomy with Ileal Pouch Anal Anastomosis for Ulcerative Colitis.

Background: Defecation status is an important determinant of quality of life. Previous studies showed that postoperative defecation disorders occurred after open surgery for ulcerative colitis (UC), but few have investigated defecation status after laparo-assisted surgery. The added precision and magnification provided with laparo-assisted surgery should lead to less damage to the anal sphincter muscle. This study investigated defecation function after a laparo-assisted restorative proctocolectomy (RPC) with ileal pouch anal anastomosis (IPAA). We also clarified factors that worsened defecation status. Methods: This retrospective study included 57 patients who underwent laparo-assisted RPC with IPAA for UC from January 2000 to May 2019. At 1 year after surgery, functional outcomes were evaluated with the Kirwan classification and Wexner score. Risk factors for poor defecation status were investigated with multiple regression. Results: At 1 year after surgery, the median Kirwan classification score was 2 and the median Wexner score was 8. Defecation disorder was observed in 19 (33.3%) patients, according to the Kirwan classification, and 15 (26.3%) patients, according to the Wexner score. Hand-sewn IPAA was associated with defecation disorder (P = .04), evaluated with the Kirwan classification. Hand-sewn IPAA (P = .01), older age (P = .03), high body mass index (P = .04), and the surgical indication (cancer/dysplasia; P = .03) were significantly associated with defecation disorder, evaluated with the Wexner score. The multivariable analysis showed that hand-sewn IPAA was an independent risk factor (P = .049; odds ratio: 4.99; 95% confidence interval: 1.0-28.39). Conclusions: We found that hand-sewn IPAA was a risk factor for defecation disorders after laparo-assisted RPC for UC.

Case of laparoscopic right hemicolectomy for ascending colon cancer after aortic graft replacement and revascularization of the superior mesenteric artery.

A 67-year-old man who presented with a bloody stool was diagnosed with ascending colon cancer. He had previously experienced thoracic and abdominal aortic dissections, which were treated with thoracic and abdominal aortic grafts and superior mesenteric artery revascularization. We performed a laparoscopic right hemicolectomy with a D3 lymph node dissection. During the laparotomy, we identified the superior mesenteric artery and an enlarged anterior superior pancreaticoduodenal artery. Injury to the latter artery could lead to severe ischemia in multiple organs; therefore, it was crucial to identify the primary feeding artery and vascular anatomy before and during surgery. We chose the laparoscopic right hemicolectomy to avoid injuring the anterior superior pancreaticoduodenal artery and the intra-abdominal abscess. This case study was the first to describe a laparoscopic hemicolectomy after thoracic and abdominal aortic grafts and superior mesenteric artery revascularization.