Gastric cancer (GC) often exhibits resistance to anti-programmed death-1 (PD-1) immunotherapy. Immunogenic cell death (ICD) enhances antitumor immunity, and trifluridine/tipiracil (FTD/TPI) induces ICD and modulates immunity. Radiation therapy (RT) may trigger abscopal effects. We investigated whether FTD/TPI combined with RT enhances tumor immunity in GC and its impact with PD-1 blockade. ICD induction by FTD and RT in YTN16 mouse GC cells was assessed by calreticulin, high-mobility group box 1 (HMGB1), and ATP evaluation. A dual subcutaneous YTN16 tumor model was established in C57BL/6J mice; mice were treated with FTD/TPI and RT (with irradiation of the first tumor). ICD was induced in vitro by FTD or RT and enhanced by the combination, as indicated by increased calreticulin surface expression and HMGB1 and ATP release. ICD induction in the first tumor was confirmed by HMGB1 release. FTD/TPI + RT suppressed growth of the second tumor and enhanced antitumor immunity by increasing CD8⁺ T-cell infiltration and depleting M2 macrophages. PD-1 expression on CD8⁺ T cells increased after FTD/TPI + RT; adding anti-PD-1 further suppressed the second tumor growth. Our findings support clinical trials of this triple-combination strategy in advanced GC, particularly in subgroups refractory to immune checkpoint blockade.
BACKGROUND:Robotic gastrectomy (RG) is increasingly adopted for the treatment of gastric cancer due to its technical advantages. However, specific complications such as subcutaneous emphysema (SE) and port site dilation (PSD) may arise due to pneumoperitoneum and trocar manipulation. This study aimed to investigate the incidence and risk factors of SE and PSD, with a focus on differences between robotic platforms. METHODS:This retrospective study included 126 patients who underwent RG between April 2021 and April 2025. SE was defined as subcutaneous gas extending to the anterior chest wall on postoperative day 1. PSD was evaluated using intraoperative videos and defined as a visible gap between the trocar and abdominal wall. Multivariable logistic regression was performed to identify independent predictors of SE and PSD, including robotic system type (da Vinci Xi vs. hinotori™). RESULTS:SE and PSD were observed in 20 (15.9%) and 21 (16.7%) patients, respectively. The use of the hinotori™ was independently associated with a lower incidence of SE (OR: 0.085, 95% CI: 0.01-0.70, p = 0.02) and PSD (OR: 0.089, 95% CI: 0.016-0.39, p = 0.001). No significant association was found between SE or PSD and postoperative complications of Clavien-Dindo grade ≥ II or ≥ III. CONCLUSIONS:The docking-free hinotori™ platform significantly reduced the incidence of SE and PSD compared to the da Vinci Xi. Recognizing the mechanical features of each robotic system and tailoring platform selection to patient and procedural factors may improve surgical outcomes.
INTRODUCTION: Primary parahiatal hernias are rare in adults. We report the case of a young woman with a parahiatal hernia without obvious predisposing factors that resulted in gastric fundus necrosis. CASE PRESENTATION: A 34-year-old woman had experienced intermittent chest pain for 2 months but had not sought medical attention. She developed sudden-onset left chest pain without a history of trauma, with the pain worsening on inspiration. Her previous physician suspected a left lung abscess and referred her to our facility. Contrast-enhanced CT revealed a cavity with internal air above the diaphragm in the left thoracic cavity, which was continuous with the stomach in the abdominal cavity. We diagnosed an incarcerated diaphragmatic hernia with gastric ischemia and proceeded with emergency laparoscopic surgery. Intraoperatively, the gastric fundus was found to be incarcerated in the left diaphragm, and the hernial orifice was located just to the left of the esophageal hiatus. A diagnosis of parahiatal hernia was confirmed. The incarcerated gastric fundus was repositioned into the abdominal cavity. The hernial orifice was closed using nonabsorbable barbed sutures, and the necrotic gastric fundus was resected. The postoperative course was uneventful, and the patient was discharged on POD 13. CT at the 1-month follow-up revealed no recurrence of the parahiatal hernia. CONCLUSIONS: Parahiatal hernia is extremely rare but may be life-threatening if diagnosed late. In this case, laparoscopic repair and resection of the necrotic gastric fundus were successfully performed.
We report 2 cases in which skin grafting was avoided by utilizing thoracoepigastric following mastectomy with extensive skin defects due to advanced breast cancer extensively involving the breast.Case 1: A 53-year-old woman was diagnosed with right breast cancer extending to the midline of the chest.She underwent total mastectomy of the right breast, resection of the midline chest skin, and sentinel lymph node biopsy.Intraoperative frozen section analysis revealed positive sentinel nodes, prompting additional axillary lymph node dissection.Due to the extensive skin defect caused by resection of the midline chest skin, a thoracoepigastric flap was created to achieve wound closure.The postoperative course was uneventful.Case 2: A 64-year-old woman developed an intramammary recurrence of right breast cancer during follow-up after prior surgery.The recurrent tumor had extensively spread throughout the breast, with widespread erythema noted on the overlying skin.Multiple axillary lymph node metastases were also present, and neoadjuvant chemotherapy was initiated.Following chemotherapy, she underwent right total mastectomy and axillary lymph node dissection.A thoracoepigastric flap was used for wound closure.Her postoperative course was free of complications.
Metaplastic breast carcinoma, a rare subtype(<1% of breast cancers), is typically triple-negative with a poor prognosis. The KEYNOTE-522 trial established pembrolizumab plus chemotherapy as a standard treatment for early-stage, high-risk triple-negative breast cancer. We report a case of metaplastic carcinoma with squamous differentiation achieving pathological complete response after neoadjuvant pembrolizumab-based chemoimmunotherapy. This case suggests that pembrolizumab-based chemoimmunotherapy may be a promising option for chemoresistant metaplastic carcinoma.
BACKGROUND:The optimal reconstruction route after esophagectomy remains controversial. The retrosternal route has the advantage of a lower risk of fatal complications. However, the blind maneuver to create a retrosternal route may cause bleeding and pleural injury. Herein, we report a novel robotic technique for creating a retrosternal route. METHODS:This study included 43 consecutive patients with esophageal cancer who underwent robot-assisted minimally invasive esophagectomy with robotic retrosternal route reconstruction between April 2021 and December 2023. Clinicopathological findings and perioperative outcomes, including the time required to create the retrosternal route, were retrospectively analyzed. The creation times were also compared among surgeons. RESULTS:The median age and body mass index of the patients were 68 years (range: 46-80) and 21.4 kg/m2 (range: 16.6-30.2 kg/m2), respectively. Twenty-six patients (60%) received neoadjuvant chemotherapy. The median time to create the retrosternal route was nine minutes (range, 5-14 min). No cases showed pleural injury or postoperative hemorrhage associated with this procedure. There was no significant difference in the time taken to create the retrosternal route between the four surgeons (p = 0.434). CONCLUSIONS:Robotic creation of a retrosternal route for gastric conduit reconstruction is simple, easy to learn, and results in a safe and feasible procedure.
BACKGROUND:Thoracic epidural analgesia (TEA) is widely used for postoperative pain control in abdominal surgery, but its role in minimally invasive procedures remains unclear. This pragmatic multicentre open-label randomized non-inferiority trial evaluated whether scheduled intravenous acetaminophen combined with local wound infiltration provides non-inferior analgesia to TEA following minimally invasive gastrectomy. METHODS:Adults with gastric adenocarcinoma categorized as clinical stage I-III (according to the Japanese classification of gastric carcinoma) who were undergoing laparoscopic or robot-assisted gastrectomy were randomized 1 : 1 to TEA or scheduled intravenous acetaminophen (1 g every 6 hours (h) for 72 h). All patients received wound infiltration with ropivacaine. Participants and clinicians were not blinded to the randomization; statisticians were masked. The primary endpoint in the study was the proportion of patients with a numerical rating scale (NRS) pain score ≥ 4 at rest 24 h after surgery, with a prespecified non-inferiority margin of 20 percentage points. Analyses used the modified intention-to-treat population. RESULTS:Between June 2020 and May 2024, 140 patients were randomized and 135 were analysed (TEA 68, acetaminophen 67). At 24 h after surgery, 27.9% of patients in the TEA group and 23.9% in the acetaminophen group had an NRS score ≥ 4 at rest (risk difference -4.1%; 95% confidence interval -24.3 to 16.6), confirming non-inferiority. Pain trajectories, rescue analgesic use, patient satisfaction, and recovery were comparable between the two groups. No patient required rescue opioids, and there were no serious catheter- or acetaminophen-related adverse events. CONCLUSION:Scheduled intravenous acetaminophen with wound infiltration was non-inferior to TEA for postoperative pain after minimally invasive gastrectomy and provided safe, effective, and opioid-sparing analgesia consistent with enhanced recovery principles. Registration number: UMIN000039505 (https://www.umin.ac.jp/english/).
INTRODUCTION:The onset of colorectal cancer during pregnancy is rare, and no standard treatment has been established. In this report, we present the case of a woman with clinical stage II rectal cancer diagnosed in the second trimester, in which neoadjuvant chemotherapy was administered, followed by delivery once fetal development was sufficiently advanced, and surgery was performed afterward. CASE PRESENTATION:The patient was a 36-year-old woman at 22 weeks of gestation. Sigmoidoscopy was performed for hematochezia, which revealed a semicircular type 2 tumor in the rectum. A biopsy confirmed the presence of adenocarcinoma. A thorough systemic examination revealed no lymph nodes or distant metastases. After discussing the risks and benefits with the patient, her family, a pediatrician, and an obstetrician, we decided to administer neoadjuvant chemotherapy. The plan was to deliver the fetus after it had adequately developed and then perform radical surgery for rectal cancer after delivery. Neoadjuvant chemotherapy comprised 4 courses of the modified FOLFOX6 regimen, including leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin. The patient had a vaginal delivery at 35 weeks and 5 days of gestation, 23 days after the last chemotherapy dose. The newborn was healthy with no congenital anomalies. On the 27th day after delivery, a robot-assisted low anterior resection of the rectum was performed. The pathological findings revealed rectal cancer located above the peritoneal reflection, ypT2N0M0, and ypStage I. The patient recovered well and was discharged 12 days after surgery. At the time of writing, both the mother and child are doing well, with no evidence of recurrence 6 months after surgery. CONCLUSIONS:In cases of colorectal cancer during pregnancy, it is important to select a treatment plan that considers the site and stage of the tumor, number of weeks of pregnancy, and conditions of the fetus and mother. Even in cases of clinical stage II colorectal cancer diagnosed during the second trimester, where immediate surgery is not feasible, neoadjuvant chemotherapy can be considered a viable treatment option.
Single-incision laparoscopic surgery (SILS) and needle forceps have been introduced to enhance cosmetic outcomes and reduce postoperative pain. However, in demanding procedures like total gastrectomy, these approaches can be technically challenging due to limited triangulation and lack of assistant support. We report the case of a 31-year-old woman with gastric cancer who requested a cosmetically favorable procedure. A total gastrectomy with D2 lymphadenectomy was performed using a SILS approach with one 3-mm needle forceps. To maintain adequate exposure without an assistant port, we utilized an adjustable organ retractor that allows multidirectional traction by repositioning external sutures. This technique provided stable visualization and facilitated a safe, oncologically appropriate dissection. The patient was discharged uneventfully without major complications and remains recurrence-free at 3 years. We report a technical modification that enabled the safe performance of SILS total gastrectomy using a needle forceps in combination with an adjustable organ retractor.
Double-tract reconstruction is commonly performed after proximal gastrectomy to prevent gastroesophageal reflux and ensure adequate nutrition. We developed a modified double-tract reconstruction intervention, denominated the NI method, in which the anastomosis between the remnant stomach and jejunum was strategically configured to optimize food passage and suppress gastroesophageal reflux. This retrospective study included patients with upper-third gastric cancer and adenocarcinoma of the esophagogastric junction who underwent proximal gastrectomy with either conventional or NI-modified double-tract reconstruction at two institutions. Postoperative outcomes, including body weight loss and incidence of reflux esophagitis, were compared. In total, 115 patients underwent proximal gastrectomy with double-tract reconstruction, including 35 with the NI method and 110 using the conventional method. No significant differences were observed in the baseline characteristics between the two groups. The incidence of reflux esophagitis was significantly lower in the NI group (0
The malignancy risk has increased following improvements in the long-term survival rates after liver transplantation. Reports show a 23.4-fold increase in the risk of de novo esophageal cancer after liver transplantation compared to the general population. We report the case of a 47-year-old female diagnosed with early esophageal cancer after liver transplantation. Endoscopic submucosal dissection was performed; however, due to it being a noncurative resection, additional treatment was required. Total robot-assisted minimally invasive esophagectomy (RAMIE) was performed using a robot for thoracic and abdominal procedures. Although extensive adhesions were observed after liver transplantation, precise surgery using the robot did not damage any vital organs, such as the graft blood vessels. The patient was discharged without postoperative complications. Total RAMIE for esophageal cancer after liver transplantation is a feasible and safe option following careful evaluation of the patient's condition, and expands the possibilities of successful complex posttransplant surgeries through robotic precision.
We report a 58‒year‒old woman with Stage Ⅳb sigmoid colon cancer, presenting with hematochezia and lower abdominal pain, and diagnosed with over 15 liver metastases and para‒aortic lymph node (PALN) metastases. After laparoscopic sigmoid colectomy, FOLFOXIRI plus bevacizumab achieved marked liver tumor reduction and complete PALN response, enabling hepatic resection. Multiple recurrences were managed with repeated liver resections, PALN dissection, and chemoradiotherapy. Following fifth‒line of chemotherapy, oxaliplatin was reintroduced, and fruquintinib initiated, leading to 6 years and 3 months of survival. This case highlights multidisciplinary strategies for initially unresectable colorectal cancer.
The patient was a woman in her 60s with a history of congenital patent ductus arteriosus complicated by severe pulmonary hypertension and Eisenmenger syndrome. She had previously undergone surgery for right-sided breast cancer 11 years earlier. Nine years after surgery, she was diagnosed with bilateral breast cancer. At that time, mediastinal lymph node metastasis was suspected, and the disease was considered unresectable, leading to the initiation of pharmacological therapy. Although treatment was started, tumor progression was observed, prompting a shift toward surgery. Due to the presence of severe pulmonary hypertension, general anesthesia was deemed extremely high risk. Therefore, a surgical plan was made to perform bilateral mastectomy under local anesthesia with the aid of nerve blocks. Pectoral nerve blocks(Pecs blocks)combined with local anesthesia were used, resulting in effective pain control. No intraoperative or postoperative complications occurred. This case suggests that surgery using nerve blocks and local anesthesia may be a valuable option for patients with severe underlying and comorbid conditions in whom general anesthesia poses significant risk.
Oncotype DX is performed to predict prognosis and the added benefit of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, with the goal of individualizing chemotherapy decisions. Here, we report 2 cases of early- stage hormone receptor-positive, HER2-negative breast cancer with lymph node metastases in which the oncotype DX test was performed but yielded inconclusive results. Case 1:A 53-year-old woman was diagnosed with left breast cancer following bloody nipple discharge. She underwent total mastectomy and axillary lymph node dissection. Two positive lymph nodes were identified;however, it was difficult to assess the invasive component of the primary tumor. When oncotype DX was performed, it was deemed inconclusive due to insufficient tumor tissue. Case 2:A 46-year-old woman was diagnosed with right breast cancer during routine follow-up at our department. She underwent total mastectomy and axillary lymph node dissection. Although the primary tumor was widely spread within the breast, assessment of the invasive component was challenging. Three lymph node metastases were identified. Oncotype DX was performed but was judged inconclusive due to insufficient tumor tissue.
BACKGROUND:Robotic systems offer the great advantage of articulation; however, high cost is a limitation. ArtiSential® is a laparoscopic forceps that combines the advantages of low cost and articulation. This study was conducted to determine the learning effect of ArtiSential®. METHODS:Participants were divided into two groups: those who had performed >100 laparoscopic surgeries (experts) and those who had not (novices). The participants were assigned the task of peg transfer three times a day, for a total of 15 times over five days. The time spent on the task and the number of pegs that dropped during the transfer were recorded. RESULTS:Thirty surgeons (15 experts and 15 novices) participated in the study. Both the average time and the number of pegs dropped decreased progressively with practice. The learning effect for task completion time reached a plateau after 11 tasks (p < 0.05). There was no significant difference between experts and novices in either the time or the number of pegs dropped. CONCLUSIONS:ArtiSential® can be learned in a relatively short period of time and prior laparoscopic experience does not significantly affect the learning curve. Articulating forceps are inexpensive, easy to learn, and provide a valuable alternative to achieve greater freedom in surgery.
BACKGROUND:Glucose transporter 1 (GLUT1) is known to play a crucial role in glucose uptake in malignant tumors. GLUT1 inhibitors reportedly exhibit anti-tumor effects by suppressing cancer cell proliferation. BAY-876, a selective GLUT1 inhibitor, has been shown to inhibit tumor growth in ovarian and breast cancers. In this study, we investigated the anti-proliferative effects of BAY-876 treatment in human colorectal cancer (CRC) cell lines. METHODS:We investigated the metabolic changes and effects on proliferation from BAY-876 treatment in HCT116, DLD1, COLO205, LoVo, and Caco-2 cells in vitro. Additionally, a mouse xenograft model was established using HCT116 cells to examine the tumor-inhibitory effects of BAY-876 treatment in vivo. RESULTS:BAY-876 treatment inhibited cell proliferation in HCT116, DLD1, COLO205, and LoVo cells. Reduced GLUT1 protein expression levels were observed through western blot analysis. Flux analysis indicated enhanced mitochondrial respiration, accompanied by increased reactive oxygen species levels and apoptosis rates. Tumor-inhibitory effects were also observed in the xenograft model, with the BAY-876-treated groups showing GLUT1 suppression. CONCLUSIONS:BAY-876 treatment induced metabolic changes and inhibited cell proliferation in human CRC cell lines. Using BAY-876 is a potential novel approach for treating CRC.
BACKGROUND:Esophagogastric junction (EGJ) cancer is becoming increasingly prevalent worldwide. Among surgical challenges, anastomotic leakage remains a significant concern. The optimal approach for Siewert type II tumors with an esophageal invasion of 2.1-4.0 cm is still debated. We employed a combined left thoracoscopic and laparoscopic approach with the patient in the right hemilateral position, enabling simultaneous thoracic and abdominal procedures without intraoperative repositioning. METHODS:We retrospectively reviewed patients with EGJ cancer and an esophageal invasion length of 2.1 to 4.0 cm who underwent the combined left thoracoscopic and laparoscopic approach between January 2021 and December 2024. Clinicopathological characteristics and surgical outcomes were evaluated and compared with those of patients treated with conventional laparoscopic transhiatal surgery during the same period. RESULTS:Eight patients underwent the combined approach. Surgical procedures included six proximal gastrectomies with single-flap esophagogastrostomy and two total gastrectomies. Compared with 12 patients who underwent conventional laparoscopic surgery, no anastomotic leakage was observed in the combined group, whereas leakage occurred in the conventional group. CONCLUSIONS:The combined left thoracoscopic and laparoscopic approach appears to be a feasible and safe option for EGJ cancer with esophageal invasion of 2.1-4.0 cm. No anastomotic leakage was observed, and this approach allows for stable anastomosis under direct visualization without repositioning.
Peritoneal metastasis (PM) of gastric cancer (GC) has an immune escape environment. Regulatory B cells (Bregs), characterized by IL-10 production, play an important role in the tumor immunity; however, the function of Bregs in PM remains unclear. We investigated the frequency and effects of Bregs on other immune cells in the PM using clinical specimens and mouse models of PM. In the peripheral blood and ascites, Breg frequency was significantly higher in patients with GC with PM than in those without PM. In clinical PM samples, Breg frequency was an independent prognostic factor. In the mouse PM model, peritoneal tumors showed higher Breg infiltration than subcutaneous tumors. In the PTEN-deficient PM model, activation of Bregs promoted ascites and peritoneal tumor growth, decreased the infiltration of CD8+ T cells, and increased the infiltration of M2 macrophages. In contrast, treatment with wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, suppressed Breg infiltration, resulting in decreased M2 macrophage infiltration and increased CD8+ T cell infiltration. Bregs are indicated to be involved in immunosuppression of PM and are promising targets for improving the efficacy of immunotherapy against PM.