The integration of the intracorporeal triangular anastomotic technique in robotic distal gastrectomy: advancing patient safety and procedural simplicity.

BACKGROUND: Robotic distal gastrectomy (RDG) with Billroth I (BI) reconstruction is predominantly performed due to its physiological congruence and simplicity. The Intracorporeal Triangular Anastomotic Technique (INTACT) aims to reduce ischemic areas compared to the conventional Delta-shaped anastomosis using the unique characteristics of robotic surgery to standardize procedures, thereby ensuring safe, simple, and reliable reconstruction. This study aims to investigate the efficacy of the INTACT in RDG with BI reconstruction, focusing on its robotic precision in minimizing ischemic zones and improving surgical reliability. SURGICAL TECHNIQUE: The posterior duodenal wall is dissected before reconstruction, and the hepatoduodenal ligament is severed to facilitate passive duodenal manipulation. A quarter-circumference incision is created centrally on the anterior wall of the duodenal stump to avoid excessive tension during anastomosis and to ensure an adequate anastomotic diameter. A small opening is established on the greater curvature of the remaining stomach, and the posterior walls of the stomach and duodenum are joined using a Linear stapler in the first fire. A V-shape is created, and two EndoWrist instruments (robotic first and fourth arms) are utilized to grip and extend the anastomosis diameter, completing the anastomosis with a shared hole closure using the Linear stapler. The robotic arms' features improve the physiological integrity and stability of the BI reconstruction. RESULTS: A total of 81 patients underwent RDG with INTACT from September 2020 to January 2024. The median age was 72 years (range: 31-91), with 49 males and 32 females. The median blood loss was 0 ml (range: 0-200 ml), and the median postoperative hospital stay was 8 days (range: 6-20 days). No cases required reanastomosis during surgery, and no postoperative anastomotic leakage, surgery-related reoperations, or anastomotic strictures were reported. CONCLUSION: INTACT in RDG can be safely performed. The characteristics of the EndoWrist instruments helped in stabilizing the technique, making it a viable option in robotic-assisted surgeries.

Therapeutic targeting of Syndecan-1 axis overcomes acquired resistance to KRAS-targeted therapy in gastrointestinal cancers.

The therapeutic benefit of recently developed mutant KRAS (mKRAS) inhibitors has been limited by the rapid onset of resistance. Here, we aimed to delineate the mechanisms underlying acquired resistance to mKRAS inhibition and identify actionable targets for overcoming this clinical challenge. Previously, we identified Syndecan-1 (SDC1) as a key effector for pancreatic cancer progression whose surface expression is driven by mKRAS. By leveraging both pancreatic and colorectal cancer models, we found that surface SDC1 expression was initially diminished upon mKRAS inhibition, but recovered in tumor cells that bypass mKRAS dependency. Functional studies showed that these tumors depended on SDC1 for survival, further establishing SDC1 as a driver for the acquired resistance to mKRAS inhibition. Mechanistically, we revealed that the YAP1-SDC1 axis was the major driving force for bypassing mKRAS dependency to sustain nutrient salvage machinery and tumor maintenance. Specifically, YAP1 activation mediated the recovery of SDC1 localization on cell surface that sustained macropinocytosis and enhanced the activation of multiple RTKs, promoting resistance to KRAS-targeted therapy. Overall, our study has provided the rationale for targeting the YAP-SDC1 axis to overcome resistance to mKRAS inhibition, thereby revealing new therapeutic opportunities for improving the clinical outcome of patients with KRAS-mutated cancers.

Enhancing surgical outcomes in elderly gastric cancer patients: the role of comprehensive preoperative assessment and support.

BACKGROUND: As the prevalence of gastric cancer rises in aging populations, managing surgical risks and comorbidities in elderly patients presents a unique challenge. The Comprehensive Preoperative Assessment and Support (CPAS) program, through comprehensive preoperative assessments, aims to mitigate surgical stress and improve outcomes by enhancing patient awareness and preparation. This study investigates the efficacy of a CPAS program, incorporating frailty and sarcopenia evaluations, to improve short-term outcomes in elderly gastric cancer patients. METHODS: A retrospective analysis was conducted on 127 patients aged 75 or older who underwent surgery with CPAS between 2018 and August 2023, compared to 170 historical controls from 2012 to 2017. Propensity score matching balanced both groups based on age-adjusted Charlson Comorbidity Index and surgical details. The primary focus was on the impact of CPAS elements such as rehabilitation, nutrition, psychological support, oral frailty, and social support on short-term surgical outcomes. RESULTS: Among 83 matched pairs, the CPAS group, despite 40.4% of patients in the CPAS group and 21.2% in the control group had an ASA-PS score of 3 or higher (P < 0.001), demonstrated significantly reduced blood loss (100 ml vs. 190 ml, P = 0.026) and lower incidence of serious complications (19.3% vs. 33.7%, P = 0.034), especially in infections and respiratory issues. Sarcopenia was identified in 38.6% of CPAS patients who received tailored support. Additionally, the median postoperative hospital stay was notably shorter in the CPAS group (10 days vs. 15 days, P < 0.001), with no in-hospital deaths. These results suggest that personalized preoperative care effectively mitigates operative stress and postoperative complications. CONCLUSION: Implementing CPAS significantly enhances surgical safety and reduces complication rates in elderly gastric cancer patients, emphasizing the critical role of personalized preoperative care in surgical oncology for this demographic.

Early detection of occupational cholangiocarcinoma in a high-risk patient under intensive surveillance: a case study.

BACKGROUND: Occupational cholangiocarcinoma is associated with exposure to organic solvents, such as dichloromethane (DCM) and 1,2-dichloropropane (DCP). This report describes a case of occupational cholangiocarcinoma detected through regularly imaging following the discovery of elevated serum γ-glutamyl trans peptidase (γ-GTP) levels revealed during regular checkup. CASE PRESENTATION: A 43-year-old man who had been working in a printing company with 15 years of exposure to organic solvents presented to our hospital owing to abnormalities found during a routine checkup. Ultrasound (US) imaging revealed thickening of the gallbladder wall accompanied by gallstones, although in the blood tests, γ-GTP levels were within normal range. Given the high risk of cholangiocarcinoma development, the patient underwent regular monitoring with abdominal US and blood tests at a local doctor's office. At the age of 48, his serum γ-GTP level mildly elevated for the first time, prompting the initiation of semi-annual magnetic resonance cholangiopancreatography (MRCP). By the age of 50 years, dilation in B8 was detected, and one and a half years later, a tumor on the central side of the B8 dilation appeared. The patient was diagnosed with intrahepatic cholangiocarcinoma, which was treated with anterior sectionectomy. Pathological examination revealed an adenocarcinoma with a papillary glandular ductal structure at the root of the B8. In addition, biliary intraepithelial neoplasia (BilIN) and dysplasia have been identified around the tumor and periphery bile ducts and in noncancerous bile ducts. Postoperatively, the patient received 6 months of adjuvant chemotherapy with S-1monotherapy. Eight months after surgery, the patient remained under observation with no signs of recurrence. CONCLUSIONS: We report a case of occupational cholangiocarcinoma detected during a prolonged period of regular follow-up after exposure to DCM and DCP. Given the delayed carcinogenesis process, occupational cholangiocarcinomas manifest long after exposure to organic solvents, therefore, ongoing screening is extremely important. Vigilance is essential to avoid underdiagnosis, particularly for individuals who are at an increased risk of developing this form of cancer. Continuous monitoring is key to the early detection and effective management of occupational cholangiocarcinoma.

A comprehensive study on non-cancer-related mortality risk factors in elderly gastric cancer patients post-curative surgery.

BACKGROUND: The increasing incidence of gastric cancer in the elderly underscores the need for an in-depth understanding of the challenges and risks associated with surgical interventions in this demographic. This study aims to investigate the risk factors and prognostic indicators for non-cancer-related mortality following curative surgery in elderly gastric cancer patients. METHODS: This retrospective analysis examined 684 patients with pathological Stage I-III gastric cancer who underwent curative resection between January 2012 and December 2021. The study focused on patients aged 70 years and above, evaluating various clinical and pathological variables. Univariate analysis was utilized to identify potential risk factors with to non-cancer-related mortality and to access prognostic outcomes. RESULTS: Out of the initial 684 patients, 244 elderly patients were included in the analysis, with 33 succumbing to non-cancer-related causes. Univariate analysis identified advanced age (≥ 80 years), low body mass index (BMI) (< 18.5), high Charlson Comorbidity Index (CCI), and the presence of overall surgical complications as significant potential risk factors for non-cancer related mortality. These factors also correlated with poorer overall survival and prognosis. The most common cause of non-cancer-related deaths were respiratory issues and heart failure. CONCLUSION: In elderly gastric cancer patients, managing advanced age, low BMI, high CCI, and minimizing postoperative complications are essential for reducing non-cancer-related mortality following curative surgery.

A rare intrahepatic splenosis mimicking hepatocellular carcinoma: A case report.

Intrahepatic splenosis (IHS) is a rare disease that is considered to result from heterotopic autotransplantation or implantation of splenic tissue after splenic trauma or surgery. A 46-year-old man with a treatment history of a left lateral liver segmentectomy and splenectomy for a road traffic injury 30 years earlier presented to Sakai City Medical Center (Sakai, Japan) with acute abdominal pain in November 2019. Physical examination showed no significant signs, and serum data were normal. Computed tomography revealed a hypodense mass measuring 2.5x1.7 cm in segment 7 of the liver. Gadoxetic acid-enhanced magnetic resonance imaging showed early enhancement in the arterial phase and washout in the delayed phase. Therefore, laparoscopic surgery was performed with a preoperative diagnosis of hepatocellular carcinoma. Pathological examination of the tumor showed IHS. The postoperative course was uneventful, and the patient developed no new abnormal region in the liver during 2 years of follow-up. The present study presented a case of IHS assumed to be hepatocellular carcinoma. IHS should be considered as a differential diagnosis of a liver mass detected years after splenic trauma or surgery, even in cases with imaging patterns suggesting malignancy.

Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer.

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. This work provides critical knowledge on drivers of renal cell carcinoma progression and defines the primary role of interferon signaling in constraining the propagation of aneuploid clones in cancer evolution.

Minimizing invasiveness and simplifying the surgical procedure for upper and middle early gastric cancer with near-infrared light and organ traction.

BACKGROUND: Surgeons are often faced with optimal resection extent and reconstructive method problems in laparoscopic gastrectomy for gastric cancer in the upper and middle body of the stomach. Indocyanine green (ICG) marking and Billroth I (B-I) reconstruction were used to solve these problems with the organ retraction technique. CASE PRESENTATION: A 51-year-old man with upper gastrointestinal endoscopy revealed a 0-IIc lesion in the posterior wall of the upper and middle gastric body 4 cm from the esophagogastric junction. Clinical T1bN0M0 (clinical stage IA) was the preoperative diagnosis. Laparoscopic distal gastrectomy (LDG) and D1 + lymphadenectomy was decided to be performed considering postoperative gastric function preservation. The ICG fluorescence method was used to determine the accurate tumor location since the determination was expected to be difficult to the extent of optimal resection with intraoperative findings. By mobilizing and rotating the stomach, the tumor in the posterior wall was fixed in the lesser curvature, and as large a residual stomach as possible was secured in gastrectomy. Finally, delta anastomosis was performed after increasing gastric and duodenal mobility sufficiently. Operation time was 234 min and intraoperative blood loss was 5 ml. The patient was allowed to be discharged on postoperative day 6 without complications. CONCLUSION: The indication for LDG and B-I reconstruction can be expanded to cases where laparoscopic total gastrectomy or LDG and Roux-en-Y reconstruction has been selected for early-stage gastric cancer in the upper gastric body by combining preoperative ICG markings and gastric rotation method dissection.

[Postoperative Chylothorax Following Gastric Tube Cancer Surgery Cured after Pneumonia and Empyema-A Case Report].

A 74-year-old man was under follow-up after esophageal cancer surgery and CRT for hypopharyngeal cancer. Follow-up endoscopy revealed an ulcerative lesion in the lower gastric tube, and biopsy showed group 5(tub1). Endoscopic resection was difficult, and surgery was decided. Gastric tube resection and subcutaneous jejunum reconstruction were performed. Postoperatively, chylothorax was observed. Enteral nutrition was discontinued, and the patient was managed with TPN, and continuous subcutaneous octreotide and continuous intravenous etyrefrine were started. Even after conservative treatment was started, the pleural effusion of about 2,000 mL/day was observed from the right thoracic drain. On postoperative day 14, lymphangiography was performed with lipiodol from the left inguinal lymph node. The pleural fluid was temporarily decreased to less than 500 mL/day, but it began to drain again at a rate of 1,000 mL/day. On postoperative day 30, the patient developed fever and elevated inflammatory findings due to pneumonia and empyema, and drain drainage gradually decreased. The drain was removed on postoperative day 41. The patient was discharged home on postoperative day 72.

[Subtotal Stomach-Preserving Pancreaticoduodenectomy for Large Laterally Spreading Early Duodenal Cancer-A Case Report].

A 76-year-old man came to our hospital for a close examination after an abnormal finding during a medical checkup. Upper gastrointestinal endoscopy revealed a circumferential flat lesion with irregularity in the second to third portions of the duodenum. Biopsy diagnosed papillary adenocarcinoma. Contrast-enhanced CT of the abdomen showed no evidence of lymph node enlargement and distant metastasis. Endoscopic depth of the lesion was estimated to be intramucosal carcinoma, but it was approximately 60 mm in size, circumferential, and located near the papilla Vater. Therefore, endoscopic resection was deemed difficult. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Postoperative pathological examination revealed type 0-Ⅱa, tub1>pap, pTis, Ly0, V0, 80×50 mm, BD1, Ex0, Pn0, pPM0, pDM0, pN0, pStage 0. There has been no recurrence since then. Lateral spreading duodenal carcinoma is a rare disease, and endoscopic resection, local resection, and pancreaticoduodenectomy have been reported as treatment options. We report a case of resection of a large lateral spreading duodenal carcinoma with a review of the literature.

Simple Detection and Culture of Circulating Tumor Cells from Colorectal Cancer Patients Using Poly(2-Methoxyethyl Acrylate)-Coated Plates.

Here we aimed to establish a simple detection method for detecting circulating tumor cells (CTCs) in the blood sample of colorectal cancer (CRC) patients using poly(2-methoxyethyl acrylate) (PMEA)-coated plates. Adhesion test and spike test using CRC cell lines assured efficacy of PMEA coating. A total of 41 patients with pathological stage II-IV CRC were enrolled between January 2018 and September 2022. Blood samples were concentrated by centrifugation by the OncoQuick tube, and then incubated overnight on PMEA-coated chamber slides. The next day, cell culture and immunocytochemistry with anti-EpCAM antibody were performed. Adhesion tests revealed good attachment of CRCs to PMEA-coated plates. Spike tests indicated that ~75% of CRCs from a 10-mL blood sample were recovered on the slides. By cytological examination, CTCs were identified in 18/41 CRC cases (43.9%). In cell cultures, spheroid-like structures or tumor-cell clusters were found in 18/33 tested cases (54.5%). Overall, CTCs and/or growing circulating tumor cells were found in 23/41 CRC cases (56.0%). History of chemotherapy or radiation was significantly negatively correlated with CTC detection (p = 0.02). In summary, we successfully captured CTCs from CRC patients using the unique biomaterial PMEA. Cultured tumor cells will provide important and timely information regarding the molecular basis of CTCs.

[A Case of Locally Advanced Giant Sigmoid Colon Cancer Successfully Treated with Neoadjuvant Chemotherapy].

A 51-year-old woman presented to our hospital complaining of a lower abdominal mass and dysuria. She was diagnosed with advanced sigmoid colon cancer. The tumor was large, involving the bladder, and occupying the pelvic cavity. She received neoadjuvant chemotherapy with 4 courses of mFOLFOX6, in addition to panitumumab. The treatment resulted in a marked reduction of the tumor. A laparoscopic sigmoid colon resection, total cystectomy, neobladder reconstruction, complete uterine and bilateral adnexa resection and partial ileal resection were performed. The histopathological diagnosis was ypT4b(bladder), ypN0, ypStage Ⅱc, all with negative surgical margins. Adjuvant chemotherapy was not administered owing to the patient's refusal. She remained recurrence-free for 3 years of postoperative follow up.

Spontaneous rupture of an undifferentiated carcinoma with osteoclast-like giant cells of the pancreas presenting as intra-abdominal bleeding: a case report.

BACKGROUND: Undifferentiated carcinoma is a very rare histologic subtype, representing only 0.8% to 5.7% of all pancreatic exocrine neoplasms. Additionally, spontaneous abdominal hemorrhage is a particularly rare, life-threatening cause. CASE PRESENTATION: A 68-year-old man was taken by ambulance to our hospital because of sudden-onset abdominal pain. Contrast-enhanced abdominal computed tomography revealed a huge mass measuring 99 × 70 mm in the pancreatic tail with enhanced rim staining in the peripheral area. Imaging also showed extravasation and fluid collection beside the tumor. Hence, spontaneous rupture of the pancreatic tumor and intra-abdominal bleeding were diagnosed. Emergency laparotomy was performed because of acute abdominal pain with peritoneal signs. With an intraoperative diagnosis of rupture of the pancreatic tumor, distal pancreatectomy was successfully performed. Histologically, hematoxylin and eosin staining showed round to spindle-shaped, highly pleomorphic mononuclear cells and multinucleated giant cells as well as a component of ductal adenocarcinoma. Immunohistochemical staining showed that the tumor cells were negative for AE1/AE3, whereas the non-neoplastic osteoclast-like giant cells were positive for CD68. Taken together, these results led to a diagnosis of undifferentiated carcinoma with osteoclast-like giant cells. The patient's postoperative course was uneventful. CONCLUSION: We experienced an extremely rare case of spontaneous rupture of an undifferentiated carcinoma with osteoclast-like giant cells presenting as intra-abdominal bleeding. Obtaining a correct preoperative diagnosis is quite difficult at the first evaluation. Undifferentiated carcinoma should be considered as a differential diagnosis in the case with spontaneous rupture of a pancreatic tumor.

Preoperative risk score to predict subtotal cholecystectomy after gallbladder drainage for acute cholecystitis: Secondary analysis of data from a multi-institutional retrospective study (CSGO-HBP-017B).

INTRODUCTION: Subtotal cholecystectomy (STC) has become recognized as a "bailout procedure" to prevent bile duct injury in patients undergoing laparoscopic cholecystectomy (LC). Predictors of conversion to STC have not been identified because LC difficulty varies based on pericholecystic inflammation. We analyzed data from patients enrolled in a previously performed multi-institutional retrospective study of the optimal timing of LC after gallbladder drainage for acute cholecystitis (AC). These patients presumably had a considerable degree of pericholecystic inflammation. METHODS: In total, 347 patients who underwent LC after gallbladder drainage for AC were analyzed to examine preoperative and perioperative factors predicting conversion to STC. RESULTS: Three hundred patients underwent total cholecystectomy (TC) and 47 underwent conversion to STC. Eastern Cooperative Oncology Group Performance Status (ECOG PS) (P < .01), severity of cholecystitis (P = .04), previous history of treatment for common bile duct stones (CBDS) (P < .01), and surgeon experience (P = .03) were significantly associated with conversion to STC. Logistic regression analyses showed that ECOG PS (odds ratio 0.2; P < .0001) and previous history of treatment for CBDS (odds ratio 0.37; P = .0073) were independent predictors of conversion to STC. Our predictive risk score using these two variables suggested that a score ≥2 could discriminate between TC and STC (P < .0001). CONCLUSION: Poor ECOG PS and previous history of treatment for CBDS were significantly associated with conversion to STC after gallbladder drainage for AC.

[Fracture of a Gastrointestinal Stent during Chemotherapy for Unresectable Advanced Gastric Cancer-A Case Report].

A 79-year-old man with shortness of breath on exertion had right pleural effusion and ascites effusion on CT, and was diagnosed with adenocarcinoma on pleural cytology. Upper gastrointestinal endoscopy revealed a gastric cancer with pyloric stenosis, and biopsy from the same site revealed Group 5(tub2). The patient was diagnosed as unresectable advanced gastric cancer with pyloric stenosis and peritoneal and pleural dissemination. After placement of an uncovered metallic stent for the pyloric stenosis, SOX therapy was started. Three months after stent placement, a CT scan to determine the effect of chemotherapy showed stenosis in the gastrointestinal stent, partial breakage of the stent on the mouth side, and prolapse of the stent into the stomach. There were no symptoms such as abdominal pain, and the patient was placed on standby for retrieval of the dislodged stent. The prolapsed stent was retrieved endoscopically, and a covered metallic stent was additionally implanted as a"stent in stent". The patient has had no further passage obstruction and is currently undergoing chemotherapy. We report a case of fracture of a gastrointestinal stent during chemotherapy for unresectable advanced gastric cancer.

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Successful resection of a huge hepatocellular adenoma.

Hepatocellular adenoma (HCA) is a rare benign liver tumor that has been reported to occur particularly more often in women who use contraceptives. A 72-year-old woman with no history of using contraceptives presented to our hospital for further examination of a liver tumor. Contrast-enhanced computed tomography and gadoxetic acid-enhanced magnetic resonance imaging revealed a huge solitary hepatic tumor measuring 83 × 76 mm in segments 4, 5, and 8. The differential diagnoses were cholangiocarcinoma and mixed-type hepatocellular carcinoma. Percutaneous needle biopsies were performed twice, and no malignant components were found. Central bi-segmentectomy of the liver was successfully performed. Immunohistochemical staining showed that ß-catenin was positive in the membrane of the tumor cells, while fatty acid-binding protein, glutamine synthetase, and amyloid A were negative. These results led to a diagnosis of HCA, hepatocyte nuclear factor-1α-inactivated subtype. The patient's postoperative course was uneventful, and she developed no recurrence for 10 months after surgery. We experienced a rare case of benign HCA. Obtaining a correct preoperative diagnosis is sometimes difficult at the first evaluation. HCA should be considered as a differential diagnosis of liver tumors.

Synchronous gastric cancer and primary lymphoma of right adrenal gland: a case report.

This report presents an extremely rare case of synchronous gastric cancer and primary adrenal diffuse large B-cell lymphoma (DLBCL). An 82-year-old man underwent computed tomography, which revealed a heterogeneous appearing and hypodense adrenal mass and a gastric mass with no enlarged lymph nodes in the neck, mediastinum, abdomen, and inguinal region. Upper gastrointestinal endoscopy revealed a protruding gastric tumor. The specimens obtained from endoscopic biopsy were histologically confirmed to be adenocarcinoma. The hormonal findings eliminated functional adrenal tumor. The patient underwent distal gastrectomy with regional lymph node resection for gastric cancer and incisional biopsy of the adrenal mass. Based on the pathological findings, diagnoses of mixed mucinous and tubular adenocarcinomas of the stomach and adrenal DLBCL were confirmed. Postoperation, the patient received rituximab combined with low-dose doxorubicin, cyclophosphamide, vincristine, and prednisone (R-miniCHOP). Six courses of R-miniCHOP were planned, but were completed in only one course at the patient's request. The patient died 2 months after surgery.

Postoperative solitary liver metastasis from esophageal squamous cell carcinoma achieving a clinical complete response to chemotherapy with cisplatin and 5-fluorouracil followed by stereotactic body radiotherapy: A case report.

Treatment strategies for distant organ metastasis have changed markedly since the concept of oligometastasis was introduced. The perception that distant organ metastasis is a systemic disease and not eligible for local therapy is now a thing of the past. Therefore, the present report details a case of postoperative solitary liver metastasis from esophageal squamous cell carcinoma (ESCC), which achieved a clinical complete response to chemotherapy with cisplatin and 5-fluorouracil (5-FU) followed by stereotactic body radiotherapy (SBRT). A 76-year-old male patient underwent esophagectomy for lower thoracic ESCC. At 7 months after surgery, abdominal CT revealed a solitary hypovascular mass, 28 mm in size, in segment 7 of the liver. After three courses of chemotherapy with cisplatin and 5-FU, abdominal CT revealed that the liver mass had shrunk to 7 mm in size. SBRT was then administered with a 6 MV X-ray beam generated by a linear accelerator. A total dose of 50 Gy was given in 5 fractions of 10 Gy to the liver mass. At 1 month after SBRT, abdominal CT revealed that the liver mass had disappeared. The patient received no further adjuvant chemotherapy and had no recurrence at 18 months after diagnosis of liver metastasis and 13 months after SBRT.

Sequential Administration of XPO1 and ATR Inhibitors Enhances Therapeutic Response in TP53-mutated Colorectal Cancer.

BACKGROUND & AIMS: Understanding the mechanisms by which tumors adapt to therapy is critical for developing effective combination therapeutic approaches to improve clinical outcomes for patients with cancer. METHODS: To identify promising and clinically actionable targets for managing colorectal cancer (CRC), we conducted a patient-centered functional genomics platform that includes approximately 200 genes and paired this with a high-throughput drug screen that includes 262 compounds in four patient-derived xenografts (PDXs) from patients with CRC. RESULTS: Both screening methods identified exportin 1 (XPO1) inhibitors as drivers of DNA damage-induced lethality in CRC. Molecular characterization of the cellular response to XPO1 inhibition uncovered an adaptive mechanism that limited the duration of response in TP53-mutated, but not in TP53-wild-type CRC models. Comprehensive proteomic and transcriptomic characterization revealed that the ATM/ATR-CHK1/2 axes were selectively engaged in TP53-mutant CRC cells upon XPO1 inhibitor treatment and that this response was required for adapting to therapy and escaping cell death. Administration of KPT-8602, an XPO1 inhibitor, followed by AZD-6738, an ATR inhibitor, resulted in dramatic antitumor effects and prolonged survival in TP53-mutant models of CRC. CONCLUSIONS: Our findings anticipate tremendous therapeutic benefit and support the further evaluation of XPO1 inhibitors, especially in combination with DNA damage checkpoint inhibitors, to elicit an enduring clinical response in patients with CRC harboring TP53 mutations.