Preoperative factors associated with lateral lymph node metastasis in lower rectal cancer and the evaluation of the middle rectal artery.

PURPOSE: This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis. METHODS: Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA. RESULTS: pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA. CONCLUSION: Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded.

Damage to the Descending Colon after Endoscopic Balloon Dilatation following a Minor Traffic Accident in a Patient with Crohn's Disease: A Case Report.

Introduction: Crohn's disease (CD) is complicated by intestinal strictures and fistula formation; however, intestinal perforation is relatively rare. Case Presentation: Following a traffic accident in the evening, a 39-year-old woman experienced abdominal pain that worsened the following morning and was taken to the emergency department. She had a 17-year history of CD and eight endoscopic balloon dilations for descending colonic strictures. She presented with a high fever of 40.0°C, along with tenderness and rebound pain throughout her abdomen, with the most substantial point being in the lower left abdomen. Computed tomography showed thickening of the descending colon wall, increased fat concentration around the wall, and a slight presence of air in the mesentery near the intestinal wall. We diagnosed the patient with generalized peritonitis due to traumatic penetration of the mesentery of the descending colon and performed emergency surgery. Intraoperative observation of the abdominal cavity with a laparoscope revealed purulent ascites but no apparent perforation or edematous mesentery, with white moss and redness in the descending colon. This prompted the decision to perform peritoneal lavage drainage and a transverse colonic double colostomy. The postoperative course was favorable, and the patient was discharged from the hospital on the postoperative day 14. Four months after discharge, colostomy closure was performed. Conclusion: Relatively minor trauma in patients with CD can result in colon injury. An injured bowel is usually accompanied by active lesions due to CD; however, caution is required, as endoscopic balloon dilatation without accompaniment may be a background factor.

Squamous cell carcinoma of the anus successfully treated with multidisciplinary therapy for metachronous metastatic and local recurrences after DCF chemotherapy: a case report.

BACKGROUND: Docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy is reportedly an effective treatment strategy for squamous cell carcinoma of the anus (SCCA). However, studies regarding its use in Japanese patients remain scarce. CASE PRESENTATION: Here, we present the case of an 82-year-old woman with SCCA, cStage IIIB. Chemoradiotherapy was initiated after colostomy of the anorectal mass; however, para-aortic lymph node recurrence was observed 3 months after treatment completion. Five courses of DCF chemotherapy were subsequently administered, resulting in a complete response (CR). Two years and 1 month later, the aortic lymph node was enlarged again, and the patient achieved CR again after radiotherapy. Nine months later, local recurrence was detected in the anal canal, and laparoscopic perineal rectal amputation was performed. The patient remains progression-free 5 years and 10 months after the initial treatment and 1 year and 7 months after the final treatment. CONCLUSIONS: Our findings suggest that complementary treatment after DCF chemotherapy may be efficacious in Japanese patients with SCCA and help achieve CR. Despite occasional local recurrences, this approach may help achieve long-term progression-free survival.

Two-Team Transanal Total Mesorectal Excision and En Bloc Resection of the Lateral Pelvic Lymph Nodes, Main Iliac Vessels, and Pelvic Plexus for Locally Advanced Rectal Cancer With Lateral Lymph Node Metastasis.

BACKGROUND: Here, we describe the precise surgical technique for a novel procedure involving 2-team transanal total mesorectal excision with en bloc lateral pelvic lymph node (LPLN) dissection combined with resection of the involved main internal iliac vessels and pelvic plexus. METHODS: From September 2020 to May 2023, 4 patients underwent the procedure at our hospital. RESULTS: The operation time and blood loss were 272 to 412 minutes and 10 to 124 mL, respectively. No patients required conversion to open surgery or exhibited Clavien-Dindo grade III or worse postoperative complications, although 2 developed grade II urinary dysfunction. All surgical margins were negative. CONCLUSIONS: Our novel 2-team method can facilitate safe and satisfactory surgery, even for highly advanced rectal cancer. The transanal approach offers excellent visibility and operability, even during LPLN and adjacent structure dissection. Furthermore, initial dissection of the distal branches of the iliac vessels prevents excessive lymphatic tissue congestion, facilitating easier, and clearer dissection.

Prognostic value of a modified­immune scoring system in patients with pathological T4 colorectal cancer.

Tumor-infiltrating immune cells, such as lymphocytes and macrophages, have been associated with tumor aggressiveness, prognosis and treatment response in colorectal cancer (CRC). An immune scoring system, Immunoscore (IS), based on tumor-infiltrating T cells in stage I-III CRC, was used to predict prognosis. An alternative immune scoring signature of immune activation (SIA) reflects the balance between anti- and pro-tumoral immune components. The present study aimed to evaluate the prognostic value of modified IS (mIS) and modified SIA (mSIA) in locally advanced pathological T4 (pT4) CRC, including stage IV CRC. Immunohistochemical staining for immune cell markers, such as CD3 (pan-T cell marker), CD8 (anti-tumoral cytotoxic T cell marker) and CD163 (tumor-supportive macrophage marker), in specimens from patients with radically resected pT4 CRC at stages II-IV was performed. mIS levels in the T4 CRC cohort were not associated with prognosis. However, low mSIA levels were associated with low survival. Furthermore, low mSIA was an independent predictor of recurrence in patients with radically resected pT4 CRC. In patients with CRC who did not receive postoperative adjuvant chemotherapy, low mSIA was a major poor prognostic factor; however, this was not observed in patients receiving adjuvant chemotherapy. Evaluation of the tumor-infiltrating immune cell population could serve as a valuable marker of recurrence and poor prognosis in patients with locally advanced CRC. mSIA assessment after radical CRC resection may be promising for identifying high-risk patients with pT4 CRC who require aggressive adjuvant chemotherapy.

Retrograde drainage for duodenal stump leakage using ileal decompression tube guided by double-balloon endoscopy: a novel case report.

BACKGROUND: Duodenal stump leakage is a serious post-gastrectomy complication, and there have been no reports on endoscopic drainage. CASE PRESENTATION: We report a case of duodenal stump leakage after laparoscopic gastrectomy with Roux-en-Y reconstruction in a 68-year-old man. First-line conservative management was ineffective. Reoperation was performed because of severe abdominal pain and increased ascites. After reoperation, duodenal stump leakage recurred with bleeding from the anterior superior pancreaticoduodenal artery. Coil embolization and pigtail catheter insertion were performed. Furthermore, we retrogradely inserted an ileal tube for tube decompression near the duodenal stump using double-balloon endoscopy for effective drainage. After tube insertion, duodenal stump leakage decreased; on the 47th primary postoperative day, the patient was discharged. The primary postoperative course was uneventful after 1 year and 9 months of follow-up. CONCLUSIONS: This is the first successful case of duodenal stump leakage treated with retrograde decompression tube insertion near the duodenal stump using double-balloon endoscopy.

Adjuvant Chemotherapy With UFT/LV Versus UFT/LV Plus PSK in Stage II/III Colorectal Cancer.

BACKGROUND/AIM: Uracil-tegafur+leucovorin (UFT/LV), an oral adjuvant therapy for stage II/III colorectal cancer, is non-inferior to standard weekly fluorouracil and folinate. Although polysaccharide K (PSK) has been evaluated as a postoperative adjuvant colorectal cancer drug, its efficacy remains unclear. This randomized phase II trial compared UFT/LV+PSK with UFT/LV as adjuvant chemotherapy. PATIENTS AND METHODS: Between April 2011 and August 2016, 186 patients who underwent radical resection randomly received 6 months of UFT/LV (Group A: 300 mg/m2/day UFT and 75 mg/day LV, every 35 days for five cycles), 6 months of UFT/LV+PSK (Group B: standard UFT/LV regimen and daily administration of 3 g/day of PSK), or 12 months of UFT/LV+PSK (Group C). The primary endpoint was the 3-year disease-free survival. RESULTS: Groups A, B, and C consisted of 37, 75, and 74 patients, of which treatment was completed by 33 (89.2%), 63 (84.9%), and 53 (70.4%) patients, respectively (p=0.0279). Adverse event incidence for all grades were 59.5%, 52.1%, and 59.2%, and for grade ≥3 were 13.5%, 9.6%, and 9.9%, respectively. The 3-year disease-free survival rates were 72.5%, 82.2%, and 74.2%, respectively, with no significant differences. The preoperative lymphocyte ratio did not significantly differ between groups. CONCLUSION: UFT/LV+PSK is comparable to UFT/LV therapy in terms of prognostic efficacy and reduced adverse effects. Thus, UFT/LV+PSK is a useful adjuvant chemotherapy option for patients with high-risk stage II/III colorectal cancer.

A Novel Method for Thoracoscopic Overlap Esophagogastric Reconstruction With Pleural Closure following Minimally Invasive Ivor-Lewis Esophagectomy for Esophagogastric Junction Cancer.

BACKGROUND: Intrathoracic esophagogastric anastomosis following minimally invasive Ivor-Lewis esophagectomy is a technically demanding surgical technique that can result in serious intrathoracic infections when anastomotic leakage occurs. Herein, we report a novel side-overlap esophagogastric anastomosis with pleural closure for esophagogastric junction cancer. METHODS: The 3 key points of our novel technique were the following: (1) overlap esophagogastric anastomosis and closure of the entry hole were all performed using a linear stapler; (2) the pleura was closed to separate the anastomotic site from the thoracic cavity; and (3) the mediastinal drain was inserted transhiatally from the abdominal cavity. RESULTS: This modified anastomosis procedure was performed on 8 consecutive patients at our institution. The median overall/thoracoscopic operating time and estimated blood loss were 652.5/241.5 min and 89 mL, respectively. No mortality or serious postoperative complications occurred, and the median postoperative hospital stay was 22 days (range, 17 to 37 d). CONCLUSION: This novel thoracoscopic overlap esophagogastric reconstruction procedure with pleural closure is safe and feasible.

Importance of Progression-free Survival in Second-line Chemotherapy in Patients With Advanced or Recurrent Gastric Cancer.

BACKGROUND/AIM: Impact of second-line chemotherapy in unresectable advanced/recurrent gastric/esophagogastric junction cancer (AGC) remains unclear. This retrospective analysis aimed to identify factors affecting prognosis in chemotherapy for patients with AGC, including the importance of progression-free survival in second-line chemotherapy (PFS-2). PATIENTS AND METHODS: Data from a total of 109 patients with AGC that received second-line treatment were analyzed with the aim of clarifying prognostic factors. Furthermore, the correlation between PFS-2 and clinical characteristics and the association between PFS-2 and inflammation-based and/or nutritional markers were investigated. RESULTS: Multivariate analysis identified the following prognostic factors: ECOG PS ≥1, presence of peritoneal dissemination, metastasis in two or more organs, and taxane use on second-line chemotherapy. Short PFS-2 was strongly associated with prognosis in the univariate analysis [hazard ratio (HR)=3.107, 95% confidence interval (CI)=1.969-4.904, p<0.001]. The duration of PFS-2 was significantly correlated with ECOG PS (p=0.019), liver metastasis rates (p=0.035) and taxane use on second-line chemotherapy (p=0.001). In addition, weight loss rate during first-line treatment (p=0.042), white blood cell count (p=0.008), C-reactive protein (p=0.032), c-reactive protein to albumin ratio (p=0.039), prognostic index (p=0.028), and modified Glasgow prognostic score (p=0.027) were significantly associated with the duration of PFS-2. CONCLUSION: The duration of PFS-2 significantly correlated with ECOG PS, liver metastasis, and taxane use on second-line treatment, and strongly affected OS. It was suggested that the presence of malnutrition and inflammation at the start of second-line therapy had a negative impact on PFS-2 and OS.

Validation of a New Methodology to Create Oral Drugs beyond the Rule of 5 for Intracellular Tough Targets.

Establishing a technological platform for creating clinical compounds inhibiting intracellular protein-protein interactions (PPIs) can open the door to many valuable drugs. Although small molecules and antibodies are mainstream modalities, they are not suitable for a target protein that lacks a deep cavity for a small molecule to bind or a protein found in intracellular space out of an antibody's reach. One possible approach to access these targets is to utilize so-called middle-size cyclic peptides (defined here as those with a molecular weight of 1000-2000 g/mol). In this study, we validated a new methodology to create oral drugs beyond the rule of 5 for intracellular tough targets by elucidating structural features and physicochemical properties for drug-like cyclic peptides and developing library technologies to afford highly N-alkylated cyclic peptide hits. We discovered a KRAS inhibitory clinical compound (LUNA18) as the first example of our platform technology.

HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis.

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.

Surgical Techniques and Stoma-related Complications Associated With Emergency Stoma Creation.

BACKGROUND/AIM: Determination of risk factors for stoma-related complications associated with emergency stoma creation may impact on reducing complications and improving the quality of life of ostomy patients; however, there are only few reports on stoma-related complications associated with emergency stoma creation. Our study aimed to identify risk factors associated with stoma-related complications after emergency surgery, and evaluate surgical techniques for good stoma creation in the emergency setting. PATIENTS AND METHODS: A retrospective analysis of patient and surgical characteristics was performed in 104 consecutive patients who underwent ileostomy or colostomy as emergency surgery between January 2020 and December 2022 at the Gunma University Hospital. RESULTS: Preoperative stoma site marking was performed in 70 (67.3%) patients. Colostomies and ileostomies were performed in 78 (75.0%) and 26 (25.0%) patients, respectively. The skin bridge technique was used in 13 (12.5%) patients. Stoma-related complications were diagnosed in 62 (59.6 %) patients, with peristomal skin disorders (47.1%) as the most common complication, followed by mucocutaneous separation (31.7%), and stoma retraction (19.2%). In the multivariate analysis, body mass index (BMI) [odds ratio (OR)=5.570, 95% confidence interval (CI)=1.233-25.167, p=0.026], skin bridge technique (OR=0.144, 95% CI=0.031-0.670, p=0.014), and stoma height (OR=0.134, 95% CI=0.038-0.469, p=0.002) were independent risk factors for stoma-related complications after emergency stoma creation. CONCLUSION: In emergency stoma creation, higher BMI and lower stoma height are associated with stoma-related complications. Using the skin bridge technique could reduce the risk of stoma-related complications after emergency stoma creation.

Development of Orally Bioavailable Peptides Targeting an Intracellular Protein: From a Hit to a Clinical KRAS Inhibitor.

Cyclic peptides as a therapeutic modality are attracting a lot of attention due to their potential for oral absorption and accessibility to intracellular tough targets. Here, starting with a drug-like hit discovered using an mRNA display library, we describe a chemical optimization that led to the orally available clinical compound known as LUNA18, an 11-mer cyclic peptide inhibitor for the intracellular tough target RAS. The key findings are as follows: (i) two peptide side chains were identified that each increase RAS affinity over 10-fold; (ii) physico-chemical properties (PCP) including Clog P can be adjusted by side-chain modification to increase membrane permeability; (iii) restriction of cyclic peptide conformation works effectively to adjust PCP and improve bio-activity; (iv) cellular efficacy was observed in peptides with a permeability of around 0.4 × 10-6 cm/s or more in a Caco-2 permeability assay; and (v) while keeping the cyclic peptide's main-chain conformation, we found one example where the RAS protein structure was changed dramatically through induced-fit to our peptide side chain. This study demonstrates how the chemical optimization of bio-active peptides can be achieved without scaffold hopping, much like the processes for small molecule drug discovery that are guided by Lipinski's rule of five. Our approach provides a versatile new strategy for generating peptide drugs starting from drug-like hits.

Two-team Total Mesorectal Excision and Lateral Pelvic Lymph Node Dissection Using Transanal Approach for Rectal Cancer: A Retrospective Study.

BACKGROUND/AIM: Lateral lymph node dissection is a locally advanced rectal cancer treatment option. Despite its complexities, such as prolonged operative time and increased blood loss, a transanal approach with an abdominal approach may help mitigate these drawbacks. PATIENTS AND METHODS: Between July 2013 and June 2022, 40 patients underwent radical laparoscopic surgery with lateral lymph node dissection for rectal cancer. Among them, 29 and 11 patients underwent total mesorectal excision and lateral lymph node dissection without transanal approach (conventional surgery) and with transanal approach (two-team surgery), respectively. The clinical findings, surgical outcomes, pathology results, and prognoses of conventional and two-team surgeries were retrospectively compared. RESULTS: Compared to conventional surgery, two-team surgery involves increased organ and nerve resections, shorter operation time (286 vs. 548 min, p<0.001), and less blood loss (20 vs. 158 ml, p<0.001). Although postoperative complications were similar between groups, the two-team surgery group had a shorter hospital stay (p=0.006). Pathologically, all patients who underwent two-team surgery had a distal resection margin of at least 20 mm, and no recurrence was observed. With conventional surgery, 63.6% of patients had a 10-19 mm margin, and 36.4% had a margin of ≥20 mm, except for abdominoperineal resection. CONCLUSION: Total mesorectal excision and lateral lymph node dissection with the transanal approach as a two-team surgery are safe and feasible. Two-team surgery resulted in better outcomes than conventional surgery regarding operative time, blood loss, shorter postoperative hospital stay, and adequate distal resection margin.

Sigmoid colon schwannoma difficult to distinguish from peritoneal dissemination 13 years after pancreatic neuroendocrine tumor surgery.

BACKGROUND: Schwannoma, which clinicians sometimes struggle to diagnose, is a tumor arising from Schwann cells of peripheral nerves, often in the soft tissues and rarely in the gastrointestinal tract. Pancreatic neuroendocrine tumor (PNET) is rare among pancreatic tumors, and recurrence can occur long after resection. Here, we were presented with a case where a sigmoid colon schwannoma was difficult to distinguish from a postoperative recurrence of PNET and was diagnosed after laparoscopic resection. CASE PRESENTATION: A 51-year-old man was diagnosed with PNET (NET G2) after a distal pancreatectomy (DP) 13 years ago. The patient underwent hepatectomy due to liver metastasis 12 years after initial radical surgery. The follow-up magnetic resonance imaging (MRI) after hepatectomy showed pelvic nodules, and laparoscopic surgery was performed for both diagnosis and treatment because peritoneal dissemination of PNET could not be ruled out. Since the tumor was in the sigmoid colon, a partial colon resection was performed. The histopathological diagnosis was a schwannoma, and the patient was discharged on the seventh postoperative day. CONCLUSIONS: We experienced a case of sigmoid colon schwannoma that was difficult to differentiate from peritoneal dissemination of PNET and was later diagnosed after laparoscopic resection. In addition, this case involved a long-term postoperative recurrence of PNET that was amenable to radical resection, further establishing the importance of long-term imaging follow-up.

Retroperitoneal urothelial carcinoma arising after bladder diverticulectomy: a case report.

BACKGROUND: Urothelial carcinoma arises from the inner urothelial membrane of the renal pelvis, ureter, and bladder and often causes macrohematuria. Here, we report a rare case in which the patient developed non-symptomatic urothelial carcinoma anatomically outside the bladder wall 17 years after bladder diverticulectomy. CASE PRESENTATION: An 82-year-old male patient previously underwent gastrectomy for stomach cancer and partial hepatectomy for intrahepatic cholangiocarcinoma. Follow-up computed tomography revealed a tumor in the retroperitoneal space, where a bladder diverticulum was removed 17 years earlier. Multiparametric magnetic resonance imaging suggested that the tumor was malignant with rectal invasion. Subsequent computed tomography-guided percutaneous biopsy revealed that the tumor was urothelial carcinoma. The patient underwent two courses of neoadjuvant chemotherapy followed by pelvic exenteration with pelvic lymph node dissection. He is currently receiving adjuvant therapy with an immune checkpoint inhibitor and has had no recurrence for 3 months. CONCLUSIONS: Multiparametric magnetic resonance imaging is a helpful tool for predicting both tumor malignancy and invasion before a pathologically confirmed diagnosis. Although this case is rare, urologists should be aware of the occurrence of urothelial carcinoma after bladder diverticulectomy in cases of incomplete resection of the diverticulum.

Comparison between preoperative chemoradiotherapy and lateral pelvic lymph node dissection in clinical T3 low rectal cancer without enlarged lateral lymph nodes.

AIM: The standard strategy for clinical T3 rectal cancer without enlarged lateral lymph nodes is preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) in Western countries and TME with bilateral lateral pelvic lymph node dissection (LPLND) in Japan. This study compared surgical, pathological and oncological results of these two strategies. METHOD: Patients who underwent preoperative CRT followed by TME in France (CRT + TME group) and those who underwent TME with LPLND in Japan (TME + LPLND group) for clinical T3 rectal adenocarcinoma without enlarged lateral lymph nodes from 2010 to 2016 were retrospectively analysed. RESULTS: In total, 439 patients were included in this study. The estimated local recurrence rate (LRR), disease-free survival and overall survival at 5 years post-surgery was 4.9%, 71% and 82% in the CRT + TME group, and 8.6%, 75% and 90% in the TME + LPLND group, respectively. Lateral LRR versus non-lateral LRR was 0.5% versus 4.2% in the CRT + TME group and 1.8% versus 6.2% in the TME + LPLND group. Obturator nerve injury and isolated pelvic abscess were shown only in the TME + LPLND group. Urinary complications were more frequent in the TME + LPLND group than in the CRT + TME group. CONCLUSION: Disease-free survival was not significantly different after TME with LPLND and after CRT followed by TME. LRR was not significantly different after both strategies; however, there was a trend for higher LRR after TME with LPLND than after CRT followed by TME. Obturator nerve injury, isolated lateral pelvic abscess and urinary complications should be noted when TME with LPLND is applied.

Association of High LAT1 Expression with Poor Prognosis and Recurrence in Colorectal Cancer Patients Treated with Oxaliplatin-Based Adjuvant Chemotherapy.

The mammalian target of rapamycin (mTOR) is often activated in several cancers. We focused on two mTOR regulatory mechanisms: oxaliplatin-induced mTOR signaling and L-type amino acid transporter 1 (LAT1)-induced mTOR activation. High LAT1 expression in several cancers is associated with mTOR activation and resistance to chemotherapy. However, the significance of LAT1 has not yet been elucidated in colorectal cancer (CRC) patients treated with post-operative adjuvant chemotherapy. Immunohistochemistry was conducted to examine the significance of membrane LAT1 expression in 98 CRC patients who received adjuvant chemotherapy, including oxaliplatin. In vitro analysis was performed using CRC cell lines to determine the effects of LAT1 suppression on proliferation, oxaliplatin sensitivity, and mTOR signaling. LAT1 expression was associated with cancer aggressiveness and poor prognosis in 98 CRC patients treated with adjuvant chemotherapy. We found that positive LAT1 expression correlated with shorter survival in 43 patients treated with the capecitabine-plus-oxaliplatin (CAPOX) regimen. LAT1 suppression in CRC cells inhibited the proliferation potency and oxaliplatin-induced activation of mTOR signaling, and improved oxaliplatin sensitivity. LAT1 evaluation before adjuvant treatment may therefore be a sensitive marker for oxaliplatin-based regimens. Moreover, LAT1 may be a promising target for patients with refractory CRC.

Differences in prognosis and underuse of adjuvant chemotherapy between elderly and non-elderly patients in stage III colorectal cancer.

Aim: We aimed to clarify the use of adjuvant chemotherapy and the prognosis of elderly colorectal cancer patients compared with non-elderly patients, and the usefulness of sarcopenia as an indicator for the introduction and completion of adjuvant chemotherapy. Methods: Between 2013 and 2021, 215 patients with pStage III disease were included. We investigated perioperative clinicopathological factors, adjuvant chemotherapy details, and prognosis. Preoperative sarcopenia status was evaluated using computed tomography images. Elderly patients were defined as those aged ≥70 years. Results: We included 121 (56.3%) and 94 (43.7%) non-elderly and elderly patients, respectively. Among the elderly patients, 47 had sarcopenia. There were no significant differences in the incompletion rate of adjuvant chemotherapy between elderly and non-elderly patients (27.1%/16.2%, P = 0.119). The most common reason for the discontinuation of adjuvant chemotherapy was side effects, regardless of age. The respective 3-year-disease free survival of patients with no/completed/incomplete adjuvant chemotherapy were 65.5%, 80.2%, and 57.7% for non-elderly patients (P = 0.045) and 73.4%, 70.6%, and 71.6% for elderly patients (P = 0.924). The number of elderly patients with sarcopenia was significantly higher in patients without adjuvant chemotherapy (P = 0.004) and those with incomplete adjuvant chemotherapy (P = 0.004). The 3-year-disease free survival of elderly sarcopenic patients without and with adjuvant chemotherapy were 78.3% and 59.2%, respectively (P = 0.833). Conclusion: Elderly patients did not show a benefit of adjuvant chemotherapy regardless of whether they had completed adjuvant chemotherapy, unlike non-elderly patients. Moreover, the evaluation of preoperative sarcopenia in elderly colorectal cancer patients may be useful in determining the indication for adjuvant chemotherapy.

Relationship Between C-reactive Protein-to-albumin Ratio Before and After Bowel Decompression and Prognosis in Acute Malignant Large Bowel Obstruction.

BACKGROUND/AIM: We investigated the relationship between prognosis and the necessity of decompression of large bowel obstruction (LBO) among patients with colorectal cancer admitted to the hospital in an emergency, as well as the correlation between prognosis and improvement in the C-reactive protein-to-albumin ratio (CAR) after decompression. PATIENTS AND METHODS: Seventy-four patients admitted to the hospital between 2013 and 2021 in an emergency due to LBO were included. We examined perioperative clinicopathological factors, bowel decompression type, and prognosis. RESULTS: Of the 74 patients, 24 (32.4%) required bowel decompression. A higher percentage of patients who required bowel decompression had a colorectal obstruction scoring system (CROSS) score 0 (p<0.001) with higher frequency of nutritional disorders (p=0.063) than that in no bowel decompression-requiring patients. The 3-year-disease-free survival was 70.8% in the no decompression-requiring group and 26.9% in the bowel decompression group (p=0.007), while the 3-year-overall survival was 90.8% and 76.5%, respectively (p=0.001). The 3-year-disease-free survival was 49.2% in the improved CAR group and 0.0% in the non-improved CAR group (p=0.024), while the 3-year-overall survival was 91.7% and 56.3%, respectively (p=0.061). CONCLUSION: The necessity of emergency decompression was associated with a poorer prognosis, compared to the no decompression-requiring group. Similarly, a CROSS score of 0 was an independent poor prognostic factor. Among patients who required emergency bowel decompression, those who showed improvement in CAR before and after decompression treatment had a better prognosis than those who did not.