Impact of Tumoral ß2-Adrenergic Receptor Expression on Chemotherapeutic Response and Prognosis in Patients with Advanced Colorectal Cancer.

BACKGROUND: The ß2-adrenergic receptor (ß2-AR) is a therapeutic target for circulatory agonists and exhibits oncogenic activity in several cancers. However, its role in advanced colorectal cancer (CRC) treated using chemotherapy remains unclear. We investigated the potential of ß2-AR as a novel chemosensitivity marker and therapeutic target in inoperable CRC. METHODS: ß2-AR expression was evaluated immunohistochemically in 80 advanced or recurrent CRC cases for which untreated resected specimens were available before systemic chemotherapy implementation. We assessed the relationship among ß2-AR protein expression, clinicopathological factors, therapeutic response, and prognosis. Furthermore, we evaluated the significance of ß2-AR as an in vitro and in vivo therapeutic target using CRC cell lines and a CRC xenograft model treated with the ß-blocker, propranolol, and other anticancer agents. RESULTS: High tumoral ß2-AR expression was associated with shorter progression-free survival and chemotherapeutic resistance in patients treated with oxaliplatin-based regimens and bevacizumab-based regimens. We found no synergistic effect between propranolol and oxaliplatin. However, combined administration of propranolol and bevacizumab induced significant tumor shrinkage in the CRC xenograft model. CONCLUSIONS: ß2-AR is a possible biomarker for chemosensitivity and prognosis in advanced CRC. Repositioning existing ß-blockers could be beneficial for treating CRC resistant to existing treatment regimens.

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.

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.

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.

Retrospective study of online ligation student practice incorporating flipped learning into e-learning.

PURPOSE: Flipped learning has been applied in various fields, including medical professional education. E-learning is compatible with flipped learning; however, it is considered to be unsuitable for providing training on surgical techniques. In this study, we retrospectively examined the ligation performance of online students who underwent training with flipped learning incorporated into e-learning. METHODS: We conducted a retrospective study of the ligation practices of online students at the Department of General Surgery from March 2020 to June 2021. The subjects included 134 fourth- and fifth-year medical students from Gunma University School of Medicine. We conducted mid-term checks on the 8th day of practice and an examination on the 19th day. Two instructors independently evaluated and calculated scores using the original Global Rating Scale of Gunma University. We also conducted a questionnaire survey on the ligation practice of online students. RESULTS: The total average score of the three tasks was 12.4 for Instructor 1 and 12.0 for Instructor 2. All students had a passing score. The questionnaire survey showed that 70% of the students were trained in ligation at the time of the first evaluation. CONCLUSIONS: Our online training materials and training methods enabled the acquisition of ligation skills by students who had not previously received ligation training.

Who needs diverting ileostomy following laparoscopic low anterior resection in rectal cancer patients? Analysis of 417 patients in a single institute.

BACKGROUND: Anastomotic leakage (AL) is one of the most serious complications after low anterior resection (LAR) for rectal cancer, and the significance of diverting stoma to prevent AL is still controversial. The aim of this study is to clarify the potential benefits and safety of diverting ileostomy (DI) following laparoscopic LAR in rectal cancer patients. METHODS: This was a retrospective cohort study of 417 rectal cancer patients who underwent laparoscopic LAR in a single institute. The risk factors for AL and the DI-related morbidity were assessed. RESULTS: DI was performed in 226 patients (54.2%). The incidence rates of symptomatic AL showed no significant difference between patients with and without DI (8.4% vs. 10.0%, p = 0.612). AL requiring a surgical intervention was relatively lower in patients with DI than in those without DI (1.8% vs. 4.7%, p = 0.097). DI construction was an independent risk factor for AL requiring a surgical intervention (OR 3.47, p = 0.041), as was the serum albumin level (p = 0.003), and being male was a relative risk factor (p = 0.058). Focusing on sex, the rate of AL requiring a surgical intervention was significantly different in male (1.7 and 7.9%, p = 0.021) but not in female patients (1.9 and 1.1%, p = 1.000) with and without DI. The DI construction-related morbidity was 9.7%, and no patient required a reoperation. Of 226 patients with DI, 209 (92.5%) underwent stoma closure 118 days (median 30-509 days) after LAR. The stoma closure-related morbidity was 9.1% and 1 patient (0.5%) required a reoperation due to anastomotic leakage. CONCLUSIONS: DI following laparoscopic LAR can decrease the risk of AL, requiring a surgical intervention, especially in male patients with malnutrition. However, due to DI-related morbidity, DI is not recommended in female patients.

[A Case of Laparoscopic Ileocecal Resection for Ascending Colon Cancer with Portosystemic Shunt].

A 72-year-old woman who underwent colorectal endoscopy because of positive fecal occult blood test results was diagnosed with ascending colon cancer.Preoperative CT revealed advanced ascending colon cancer and portosystemic shunt between the ileocecal vein and inferior vena cava.It was necessary to cut the shunt when ileocecal resection was performed. The patient had no symptoms caused by the shunt, and blood examination results showed no liver enzyme abnormalities. Abdominal ultrasound examination revealed no liver cirrhosis and normal blood flow in the portal vein and shunt flow from the ileocecal vein to the inferior vena cava.We assessed that surgery could be safely performed without increasing portal vein pressure.Laparoscopic ileocecal resection was performed by cutting the shunt.Partial jejunum resection was also performed for a mesenteric tumor observed intraoperatively, and pathological findings revealed a lymphangioma.The patient was discharged home on postoperative day 7 without any symptoms, liver enzyme abnormalities, or ascites suggestive of increased portal vein pressure on abdominal ultrasound examination.Colorectal cancer surgery with simultaneous cutting of a portosystemic shunt has rarely been reported.It is necessary to consider the causes of portosystemic shunt and then cut the shunt during surgery when needed.

[Surgical Therapy for Locally Recurrent Rectal Cancer].

We examined 40 cases of locally recurrent rectal cancer surgically treated at our hospital. The sites of recurrence were the anastomosis site(16 cases), pelvic lymph nodes(10 cases), pelvis(10 cases), and perineum(5 cases). Intraoperative complications were confirmed in 5% and postoperative complications in 45% of cases. The R0 resection rate was 60.0%, and positive radial margins were confirmed in 35.0% of cases. Second recurrences were confirmed in 60.0% of cases. The 3-year overall survival rate was 68.7%, and the 3-year relapse-free survival rate was 20.3%. Surgery for locally recurrent rectal cancer was performed relatively safely; however, the R1 resection rate and recurrence rate after surgery were high. R0 resection significantly improved the overall survival rate, and it seems that a treatment strategy to raise R0 resection rate is necessary.

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.

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 case of completely resected cecum cancer with synchronous metastases to the small intestine found in acute appendicitis.

PURPOSE: Risk of malignant tumors increase with age;hence, careful examination of older patients should be consdiered when identifying the causes of acute appendicitis. Here, we report a case of a patient with cecum cancer with synchronous metastases to the small intestine that was found during acute appendicitis. CASE REPORT: A 74-year-old man presented with right lower abdominal pain. Physical examination revealed deep tenderness at McBurney's point. Enhanced computed tomography scan showed an abscess around the enlarged appendix and a thickened cecum wall. Colonoscopy revealed a type 2 tumor in the ileocecal region, and pathological examination of the biopsied specimen revealed adenocarcinoma. Microscopic findings revealed two type 2 tumors in the small intestine, pathologically diagnosed as cecum cancer metastases. The final diagnosis was acute appendicitis caused by cecum cancer with synchronous metastases to the small intestine, pStage ⅣB pT4bN1aM1b. The patient received adjuvant chemotherapy and has currently been disease-free for 24 months. CONCLUSIONS: In prolonged appendicitis among older adults, the possibility of malignancy should be considered during preoperative examination and prior to selecting a treatment plan. Delays in the diagnosis of colorectal cancer and metastases may lead to missed opportunities for complete resection and poor prognosis. J. Med. Invest. 71 : 293-297, August, 2024.

C-reactive Protein/Albumin Ratio Predicts Short-term Postoperative Outcomes and Intraabdominal Abscess Formation in Colorectal Perforation.

Objectives: This study aimed to investigate preoperative factors, including the C-reactive protein (CRP)/albumin ratio (CAR), associated with postoperative outcomes in patients with colorectal perforation who underwent emergency surgery to improve postoperative prognosis. Methods: Twenty-eight consecutive patients who underwent emergency surgery for colorectal perforations were included. We retrospectively investigated the clinical factors associated with their postoperative outcomes. Results: The median patient age was 69.5 years (range, 46.0-93.0 years); 13 patients (46.4%) were males and 15 (53.6%) were females. Colorectal cancer (8 [28.6%]) was the most common cause of colorectal perforation. Postoperative complications were diagnosed in 18 patients (64.3%), with intraabdominal abscess as the most common (6 [21.4%]). Multivariate analysis revealed that CAR (odds ratio, 1.357; 95% confidence interval, 1.056-1.743; p=0.017) was an independent risk factor for postoperative complications. A cutoff value of 4.9 was selected to predict the development of postoperative complications based on the CAR. The proportion of all postoperative complications (p=0.016), postoperative complications of Clavien-Dindo classification grade II or higher (p=0.002), and death during hospitalization (p=0.049) were significantly higher in the group of patients with CAR ≥ 4.9 than in those with CAR < 4.9. Additionally, intraabdominal abscess (p=0.049) was significantly higher in the group of patients with a non-improvement in CAR on postoperative day 3 than in those with an improvement in CAR on postoperative day 3. Conclusions: Perioperative CAR could be a predictor of perioperative complications and death and might be useful in improving the postoperative prognosis of colorectal perforations.

Risk Factors of Poor Outcomes After Colorectal Cancer Surgery for Patients With Severe Comorbidities.

BACKGROUND/AIM: An increasing number of patients with complicated systemic comorbidity can undergo colorectal cancer (CRC) surgery. Such patients have a high risk of developing poor postoperative outcomes. This study aimed to identify preoperative factors, including nutritional and sarcopenia statuses, leading to poor postoperative outcomes in patients with severe systemic comorbidities. PATIENTS AND METHODS: This study included 114 patients who underwent radical CRC resections and had American Society of Anesthesiologists Physical Statuses ≥3. We retrospectively analyzed the relationships between clinical factors, postoperative complications (within 28 days postoperatively and Clavien-Dindo classification grade ≥2), length of hospital stay, discharge destination, and overall survival (OS). RESULTS: The median patient age was 74.5 years (range=41.0-93.0 years). Thirty-six patients had postoperative complications (31.6%), and the risk factors in the multivariate analyses were rectal cancer and preoperative nutritional disorders with Prognostic Nutritional Index ≤40. In patients with nutritional disorders, the postoperative hospital stay was longer, and a higher (but not statistically significant) percentage were not discharged home. Moreover, the independent factors for OS identified in the multivariate analyses were body mass index (BMI) and hemodialysis. CONCLUSION: In patients with CRC and severe systemic comorbidities, those with Prognostic Nutritional Index ≤40 have a high risk of developing postoperative complications, leading to a prolonged postoperative hospital stay and possibly preventing discharge home. Additionally, among these patients, OS was poor in those with low BMI or preoperative hemodialysis.

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.

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.

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.

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.

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.

Risks and Outcomes of Early Dose Reduction in Adjuvant CAPOX Therapy for Colorectal Cancer.

BACKGROUND/AIM: Adjuvant capecitabine and oxaliplatin (CAPOX) therapy is standard strategy for colorectal cancer with risk of recurrence. Early dose reduction (EDR) of CAPOX therapy is commonly used in real-world practice. However, there is limited evidence regarding the effectiveness of CAPOX for patients who had EDR. Therefore, this study aimed to clarify the risks of EDR and its effect on long-term outcomes and body composition factors. PATIENTS AND METHODS: Patients who received CAPOX therapy after radical surgery for colorectal cancer between June 2013 and December 2021 were included. EDR was defined as dose reduction within four courses of CAPOX therapy. Body composition factors were measured for 1 year following surgery to determine the EDR effects. RESULTS: Eighty-four patients were included; 35 (42%) of them had EDR. The multivariate analysis revealed that underweight [odds ratio (OR)=4.95, 95% confidence interval (CI)=1.13-21.7, p=0.03] was a risk factor for EDR. Relapse-free survival (RFS) was significantly better in the non-EDR group (p=0.01). The 5-year RFS rates for the non-EDR and EDR groups were 88.7% and 65.4%, respectively. The multivariate analysis revealed that age >65 years [hazard ratio (HR)=3.97; 95% CI=1.16-13.62, p=0.03] and EDR (HR=7.62; 95% CI=1.71-33.91, p=0.005) were associated with poorer RFS. The 1-year body composition analysis revealed decreases in all factors in the EDR group. CONCLUSION: Preoperative underweight status was associated with EDR, which resulted in decreased RFS and body composition factors when compared with the non-EDR group. Therefore, avoiding EDR and early nutritional intervention after EDR may improve outcomes.

A Mature Tertiary Lymphoid Structure with a Ki-67-Positive Proliferating Germinal Center Is Associated with a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer.

Tertiary lymphoid structures (TLSs) are complex lymphocyte clusters that arise in non-lymphoid tissues due to inflammation or cancer. A mature TLS with proliferating germinal centers is associated with a favorable prognosis in various cancers. However, the effect of TLS maturity on advanced colorectal cancer (CRC) remains unexplored. We analyzed the significance of TLS maturity and tumor Ki-67 expression in surgically resected tumors from 78 patients with pathological T4 CRC. Mature TLS was defined as the organized infiltration of T and B cells with Ki-67-positive proliferating germinal centers. We analyzed the relationship between TLS maturity and intratumoral immune cell infiltration. Mature TLS with germinal center Ki-67 expression was associated with microsatellite instability and improved survival; however, high tumor Ki-67 expression was associated with poor survival in the same cohort. Multivariate analysis identified the absence of mature TLS as an independent predictor of poor post-recurrence overall survival. Intratumoral infiltration of T lymphocytes and macrophages was significantly elevated in tumors with mature TLS compared to those lacking it. High Ki-67 levels and absent mature TLS were identified as poor prognostic factors in advanced CRC. Mature TLS could serve as a promising marker for patients at high-risk of CRC.