Temporal dynamics of RAS mutations in circulating tumor DNA in metastatic colorectal cancer: clinical significance of mutation loss during treatment.

PURPOSE: In metastatic colorectal cancer (mCRC), RAS mutation loss may occur during the standard-of-care regimen. In this study, we aimed to investigate the temporal dynamics of the RAS gene and its clinical significance. METHODS: This was a retrospective, single-center study that included 82 patients with tissue RAS-mutant (RAS-MT) mCRC who underwent circulating tumor DNA (ctDNA) RAS monitoring between January, 2013-April, 2023. Patients were analyzed for the rate of change over time to acquired RAS mutation loss (aRAS-ML) and clinicopathological factors. The prognostic relevance of mutation loss was assessed. RESULTS: aRAS-ML was detected in 33 (40.2%) patients, 32 of whom had a mutation loss in the first ctDNA RAS assay. Patients with a RAS mutation detected in the first assay had a median time of 8 months until the second ctDNA RAS assay, with 4.5% cases newly converted to aRAS-ML; no new conversions were detected at the third assay. The aRAS-ML group exhibited more single-organ metastases in the target organ during ctDNA measurement (aRAS-ML: 84.8% vs. RAS-MT: 59.2%, p = 0.02). Of the 33 patients with aRAS-ML, seven (21.2%) received anti-epidermal growth factor receptor (EGFR) therapy, with a median progression-free survival of 8 months. Multivariate analysis revealed that persistent ctDNA RAS mutation was an independent prognostic factor for overall survival (hazard ratio: 2.7, 95% confidence interval: 1.1-6.3, p = 0.02). CONCLUSION: The rate of ctDNA mutation loss in patients with RAS-MT mCRC decreases over time. Therefore, using a ctDNA RAS assay early in treatment will assist in challenging the use of EGFR regimens.

Prospective observational study comparing the perioperative outcomes of laparoscopic colectomy with or without epidural anesthesia: the Kanagawa Yokohama Colorectal Cancer Study Group (KYCC) 1806.

PURPOSE: There have been no adequate comparisons of the efficacy, safety, and efficiency of analgesia after laparoscopic colorectal resection (LAC), with and without epidural anesthesia (EDA). METHODS: This was a multicenter prospective observational study of patients undergoing LAC. The primary end point was the mean visual analog scale (VAS) score on postoperative days (PODs) 1-7. The secondary end points were the highest VAS, complication rate, days to first ambulation and fatigue, length of hospital stay, and time to commencement of surgery. RESULTS: We compared an EDA group (Group E, n = 48) and a no-EDA group (Group O, n = 48) after matching. The mean VAS was not significantly different between the groups (28.7 vs. 30.1, p = 0.288). On assessing the secondary end points, the highest VAS was not significantly different between the groups. In fact, the VAS was lower in Group E only on POD 2. There was no difference in the incidence of complications, the time to first postoperative evacuation was shorter in Group E, and postoperative hospitalization was similar. The time to surgery was shorter in Group O. CONCLUSION: These results suggest that LAC without EDA is a feasible option, but with the early and regular use of adjunctive measures to provide more stable analgesia.

Clinical significance of the post/preoperative anti-p53 antibody ratio in predicting the prognosis of patients with colorectal cancer after curative surgery and its usefulness in combination with carcinoembryonic antigen.

[Introduction] Anti-p53 antibody (p53Ab) is useful for monitoring colorectal cancer (CRC) recurrence. We retrospectively analyzed the clinical impact of p53Ab ratio (p53R) before and after surgery to predict recurrence in patients with CRC. [Methods] In total, 1,223 patients with stage I-III CRC who underwent curative surgery between January 2005 and December 2019 were enrolled in this retrospective study. In patients with elevated p53Ab levels, p53R was calculated by measuring p53Ab levels within one month preoperatively and three months postoperatively. The optimal p53R level was determined, and its relationship with clinicopathological factors and prognosis was examined. We also evaluated the efficacy of the combination of p53R and preoperative carcinoembryonic antigen (CEA) values. [Results] Overall, 341 patients (27.9%) showed elevated p53Ab levels. Preoperative p53Ab levels were significantly associated with tumor location, lymphatic invasion, and venous invasion. The p53R level was significantly higher in patients with recurrent disease. Patients with high p53R levels had significantly shorter relapse-free survival (RFS) than those with low p53R levels (p < 0.001). When p53R was combined with preoperative CEA values, specificity improved to 0.97, with an accuracy of 0.88. [Conclusion] In patients with CRC and elevated preoperative p53Ab levels, p53R expression may be prognostically useful after radical resection. Furthermore, the combination of p53R and preoperative CEA levels may be useful for postoperative follow-ups.

A Case of Colon Cancer with Extramural Tumor Deposits in the Main Lymph Node Area: A Case Report.

A 72-year-old man with type 2 sub-circumferential tumors in the descending colon and two nodules around the pedicle of the inferior mesenteric artery (main lymph node area) underwent laparoscopic left hemicolectomy with D3 lymphadenectomy. Two lymph nodes around the inferior mesenteric artery pedicle were completely excised. Pathological examination revealed a moderately differentiated tubular adenocarcinoma. Nodules were only found in the main lymph node area, and no lymph node structures were observed in these nodules. These tumor deposits (TDs) may be extramural TDs without lymph node structure or lymph node skip metastasis. The presence of TDs in colorectal cancer is associated with an adverse prognosis, and the requirement of chemotherapy in such cases should be examined. Therefore, it is important to correctly recognize TDs and categorize the disease into a high- or low-risk group within stage III. We report this case because it is necessary to review the definition of TDs, and the assessment of extramural TDs remains controversial.

Short- and long-term outcomes of transanal decompression tube and self-expandable metallic stent for obstructive colorectal cancer based on a multicenter database (KYCC2110).

AIM: There are well-known methods for decompressing the colorectal tract before surgery, including transanal decompression tubes (TDT) and self-expanding metallic stents (SEMS). This study aimed to compare the short and long-term results in patients with malignant large bowel obstruction in whom TDT or SEMS were placed before surgery. METHODS: This retrospective observational study enrolled 225 patients with malignant large bowel obstruction in whom TDT or SEMS were placed preoperatively and underwent R0 resection between 2008 and 2020. One-to-two propensity score matching was performed according to patient characteristics. Short- and long-term outcomes were compared. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were the overall survival (OS) and postoperative complication rate. RESULTS: Fifty-seven patients in the TDT group and 114 in the SEMS group were matched. The 3-year RFS rates were 66.7% in the TDT group and 69.9% in the SEMS group (p = 0.54), and the 3-year OS rates were 90.5% in the TDT group and 87.1% in the SEMS group (p = 0.52). No significant differences in the long-term results were observed between the two groups. Regarding short-term results, the SEMS group had significantly fewer stoma construction (p = 0.007) and shorter postoperative hospitalization (p < 0.001). The incidence of postoperative complications (grade ≥ 2) was significantly lower in the SEMS group (p = 0.04). CONCLUSION: No significant differences in the long-term results were observed between the TDT and SEMS group. The SEMS showed significant usefulness in terms of improving short-term outcomes.

Analysis of surgical outcomes of laparoscopic versus open surgery for locally advanced mid-transverse colon cancer.

PURPOSE: This study compared the surgical outcomes between laparoscopic colectomy (LC) and open colectomy (OC) for mid-transverse colon cancer (MTC). METHODS: This multicenter retrospective study compared the short- and long-term surgical outcomes for patients with advanced MTC (T3 and T4 with or without nodal involvement) who underwent LC or OC between January 2008 and December 2019 using a propensity score-matched analysis. RESULTS: A total of 177 patients with advanced MTC were enrolled. After matching, 58 cases for the OC and LC groups were selected. No significant differences in age, sex, tumor progression, or procedure type (extended resection or segmental resection) existed between groups. The LC group had significantly less blood loss (20 mL vs. 50 mL, p=0.048) and a shorter postoperative hospital stay (8 days vs. 12 days, p<0.001) than the OC group. Postoperative complications (Clavien-Dindo grade ≥ 2) occurred in 27.6% and 25.9% of the OC and LC groups respectively (p=1). Three patients (5.2%) and one patient (1.7%) of the OC and LC groups respectively developed anastomotic leakage (p=0.62). Re-operation was required in five patients (8.6%) in the OC group and one patient (1.7%) in the LC group (p=0.21). No surgery-related deaths occurred in either group. The 3-year overall survival rates (stage II: LC 100% vs. OC 92.8%, p=0.15; stage III: 88.9% vs. 84.3%, p=0.88, respectively) were similar between the two groups. CONCLUSION: LC is a minimally invasive technique with lesser blood loss, shorter postoperative hospital stays, and oncologic equivalence to OC. Hence, LC is useful for MTC treatment. TRIAL REGISTRATION: UMIN000042676.

Evaluating prognostic significance of preoperative C-reactive protein to albumin ratio in older patients with pathological stage II/III colorectal cancer.

Purpose: This study was performed to evaluate the prognostic value of preoperative C-reactive protein to albumin ratio (CAR) in older patients with colorectal cancer (CRC) undergoing curative resection. Methods: We retrospectively analyzed 244 older patients (aged 75 years or higher) with pathological stage II/III CRC who underwent curative surgery between 2008 and 2016. The optimal value of CAR was calculated and its correlation with the clinicopathological factors and prognosis was examined. Results: The optimal cutoff value of the CAR was 0.085. High preoperative CAR was significantly associated with high carcinoembryonic antigen levels (P=0.001), larger tumor size (P<0.001), and T pathological (pT) factor (P=0.001). On multivariate analysis, high CAR was independent prognostic factor for relapse-free survival (P=0.042) and overall survival (P=0.001). Conclusion: Preoperative elevated CAR could be considered as an adverse predictor of both relapse-free survival and overall survival in older patients with CRC undergoing curative surgery.

Laparoscopic extended right hemicolectomy versus laparoscopic transverse colectomy for mid-transverse colon cancer: a multicenter retrospective study from Kanagawa Yokohama Colorectal Cancer (KYCC) study group.

PURPOSE: The laparoscopic surgery approach for mid-transverse colon cancer (MTC) varies depending on tumor characteristics and the guidelines implemented by each surgeon; the optimal surgical procedure for MTC has not been established. This study aimed to compare the surgical outcomes of laparoscopic extended right hemicolectomy (Lap-ERHC) and laparoscopic transverse colectomy (Lap-TC) for MTC. METHODS: This was a multicenter, retrospective study. We surveyed eight hospitals, by questionnaire, on MTC surgery policies and retrospectively compared the short- and long-term surgical outcomes for patients with MTC who underwent Lap-ERHC or Lap-TC between January 2008 and December 2019. RESULTS: A total of 129 patients were enrolled, of whom 35 underwent Lap-ERHC and 94 underwent Lap-TC. There were no significant differences in tumor progression between the two groups. Operation time was significantly longer (202 min vs. 185 min, p = 0.026). We observed a higher complication rate (≥ grade 3) in the Lap-ERHC group than in the Lap-TC group (11.4% vs. 3.2%, p = 0.086). Three patients (8.6%) who underwent Lap-ERHC developed anastomotic leakage; none of the patients who underwent Lap-TC had this complication (p = 0.018). The 3-year overall survival rates (stage I: 100% vs. 91.9%, p = 0.64; stage II: 100% vs. 95.5%, p = 0.46; stage III: 100% vs. 88.2%, p = 0.91, respectively) were similar between the two groups. CONCLUSION: Lap-ERHC for MTC has the same long-term outcomes as Lap-TC. However, Lap-ERHC for MTC has a higher complication rate. Therefore, Lap-TC may be recommended for patients with MTC. TRIAL REGISTRATION: UMIN000042674.

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.

Modified Glasgow Prognostic Score and Carcinoembryonic Antigen Predict Poor Prognosis in Elderly Patients with Colorectal Cancer.

OBJECTIVE: To investigate the prognostic values of the preoperative modified Glasgow Prognostic Score (mGPS) and carcinoembryonic antigen (CEA) alone and combined in elderly patients with colorectal cancer (CRC) planning to receive curative surgery. METHODS: We retrospectively analyzed 130 elderly patients (aged ≥80 years) with CRC who received curative surgery between 2008 and 2016. The preoperative mGPS and CEA levels were calculated. RESULTS: Elevated preoperative mGPS or CEA level was significantly associated with shorter relapse-free survival (p = 0.005, both) and cancer-specific survival (p = 0.011 and p < 0.001, respectively). Combined use of these two factors improved the predictive accuracy for tumor recurrence relative to that of either factor. CONCLUSION: Both mGPS and CEA were independent prognostic factors of CRC in elderly patients receiving curative surgery, but their combination was more accurate.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

Utility of Preoperative Imaging for Predicting Pelvic Lateral Lymph Node Metastasis in Lower Rectal Cancer.

This study aimed to investigate the diagnostic power of preoperative imaging for lateral pelvic lymph node (LPLN) metastasis. A total of 79 patients with advanced lower rectal cancer were preoperatively examined with pelvic enhanced computed tomography and underwent primary resection and LPLN dissection (LPLD) from 2007 to 2014 in our institute. The maximum LPLN was selected to be measured in both the long- and short-axis diameters by picture archiving and communication system (PACS) and was compared with the histopathological results. Receiver operating characteristic (ROC) curves were used to identify the optimal cut-off scores, and we evaluated the accuracy of the thresholds. Twenty-one patients (26.6%) had LPLN metastasis. In the ROC analysis, the criterion of 7.6 mm or larger in the long-axis diameter was used as the optimal threshold for metastasis (area under the curve (AUC) = 0.938) and the criteria of 5.5 mm or larger in the short axis (AUC = 0.946). On the basis of these cut-off scores, the criteria in the long axis represented 95.2% sensitivity, 91.5% specificity, 83.3% positive predictive value (PPV), 98.2% negative predictive value (NPV), and 93.7% accuracy. In contrast, there was 95.2% sensitivity, 89.7% specificity, 76.9% PPV, 98.1% NPV, and 91.1% accuracy in the short axis. Preoperative PACS imaging was considered an optimal tool for diagnosing LPLN metastasis in patients with advanced lower rectal cancer. It is suggested to become the index for considering LPLD adaptation.

Beppu's Nomogram Score Is an Independent Prognostic Factor for Colorectal Liver Metastasis Receiving Perioperative Chemotherapy and/or Targeted Therapy.

BACKGROUND/AIM: We investigated the impact of Beppu's nomogram on colorectal liver metastasis in patients receiving perioperative chemotherapy and/or targeted therapy. PATIENTS AND METHODS: This study included 43 patients who underwent primary hepatic resection for colorectal liver metastasis at the Kanagawa Cancer Center from June 2006 to March 2011. The patients were classified as having a Beppu's nomogram score ≤9 (low-risk group) or ≥10 (high-risk group). The risk factors for the disease-free survival (DFS) were identified. RESULTS: The respective DFS rates at 1, 2, and 3 years after surgery were 72.0%, 43.3%, and 17.3% in the low-risk group and 27.8%, 16.7%, and 8.3% in the high-risk group, the difference being significant (p=0.009). The multivariate analysis showed that Beppu's nomogram score ≥10 was a significant independent risk factor for the DFS. CONCLUSION: Beppu's nomogram score was an independent prognostic factor for colorectal liver metastasis in patients receiving perioperative chemotherapy and/or targeted therapy. Thus, Beppu's nomogram might be a useful tool for predicting the risk of recurrence after hepatectomy, even in the era of newly-developed chemotherapy.

[The Strategy for the Treatment of Perforated Gastric Cancer].

Perforated gastric cancer reported to be relatively rare and to have a poor prognosis. This study examined 9 patients with perforated gastric cancer. Two-thirds of the patients were male and the median age was 69 years. The timing of the diagnosis of gastric cancer was preoperative clinical findings in 4 cases, intraoperative surgical findings in 3 cases, and postoperative examination in 2 cases. The depths of tumor invasion were T3 in 3 cases, T4a in 4 cases, and T4b in 2 cases and 5 patients were Stage Ⅳ. Four patients underwent palliative gastrectomy and only 1 patient underwent curative(R0)gastrectomy. Four patients underwent repair surgery, 2 of which underwent omental patch repair during the initial surgery. One of patients with omental patch repair received 2-stage curative gastrectomy; the other patient received chemotherapy after recovering from acute peritonitis. The median overall survival was 17.9 months and the prognosis was favorable in cases with curative resection or chemotherapy. For patients with perforated gastric cancer, if curative resection cannot be expected, the initial surgery should be directed toward the treatment of peritonitis and radical oncological surgery or systemic chemotherapy should be planned following patient recovery.

[Clinical Outcomes of Palliative Radiation Therapy for Gastric Cancer Bleeding].

Only a few studies have been conducted regarding the palliative radiation therapy(RT)for gastric cancer(GC)bleeding. Data of 9 patients with gastric cancer requiring blood transfusions due to gastric bleeding who were treated with RT were reviewed. All patients were men with a median age of 83(range, 70-91)years. The clinical stage was ⅡB in 2 patients, Ⅲin 1, ⅣA in 1, and ⅣB in 5. Performing gastrectomy was difficult in 4 patients with distant metastasis or tumor invasion to adjacent organ, 3 with poor performance status, and 2 with advanced age. The median hemoglobin levels before RT was 6.0 (range, 3.3-7.7)g/dL, and all patients received blood transfusions before RT. Seven patients received 30 Gy RT and 2 patients received 50 Gy. Two patients received concurrent chemotherapy. A total of 2 hematological and 4 non-hematological treatment-related adverse events occurred. All patients improved conservatively. Hemorrhage occurred in 8 patients, except for 1. Of the 8 patients who responded to RT, 1 had rebleeding on day 81. The median rebleeding-free survival time from the beginning of RT was 125(range, 21-421)days. Palliative radiation therapy was useful for bleeding control in nonresectable gastric cancer.

[Short-Term Outcomes of Laparoscopic-Assisted Total Gastrectomy Using the Endoscopic Purse-String Suture Instrument ENDO-PSI].

Laparoscopic-assisted total gastrectomy(LATG)has several complications early during the introduction of the procedure, so a careful approach is necessary. In this study, we evaluated short-term outcomes after LATG at our hospital. From 2014 to 2017, 21 patients underwent LATG using ENDO-PSI. A 6-cm midline incision was made at the epigastrium, and the abdominal esophagus was transected using ENDO-PSI. The anvil head was fixed with extracorporeal ligation, and an end loop was added to the proximal side of the first suture. Reconstruction was performed with the Roux-en-Y method. The jejunojejunal anastomosis was performed extracorporeally, and esophagojejunostomy was performed using a circular stapler through the small incision. There were 15 men and 6 women, with a mean age of 74 years. The mean operation time was 296 min, and volume of blood loss was 75 mL. The median fasting period was 3(3-10)days, and the postoperative hospitalization period was 12(8-28)days. The postoperative complications were Grade Ⅱ in 4 patients and Grade Ⅲ in 1 patient. The complication due to esophagojejunostomy was anastomotic leakage in 1 patient, while no anastomotic stenosis was found. LATG using ENDO-PSI can be safely performed.

[Short-Term Comparison between Trans-Anal Ileus Tube and Self-Expandable Metallic Stent for Obstructive Colorectal Cancer].

The aim of this study was to compare the outcome of using trans-anal ileus tube and self-expandable metallic stent(SEMS) for obstructive colorectal cancer. METHODS: Between 2014 and 2018, 14 patients received trans-anal ileus tube placement (group I)and 34 received SEMS insertion as bridge to surgery(BTS)and underwent primary resection. RESULTS: The technical success rate was 100%in both groups, and the clinical success rate was 85.7%(12/14 cases)in group I and 91.2%(31/34 cases)in group S. In group S, the CROSS score significantly improved, the rates of stoma construction and postoperative complications were significantly lower, and the period until oral intake and hospital discharge was significantly short. CONCLUSION: SEMS insertion is more effective than trans-anal ileus tube placement in terms of short-term outcome.

[Clinical Assessment of 33 Patients with Perforated Colorectal Cancer Who Underwent Surgery].

The aim of this study was to clarify the risk factors of severe postoperative complications and prognostic factors in patients who underwent emergent surgery for colorectal cancer perforation. ASA-PSB3 and Mannheim Prognostic Index(MPI)B27 were selected as the independent risk factors for postoperative severe complications on multivariate analysis. Moreover, severe postoperative complications and non-curative surgery were selected as the independent factors of poor prognosis.

[Appropriate Range of Lymph Node Dissection in Elderly Patients with Colorectal Cancer].

In elderly patients, surgical procesure is decided considering the general condition and surgical invasion. The aim of this study was to clarify the appropriate rage of lymph node dissection for elderly colorectal cancer patients. One hundred forty one colorectal cancer patients aged 75 years or more, who underwent R0 colorectal resection with D2 or D3 lymph node dissection in clinical T3/T4 or clinical N+, were enrolled in this study. The patients whose tumor located in the rectum below the peritoneal reflection(Rb)were excluded. Five-year overall survival(OS)rate and disease specific survival(DSS)rate were 79.1% and 89.4%, respectively. More than 2 preoperative co-morbidities and macroscopic type 3-5 were independent prognostic factors in OS, whereas the rage of lymph node dissection was not risk factor. When comparing the outcomes of D2 and D3 dissections by age, D3 dissection was better tendency in DSS in patients aged under 80, however, D2 dissection was better tendency in patients aged 80 or more. In elderly colorectal cancer patients, there was no difference in prognosis between D2 and D3 dissection, and especially in patients aged 80 years or more, D2 might be sufficient if R0 resection was possible.

Combining the Glasgow Prognostic Score and Serum Carbohydrate Antigen 19-9 Level Improves the Ability to Predict Early Recurrence in Resected Pancreatic Cancer Patients Receiving Adjuvant Gemcitabine.

AIM: The aim of this study was to confirm the predictive/prognostic value of the preadjuvant Glasgow Prognostic Score (GPS) and carbohydrate antigen (CA) 19-9 level in pancreatic cancer patients receiving adjuvant gemcitabine (GEM) after surgery. PATIENTS AND METHODS: A total of 67 resected pancreatic cancer patients, treated with adjuvant GEM, were included. The GPS and CA19-9 level were calculated prior to administration of adjuvant therapy and were found to correlate with the outcomes and rate of early recurrence. RESULTS: An elevated preadjuvant GPS or CA19-9 level was significantly associated with a shorter overall survival (OS) (p=0.003 and p<0.001, respectively). Either an elevated GPS or CA19-9 level predicted early recurrence and the combined use of these two factors improved the ability to predict early recurrence, with a specificity and accuracy up to 0.958 and 0.821, respectively. CONCLUSION: Both an elevated preadjuvant GPS and CA19-9 level, when used alone, are significant predictors of poor outcomes in pancreatic cancer patients receiving adjuvant GEM. The combined use of these parameters improves the ability to predict early recurrence in such patients.