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 1 month preoperatively and 3 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 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.

C-reactive protein-to-albumin ratio as a risk factor for anastomotic leakage after anterior resection for rectal cancer with intraoperative use of indocyanine green fluorescence imaging.

INTRODUCTION: Indocyanine green fluorescence imaging (ICG-FI) reduces anastomotic leakage (AL) in rectal cancer surgery. However, no studies investigating risk factors for anastomotic leakage specific to the group using ICG-FI have ever previously been conducted. The purpose of this retrospective multicenter study was to ascertain the risk factors for AL in the group using ICG-FI. METHODS: A total of 638 patients who underwent laparoscopic or robotic anterior resection for rectal cancer between April 2018 and March 2023 were included in this study. Patients were divided into two groups: the ICG-FI group (n = 269) and the non-ICG-FI group (n = 369) for comparative analysis. The effects of clinicopathological and treatment-related factors on AL in the ICG-FI group were evaluated using both univariate and multivariate analyses. RESULTS: The incidence of AL in the ICG-FI group was 4.8%. Although there was no significant difference in the incidence of AL between the two groups, it was observed to be lower in the ICG-FI group. A multivariate analysis revealed a preoperative C-reactive protein-to-albumin ratio (CAR) ≥ 0.049 (odds ratio, 3.73; 95% confidence interval, 1.01-13.70; p = 0.048) as an independent risk factor for AL in the ICG-FI group. CONCLUSIONS: In this study, CAR was the only identified risk factor for AL in the ICG-FI group. It was suggested that CAR could be a criterion for early surgical intervention, prior to the escalation of risks, or for considering interventions such as diverting stoma creation.

[A Case of Meningeal Carcinomatosis following Esophagogastric Junction Cancer Surgery].

In a 79-year-old man, upper gastrointestinal endoscopy and CT revealed an entire circumferential type 3 tumor with stenosis from the lower thoracic esophagus to the abdominal esophagus. He was diagnosed with esophageal adenocarcinoma and underwent middle and lower esophageal resection and 2 regional lymph node dissections. The postoperative pathological diagnosis was poorly differentiated adenocarcinoma, pT3N0M0, pStage ⅡA esophagogastric junction cancer(Siewert type Ⅱ). The patient was followed-up without postoperative adjuvant chemotherapy, following the Japanese Gastric Cancer Treatment Guidelines 2021(6th edition). Six months postoperatively, contrast-enhanced CT revealed multiple lymph node, small intestinal mesenteric, and left adrenal metastases, and SOX therapy was initiated. After 4 courses of SOX therapy, the patient was brought to the emergency room and admitted with anorexia and weakness, and consciousness disorder was observed on the next day. Contrast-enhanced MRI of the head was indicative of meningeal carcinomatosis, and cytological examination of the spinal fluid revealed adenocarcinoma, which was diagnosed as meningeal carcinomatosis from esophagogastric junction carcinoma. Subsequently, his consciousness disorder worsened, and he died on the 9th day of hospitalization. We report a rare case of meningeal carcinomatosis following esophagogastric junction cancer.

[A Case of Colon Metastasis after Surgery for Left Renal Pelvis Cancer].

The patient was a 73-year-old man. He was diagnosed with left renal pelvic carcinoma(papillary urothelial carcinoma, pT3aN0M0, Stage Ⅱ)at the age of 69. Left nephroureterectomy and partial cystectomy were performed at our hospital. At the age of 71, he was diagnosed with a recurrent bladder tumor and underwent radical cystectomy and ureteroenterostomy at a different hospital. At the age of 73, he visited our hospital with abdominal pain. Computed tomography(CT)revealed wall thickening of the descending colon and dilation of the oral tract. Emergency colonoscopy was performed. He was diagnosed with intestinal obstruction due to descending colon cancer. Colonoscopy revealed a circumferential type 2 lesion in the descending colon that was completely stenosed. Colonic stent placement was performed. A tumor biopsy confirmed the diagnosis of micropapillary adenocarcinoma. The preoperative diagnosis was descending colon cancer cT4aN2aM0, cStage Ⅲc. One month after stent placement, an open segmental resection of the descending colon with D2 dissection was performed. Immunostaining of the specimen showed CK7(+)and CK20(-), and the postoperative diagnosis was a recurrence of left renal pelvic carcinoma in the descending colon. We report a rare case of renal pelvic carcinoma that recurred in the descending colon 4 years after initial surgery.

[A Case of Distal Gastrectomy and Left Segmentectomy for Hepatic Invasion of Gastric Cancer].

A 66-year-old male came to our hospital because of occult blood in stool and anemia. The patient was diagnosed as unresectable advanced gastric cancer,( ML/Less, type 2, tub2, cT4b[liver], cN+, cM0, cStage Ⅳ, HER2 negative). He was given oxaliplatin plus S-1 therapy. In the 3rd course of chemotherapy, he had severe anemia, and active bleeding from the tumor. To control the bleeding he underwent distal gastrectomy, lateral segmentectomy of the liver, and S4 partial hepatectomy. The patient underwent adjuvant chemotherapy with docetaxel plus S-1. Three months after surgery, lymph nodes recurrence was observed. He underwent second-line therapy with paclitaxel and ramucirumab. Seven months after surgery, lymph nodes recurrence was increased. He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

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.

Comparison of safety and efficacy of fluorouracil + oxaliplatin + irinotecan (FOLFOXIRI) and modified FOLFOXIRI with bevacizumab for metastatic colorectal cancer: data from clinical practice.

PURPOSE: The efficacy of fluorouracil + oxaliplatin + irinotecan with bevacizumab (FOLFOXIRI + BV) has been verified for metastatic colorectal cancer (mCRC). In clinical practice, the original (O-FOLFOXIRI + BV) and modified dose settings (M-FOLFOXIRI + BV) are adopted for Asian patients. We aimed to compare the real-world efficacy and safety of these two regimens. METHODS: This retrospective cohort study reviewed clinical data of all consecutive mCRC patients treated with FOLFOXIRI + BV at a cancer centre in Japan. One hundred patients were divided into two groups: one that received O-FOLFOXIRI + BV (group O, n = 30) and another that received M-FOLFOXIRI + BV (group M, n = 70). Progression-free survival (PFS) was set as the primary endpoint, with overall survival (OS), overall response rate (ORR), and safety as secondary endpoints. RESULTS: PFS was superior in group M (median PFS; 8.7 vs. 11.5 months, P = 0.098). The use of O-FOLFOXIRI + BV emerged as an independent risk factor of poor PFS (hazard ratio = 2.155, P = 0.012). Both ORR (43.3 vs. 65.7%, P = 0.047) and OS (median OS; 17.9 vs. 27.0 months, P = 0.127) were more favourable in group M. Grade ≥ 3 adverse events were more frequently observed in group O (90 vs. 74.3%, P = 0.108), whereas dose intensity was higher in group M because a shorter duration was required for cytotoxic drug administration (2.9 vs. 2.6 weeks/course, P = 0.051) in the induction term. CONCLUSION: We found that M-FOLFOXIRI + BV had more favourable efficacy and safety than O-FOLFOXIRI + BV, which may be a better fit for Asian patients and can be potentially used as an alternative for upfront chemotherapy for mCRC.

Prospective analysis of tumor spread to the small bowel mesentery in cases of right-sided colon cancer.

PURPOSE: Guidelines advocate minimal ileal resection when right hemicolectomy is performed for right-sided colon cancer. The practice, thought to prevent malabsorption syndrome, does not appear to foster local recurrence. Little evidence based on rigorous study exists, however. To understand the pattern of lymphatic spread of right-sided colon cancer toward the small bowel and thus determine the appropriate margin size, we prospectively investigated anatomical distribution of lymph nodes (LNs) in the small bowel mesentery and of metastasis to these nodes in patients with right-sided colon cancer treated by such surgery. METHODS: In each case, the mesenteric specimen, which had been dissected along the ileocolic vessels and included intermediate LNs, was divided into 2 areas: that 0-3 cm from the vessel pedicle (area 1) and that 3-5 cm from the pedicle (area 2). The peri-intestinal mesentery was cut into 9 segments. RESULTS: Ninety-one patients were included in the study. Overall, 3366 LNs were dissected. Four hundred fifty-three of these LNs were located in area 1 (90 cases), and 15 (3.3%) were metastatic. Only 63 LNs were located in area 2 (34 cases; average of 0.69 per patient); none was metastatic. Overall, 269 LNs were found in the small bowel mesentery (in 56 of the 91 patients). Only 4 were positive (3 cases), and all were within 5 cm of the ileocecal valve. CONCLUSION: Our data indicate that a surgical margin 3 cm from the ileocecal pedicle and a short (5 cm) ileal margin are oncologically reasonable for effective right hemicolectomy.

[The Efficacy of D3 Lymph Node Dissection in Elderly Patients with Colorectal Cancer].

The effectiveness of lymph node dissection tends to be reduced clinically in elderly patients with colorectal cancer because of physical limitations, such as comorbidities and organ dysfunction. We investigated the influence of the level of lymph node dissection on the prognosis of elderly patients with colorectal cancer. A total of 137 patients with pT2 or more-advanced tumors or lymph node metastasis were retrospectively studied. The 5-year overall survival(OS)andrelapse free survival(RFS) rates were 74.1% and 63.9%, respectively. Lymph node dissection was an independent prognostic factor in the examination of prognostic factors of OS. In the propensity-matchedcohort, the 5-year OS rates were 87.2% and5 8.2%(p=0.02), and the 5-year RFS rates were 77.8% and4 6.4%(p=0.03)in the D3 andred ucedgroups, respectively. The D3 group hada significantly better prognosis than the reduced group. D3 lymph node dissection might contribute to the improvement of prognosis in elderly people with colorectal cancer.

[A Case of Solitary Adrenal Metastasis from Rectal Cancer Treated by Adrenalectomy after Preoperative Chemotherapy].

Adrenal metastasis from colorectal cancer occurs in the presence of multiple synchronous metastases at other sites. We report a case of heterochronous solitary adrenal metastasis from rectal cancer. A 55-year-old man underwent anterior resection with D3 lymph node dissection for rectal cancer. The pathological stage of the tumor was III b, and adjuvant chemotherapy with mFOLFOX6 was administered for 6 months. Eighteen months after surgery, abdominal computed tomography(CT) revealed right solitary adrenal metastasis. His tumor marker levels were considerably elevated; therefore, he received preoperative chemotherapy with FOLFIRI plus bevacizumab(BV). After preoperative chemotherapy, his tumor marker levels decreased, and CT and FDG-PET/CT did not uncover any other metastatic lesions. The patient was diagnosed with solitary adrenal metastasis, and right adrenalectomy was performed. Histological examination confirmed the tumor to be adrenal metastasis from rectal cancer, and the histopathological Grade was 2. The patient received adjuvant chemotherapy with mFOLFOX6, and he is alive 7 months after adrenalectomy without evidence of recurrence. Adrenalectomy is recommended for solitary adrenal metastasis from colorectal cancer. Additionally, adrenalectomy after preoperative chemotherapy is an effective strategy for patients with solitary adrenal metastasis and high tumor marker levels.

[A case of stage IV gastric cancer resected after chemotherapy with capecitabine plus cisplatin].

A 64-year-old woman was diagnosed with Stage IV gastric cancer with lymph node and multiple liver metastases. She was treated with 6 courses of chemotherapy, in 3-week courses, with capecitabine (1,000 mg/m/(2)) plus cisplatin(80 mg/m(2)) administered for 2 weeks, followed by a drug-free week. She underwent curative total gastrectomy with D2 lymph node dissection and reconstruction by using the Roux-en-Y method. The postoperative pathological findings revealed a T3 (SE), N1M1, Stage II B tumor; the tumor was determined to be Grade 1b owing to the chemotherapeutic effect. Postoperatively, only S-1 therapy was administered, because of the development of Grade 3 hand-foot syndrome. The patient is alive 1 year and 8 months after the initial gastrectomy.

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.

The Clinical Impact of Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) in Gastric Cancer Patients Who Receive Curative Treatment.

BACKGROUND/AIM: We hypothesized that the hemoglobin, albumin, lymphocyte, and platelet (HALP) score may be a promising marker for the treatment and management of gastric cancer (GC). To test this hypothesis, we evaluated the clinical impact of the HALP score in patients with GC who received curative treatment. PATIENTS AND METHODS: Consecutive patients who underwent curative resection for GC at the Yokohama City University between 2005 and 2020 were selected based on their medical records. The HALP score was calculated as follows: HALP=Hemoglobin (g/l) × albumin (g/l) × lymphocytes (109/l)/platelets (109/l). RESULTS: The 3-year and 5-year overall survival (OS) rates were 88.6% and 85.8%, respectively, in patients with HALP scores of >40, and 70.3% and 57.2% in patients with HALP scores of ≤40. There were significant differences between the groups analyzed (p<0.001). In univariate analysis, age, T status, lymph node metastasis status, HALP score, lymphovascular invasion status, pathological type, and postoperative complication status were identified as significant prognostic factors for OS. In multivariate analysis, the HALP score remained a significant prognostic factor for OS [hazard ratio (HR)=2.679; 95% confidence interval (CI)=1.455-4.934, p=0.002]. Similar results were observed in the analysis of recurrence-free survival. In addition, the HALP score status affects the postoperative clinical course, including the occurrence of postoperative anastomotic leakage and the introduction of postoperative adjuvant chemotherapy. CONCLUSION: The HALP score affects both short- and long-term oncological outcomes. Thus, the HALP score may be a promising prognostic factor for the treatment and management of GC.

[Curative resection of a case of advanced gastric cancer with peritoneal dissemination responding well to combination chemotherapy of docetaxel,cisplatin and S-1].

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

Correlation between endoscopic features of the anastomosis after low anterior resection and postsurgical anorectal function.

BACKGROUND: With low anterior resection (LAR) for rectal cancer, the oncologic outcomes are recently good. A diverting ileostomy is often created to protect the newly constructed anastomosis; seldom is a permanent stoma needed. Predicting postoperative anorectal function remains difficult, however. We speculated that the endoscopic appearance of the anastomosis before ileostomy closure is predictive of the post-operative anorectal function and tested our hypothesis retrospectively. METHODS: Included in the study were 80 patients who, between September 2014 and August 2017, underwent LAR at Kanagawa Cancer Center. A diverting stoma had been created during the primary surgery, and ileostomy closure was performed about 6 months later. The anastomosis was examined endoscopically just before ileostomy closure, and the features were scored by two well-trained endoscopists. Daily defecation frequency and incontinence (Kirwan Score) were assessed after closure through physician-patient interview, and correlation between endoscopic feature scores and these measures of anorectal function was tested. RESULTS: Documented endoscopic features included erythema in 79% of patients, erosion (45%), ulceration (5%), granulomatous change (41.3%), granular protrusions (17.5%); hemorrhagic (20.0%) or white-coated (30.0%) mucosa. Anastomosis stricture <9 mm was 17.5%. Median daily defecation frequency after ileostomy closure was 4 (range, 0-20). Moderate positive correlation was found between endoscopic scores and postoperative anorectal function (r=0.60, P<0.001). CONCLUSIONS: In recording and analyzing endoscopic features of the anastomosis before ileostomy closure in a large number of patients treated by LAR, we found that the features might indeed be clinically useful in predicting post-LAR anorectal function.