Introduction
We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects ...tumor recurrence and long-term survival in gastric cancer patients.
Methods
The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified.
Results
Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (
p
< 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (
p
< 0.001). A high D-dimer level on POD 7 (≥ 4.9 μg/ml) was identified as an independent predictive factor for both the OS (hazard ratio HR 1.955, 95% confidence interval CI 1.158–3.303,
p
= 0.012) and RFS (HR 2.182, 95% CI 1.327–3.589,
p
= 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (
p
= 0.014).
Conclusion
A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.
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.
The greater omentum comprises peritoneal, adipose, vascular, and lymphoid tissues. Most omental malignancies are metastatic tumors, and the incidence of primary tumors is rare. We report on a prior ...omental smooth muscle tumor case in an adult male patient.
A 54-year-old Japanese male patient with no relevant medical history was diagnosed with an abdominal mass during a routine medical checkup. Subsequent contrast-enhanced computed tomography revealed a mass of approximately 3 cm in size in the greater omentum, and a laparotomy was performed. A 27 × 25 × 20 mm raised lesion was found in the omentum. Microscopically, spindle cells were observed and arranged in whorls and fascicles. Individual tumor cells had short spindle-shaped nuclei with slightly increased chromatin and were characterized by a slightly eosinophilic, spindle-shaped cytoplasm. The mitotic count was less than 1 per 50 high-power fields. The tumor cells showed positive immunoreactivity for α smooth muscle actin, HHF35, and desmin on immunohistochemical examination. The Ki-67 labeling index using the average method was 1.76% (261/14806). No immunoreactivity was observed for any of the other tested markers. We considered leiomyoma owing to a lack of malignant findings. However, primary omental leiomyoma has rarely been reported, and it can be difficult to completely rule out the malignant potential of smooth muscle tumors in soft tissues. Our patient was decisively diagnosed with a primary omental smooth muscle tumor considering leiomyoma. Consequently, the patient did not undergo additional adjuvant therapy and was followed up. The patient was satisfied with treatment and showed neither recurrence nor metastasis at the 13-month postoperative follow-up.
We encountered a primary smooth muscle tumor of the greater omentum with no histological findings suggestive of malignancy in an adult male patient. However, omental smooth muscle tumors are extremely difficult to define as benign, requiring careful diagnosis. Further case reports with long-term follow-up and case series are required to determine whether a true omental benign smooth muscle tumor (leiomyoma) exists. In addition, proper interpretation of the Ki-67 labeling index should be established. This case study is a foundation for future research.
This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with ...the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 95% Confidence interval: 0.36–0.93 for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 1.03–4.86 for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 1.03–2.68). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.
IntroductionA new concept of ‘NeoRAS wild-type (WT)’, which means conversion of RAS status from RAS mutant to RAS WT after treatment, has been reported. Previous observational and proof-of-concept ...studies have demonstrated the efficacy of epidermal growth factor receptor inhibitors in patients with NeoRAS WT metastatic colorectal cancer (mCRC). Moreover, posthoc biomarker analyses of these studies have suggested that not only the RAS status in the circulating tumour DNA (ctDNA) but also other gene mutational status may be useful as biomarkers of epidermal growth factor receptor inhibitors for NeoRAS WT mCRC.Methods and analysisThis trial is a multicentre, single-arm, phase II trial to assess the efficacy and safety of panitumumab plus irinotecan therapy for patients with NeoRAS mCRC. The key eligibility criteria include RAS mutant mCRC initially proven in tumour tissue refractory or intolerant to fluoropyrimidine, oxaliplatin and irinotecan; RAS WT in ctDNA (defined as plasma mutant allele frequencies of all RAS ≤0.1%) within 28 days before enrolment and Eastern Cooperative Oncology Group performance status ≤2. The primary endpoint is the response rate. The target sample size is 30 patients. Biomarker analyses are planned to be performed using next-generation sequencing-based ctDNA analysis.Ethics and disseminationThis study was approved by the certified review board of National Cancer Center Hospital. The main results of the trial will be presented in international meetings and in medical journals.Trial registration numbers031210565.
Abstract
Objective
The optimal perioperative chemotherapy for lower rectal cancer with lateral pelvic lymph node metastasis remains unclear. We evaluated the efficacy and safety of perioperative ...mFOLFOX6 in comparison with postoperative mFOLFOX6 for rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection.
Methods
We conducted an open label randomized phase II/III trial in 18 Japanese institutions. We enrolled patients with histologically proven lower rectal adenocarcinoma with clinical pelvic lateral lymph node metastasis who were randomly assigned (1:1) to receive postoperative mFOLFOX6 (12 courses of intravenous oxaliplatin 85 mg/m2 with L-leucovorin 200 mg/m2 followed by 5-fluorouracil 400 mg/m2, bolus and 2400 mg/m2, continuous infusion, repeated every 2 weeks) or perioperative mFOLFOX6 (six courses each preoperatively and postoperatively). The primary endpoint was overall survival (OS). The trial is registered with Japan Registry of Clinical Trials, number jRCTs031180230.
Results
Between May 2015, and May 2019, 48 patients were randomized to the postoperative arm (n = 26) and the perioperative arm (n = 22). The trial was terminated prematurely due to poor accrual. The 3-year OS in the postoperative and perioperative groups were 66.1 and 84.4%, respectively (HR 0.58, 95% CI 0.14–2.45, one-sided P = 0.23). The pathological complete response rate in the perioperative group was 9.1%. Grade 3 postoperative surgical complications were more frequently observed in the perioperative arm (50.0 vs. 12.0%). One treatment-related death due to sepsis from pelvic infection occurred in the postoperative group.
Conclusions
Perioperative mFOLFOX6 may be an insufficient treatment to improve survival of lower rectal cancer with lateral pelvic lymph node metastasis.
This study investigated the efficacy and safety of perioperative mFOLFOX6 in comparison to postoperative mFOLFOX6 for lower rectal cancer patients undergoing total mesorectal excision with lateral lymph node dissection.
The anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability ...(MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse‐free survival (RFS) was estimated using Kaplan‐Meier method, and correlations were assessed using log‐rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI‐high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite‐stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI‐H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild‐type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI‐H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI‐H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible.
The association of KRAS/BRAF/MSI with invaded lymphatic spread pattern in colon cancer was assessed. The anatomical pattern of invaded LN varies in accordance with the molecular status, which may affect the outcome in stage III colon cancer.
Adjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of ...affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC.
We retrospectively identified patients aged 20-79 years, with stage III CC, who received adjuvant chemotherapy with or without oxaliplatin, between the years 2009 and 2012.
Among 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity score matching. Of these, 95 patients from each group were analyzed, and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7 and 77.1%, respectively. The hazard ratios for 5-year RFS following adjuvant chemotherapy (fluoropyrimidine), with and without oxaliplatin, were 1.241 (95% CI, 0.465-3.308; P = 0.67) and 0.791 (95% CI, 0.329-1.901; P = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3 and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145-1.692; P = 0.25). No differences in RFS rates were noted in the CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in patients with left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates of the MSI-like subtype in left-sided cancer patients were 100 and 53.9% with and without oxaliplatin, respectively.
Subclassification using 55GC and tumor sidedness revealed increased RFS in patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine and oxaliplatin compared to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies.
The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879 ).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator ...performing laparoscopic surgery for colon cancer.
This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed.
Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966).
Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon's qualifications.
Lymphovascular invasion (LVI) is recognized as a prognostic predictor of recurrence in certain carcinomas. According to current Japanese guidelines, however, in gastric cancer, LVI is not clinically ...useful information, except for predicting the curability of endoscopic resection. We clarified the clinical significance of LVI in gastric cancer and its correlation with disease prognosis.
A total of 2,090 cases of gastric cancer undergoing radical gastrectomy were enrolled. The correlation of LVI and other histopathological factors was evaluated with regards to patient prognosis.
LVI(+) was noted in 894 cases. A multivariate analysis showed that pT, pN, and LVI were independent risk factors for patient prognosis. In pT2-4 patients with nodal metastasis, a significant difference was revealed, and the 5-year overall survival rates in LVI(+) cases were lower than those in LVI(-) (60.9% vs. 76.7%, p=0.005).
LVI in gastric cancer is an independent prognostic factor, and tends to worsen prognosis, especially in advanced cancers with lymph node metastases.