Benefit of laparoscopic compared to standard open gastric cancer surgery for sarcopenic patients: a propensity score-matching analysis.

BACKGROUND: Laparoscopic gastrectomy (LG) is performed widely, but whether LG is the optimal treatment for sarcopenic gastric cancer patients is unclear. This study aimed to determine whether LG is particularly beneficial for gastric cancer patients with sarcopenia. METHODS: We collected data concerning 604 consecutive patients who underwent gastrectomy for gastric cancer between January 2003 and December 2019. After adjustment using one-to-one propensity score matching, short-term and long-term outcomes were compared between LG and open gastrectomy (OG) groups among patients with sarcopenia and those without. RESULTS: Among patients with and without sarcopenia, the LG group had a significantly longer operative time but less blood loss than the OG group. The two groups showed no significant differences regarding complications. Although 5-year overall and disease-specific survival were similar between LG and OG groups among patients with and without sarcopenia, LG was associated with greater 5-year non-gastric cancer-related survival than OG among patients with sarcopenia (88.3% vs. 78.1%, P = 0.048), but not those without. CONCLUSION: LG for resectable gastric cancer was not inferior to OG regarding complications and outcomes in patients with or without sarcopenia. No difference in overall survival was evident between these approaches, but LG may lessen mortality from conditions unrelated to gastric cancer in sarcopenic patients.

Absence of a weekday effect on short- and long-term oncologic outcomes of gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: Day of the week when elective gastrointestinal surgery is performed may be influenced by various background and tumor-related factors. Relationships between postoperative outcome and when in the week gastrectomy is performed remain controversial. We undertook this study to evaluate whether weekday of gastrectomy influenced outcomes of gastric cancer treatment ("weekday effect"). METHODS: Patients who underwent curative surgery for gastric cancer between 2004 and 2017 were included in this retrospective study. To obtain 2 cohorts well balanced for variables that might influence clinical outcomes, patients whose gastrectomy was performed early in the week (EW group) were matched 1:1 with others undergoing gastrectomy later in the week (LW group) by use of propensity scores. RESULTS: Among 554 patients, 216 were selected from each group by propensity score matching. Incidence of postoperative complications classified as Clavien-Dindo grade II or higher was similar between EW and LW groups (20.4% vs. 24.1%; P = 0.418). Five-year overall and recurrence-free survival were 86.0% and 81.9% in the EW group, and 86.2% and 81.1% in the LW group (P = 0.981 and P = 0.835, respectively). CONCLUSIONS: Short- and long-term outcomes were comparable between gastric cancer patients who underwent gastrectomy early and late in the week.

Association between low preoperative skeletal muscle quality and infectious complications following gastrectomy for gastric cancer.

PURPOSE: It is known that sarcopenia affects the overall short- and long-term outcomes of patients with gastric cancer (GC); however, the effect of muscle quality on infectious complications after gastrectomy for GC remains unclear. We investigated the associations between the preoperative quantity and quality of skeletal muscle on infectious complications following gastrectomy for GC. METHODS: The subjects of this retrospective study were 353 GC patients who underwent radical gastrectomy between 2009 and 2018. We examined the relationships between their clinical factors, including skeletal muscle mass index and intramuscular adipose tissue content (IMAC), and infectious complications after gastrectomy. RESULTS: Infectious complications developed in 59 patients (16.7%). The independent risk factors for infectious complications identified by multivariate analysis were male gender (P < 0.001), prognostic nutritional index below 45 (P = 0.006), and high IMAC (P = 0.011). Patients with a high IMAC were older and had a higher body mass index, as well as a greater age-adjusted Charlson comorbidity index, than those with low or normal IMAC. CONCLUSIONS: Low skeletal muscle quality defined by a high IMAC is a risk factor for infectious complications following gastrectomy. When feasible, preoperative nutritional intervention and rehabilitation aiming to improve muscle quality could reduce infectious complications after gastrectomy for GC.

p16 Methylation is frequently detected in the serum of metastatic colorectal cancer patients.

For the purpose of detection of colorectal cancers, we tried to detect p16 methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). Out of 211 serum samples derived from colorectal cancer patients, 14 (7%) exhibited p16 methylation in their serum DNA by qMSP. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis. Interestingly, a significant difference was observed in the presence of distant metastasis (P = 0.0420). Moreover, a trend was shown toward preferentially developing lymph node metastasis (P = 0.0547), thus suggesting that p16 methylation in serum could be detected more frequently in metastatic colorectal cancer patients. High sensitivity of qMSP makes it possible to detect smaller amounts of tumor DNA in the serum. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting that qMSP can be used as a screening method for cancer.

[A case of esophageal squamous cell carcinoma with an adenocarcinoma component that dedifferentiated after chemotherapy].

CASE: A 69-year-old man was diagnosed with advanced esophageal cancer(well-differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of chemotherapy, the patient was judged to have achieved a clinical complete response. The patient then decided against undergoing surgery and opted instead to continue with the chemotherapy, receiving five courses in total. However, the esophageal cancer recurred, and subtotal esophagectomy was performed in January 2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma cells, was observed at the primary site. Metastasis of the cancer to the liver was detected 2 months after surgery. The subsequent administration of four courses of docetaxel to the patient did not result in any beneficial effects, and the patient developed carcinomatous pleurisy and died of this complication in November 2011. The patient survived for a total of 21 months after starting chemotherapy. In this case, the chemotherapy itself may have resulted in the dedifferentiation of a well differentiated squamous cell carcinoma to result in a poorly differentiated squamous cell carcinoma with an adenocarcinoma component.

Percutaneous transhepatic gallbladder drainage versus endoscopic gallbladder stenting for managing acute cholecystitis until laparoscopic cholecystectomy.

INTRODUCTION: Gallbladder drainage by methods such as percutaneous transhepatic gallbladder drainage (PTGBD) or endoscopic gallbladder stenting (EGBS) is important in the early management of moderate to severe acute cholecystitis. METHODS: In patients undergoing laparoscopic cholecystectomy (LC) for acute cholecystitis after a month or more of gallbladder drainage, the clinical course was compared between patients initially treated with PTGBD or EGBS. RESULTS: Among 331 patients undergoing LC for cholecystitis between 2018 and 2022, 43 first underwent 1 or more months of gallbladder drainage. The median interval between drainage initiation and LC was 89 days (range, 28-261) among 34 patients with PTGBD and 70 days (range, 62-188) among nine with EGBS (p = 0.644). During this waiting period, PTGBD was clamped in six patients and removed in five. Cholecystitis relapsed in three PTGBD patients (9%) and four EGBS patients (44%; p = 0.026). Relapses were managed with medications. Cholecystectomy duration (p = 0.022), intraoperative blood loss (p = 0.026), frequency of abdominal drain insertion (p = 0.023), and resort to bailout surgery such as fundus-first approaches (p = 0.030) were significantly greater in patients with EGBS. Postoperative complications were somewhat likelier (p = 0.095) and postoperative hospital stays were longer (p = 0.007) in the EGBS group. CONCLUSION: Among patients whose LC was performed 1 or more months after initiation of drainage, daily living during the waiting period associated with drainage was well supported by EGBS, but LC and the postoperative course were more complicated than in PTGBD patients.

Methylation of the HACE1 gene is frequently detected in hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas. METHODOLOGY: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP). RESULTS: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC. The clinicopathological data were then correlated with these results. In the value of serum AFP (α-fetoprotein), a significant difference was observed (p=0.0025). CONCLUSIONS: All stages of HCCs presented HACE1 methylation, indicating that the HACE1 gene has been methylated from the early stages of HCCs.

Methylation of the UNC5C gene is frequently detected in hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, we detected that UNC5C expression was downregulated in colon and gastric cancer. METHODOLOGY: In the present study, the methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 42 patients with HCC. RESULTS: Methylation of the UNC5C gene was detected in 11 out of the 42 (26%) HCCs, suggesting that the methylation of UNC5C was frequently observed in HCCs. The clinicopathological data were correlated with the methylation results. CONCLUSIONS: TNM stage 1 HCC presented UNC5C methylation, indicating that the UNC5C gene has been methylated from the early stages of HCC.

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS: WNT5A was more frequently methylated in early gastric carcinomas.

[Significance of Onodera's prognostic nutritional index for treating unresectable or recurrent colorectal cancer with chemotherapy].

We analyzed the relationship between Onodera's prognostic nutritional index(PNI), classified by serum albumin level, lymphocyte level, and clinicopathological features, in 46 patients with unresectable or recurrent colorectal cancer being treated with chemotherapy.Onodera 's PNI was distributed between 29.7 and 56.1(average 45.4±6.8 ).Onodera 's PNI showed a significant correlation with performance status and surgery before chemotherapy(p=0.002 and 0.002, respectively).Next, all patients were divided into two groups according to their Onodera's PNI values, based on the receiver operator characteristic curve.We found that Onodera's PNI showed a significant correlation with overall survival times(median survival time, 548 days(Onodera's PNI<47.8 ), 902 days(Onodera's PNI≥47.8 ), p=0.00065 ).This PNI could be a prognostic factor and a very useful objective screening tool for assessing the nutritional condition of those with unresectable or recurrent colorectal cancer being treated with chemotherapy.

Impact of body fat and muscle quantity on short- and long-term outcome after gastrectomy for cancer.

BACKGROUND & AIMS: Preoperative low skeletal muscle mass and obesity have been identified as poor prognostic factors after gastrectomy for cancer, but the predictive value of combined quantitation of skeletal muscle mass and obesity remains unclear. This study examined the impact of combined body compositions on outcomes after gastrectomy for cancer. METHODS: 518 patients who had undergone gastric resection for cancer between 2004 and 2017 were analyzed retrospectively. Skeletal muscle mass (skeletal muscle mass index (SMI)) and visceral obesity (visceral fat area) were measured in preoperative computed tomographic images to categorize patients as outlined below. Impacts of these body compositions on outcomes after gastrectomy were investigated. RESULTS: Body composition was classified as high SMI without obesity in 231 patients (45%), high SMI with obesity in 202 (39%), low SMI without obesity in 55 (11%), and low SMI with obesity in 30 (6%). Postoperative complications developed in 128 patients (25%). Multivariate analysis identified low SMI with obesity as an independent risk factor for postoperative complications (odds ratio, 3.27; P = 0.010). Moreover, patients with low SMI without obesity had lower 5-year overall survival rates than patients with high SMI without obesity (64.4% vs. 88.0%; P < 0.001) and worse 5-year relapse-free survival rates (61.3% vs. 81.3%; P = 0.002). Multivariate analysis identified low SMI without obesity as a significant risk factor for overall survival (hazard ratio, 3.033; P < 0.001) and relapse-free survival (hazard ratio, 2.144; P = 0.008) after gastrectomy. CONCLUSION: Preoperative low SMI with obesity was an independent risk factor for postoperative complications, while low SMI without obesity was an independent risk factor for overall and relapse-free survival following gastrectomy for cancer.

Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma.

The Mus81 gene encodes a critical endonuclease involved in DNA repair and tumor suppression. Our previous study has shown reduced expression of Mus81 in hepatocellular carcinoma and its association with the metastatic potential and prognosis of hepatocellular carcinoma. However, the role of Mus81 in colorectal carcinoma is currently unknown. We therefore carried out the present study to explore the correlation between Mus81 expression and the progression of colorectal carcinoma. Mus81 expression in 92 cases of colorectal carcinoma and matched normal tissues was determined by quantitative real-time polymerase chain reaction. Our results showed that Mus81 expression in colorectal carcinoma tissues was significantly reduced compared with the corresponding normal tissues (P < 0.001) and the downregulation of Mus81 (decreased by more than 50%) was found in 60.9% (56/92) of colorectal carcinoma. Moreover, Mus81 downregulation correlated significantly to hepatic metastasis (P = 0.019) and a high TNM stage (P = 0.025) of colorectal carcinoma. In addition, the decrease of Mus81 was also detected in 10 cases of hepatic metastasis tissues compared with the corresponding primary colorectal carcinoma tissues (P = 0.016). More importantly, colorectal carcinoma patients with apparent Mus81 downregulation have shown significantly poorer overall survival than those with little Mus81 downregulation (P = 0.0374). Also, multivariable Cox regression analysis identified Mus81 downregulation as an independent prognostic factor for colorectal carcinoma (hazard ratio, 1.678; P = 0.040). In conclusion, the reduced expression of Mus81 is closely related to hepatic metastasis and poor prognosis of colorectal carcinoma, indicating Mus81 as a novel prognostic marker for colorectal carcinoma.

[Complete response to S-1/CDDP combination in a patient with obstructive jaundice secondary to lymph node metastasis by gastric cancer - a case report].

A 55-year-old woman was found to have a type-4 lesion centered on the greater curvature of the lower portion of her stomach during an upper gastrointestinal endoscopic examination.A diagnosis of inoperable advanced gastric carcinoma [type 4, tub 2/por, T3 (SE), N3, H0, P1, cStage IV], complicated by pyloric stenosis, liver dysfunction, and obstructive jaundice untreatable by bile drainage, was made.After obtaining the informed consent of the patient and her family and explain- ing that under the circumstances surgery was not indicated, chemotherapy [S-1 (granules) 80 mg/m2, CDDP 60 mg/m2] was selected. After starting treatment, an improvement in liver dysfunction and jaundice was observed, and at the start of the second course, the patient had become capable of oral feeding.The patient was discharged after completion of the second course. No choices associated with evidence exist for treatment of patients with inoperable advanced gastric cancer (complicated by obstructive jaundice), who are not elderly and have good performance status (PS).We report this case in which improvement of activity of daily living (ADL) was achieved relatively safely by treatment with S-1/CDDP, together with a brief discussion based on the literature.

Aberrant methylation of the UNC5C gene is frequently detected in advanced colorectal cancer.

BACKGROUND: UNC5C, one of the Netrin-1 receptors, belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Recently, two reports indicated that UNC5C methylation was closely associated with loss of gene expression in colorectal cancer. MATERIALS AND METHODS: The methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 49 patients with colorectal cancer using quantitative methylation-specific polymerase chain reaction (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the UNC5C gene was detected in 34 out of the 49 (69%) primary colon carcinomas, suggesting that the aberrant methylation of UNC5C was frequent in colorectal cancer. The clinicopathological data were then tested for correlation with this result. A significantly greater proportion of cases with methylated UNC5C was found in Dukes' stage C (p = 0.0380) than in earlier stages. CONCLUSION: UNC5C might act as a tumor suppressor and UNC5C methylation might present a malignant potential in colorectal cancer.

Aberrant methylation of the p16 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: A tumor suppressor gene, p16, was found to harbor promoter hypermethylation associated with the loss of protein expression in cancer cells, suggesting that p16 inactivation due to promoter methylation was important for colorectal tumorigenesis. MATERIALS AND METHODS: The methylation status of the p16 gene was examined in primary carcinomas and the corresponding normal tissues derived from 50 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the p16 gene was detected in 20 out of the 50 (40%) primary colon carcinomas, suggesting that the aberrant methylation of p16 was frequently observed in colorectal carcinomas. The clinicopathological data were then correlated with these results. Significant differences were observed with Dukes' stage (p = 0.0495) and lymphatic invasion (p = 0.0277). CONCLUSION: p16 might act as a tumor suppressor in colorectal carcinomas and was more frequently methylated in advanced colorectal carcinomas.

Vimentin methylation as a marker for advanced colorectal carcinoma.

BACKGROUND: Recently, it was shown that the Vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma. Moreover, Vimentin methylation can be applied for the screening or as a diagnostic tool of colorectal carcinomas in the fecal DNA test. MATERIALS AND METHODS: The methylation status of the Vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 48 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the Vimentin gene was detected in 31 out of 48 (65%) primary colorectal carcinomas. This result suggested that the aberrant methylation of the Vimentin gene was frequent in colorectal carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in age and Dukes' stage (p = 0.001 and p = 0.034, respectively). Moreover, a trend was shown toward preferentially developing liver metastasis and peritoneal dissemination in colorectal carcinomas with Vimentin methylation (p = 0.052 and p = 0.080, respectively). CONCLUSION: Vimentin was frequently methylated in advanced colorectal carcinoma.

Demethylation of the CDH3 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been proven that the CDH3 promoter was hypomethylated in colonic aberrant foci and colorectal cancer. The hypomethylation was also associated with induction of CDH3 expression in colorectal cancer. These results indicated that epigenetic demethylation of the CDH3 promoter in the human intestine permits its ectopic expression in colorectal cancer. MATERIALS AND METHODS: The demethylation status of the CDH3 gene was examined in primary carcinomas and the corresponding normal tissues derived from 53 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the demethylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant demethylation of the CDH3 gene was detected in 41 out of the 53 (77%) primary colon carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the tumor site and Dukes' stage (p=0.0187 and p=0.0192, respectively). Moreover, a trend was shown toward preferentially developing tumor size (p=0.140). CONCLUSION: These results indicated that CDH3 was more frequently demethylated in advanced colorectal carcinomas.

Frequent methylation of Vimentin in well-differentiated gastric carcinoma.

BACKGROUND: Recently, it was shown that the vimentin gene, usually activated in mesenchymal cells, was highly methylated in colorectal carcinoma. MATERIALS AND METHODS: The methylation status of the vimentin gene was examined in primary carcinomas and the corresponding normal tissues derived from 37 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the vimentin gene was detected in 14 out of 37 (38%) primary gastric carcinomas. This result suggested that the aberrant methylation of the vimentin gene was frequent in gastric carcinomas. Subsequently, clinicopathological data were correlated with the methylation score. A significant difference was observed in histology (p=0.0429). In addition, a trend was shown toward advancement of gastric carcinomas with vimentin methylation (p=0.0588). CONCLUSION: In gastric carcinomas, well-differentiated adenocarcinoma was significantly methylated compared to poorly differentiated.

Demethylation of the CD133 gene is frequently detected in advanced colorectal cancer.

BACKGROUND: Recently, it has been reported that colorectal carcinoma is created and propagated by a small number of undifferentiated tumorigenic CD133(+) cells. Furthermore, it has been reported that CD133 expression is directly regulated by epigenetic modifications. Therefore, it is possible that CD133 expression by gene demethylation is related to colorectal carcinogenesis. MATERIALS AND METHODS: The methylation status of the CD133 gene was examined in primary carcinomas and the corresponding normal tissues derived from 48 patients with colorectal cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Demethylation of the CD133 gene was detected in 19 out of the 48 (40%) primary colon carcinomas, suggesting that the demethylation of CD133 is frequently observed in colorectal carcinomas. The clinicopathological data were correlated with the demethylation results. A significant difference was observed in the maximal tumor size (p=0.0222). Moreover, a trend was shown toward preferentially developing lymph node metastasis in demethylated tumors (p=0.214). CONCLUSION: CD133 was more frequently demethylated in advanced colorectal carcinomas.

Methylation of HACE1 in gastric carcinoma.

BACKGROUND: We recently examined the methylation status of the HACE1 gene in primary carcinomas derived from 32 patients with colorectal cancer. A significant increase was observed in the maximal tumor size of the tumors with methylated HACE1 (p=0.0304). Moreover, a trend was shown toward preferentially developing lymph node metastasis in the carcinomas with methylated HACE1 (p=0.0612), suggesting that HACE1 might present a malignant potential in colorectal cancer. These results prompted us to examine the methylation status of the HACE1 gene in gastric carcinomas. MATERIALS AND METHODS: The methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 34 patients with gastric carcinoma using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: An aberrant methylation of the HACE1 gene was detected in 9 out of 34 (26%) primary gastric carcinomas. Subsequently, clinicopathological data were tested for correlation with the methylation score. A significant difference was observed in patient gender (p=0.0429). CONCLUSION: HACE1 was frequently methylated in gastric carcinoma derived from male patients.