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.

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.

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.

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.

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.

Toward standardized patient positioning to avoid peripheral nerve injury during laparoscopic colorectal surgery: Application of a protocol and study of the resulting relationship between total rotation time and contact pressure at the shoulder.

INTRODUCTION: Generally, laparoscopic colorectal surgery is performed with the patient in the lithotomy and rotated positions. The lithotomy position, however, is associated with intraoperative peripheral nerve injury (IPNI). We studied the relationship between patient positioning during laparoscopic colorectal surgery, contact pressure at the shoulder, and the occurrence of IPNI and tested a positioning protocol aimed at surgical safety in addition to maintenance of a good surgical field. METHODS: We applied our positioning protocol in 44 cases and collected data that could be used to answer our study questions. We set limits for shoulder contact pressure and time in the rotation position. When the time limit was reached, we returned the patient to the supine position for 5 min. RESULTS: Patients' median age was 71 years; mean BMI was 22.4 kg/m2 . Median time in the rotation position was 126 min. For the 22 patients for whom validated data was obtained, mean lower shoulder pressure changed from 8.5 mmHg just after rotation to 11.4 mmHg 120 min after rotation (P = 0.013). Absence of IPNI in our patients confirmed the proposed relation between patient positioning and IPNI. Our data indicate that a prolonged period in the rotation position increases contact pressure at the shoulder, which can increase the risk of IPNI. CONCLUSION: Our patient positioning protocol appears to have prevented laparoscopic colectomy-related IPNI. Future studies are warranted to confirm the relationship between patient positioning and IPNI and, if necessary, to further refine the protocol to ensure prevention of IPNI during laparoscopic colorectal surgery.

[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.

Gastric mixed adenoneuroendocrine carcinoma occurring 50 years after a gastroenterostomy with braun anastomosis.

A 75-year-old man was diagnosed with gastric cancer. Fifty years previously, he had undergone gastroenterostomy with a Braun enteroenterostomy. At present, a distal gastrectomy and small intestinal partial resection were performed. Intraoperatively, the tumor was localized to the previous stomal site. HE staining showed that the tumor comprised two elements: a tubular adenocarcinoma on the gastric side and a neuroendocrine carcinoma (NEC) on the jejunal side. The final pathologic diagnosis was mixed adenoneuroendocrine carcinoma based on an immunohistochemical analysis of endocrine markers and an elevated Ki-67 labeling index. The risk of later cancer development cancer recurrence near the gastrojejunostomy site is well known. Potentially, chronic enterogastric bile reflux may irritate the gastric mucosa and act as a promoter. Gastric NEC has a strong malignant potential. We suspect that, in the present case, the constant exposure to secondary bile may have induced a gastric mucosal adenocarcinoma, which finally differentiated into a NEC.

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.

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.

Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associated not only with malignant pleural mesothelioma, but also with WDPMP.

FBN2 methylation is detected in the serum of colorectal cancer patients with hepatic metastasis.

BACKGROUND, MATERIALS AND METHODS: For the purpose of colorectal cancer detection, we investigated fibrillin-2 (FBN2) methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). RESULTS: Out of 78 patients with colorectal cancer, 49 (63%) exhibited methylation of FBN2 in their tumor tissue DNA, suggesting that FBN2 methylation frequently exists in colorectal cancer. We next examined the methylation status of FBN2 in the serum DNA of patients with colorectal cancer. Out of 49 serum samples, four (8%) exhibited FBN2 methylation in their serum DNA by qMSP, suggesting that FBN2 methylation exists in the serum of colorectal cancer patients. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis findings. Interestingly, methylation of FBN2 was found in the serum DNA of male (p=0.0167) patients, and in those with hepatic metastasis (p<0.0001). CONCLUSIONS: The clinical sensitivity of this assay can be potentially improved by incorporating other common genetic targets such as p53 and KRAS. Advances in technology which will permit for rapid detection of an array of specific mutations and methylation would enhance the utility of this approach.

Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer.

BACKGROUND: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer. PATIENTS AND METHODS: Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer. The relations of expression levels with clinicopathological factors and outcomes were studied. RESULTS: Higher TYMS expression was associated with greater age, DPYD expression with greater age, poorer differentiation and low invasion, and TYMP expression with poorer differentiation and lack of peritoneal metastasis. DPYD expression positively correlated with TYMP expression. In patients with stage IV disease, high DPYD or TYMP expression was associated with poor outcomes. CONCLUSION: mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.

Methylation of the DFNA5 gene is frequently detected in colorectal cancer.

BACKGROUND: Recently, the human deafness, autosomal dominant 5 gene, DFNA5, has frequently been detected in cancer tissues. The methylation status of the DFNA5 gene in colorectal cancer was examined and was compared to the clinocopathological findings. MATERIALS AND METHODS: Eighty-five tumor samples and corresponding normal tissues were obtained from patients with colorectal cancer who underwent surgery at our hospital. The methylation status of the DFNA5 gene in these samples was examined by quantitative methylation-specific PCR (qMSP). Subsequently, the clinicopathological findings were correlated with the methylation status of the DFNA5 gene. RESULTS: DFNA5 gene methylation was found in 29 (34%) out of the 85 colorectal carcinomas, suggesting that it was frequently observed in colorectal cancer. A significant correlation with methylation was observed for lymphatic vessel invasion and TNM stage (p=0.0268 and p=0.0189, respectively). CONCLUSION: DFNA5 might act as a tumor suppressor gene and DFNA5 gene methylation might play an important role in the development of colorectal cancer. Our data implicate DFNA5 gene methylation as a novel molecular biomarker in colorectal cancer.

Methylation of TFPI2 no longer detected in the serum DNA of colorectal cancer patients after curative surgery.

In our previous study, we used quantitative methylation-specific polymerase chain reaction (qMSP) to examine the methylation status of tissue factor pathway inhibitor 2 (TFPI2) in the preoperative serum DNA of 215 colorectal cancer patients and found that TFPI2 was methylated in serum DNA from 39 of these patients. In this study, we examined postoperative serum DNA, obtained within one month after surgery from 38 out of the 39 patients and found that TFPI2 was methylated in the serum DNA of only 18 (47%) of these patients, suggesting that TFPI2 methylation in the serum of the remaining colorectal cancer patients was abolished by surgical tumor reduction. Next, we examined the correlation between the presence of TFPI2 methylation in postoperative serum DNA and residual cancer status after surgery. If R0 (no residual cancer) operations were successfully performed, TFPI2 methylation was not detected in postoperative serum. However, if R2 (obvious residual cancer) operations were performed, 17 (77%) out of 22 postoperative sera, still exhibited TFPI2 methylation. Taken together, our results confirm that detection of methylated TFPI2 in serum DNA was derived from colorectal cancer and could serve as a marker of surgical outcome.

Detection of vimentin methylation in the serum of patients with gastric cancer.

AIM: Detection of gastric cancer using serum assay of vimentin methylation. METHODS: A quantitative methylation-specific polymerase chain reaction assay was used to detect vimentin gene (VIM) methylation in the serum of 71 patients with gastric cancer. RESULTS: Mean VIM methylation in cancer patients (0.304 ± 0.558) was significantly higher than that in healthy donors (0.011 ± 0.015, p=0.018). The sensitivity of VIM methylation (33.8%) was similar to the one of carbohydrate antigen 19-9 (CA19-9) (25.4%), higher than the one of carcinoembryonic antigen (CEA) (12.7%), and significantly higher than the sensitivity of both markers for patients with stage I and IV disease (p=0.010 and 0.044, respectively). At all stages, the sensitivity of a combination of markers was higher than the sensitivity of any in isolation marker and was similar for stages I, II and III, reaching 76.9% for stage IV disease. CONCLUSION: VIM methylation may represent a useful marker for the detection of tumor DNA in the serum of patients with gastric cancer.

[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.

Detection of TFPI2 methylation in the serum of gastric cancer patients.

BACKGROUND: Methylation of tissue factor pathway inhibitor-2 (TFPI2) has been detected in the stool of colorectal cancer patients. Using quantitative methylation-specific polymerase chain reaction (qMSP), 39 out of 215 (18%) patients exhibited TFPI2 methylation in their serum DNA, suggesting that a significant number of methylated TFPI2 existed in colorectal cancer patients' sera. MATERIALS AND METHODS: Methylation status of the TFPI2 gene was examined in sera derived from 73 patients with gastric cancer using qMSP and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Out of 73 serum samples, 7 (10%) exhibited TFPI2 methylation in their serum DNA by qMSP, suggesting that TFPI2 methylation existed in the serum of gastric cancer patients. After completion of qMSP analysis of all specimens, clinicopathological data were correlated with the molecular analysis. TFPI2 methylation was significantly more frequently found in serum of patients with lymph node metastasis (p=0.0040) and distant metastasis (p=0.0115). CONCLUSION: In principle, knowledge of the methylation status of a primary tumor is not required in advance in order to be able to detect circulating tumor DNA. Therefore, qMSP could be used as a cancer screening method.