BMP Signaling Is a Prognostic Marker in Patients With Colorectal Cancer and Associates With Frailty.

Background/Aim: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-ß superfamily of ligands and have been shown to promote or suppress colorectal cancer (CRC) growth. Developing treatments that target BMPs is challenging due to their multiple roles, including involvement in the inflammatory response and nutritional status. The present study evaluated the prognostic value of BMP-4, which is believed to be highly expressed in CRC, and its correlation with inflammatory and nutrition statuses in patients with CRC. Materials and Methods: We analyzed BMP-4 expression in tumor tissues from 144 patients who underwent CRC surgery using immunohistochemistry and evaluated the relationship between BMP-4 levels and clinical outcomes. Results: Kaplan-Meier analysis revealed that patients with high expression levels of BMP-4 exhibited a shorter overall survival rate than those with low levels of expression. Multivariate analysis revealed that BMP-4 expression was an independent prognostic factor for overall survival and death from other diseases in CRC patients. Furthermore, high BMP-4 expression was significantly correlated with high C-reactive protein/Albumin ratio, sarcopenia, and osteopenia. Conclusion: BMP-4 is a significant prognostic factor in CRC, particularly in predicting death from other diseases, while also showing associations with inflammatory and nutritional statuses.

The cachexia index is a prognostic factor for patients with recurrent pancreatic cancer.

PURPOSE: Cancer cachexia leads to poor outcomes, especially for patients with advanced stage disease. The cachexia index (CXI), a novel biomarker for cancer cachexia, has been identified as a prognostic indicator for several malignancies. The present study aimed to clarify the prognostic significance of the CXI for patients with recurrent pancreatic cancer. METHODS: This retrospective study enrolled 113 patients diagnosed with recurrence following pancreatectomy for pancreatic cancer, to analyze the association between the CXI and prognostic survival. RESULTS: The 2-year overall survival rate and median survival of all patients were 28.5% and 12.6 months, respectively. The 2-year overall survival curve in the high CXI group was significantly better than that in the low CXI group (p < 0.001). The rate of chemotherapy after recurrence was significantly lower in the low CXI group than in the high CXI group (p = 0.002). Multivariate analysis identified the CXI as an independent prognostic factor for patients with recurrent pancreatic cancer (p = 0.011). CONCLUSIONS: The CXI proved useful for predicting the post-recurrence prognosis of patients with recurrent pancreatic cancer. Patients with a low CXI at the time of recurrence have poorer prognostic outcomes than those with a high CXI.

Exosomal miR-493 suppresses MAD2L1 and induces chemoresistance to intraperitoneal paclitaxel therapy in gastric cancer patients with peritoneal metastasis.

Intraperitoneal (IP) chemotherapy with paclitaxel (PTX) for gastric cancer (GC) with peritoneal metastasis (PM) is considered a promising treatment approach, however, there are no useful biomarkers to predict the efficacy of IP therapy. We examined the association between intra-peritoneal exosomes, particularly exosomal micro-RNAs (exo-miRNAs), and IP-chemo sensitivity. MKN45 cells that were cultured with intra-peritoneal exosomes from patients who did not respond to IP therapy with PTX (IPnon-respond group) exhibited resistance to PTX compared with exosomes from responding patients (IPrespond group) (p = 0.002). A comprehensive search for exo-miRNAs indicated that miR-493 was significantly up-regulated in exosomes from the IPnon-respond group compared with those collected from the IPrespond group. The expression of miR-493 in PTX-resistant MKN45 cells (MKN45PTX-res) was higher compared with that in MKN45. In addition, MKN45PTX-res cells exhibited lower MAD2L1 gene and protein expression compared with MKN45. Finally, miR-493 enhancement by transfection of miR-493 mimics significantly down-regulated MAD2L1 expression in MKN45 cells and reduced PTX sensitivity. Our results suggest that intra-peritoneal exo-miR-493 is involved in chemoresistance to PTX by downregulating MAD2L1 in GC with PM. Exo-miR-493 may be a biomarker for chemoresistance and prognosis of GC patients with PM and may also be a promising therapeutic target.

Correlation between relative dose intensity of adjuvant S-1 chemotherapy and psoas muscle mass volume and survival after resection of pancreatic ductal adenocarcinoma: A retrospective study.

This study aimed to investigate the prognostic relationship between relative dose intensity (RDI) of adjuvant S-1 chemotherapy and psoas muscle mass volume (PMV) in patients with resected pancreatic ductal adenocarcinoma. We enrolled 105 patients with histologically confirmed pancreatic ductal adenocarcinoma who had undergone pancreatectomy. Adjuvant S-1 chemotherapy was administered to 72 (68.6%) of the 105 patients and not to the remaining 33 patients. Patients who received adjuvant S-1 chemotherapy were stratified into high- and low-RDI groups by the cutoff value for RDI. Five-year overall survival (OS) and relapse-free survival (RFS) rates were significantly higher in the high- than in the low-RDI group. Similarly, both the 5-year OS and RFS rates were significantly greater among patients in the high-PMV group than among patients in the low-PMV group. The RDI was an independent prognostic factor in our study patients. Furthermore, patients who received adjuvant S-1 chemotherapy were stratified into 3 groups: those with both high RDI and high-PMV, Group A; those with either high RDI or high PMV (but not both), Group B; and those with both low RDI and low-PMV, group C. There were statistically significant differences in 5-year OS and RFS between 3 patient groups (5-year overall survival: P = .023, 5-year relapse-free survival: P = .001). The area under the curve for the combination of RDI and PMV (0.674) was greater than that for RDI alone (0.645). A sufficient dosage of adjuvant S-1 chemotherapy is important in improving survival of patients with resected pancreatic ductal adenocarcinoma. A combination of RDI and PMV may predict the prognosis of patients with resected pancreatic ductal adenocarcinoma more effective than RDI alone.

Using the geriatric nutritional risk index to predict outcomes in older patients with remnant gastric cancer after gastrectomy: a retrospective multicenter study in Japan.

PURPOSE: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC). METHODS: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed. RESULTS: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS. CONCLUSIONS: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC.

An Intrahepatic Fluorodeoxyglucose (FDG)-PET/CT False-Positive Tumor Secondary to Foreign Body Granuloma Masquerading as Colon Cancer Liver Metastasis: A Case Report.

A suture placed next to a dissected liver section during the initial hepatectomy may become an unlikely intrahepatic foreign body granuloma. In this report, we describe a case where a silk suture in the liver section plane placed during initial hepatectomy for synchronous colon cancer metastasis became an intrahepatic foreign body granuloma that exhibited fluorodeoxyglucose (FDG) accumulation on positron emission tomography/computed tomography (PET/CT). The granuloma was resected as the second metachronous liver metastatic lesion. A 73-year-old female was referred for a planned second hepatectomy. She had undergone colectomy and hepatectomy for advanced cancer of the ascending colon and synchronous liver metastasis approximately two years ago. However, two possible liver metastases with FDG accumulation were identified in hepatic segments IV and V after one year and nine months after the initial resection. A second hepatectomy was planned after administering systemic chemotherapy. She underwent a left lobectomy with a middle hepatic vein and partial segment V hepatectomy six months after liver lesion identification. The segment IV lesion was histologically proven to be a liver metastasis adenocarcinoma. The segment V lesion revealed a silk thread on the residual liver side at the initial hepatectomy, which was histologically diagnosed as a foreign body granuloma. The possibility of intrahepatic foreign body granuloma development should be considered in subsequent follow-ups in cases where sutures were applied to the dissected residual liver plane during the initial hepatectomy. Additionally, a thorough second hepatectomy should be considered if recurrence is suspected.

Effects of postoperative oral elemental nutritional supplement on skeletal muscle loss after gastrectomy for gastric cancer.

BACKGROUND: We previously showed that daily nutritional intervention with an oral elemental diet (ED) at 300 kcal/day for 6-8 weeks postoperatively decreased the percentage of body weight loss (%BWL), and that the effect was maintained for 1 year. This post hoc analysis aimed to determine whether this intervention decreased skeletal muscle mass loss 1-year post-gastrectomy. METHODS: Data from consecutive, untreated patients with histopathologically confirmed stage I-III gastric adenocarcinoma who planned to undergo total gastrectomy (TG) or distal gastrectomy (DG) and were enrolled in a previously published randomized trial were used. The primary endpoint was the percentage of skeletal muscle mass index (%SMI) loss from baseline at 1 year postoperatively, based on abdominal computed tomography images obtained preoperatively and at 1 year postoperatively. RESULTS: The overall median %SMI loss was lower in the ED versus control group, but the difference was not significant. The difference in %SMI loss in the ED and control groups was greater in patients with TG (10.1 vs. 13.0; P = 0.12) than in those with DG (5.5 vs. 6.8; P = 0.69). A correlation was observed between %BWL and %SMI loss in both groups (ED group, coefficient 0.591; control group, coefficient 0.644; P < 0.001 for both). Type of gastrectomy (coefficient 7.38; P = 0.001) and disease stage (coefficient - 6.43; P = 0.04) were independent predictors of postoperative skeletal muscle mass loss. CONCLUSION: ED administration for 6-8 weeks following gastrectomy had no inhibitory effect on skeletal muscle loss at 1 year postoperatively. CLINICAL TRIAL REGISTRATION: UMIN000023455.

A gastroduodenal artery that branched from the celiac artery in gastrectomy: A rare case of an anatomical variant.

Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

Prognostic significance of the cachexia index in patients with unresectable advanced gastric cancer receiving palliative chemotherapy: a retrospective single-center study.

PURPOSE: To investigate the prognostic utility of the cachexia index (CXI) in unresectable advanced gastric cancer (UAGC). METHODS: The relationship between CXI and the outcomes was evaluated in 102 patients with UAGC who had received first-line palliative 5-fluorouracil-based chemotherapy between January 2012 and December 2021. RESULTS: The median survival time (MST) from first-line chemotherapy initiation was 16.2 months, and the cohort included 60 and 42 patients with high and low CXIs, respectively, based on the optimal CXI cutoff. The rates of patients with a performance status score of 0, recurrence, third-line chemotherapy, and all grade 3-4 side effects, including febrile neutropenia (FN), were significantly higher in the CXIhigh group than in the CXIlow group. The prognosis based on MST was significantly better in the CXIhigh group than in the CXIlow group (22.5 vs. 11.6 months, p < 0.001). According to a multivariate analysis, a low CXI and performance status score of 1-2 were poor prognostic factors. CONCLUSIONS: Patients with UAGC and a low CXI had poorer prognoses and more frequent grade 3-4 side effects, including FN, than those with a high CXI. Patients with UAGC and a low CXI should be carefully managed to control for side effects to receive subsequent treatment.

Retrospective Analysis of Neonatal Surgery at Tottori University over the Past Ten Years.

Background: In recent years, the number of neonatal surgeries has been on the rise despite the decline in the number of births, and we examined the actual trends and problems at Tottori University Hospital located in the Sanin region. Methods: Medical records were retrospectively searched for patients who underwent major surgery during the neonatal period (within 30 days of age) at the Tottori University Hospital over the past 10 years (Jan. 2011 to Dec. 2020). Results: Sixty-five cases were included. Early birth infants (< 37 gestational weeks) comprised 15 cases (23%) and low birth weight (< 2500 g) infants involved 27 cases (42%). In the latter half (2016-2020), early birth and low birth weight infants were significantly less than in the first half (2011-2015). The common diseases were anorectal malformation (14 cases), esophageal atresia (10), duodenal atresia (10), and diaphragmatic hernia (9). Prenatal diagnosis was obtained in 26 cases (40%), with high diagnostic rate obtained in duodenal atresia (100%), abdominal wall defect (100%), ileal atresia (75%), meconium peritonitis (67%), and diaphragmatic hernia (67%). Fifty-five cases (85%) were operated on within 7 days of age. Other major malformations were associated in 23 cases (35%). There were 6 deaths (9%), of which 3 cases were low birth weight infants with gastrointestinal perforation, 2 cases with severe chromosomal abnormalities (esophageal atresia, omphalocele), and 1 case with diaphragmatic hernia with severe pulmonary hypertension. Home medical care has been required with gastrostomy tube in 2 cases. Conclusion: Neonatal surgery at Tottori University has been well performed as required with acceptable results along with the progression of other perinatal care. However, further investigation for improvements in premature delivery or organ hypoplasia may be required.

A Prospective Randomized Study of the Herbal Medicine Yokukansan for Preventing Delirium After Gastrointestinal Cancer Surgery.

Background: Yokukansan, the Chinese Herbal Medicine, may be effective for treating postoperative delirium. However, there is no sufficient evidence supporting this notion. This study aimed to investigate whether yokukansan was effective for preventing delirium after gastrointestinal cancer surgery by the prospective randomized study. Methods: This was a double-blind, randomized, controlled trial. Patients aged 75 years or older who underwent surgery between May 2017 and December 2019 were randomized to the yokukansan or anchusan (another Herbal Medicine) group. They received treatments with oral intake of assigned medicine from the day before surgery until postoperative day 3. Then, the incidence of postoperative delirium was compared. A psychiatrist diagnosed patients with postoperative delirium. Results: Seventy-seven patients were enrolled in this study, and the full analysis set comprised 68 patients. In total, 25 of 68 (36.8%) patients presented with postoperative delirium. Specifically, 13 (37.1%) patients in the control group and 12 (36.4%) in the yokukansan group were diagnosed with postoperative delirium. However, the results did not differ significantly in both groups. Moreover, there was no remarkable difference in terms of delirium severity, and adverse events correlated with the medications were not observed. Conclusion: Yokukansan was ineffective in preventing delirium after gastrointestinal cancer surgery.

Skeletal Muscle Mass Before Second-line Chemotherapy Correlates With Subsequent Prognosis and Rate of Late-line Chemotherapy in Patients With Unresectable Gastric Cancer.

BACKGROUND/AIM: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC. PATIENTS AND METHODS: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m2), and SMI before second-line chemotherapy was defined as 2ndSMI. RESULTS: Using 2ndSMI for men and women (35.4 and 31.7 cm2/m2, respectively) as the cutoff value, patients were divided into high (2ndSMIHigh; n=54) and low (2ndSMILow; n=25) 2ndSMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2ndSMILow than in the 2ndSMIHigh group (p=0.028). The multivariate analysis identified 2ndSMI as independent prognostic factor after the start of second-line chemotherapy. CONCLUSION: The 2ndSMILow group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2ndSMIHigh group. Moreover, 2ndSMILow was associated with grade 3 or 4 side effects of second-line chemotherapy.

High Glucose-stimulated aPKC Activation Promotes Pancreatic Cancer Cell Progression Through YAP Signaling.

BACKGROUND/AIM: Persistent hyperglycemia caused by diabetes mellitus is a risk factor for pancreatic cancer (PC). We have previously reported that aberrant activation of atypical protein kinase C (aPKC) enhances PC cell progression. However, no reports have elucidated whether hyperglycemia promotes PC cell progression and whether aPKC activation is related to PC cell progression mechanisms. MATERIALS AND METHODS: We examined whether high-glucose stimulation accelerates PC cell proliferation, migration, and invasion. Furthermore, to determine whether PC cells activate aPKC upon high-glucose stimulation, we measured the phosphorylation of aPKC at T560 in PC cells. RESULTS: High-glucose stimulation accelerated PC cell proliferation, migration, and invasion. High-glucose treatment increased aPKC's activated form, with T560 phosphorylation, in PC cells. However, aPKC knockdown attenuated these effects. aPKC reportedly induces cell transformation through Yes-associated protein (YAP) activation. YAP expression was increased in high glucose-treated PC cells but not in aPKC-knockdown cells. aPKC interacts with partitioning defective 3 (Par-3), which aids in establishing cell polarity and inhibits aPKC by binding as a substrate. In Par-3-knockdown PC cells, YAP expression increased independently of high-glucose treatment. Over-expression of Par-3 and aPKC-dominant negative mutants prevented the high glucose-stimulated nuclear localization of YAP. YAP forms a complex with the zinc finger E-box binding homeobox 1 protein (ZEB1), an activator of epithelial-mesenchymal transition. ZEB1 expression was increased by high glucose treatment or Par-3 knockdown, but aPKC knockdown suppressed this increase. CONCLUSION: High glucose-induced aPKC activation promotes PC progression by enhancing the YAP signaling pathway.

Preoperative Osteopenia as Risk Factor for Death from Other Diseases After Gastrectomy in Elderly Patients.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density, is a prognostic factor in patients with digestive tract cancers, including gastric cancer (GC). However, the correlation between preoperative osteopenia and GC in elderly patients is unclear. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. Patients were classified into the non-elderly group (n=169) and the elderly group (n=82). Bone mineral density was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Although overall survival was significantly shorter in the elderly compared to the non-elderly group (p=0.0062), there was no significant difference in disease-specific survival between the two groups (p=0.71) because of the higher rate of death from other diseases. In addition, the elderly group had a significantly higher incidence of osteopenia (p<0.001) and a significantly lower prognostic nutritional index (p<0.001). Multivariate analysis revealed that preoperative osteopenia and a low preoperative prognostic nutritional index were significant risk factors for death from other diseases after gastrectomy in elderly patients. CONCLUSION: In elderly patients with GC, preoperative osteopenia is an important factor to consider in terms of both curability and death from other diseases.

Impact of Frailty and Sarcopenia on Short- and Long-Term Outcomes in Elderly Patients Undergoing Radical Gastrectomy for Gastric Cancer.

BACKGROUND: The impact of frailty and sarcopenia in patients with gastric cancer is unclear. This study aimed to comprehensively examine the impact of frailty and sarcopenia on the short- and long-term outcomes in elderly patients undergoing radical gastrectomy for gastric cancer. METHODS: We retrospectively assessed 246 patients aged ≥ 65 years who underwent radical gastrectomy. Frailty and sarcopenia were assessed using the modified frailty index (mFI) and psoas muscle mass index (PMI), respectively. RESULTS: There were 30 (12.2%) and 60 (24.4%) patients with High-mFI and Low-PMI, respectively. As the age increased, both sexes showed significant correlations with PMI and mFI (r = - 0.238, 0.322, P = 0.003 and 0.002, respectively). High-mFI and Low-PMI did not affect the short-term outcomes. However, High-mFI was an independent risk factor for non-home discharge (P = 0.004) and was a significant predictor of 3- and 5-year overall survival (OS) (HR = 2.76 and 2.26; P = 0.002 and 0.005, respectively) and 1-, 3- and 5-year non-cancer-specific survival (non-CSS) (HR = 4.88, 8.05, and 4.01; P = 0.017, < 0.001, < 0.001, respectively). Low-PMI was a significant predictor of only 5-year OS (HR = 2.03, P = 0.003) and non-CSS (HR = 2.10, P = 0.020). CONCLUSIONS: Frailty is significant predictor of non-home discharge and 1-, 3-, 5-year OS and 3- and 5-year non-CSS. Sarcopenia is a significant predictor of 5-year OS and non-CSS. Preoperative assessment of both frailty and sarcopenia can help surgeons to select adequate treatment strategies for the elderly population.

Hepatectomy for massive hepatic necrosis after transcatheter arterial embolization hemostasis for hepatic hemorrhage following hepatic trauma: A case report.

Key Clinical Message: Although partial hepatic necrosis often occurs following endovascular treatment for bleeding associated with hepatic trauma, it is relatively rare that additional treatment is required. However, invasive procedures such as hepatic resection should sometimes be considered when infection occurs over massive hepatic necrosis. Abstract: Although partial hepatic necrosis following endovascular treatment for bleeding associated with hepatic trauma is occasionally experienced, it is relatively rare for the necrotic area of the liver to require additional treatment. However, invasive procedures such as hepatic resection should sometimes be considered when infection occurs over massive hepatic necrosis.

Surgical Outcomes of Robotic Distal Pancreatectomy Versus Laparoscopic Distal Pancreatectomy at a Hospital in a Sparsely Populated Area.

Background: Robotic distal pancreatectomy (RDP) has a better or comparable surgical outcome when compared with laparoscopic distal pancreatectomy (LDP). However, whether the surgical outcome for these procedures in local, low-volume hospitals are comparable with those of the typically larger centers described in published reports remains unclear. Methods: This study enrolled 48 patients who underwent either RDP or LDP between August 2012 and April 2023. Data were retrospectively analyzed to evaluate the short-term surgical outcomes of RDP versus LDP in our hospital, which is a low-volume center. Results: The use of stapling with reinforcement in RDP was significantly higher than in LDP, and the postoperative hospital stay for RDP was significantly shorter than for LDP. Except for these two variables, there were no statistically significant differences between RDP and LDP in preoperative, intraoperative, or postoperative patient characteristics. Conclusion: RDP can be performed as safely and effectively as LDP in a low-volume hospital located in a sparsely populated area.

Preoperative Osteopenia Is a Risk Factor for Death in Patients Undergoing Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia. CONCLUSION: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC.

Inhibition of the bone morphogenetic protein pathway suppresses tumor growth through downregulation of epidermal growth factor receptor in MEK/ERK-dependent colorectal cancer.

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, its role in colorectal cancer (CRC) is controversial, where it can act as context-dependent tumor promoter or tumor suppressor. Here we have found that CRC cells reside in a BMP-rich environment based on curation of two publicly available RNA-sequencing databases. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of select CRC organoids. Colorectal cancer organoids treated with LDN193189 showed a decrease in epidermal growth factor receptor, which was mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) expression. Among 18 molecularly characterized CRC organoids, suppression of growth by BMP inhibition correlated with induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, in CRC organoids, which are susceptible to growth suppression by LDN193189, simultaneous treatment with LDN193189 and trametinib, an FDA-approved MEK inhibitor, resulted in cooperative growth inhibition both in vitro and in vivo. Taken together, the simultaneous inhibition of BMP and MEK could be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders to this regimen.