Clinical utility of sarcopenia dynamics assessed by psoas muscle volume in patients with colorectal cancer.

BACKGROUND: Sarcopenia affects the postoperative prognosis of patients with colorectal cancer (CRC). Recently, it has become possible to measure psoas volume from computed tomography images, and an index called psoas volume index (PVI) has been reported. However, it is unclear whether the dynamics of PVI before and after surgery is associated with clinical outcomes after CRC surgery. This study aimed to evaluate the association between pre- and postoperative PVI dynamics and clinical outcomes after CRC surgery. METHODS: This study analyzed 1115 patients diagnosed with primary CRC and operated on for treatment between January 2014 and December 2017. Sarcopenia was defined as PVI below the lowest tertile in the preoperative assessment for each sex. The overall population was divided into four groups according to the dynamics of sarcopenia from preoperative to postoperative: group 1 (pre-to postoperative sarcopenia), group 2 (preoperative nonsarcopenia to postoperative sarcopenia), group 3 (pre-to postoperative nonsarcopenia), and group 4 (pre-to postoperative nonsarcopenia). RESULTS: Based on pre- and postoperative sarcopenia dynamics, 343 patients (29.7%) were classified into group 1, 105 patients (9.1%) into group 2, 42 patients (3.6%) into group 3, and 665 patients (57.6%) into group 4. Comparison of overall survival (OS) by the Kaplan-Meier method showed that Group 2 tended to have the worst prognosis (p = 0.007). Multivariate analysis showed an increased OS risk in Group 2 in sarcopenia dynamics (Hazard ratio: 2.103, 95% CI: 1.202-3.681, p = 0.009). CONCLUSIONS: Sarcopenia dynamics using PVI is an independent prognostic predictor of OS in patients with CRC.

Fluorescence guidance using near-infrared fluorescent clips in robotic rectal surgery: a case series.

PURPOSE: Tattoo markings are often used as preoperative markers for colorectal cancer. However, scattered ink markings adversely affect tumor site recognition intraoperatively; therefore, interventions for rectal cancer may lead to an inaccurate distal resection margin (DRM) and incomplete total mesorectal excision (TME). This is the first case series of fluorescence-guided robotic rectal surgery in which near-infrared fluorescence clips (NIRFCs) were used to localize rectal cancer lesions. METHODS: We enrolled 20 consecutive patients who underwent robotic surgery for rectal cancer between December 2022 and December 2023 in the current study. The primary endpoints were the rate of intraoperative clip detection and its usefulness for marking the tumor site. Secondary endpoints were oncological assessments, including DRM and the number of lymph nodes. RESULTS: Clip locations were confirmed in 17 of 20 (85%) patients. NIRFCs were not detected in 3 out of 7 patients who underwent preoperative chemoradiation therapy. No adverse events, including bleeding or perforation, were observed at the time of clipping, and no clips were lost. The median DRM was 55 mm (range, 22-86 mm) for rectosigmoid (Rs), 33 mm (range, 16-60 mm) for upper rectum (Ra), and 20 mm (range, 17-30 mm) for low rectum (Rb). The median number of lymph nodes was 13 (range, 10-21). CONCLUSION: The rate of intraoperative clip detection, oncological assessment, including DRM, and the number of lymph nodes indicate that the utility of fluorescence-guided methods with NIRFCs is feasible for rectal cancer.

Recurrent severe anemia associated with a jejunal arteriovenous malformation in pregnancy: A case report.

Background: Small intestinal arteriovenous (AV) malformations may cause gastrointestinal hemorrhage, occasionally leading to anemia; however, they are rarely seen in pregnancy. This report presents a case of a pregnant woman who had recurrent severe anemia that was attributed to a small hemorrhagic intestinal arteriovenous malformation. Case Presentation: A 24-year-old pregnant woman (gravida 2, para 1) presented with a low hemoglobin concentration (3.6 g/dL) in her first pregnancy and underwent an emergency cesarean section at 36 weeks due to non-reassuring fetal status. In her second pregnancy, she was hospitalized at 30 weeks with epigastric pain and nausea. A low hemoglobin level (6.6 g/dL) and scant fecal occult blood were revealed upon examination. She was referred to the hospital for further evaluation and pregnancy management. Recurrent blood transfusions were required; however, neither hematemesis nor obvious fecal hemorrhage was observed. At 31 weeks, a cesarean section was performed owing to persistent anemia. Postoperative small intestinal capsule endoscopy and flexible fiberoptic proximal small intestinal endoscopy revealed a suspected bleeding small intestinal arteriovenous malformation. The patient underwent partial resection of the small intestine on hospitalization day 16. Histopathological examination confirmed a small intestinal arteriovenous malformation. The patient had a good postoperative course and was discharged on hospitalization day 24. Conclusions: Small intestinal arteriovenous malformations can bleed during pregnancy. They can go undetected if they spontaneously shrink postpartum. In severe anemia during pregnancy, hemorrhage from small intestinal arteriovenous malformations should be included in the differential diagnosis and promptly investigated even in the absence of gastrointestinal symptoms.

Inhibition of protein kinase C delta leads to cellular senescence to induce anti-tumor effects in colorectal cancer.

Protein kinase C delta (PKCδ) is a multifunctional serine-threonine kinase implicated in cell proliferation, differentiation, tumorigenesis, and therapeutic resistance. However, the molecular mechanism of PKCδ in colorectal cancer (CRC) remains unclear. In this study, we showed that PKCδ acts as a negative regulator of cellular senescence in p53 wild-type (wt-p53) CRC. Immunohistochemical analysis revealed that PKCδ levels in human CRC tissues were higher than those in the surrounding normal tissues. Deletion studies have shown that cell proliferation and tumorigenesis in wt-p53 CRC is sensitive to PKCδ expression. We found that PKCδ activates p21 via a p53-independent pathway and that PKCδ-kinase activity is essential for p21 activity. In addition, both repression of PKCδ expression and inhibition of PKCδ activity induced cellular senescence-like phenotypes, including increased senescence-associated ß-galactosidase (SA-ß-gal) staining, low LaminB1 expression, large nucleus size, and senescence-associated secretory phenotype (SASP) detection. Finally, a kinase inhibitor of PKCδ suppressed senescence-dependent tumorigenicity in a dose-dependent manner. These results offer a mechanistic insight into CRC survival and tumorigenesis. In addition, a novel therapeutic strategy for wt-p53 CRC is proposed.

Short-term Postoperative Outcomes of Colorectal Cancer Patients With Chronic Renal Failure on Dialysis.

BACKGROUND/AIM: Surgery for dialysis patients requires special attention because of their physical characteristics. This study aimed to investigate the short-term postoperative outcomes of colorectal cancer patients with chronic renal failure (CRF) on dialysis and aimed to investigate safer treatment options for these patients. PATIENTS AND METHODS: A total of 1,504 colorectal cancer patients who underwent primary resection between January 2008 and December 2018 were included. A retrospective analysis of clinical data, preoperative tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9), and the Clavien-Dindo (CD) classification was performed. Patients were stratified into Groups A and B based on their need for dialysis or not, respectively. RESULTS: There were 20 and 1,484 patients in Groups A and B, respectively. No differences were observed regarding age, body mass index, and preoperative tumor markers. The rate of laparoscopic surgery was significantly lower in Group A than in Group B. There was one mortality in Group A due to pulmonary disease. Group A had a significantly higher rate of complications. CONCLUSION: CRF patients on dialysis who underwent colorectal cancer surgery tended to be ruled out of laparoscopic surgery, and their rates of postoperative complications were higher.

The time-dependent changes in serum carcinoembryonic antigen impact on posthepatectomy outcomes of colorectal liver metastasis.

BACKGROUND: Only a few studies have examined the impact of carcinoembryonic antigen variation in patients before and after curative resection of colorectal liver metastasis . This study examined the correlation between carcinoembryonic antigen levels and patient prognosis. METHODS: Patients who underwent curative resection for colorectal liver metastasis between 2000 and 2017 were enrolled. This study examined patients with high preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis and the correlation between prognosis and time-dependent changes in carcinoembryonic antigen levels. The similarity in the risk of recurrence in patients with normal preoperative carcinoembryonic antigen levels was evaluated. RESULTS: A total of 143 consecutive patients were included in the study cohort and classified into the normal preoperative (46 patients), normalized postoperative (57 patients), and elevated preoperative and postoperative (40 patients) carcinoembryonic antigen groups. All clinicopathologic characteristics were comparable between patients grouped according to carcinoembryonic antigen levels. The 5-year disease-free survival and overall survival rates for all patients were 30.4% and 56.0%, respectively. Multivariate analysis confirmed that elevated preoperative and postoperative carcinoembryonic antigen levels (hazard ratio = 1.73, 95% confidence interval: 1.04-2.87) were independently associated with poor disease-free survival; normalization of postoperative carcinoembryonic antigen (hazard ratio = 0.94, 95% confidence interval: 0.57-1.53) was statistically indistinguishable from normal preoperative carcinoembryonic antigen levels. The risk of recurrence was similar to that of patients with normal preoperative carcinoembryonic antigen levels CONCLUSION: Patients with elevated preoperative carcinoembryonic antigen levels that normalized after resection of colorectal liver metastasis were not at risk of poor disease-free survival. Elevated carcinoembryonic antigen levels after surgery are independent prognostic factors for disease-free survival.

Evaluation of the Outcome of Local Surgery for Stomal Prolapse.

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors' and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Transferrin predicts outcome in patients who underwent liver resection for colorectal liver metastases.

INTRODUCTION: The aim of this study is to investigate the relationship between preoperative serum transferrin level and long-term outcomes in patients with colorectal liver metastases after hepatic resection. METHODS: We retrospectively investigated 72 patients who underwent hepatic resection for colorectal liver metastases and explored the relationship between serum transferrin level and long-term outcomes. RESULTS: In multivariate analysis, H3 (odds ratio 3.43, 95% confidence interval 1.11-10.89 and P = 0.03) was an independent and significant predictor of the disease-free survival, and a transferrin level ≥ 190 mg/dl (odds ratio 0.20, 95% confidence interval 0.05-0.79 and P = 0.02) and the time to recurrence after hepatectomy <1 year (odds ratio 11.30, 95% confidence interval 2.63-48.59 and P < 0.01) were independent and significant predictors of the overall survival. CONCLUSIONS: The serum transferrin level is a useful predictor of poor overall survival in patients with colorectal liver metastases after hepatic reaction.

Unconventional Secretion of PKCδ Exerts Tumorigenic Function via Stimulation of ERK1/2 Signaling in Liver Cancer.

Expression of human protein kinase C delta (PKCδ) protein has been linked to many types of cancers. PKCδ is known to be a multifunctional PKC family member and has been rigorously studied as an intracellular signaling molecule. Here we show that PKCδ is a secretory protein that regulates cell growth of liver cancer. Full-length PKCδ was secreted to the extracellular space in living liver cancer cells under normal cell culture conditions and in xenograft mouse models. Patients with liver cancer showed higher levels of serum PKCδ than patients with chronic hepatitis or liver cirrhosis or healthy individuals. In liver cancer cells, PKCδ secretion was executed in an endoplasmic reticulum (ER)-Golgi-independent manner, and the inactivation status of cytosolic PKCδ was required for its secretion. Furthermore, colocalization studies showed that extracellular PKCδ was anchored on the cell surface of liver cancer cells via association with glypican 3, a liver cancer-related heparan sulfate proteoglycan. Addition of exogenous PKCδ activated IGF-1 receptor (IGF1R) activation and subsequently enhanced activation of ERK1/2, which led to accelerated cell growth in liver cancer cells. Conversely, treatment with anti-PKCδ antibody attenuated activation of both IGF1R and ERK1/2 and reduced cell proliferation and spheroid formation of liver cancer cells and tumor growth in xenograft mouse models. This study demonstrates the presence of PKCδ at the extracellular space and the function of PKCδ as a growth factor and provides a rationale for the extracellular PKCδ-targeting therapy of liver cancer. SIGNIFICANCE: PKCδ secretion from liver cancer cells behaves as a humoral growth factor that contributes to cell growth via activation of proliferative signaling molecules, which may be potential diagnostic or therapeutic targets.

Umbilical Defunctioning Ileostomy for Rectal Cancer Results in Reduced Risk for Incisional Hernia.

BACKGROUND/AIM: Umbilical defunctioning ileostomy (UDI) spares one incision, which may reduce the overall incidence of incisional hernia. Our aim was to evaluate the occurrence and risk factors of incisional hernias between UDI and conventional defunctioning ileostomy (CDI) after ileostomy closure. PATIENTS AND METHODS: Incidence of incisional hernia after ileostomy closure was compared between UDI (n=51) and CDI (n=86) groups. Risk factors for incisional hernia were also considered through a retrospective analysis. RESULTS: The overall incidence of incisional hernia was 5.9% in the UDI group, which was significantly lower than the 22.1% (7.0% at the midline incision and 15.1% at the stoma site) in the CDI group (p=0.012). Multivariate analysis showed higher BMI (p=0.035) and CDI (p=0.031) as risk factors for developing incisional hernias overall. CONCLUSION: UDI results in fewer incisional hernias than CDI and seems to be superior to CDI from the standpoint of overall incidence of incisional hernias.

Comparison of Strength of Anastomosis Between Four Different Techniques for Colorectal Surgery.

BACKGROUND/AIM: Advances in stapling devices have led to their widespread use in colorectal surgery. We compared the strength of four types of anastomoses using bursting pressure. MATERIALS AND METHODS: We created stapled anastomosis models [double stapling technique (DST), functional end-to-end anastomosis (FEEA) unbuttressed or buttressed, and triangulating anastomosis (TA) with two- or three-row stapling] and a hand-sewn anastomosis model. Bursting pressures of each method were measured. The primary end point was the bursting pressure. The effectiveness of buttressing and three-row stapling were the secondary endpoints. RESULTS: The DST group had significantly lower bursting pressure than TA with three-row stapling, FEEA buttressed, and hand-sewn groups. No significant difference was found between the bursting pressure of the FEEA unbuttressed and FEEA buttressed groups and that of the TA with two-row and three-row stapling groups. CONCLUSION: DST has the lowest bursting pressure compared to other anastomotic techniques. Buttressing suture and three-row stapling have no effect on the strength of anastomosis.

Impairment of DYRK2 by DNMT1­mediated transcription augments carcinogenesis in human colorectal cancer.

Dual specificity tyrosine­phosphorylation­regulated kinase 2 (DYRK2) is a protein kinase that functions as a novel tumor suppressor. Previous studies have reported that DYRK2 expression is decreased in colorectal cancer compared with adjacent non­tumor tissues. However, the regulatory mechanisms by which the expression of DYRK2 is diminished remain unknown. The aim of the present study was to determine the regulatory mechanisms of DYRK2 expression. The present study identified the promoter regions of the DYRK2 gene and demonstrated that they contained CpG islands in human cancer cells. In addition, the DYRK2 promoter region exhibited a higher level of methylation in colorectal cancer tissues compared with healthy tissues from clinical samples. DYRK2 expression was increased at the mRNA and protein level in colorectal cancer cell lines by treatment with 5­Azacytidine, a demethylating agent. The results further demonstrated that knockdown of DNA methyltransferase (DNMT) 1 elevated DYRK2 expression in colorectal cancer cell lines. A colitis­related mouse carcinogenesis model also exhibited a lower DYRK2 level in colorectal cancer tissues compared with adjacent non­tumor tissues. In this model, nuclear staining of DNMT1 was detected in colorectal cancer cells, whereas a cytoplastic distribution pattern of DNMT1 staining was exhibited in healthy tissue. Overall, these findings suggested that DYRK2 expression was downregulated via transcriptional regulation by DNMT1 to elevate the proliferation of colorectal cancer cells.

Effective method of gallbladder retraction for single-incision laparoscopic cholecystectomy.

INTRODUCTION: Recently, single-incision laparoscopic cholecystectomy has been accepted as an alternative to conventional laparoscopic cholecystectomy. The aim of this study was to retrospectively evaluate the safety and feasibility of unique gallbladder retraction methods using an ENDOLOOP® (Ethicon, Tokyo, Japan) and Lapaherclosure™ (Hakko Medical, Tokyo, Japan). MATERIALS AND SURGICAL TECHNIQUE: From May 2013 to April 2015, 77 patients underwent single-incision laparoscopic cholecystectomy with this retraction technique. During the same period, conventional laparoscopic cholecystectomy was performed in 85 patients; these patients were the control group. The patients' data, including the operative time, total blood loss, conversion rate to laparotomy, and perioperative complications, were compared. Alexis® Wound Retractor XS (Applied Medical, Tokyo, Japan) was inserted through a 25-30-mm vertical transumbilical incision to prevent bile contamination. Next, a SILS Port (Covidien, Tokyo, Japan) was inserted. A flexible 5-mm laparoscope was inserted through the port with a grasper (SILS Clinch, Covidien) and a normal 5-mm scalpel. The fundus of the gallbladder was tied by the ENDOLOOP. The Lapaherclosure was then directly inserted through a right lower intercostal space to capture and pull the Lapaherclosure out. After the cystic artery and duct were cut, the resected gallbladder was directly extracted from the umbilical incision. DISCUSSION: Several methods and devices have been developed to perform single-incision laparoscopic cholecystectomy, including the suturing method, the Mini Loop Retractor II (Covidien), and the EndoGrab (Virtual Ports, Caesarea, Israel). However, considering medical costs and safety, our retraction method seems to be feasible and comparable to existing methods.

Intestinal Obstruction Caused by Persimmon Bezoar: A Case Report.

Owing to their rare occurrence, persimmon bezoars are often overlooked as a cause of small bowel obstruction. We herein report a small bowel obstruction in a 67-year-old Japanese female who regularly consumed persimmons in autumn. The patient presented to our hospital with typical complaints of abdominal distension with pain for 2 days. Based on the patient's history of a cesarean section 34 years ago, we initially diagnosed her with small bowel obstruction resulting from adhesions and placed an ileus tube. At first, the patient rejected the operation in spite of our recommendation. After 10 days, because the ileus tube was unable to relieve the obstruction, finally surgery was scheduled. Upon releasing the obstruction by partial resection of the small bowel, we found an impacted bezoar without any evidence of adhesions. After stone analysis, we first realized her regular persimmon intake. This case serves as an important reminder to obtain dietary history in order to investigate all possible causes of small bowel obstruction when intestinal obstruction is suspected.