Usefulness of a powered circular stapler compared with a manual circular stapler in patients undergoing colorectal cancer surgery: A retrospective cohort study and systematic review.

Postoperative complications related to anastomosis, including postoperative anastomotic bleeding and anastomotic leakage, remain a serious issue. The effect of anastomotic devices on suture complications during intestinal anastomosis remains unclear. The present study examined the utility of automated anastomotic devices for reducing anastomotic complication risks. A retrospective cohort study of colorectal cancer surgeries in which an anastomosis device was used at Osaka University Hospital (Suita, Japan) between January 2018 and December 2022 was conducted. Cases of emergency surgery, inflammatory bowel disease and simultaneous surgery for other cancers were excluded. Experienced gastrointestinal surgeons performed manual anastomosis using the ETHICON Circular Stapler CDH or EEA Circular Stapler, and automatic anastomosis using the ECHELON CIRCULAR Powered Stapler, with no observed operator bias. Additionally, a meta-analysis that included other study results was performed. The outcomes included postoperative complications, mainly anastomotic leakage. The study included 414 patients: 183 in the manual circular stapler group and 231 in the powered circular stapler (PCS) group. Although this retrospective study found no statistically significant association between the anastomotic device used and anastomotic complications, an increased risk ratio was observed in the manual group compared with the automatic group when restricted to elderly patients. Similarly, a meta-analysis found a significantly higher anastomotic complication risk in the manual group compared with the automatic group (random-effects model; odds ratio, 0.376; 95% confidence interval, 0.232-0.610; P<0.0001). The findings of the present study suggested that a PCS is useful for reducing the anastomotic complication risk in patients undergoing colorectal cancer surgery.

A Case of Transanal Endoscopic Excision for Rectal Tumor Using Surgical Instruments With Multi-jointed Structures.

BACKGROUND/AIM: Transanal endoscopic local excision requires fine operation in a very narrow space in the rectum. We report a case in which the use of surgical instruments with a multi-jointed structure allowed safe resection of a lesion with a stable field of view, resulting in preservation of postoperative function. CASE REPORT: The patient was a 49-year-old man who had a rectal neuroendocrine tumor (NET) (G1) with erosive changes in the lower rectum. Preoperative imaging showed no evidence of surrounding lymph node or distant metastasis; thus, we performed a transanal endoscopic local excision of the tumor. After positioning the patient under general anesthesia and securing the field of view in the intra-rectal cavity, the flexion of the surgical instruments with a multi-jointed structure was used to secure the operating space to not interfere with the camera and the surgeon's right hand. The operating field was developed, and the tumor was incised by stable traction. After the excision, the needle was advanced in the direction of the intestinal axis using the multi-jointed holder, and continuous suturing was performed. The patient has no recurrence without any defecation disorder. CONCLUSION: The use of multi-jointed surgical instruments in transanal endoscopic excision of rectal tumors can provide a stable operative field and preserve postoperative function. The advanced flexibility of these instruments allows precise manipulation in the narrow rectal space, resulting in successful tumor resection with minimal invasiveness and no postoperative complications. These findings suggest that multi-jointed instruments are valuable for enhancing the safety and efficacy of minimally invasive rectal surgery.

A case of intestinal intussusception with unique hemorrhagic polyps due to AL amyloidosis and excessive anticoagulation.

Most adult intussusceptions are secondary to various pathological conditions that serve as a lead point. Because of their serious nature, intussusceptions often require emergency surgery. We report a surgical case of amyloidosis associated with intussusception, probably due to polypoid protrusions and bleeding tendencies. An 80-year-old man with abdominal pain was suspected of having jejunal intussusception on computed tomography. He had been prescribed warfarin for atrial fibrillation, and excessive anticoagulation was observed with a prolonged prothrombin time/international normalized ratio of 5.44 at presentation. After the excessive anticoagulation was resolved, emergency surgery was performed. The intussuscepted jejunum was resected, and a 7 cm long dark-red pedunculated polyp was identified as the lead point, which was accompanied by multiple small pedunculated polyps. Histopathological examination showed that these were all hemorrhagic polyps. Amyloid depositions were observed in the muscularis mucosae, submucosa, and the walls of the blood vessels. Immunohistochemical analysis revealed immunoglobulin light chain amyloidosis. This case is informative to discuss the clinical sequelae of gastrointestinal amyloid deposition.

Metastases and treatment-resistant lineages in patient-derived cancer cells of colorectal cancer.

Circulating tumor cells (CTCs) play an important role in metastasis and recurrence. However, which cells comprise the complex tumor lineages in recurrence and are key in metastasis are unknown in colorectal cancer (CRC). CRC with high expression of POU5F1 has a poor prognosis with a high incidence of liver metastatic recurrence. We aim to reveal the key cells promoting metastasis and identify treatment-resistant lineages with established EGFP-expressing organoids in two-dimensional culture (2DOs) under the POU5F1 promotor. POU5F1-expressing cells are highly present in relapsed clinical patients' blood as CTCs. Sorted POU5F1-expressing cells from 2DOs have cancer stem cell abilities and abundantly form liver metastases in vivo. Single-cell RNA sequencing of 2DOs identifies heterogeneous populations derived from POU5F1-expressing cells and the Wnt signaling pathway is enriched in POU5F1-expressing cells. Characteristic high expression of CTLA4 is observed in POU5F1-expressing cells and immunocytochemistry confirms the co-expression of POU5F1 and CTLA4. Demethylation in some CpG islands at the transcriptional start sites of POU5F1 and CTLA4 is observed. The Wnt/ß-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.

Treatment response prediction of neoadjuvant chemotherapy for rectal cancer by deep learning of colonoscopy images.

In current clinical practice, several treatment methods, including neoadjuvant therapy, are being developed to improve overall survival or local recurrence rates for locally advanced rectal cancer. The response to neoadjuvant therapy is usually evaluated using imaging data collected before and after preoperative treatment or postsurgical pathological diagnosis. However, there is a need to accurately predict the response to preoperative treatment before treatment is administered. The present study used a deep learning network to examine colonoscopy images and construct a model to predict the response of rectal cancer to neoadjuvant chemotherapy. A total of 53 patients who underwent preoperative chemotherapy followed by radical resection for advanced rectal cancer at the Osaka University Hospital between January 2011 and August 2019 were retrospectively analyzed. A convolutional neural network model was constructed using 403 images from 43 patients as the learning set. The diagnostic accuracy of the deep learning model was evaluated using 84 images from 10 patients as the validation set. The model demonstrated a sensitivity, specificity, accuracy, positive predictive value and area under the curve of 77.6% (38/49), 62.9% (22/33), 71.4% (60/84), 74.5% (38/51) and 0.713, respectively, in predicting a poor response to neoadjuvant therapy. Overall, deep learning of colonoscopy images may contribute to an accurate prediction of the response of rectal cancer to neoadjuvant chemotherapy.

Surgery for Rectal Cancer With Mixed Reality of 3D Model During Operation: A Case Report.

Background/Aim: Recently, robotic surgery for rectal cancer has become a common minimally invasive surgery. In addition, the technology of augmented and mixed reality is applied in various living environments, including medicine. We successfully performed robotic surgery for rectal cancer with three-dimensional (3D) images as mixed reality (MR) using HoloLens2. Case Report: The patient was diagnosed with rectal cancer by colonoscopy and a positron-emission computed-tomography scan, and we performed robot-assisted anterior resection. The operator used HoloLens2 and performed the surgery while visualizing 3D images of pelvic anatomy with the location of the rectal cancer as hologram. The operation was performed completely and safely, and she was discharged 11 days after surgery with no postoperative complications. Conclusion: This case presents the usefulness of a MR system offering organ visualization as hologram during surgery.

Clinical Impact of Two-Week Placement of a Subcutaneous Suction Drain in Preventing Incisional Surgical Site Infection in Open Gastrointestinal Surgery with Class 4 Dirty Wound: A Retrospective Study.

Background: Two recent randomized controlled trials demonstrated the beneficial effects of subcutaneous drainage in preventing incisional surgical site infection (SSI) in colorectal surgery. This study aimed to evaluate the efficacy of subcutaneous suction drains (SSDs) compared with primary skin closure (PC) in class 4 dirty wound surgery. Patients and Methods: Eighty-one patients undergoing open gastrointestinal surgery with class 4 dirty wounds were enrolled in this study, 30 of whom underwent SSD insertion, whereas the other 51 were treated with PC. Because several studies have reported that the median onset of the development of incisional SSI was eight to 13 days after surgery, we used a two-week placement of an SSD. Comparison of patients treated with SSD and PC and multivariable analysis were performed to test the ability of SSD in decreasing the SSI rate. Results: No differences were observed between the two groups in terms of gender, body mass index, American Society of Anesthesiology score, steroid use, presence of diabetes mellitus, peri-operative transfusion, and surgery type. Surgical site infection incidence was lower in the SSD group (6.6%; 2/30) than that in the PC group (23.5%; 12/51; p = 0.069). Multivariable analysis revealed that the presence of diabetes mellitus was an important independent risk factor for incisional SSI, and the placement of an SSD has substantial preventive effects on incisional SSI (p = 0.018 and p = 0.014, respectively). Conclusions: This study suggested the potential importance of a two-week placement of an SSD for preventing incisional SSI in class 4 dirty wound surgery.

Rapid genomic profiling of circulating tumor DNA in non-small cell lung cancer using Oncomine Precision Assay with Genexus™ integrated sequencer.

Background: Genomic profiling of tumors from cancer patients facilitates molecular-guided therapy. The turnaround time is one of important issues to deliver results timely for clinical decisions. The Ion Torrent™ Genexus™ Integrated Sequencer automates all next generation sequencing (NGS) workflows and delivers results within a day. Methods: In this study, we conducted a feasibility study to evaluate the detection rate of genomic alterations from cell-free total nucleic acid (cfTNA, containing cfDNA and cfRNA) of 119 non-small cell lung cancer using Oncomine Precision Assay on Genexus™ Integrated Sequencer. Oncomine Precision Assay (OPA) covers actionable mutations, copy number variations and fusion genes and that are applicable for the selection of targeted therapy. cfTNA isolated from plasma (derived from 14 ml of blood) were subjected to the Genexus system for library construction, templating, sequencing, and data analyses. Results: The sequencing resulted in median overall depth of 35,773× and median molecular coverage of 2,192× with cfTNA input ranged from 11 to 36 ng. Among the 119 samples evaluated, we detected at least one genomic alteration in plasma cfTNA of 79 cases (66%). When comparing to standard-of-care testing, the sensitivity and specificity of mutation detection in non-small cell lung cancer related genes using liquid biopsy with Genexus-OPA ranged between 49-67% and 93-100%, respectively. 59% of actionable mutations, which were present in tumor tissues, were detected by the Genexus- Oncomine Precision Assay using plasma cfTNA. Among the 5 mutations detected from liquid biopsy only, three mutations are of level 1 evidence according to OncoKB database, highlighting the clinical utilities of liquid biopsy in addressing tumor heterogeneity. Extrathoracic metastasis and levels of lactate dehydrogenase (LDH), C-reactive protein (CRP) and Carcinoembryonic Antigen (CEA) are found to be associated with increased circulating tumor DNA detection. Conclusions: The Genexus™ Integrated Sequencer system is an automated, accurate NGS system with short turnaround time (TAT) that could assist clinicians to make more timely decision.

Clinical significance of clonal hematopoiesis in the interpretation of blood liquid biopsy.

As the use of next-generation sequencing (NGS) for plasma cell-free DNA (cfDNA) continues to expand in clinical settings, accurate identification of circulating tumor DNA mutations is important to validate its use in the clinical management for cancer patients. Here, we aimed to characterize mutations including clonal hematopoiesis (CH)-related mutations in plasma cfDNA and tumor tissues using the same ultradeep NGS assay and evaluate the clinical significance of CH-related mutations on the interpretation of liquid biopsy results. Ultradeep targeted NGS using Oncomine Pan-Cancer Panel was performed on matched surgically resected tumor tissues, peripheral blood cells (PBCs), and 120 plasma cfDNA samples from 38 colorectal cancer patients. The clinical significance of the CH-related mutations in plasma cfDNA was evaluated by longitudinal monitoring of the postoperative plasma samples. Among the 38 patients, 74 nonsynonymous mutations were identified from tumor tissues and 64 mutations from the preoperative plasma samples. Eleven (17%) of the 64 mutations identified in plasma cfDNA were also detected in PBC DNA and were identified to be CH-related mutations. Overall, 11 of 38 (29%) patients in this cohort harbored at least one CH-related mutation in plasma cfDNA. These CH-related mutations were continuously detected in subsequent postoperative plasma samples from three patients which could be misinterpreted as the presence of residual disease or as lack of treatment response. Our results indicated that it is essential to integrate the mutational information of PBCs to differentiate tumor-derived from CH-related mutations in liquid biopsy analysis. This would prevent the misinterpretation of results to avoid misinformed clinical management for cancer patients.

[Early Liver Metastases after Curative Surgery for Stageâ Gastric Cancer with Neuroendocrine Differentiation-A Case Report].

An 87-year-old male patient was admitted to our hospital with a chief complaint of vomiting. Gastroscopy revealed Type 0-Ⅱc+Ⅱa tumor at the posterior wall in the middle third of the stomach. A biopsy indicated moderately differentiated adenocarcinoma. Abdominal CT revealed no lymph node or distant metastases. The clinical diagnosis was cT2(MP), N0, M0, cStage Ⅰ. Laparoscopic distal gastrectomy with D2 lymphadenectomy was performed. The pathological findings revealed moderately differentiated adenocarcinoma containing synaptophysin, chromogranin A, and CD56-positive tumor cells. He was then diagnosed with adenocarcinoma with neuroendocrine differentiation. The pathological diagnosis was pT2(MP), pN0, M0, pStage ⅠB. MRI revealed multiple liver metastases 5 months postoperatively. S-1 alone chemotherapy was started, and the patient showed partial response(PR)after 3 courses, according to the Response Evaluation Criteria in Solid Tumor (RECIST).

Occupational physical activity in relation to risk of cardiovascular mortality: The Japan Collaborative Cohort Study for Evaluation for Cancer Risk (JACC Study).

We examined the association between patterns of occupational physical activity (OPA) and mortality from cardiovascular disease (CVD) in a Japanese population. A community-based, prospective cohort of 66,161 men and women aged 40-79years without a history of CVD or cancer at baseline (1988-1990) was followed until 2009. OPA was divided into four types: mostly sitting, sitting and standing (sitting/standing), mostly standing, and standing and walking (standing/walking). During follow-up for a median of 19.2years, 3728 deaths from CVD were registered. Compared with mostly sitting OPA, standing/walking OPA was not associated with a reduced risk of CVD mortality for all subjects, but it was associated with a 20% lower risk of CVD mortality among overweight individuals (body mass index ≥25kg/m(2)). Compared with mostly sitting OPA, mostly standing OPA was associated with an approximately 20% higher risk of CVD mortality, especially among overweight individuals or those with lower exercise (<2.5h/week). In conclusion, compared with mostly sitting OPA, standing/walking OPA is associated with lower CVD mortality among overweight individuals, while mostly standing OPA is associated with higher CVD mortality, especially in physically inactive individuals.

Development of a drug-coated microneedle array and its application for transdermal delivery of interferon alpha.

Interferon alpha (IFNα) is one of the most famous drugs for the treatment of chronic hepatitis C and various types of human malignancy. Protein drugs, including IFNα, are generally administered by subcutaneous or intramuscular injection due to their poor permeability and low stability in the bloodstream or gastrointestinal tract. Therefore, in the present study, novel IFNα-coated polyvinyl alcohol-based microneedle arrays (IFNα-MNs) were fabricated for the transdermal delivery of IFNα without the painful injection. IFNα was rapidly released from MNs in phosphate buffered solution and these MNs presented piercing ability in the rat skin. Slight erythema and irritation were observed when MNs were applied to the rat skin, but these skin damages completely disappeared within 24 h after removing the IFNα-MNs. Furthermore, the pharmacokinetic parameters of IFNα-MNs were similar to those of IFNα subcutaneous administration. Finally, IFNα-MNs showed a significant antitumor effect in tumor bearing mice similar to that of IFNα subcutaneous administration. These results indicate that IFNα-MNs are a useful biomaterial tool for protein drug therapy and can improve the quality of life in patients by avoidance of painful injections.

Development of a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of osteoporosis.

Bisphosphonates are widely used for the treatment and prevention of bone diseases, including Paget disease, hypercalcemia of malignancy, and postmenopausal osteoporosis. In this study, we developed a novel transdermal patch of alendronate, a nitrogen-containing bisphosphonate, for the treatment of bone diseases. The maximum permeation fluxes of alendronate through rat and human skin after application of this patch were 1.9 and 0.3 µg/cm(2) per hour, respectively. The bioavailability (BA) of alendronate in rats was approximately 8.3% after the application of alendronate patch and approximately 1.7% after oral administration. These results indicated that the transdermal permeation of alendronate using this patch system was sufficient for the treatment of bone diseases. The plasma calcium level was effectively reduced after application of the alendronate patch in 1α-hydroxyvitamin D(3) -induced hypercalcemia model rats. The alendronate patch also effectively suppressed the decrease in bone mass in model rats with osteoporosis. Modest alendronate-induced erythema of rat skin was observed after application of the alendronate patch. Incorporation of butylhydroxytoluene in the alendronate patch almost completely suppressed this alendronate-induced skin damage while maintaining the transdermal permeation and pharmacologic effects of alendronate. These findings indicate that our novel transdermal delivery system for alendronate is a promising approach to improve compliance and quality of life of patients in the treatment of bone diseases.

Molecular cloning and characterization of rat brain endothelial cell derived gene-1 (tumor suppressor candidate 5) expressing abundantly in adipose tissues.

We report the cloning and expressional analysis of rat brain endothelial cell derived gene-1 (BEC-1), detected as a gene dominantly expressed in rat brain endothelial cells by the use of suppression subtractive hybridization technique. The complementary deoxyribonucleic acid sequence of BEC-1 messenger ribonucleic acid was completely determined with a full length of 3410 bp. The open reading frame within the sequence consisted of 522 bp, and the predicted protein sequence was 173 amino acid residues. BEC-1 gene was thought to be rat tumor suppressor candidate 5 (TUSC5), since BEC-1 had considerable homology with both mouse TUSC5 and human located at 17-p-13 point three 1 (LOST1) categorized as human TUSC5 (identities of 97% and 85%, respectively), which were recently identified as a novel tumor suppressor gene candidate. Expressional analyses for BEC-1 mRNA with real-time PCR and of BEC-1 protein by Western blotting demonstrated that both were dominantly expressed in the adipose tissues of Sprague-Dawley (SD) rats. We analyzed and compared the differential expressions of BEC-1 (TUSC5) mRNA and protein in fat tissues between obese homozygous (fa/fa) and lean wild-type (+/+) Zucker rats. Both expressions in the epididymal white adipose tissue (WAT) were highest, followed by those in the interscapular brown adipose tissue (BAT), subcutaneous, and mesenteric WATs, respectively. Interestingly, both expressions in epididymal WAT of obese Zucker rats were significantly lower than those in lean rats. Although cold exposure at 4 degrees C for 6 h significantly stimulated uncoupling protein-1 (UCP-1) mRNA expression, it significantly inhibited BEC-1 (TUSC5) mRNA expression in the interscapular BAT. These data indicated that rat BEC-1 (TUSC5) was abundantly expressed in adipose tissues, and that it might be involved in their regulation independently of UCP-1.