Effects and risk factors of TAS-102 in real-world patients with metastatic colorectal cancer, EROTAS-R study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an anticancer drug for metastatic colorectal cancer (CRC). This study aimed to analyze the effects and risk factors about effects of TAS-102 in real-world patients with metastatic CRC (the EROTAS-R study). METHODS: This study retrospectively analyzed 271 patients aged ≥ 20 years who underwent TAS-102 for metastatic CRC at nine related institutions from 2014 to 2021. Therapeutic results of TAS-102 + bevacizumab (Bev) and TAS-102, effect predictors, adverse events (AE), and AE predictors were examined. RESULTS: The backgrounds of all cases were as follows: average age, 66.7 ± 10.9 years; male ratio, 59.5%; performance status (PS) 0/1/2, 43.5%/50.6%/5.9%; and tumor site right/left, 25.5%/74.5%. The therapeutic results of 109 cases receiving TAS-102 + Bev and 162 cases receiving TAS-102 were as follows: disease control rate, 53.2% vs. 28.0% (p < 0.01); progressive free survival (PFS), 6.2 vs. 4.2 months (p < 0.01); and overall survival (S), 11.8 vs. 9.3 months (p = 0.03). Multivariate analysis for effect-related factors (odds ratio (OR), 95%confidence interval (CI)) showed the following: PS1 + 2 (0.257, 0.134-0.494, p < 0.01) and a combination of Bev (3.052, 1.598-5.827, p < 0.01). The rates of grade 3 AE for TAS-102 + Bev and TAS-102 were 53.2% and 48.8%, respectively (p = 0.47). Various AE predictors were as follows: male sex (p = 0.69), age ≥ 75 years (p = 0.59), PS1 + 2 (p = 0.20), body surface area < 1.53 m2 (p = 0.26), eGFR < 50 ml/min (p = 0.02), and AST ≥ 50 IU/L (p = 0.64). CONCLUSION: A better OS and PFS comparing TAS-102 + Bev to TAS-102 for CRC was achieved in a large number of real-world patients.

Disruption of Th2a and Th2b genes causes defects in spermatogenesis.

The variant histones TH2A and TH2B are abundant in the testis, but their roles in spermatogenesis remain elusive. Here, we show that male mutant mice lacking both Th2a and Th2b genes were sterile, with few sperm in the epididymis. In the mutant testis, the lack of TH2B was compensated for by overexpression of H2B, whereas overexpression of H2A was not observed, indicating a decrease in the total histone level. Mutant mice exhibited two defects: incomplete release of cohesin at interkinesis after meiosis I and histone replacement during spermiogenesis. In the mutant testis, secondary spermatocytes at interkinesis accumulated and cohesin was not released normally, suggesting that the retained cohesion of sister chromatids delayed the subsequent entry into meiosis II. In addition, impaired chromatin incorporation of TNP2 and degenerated spermatids were observed in the mutant testis. These results suggest that a loss of TH2A and TH2B function in chromatin dynamics or a decrease in the total histone levels causes defects in both cohesin release and histone replacement during spermatogenesis.

[An Elderly Case of Recurrent Neuroendocrine Carcinoma of the Stomach Treated with Ramucirumab].

An 84-years-old man underwent total gastrectomy with D1 plus lymph node dissection in December 2015, and diagnosed as Stage III B neuroendocrine carcinoma of the stomach. An abdominal computed tomography revealed swollen paraaortic lymph nodes and left adrenal grand in May 2016. Since his serum level of CA19-9 was elevated, he was thus diagnosed as having recurrence, and was started chemotherapy with ramucirumab(RAM). After introduction of the chemotherapy, his serum level of CA19-9 was decreased gradually and metastatic foci were also decreased in size. Although the patient required relatively longer administration interval according to the severity of general fatigue, he continued the chemotherapy without severe adverse effects until he rejected further treatment in January 2017, and satisfactory therapeutic result was acquired. While the prognosis of gastric neuroendocrine carcinoma is reported to be very poor, no definitive therapeutic guideline is available at present. Especially in elderly patients, we should pay considerable attention to the selection of chemotherapeutic agents because of their own adverse effects. In the present case, RAM could be administered safely, and it seemed that RAM might become a useful therapeutic option for gastric neuroendocrine carcinoma even in elderly patients.

De novo inbred heterozygous Zeb2/Sip1 mutant mice uniquely generated by germ-line conditional knockout exhibit craniofacial, callosal and behavioral defects associated with Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MOWS) is caused by de novo heterozygous mutation at ZEB2 (SIP1, ZFHX1B) gene, and exhibit moderate to severe intellectual disability (ID), a characteristic facial appearance, epilepsy and other congenital anomalies. Establishing a murine MOWS model is important, not only for investigating the pathogenesis of this disease, but also for identifying compounds that may improve the symptoms. However, because the heterozygous Zeb2 knockout mouse could not be maintained as a mouse line with the inbred C57BL/6 background, it was difficult to use those mice for the study of MOWS. Here, we systematically generated de novo Zeb2 Δex7/+ mice by inducing the Zeb2 mutation in the germ cells using conditional recombination system. The de novo Zeb2 Δex7/+ mice with C57BL/6 background developed multiple defects relevant to MOWS, including craniofacial abnormalities, defective corpus callosum formation and the decreased number of parvalbumin interneurons in the cortex. In behavioral analyses, these mice showed reduced motor activity, increased anxiety and impaired sociability. Notably, during the Barnes maze test, immobile Zeb2 mutant mice were observed over repeated trials. In contrast, neither the mouse line nor the de novo Zeb2 Δex7/+ mice with the closed colony ICR background showed cranial abnormalities or reduced motor activities. These results demonstrate the advantages of using de novo Zeb2 Δex7/+ mice with the C57BL/6 background as the MOWS model. To our knowledge, this is the first time an inducible de novo mutation system has been applied to murine germline cells to produce an animal model of a human congenital disease.

Dampening of death pathways by schnurri-2 is essential for T-cell development.

Generation of a diverse and self-tolerant T-cell repertoire requires appropriate interpretation of T-cell antigen receptor (TCR) signals by CD4(+ ) CD8(+) double-positive thymocytes. Thymocyte cell fate is dictated by the nature of TCR-major-histocompatibility-complex (MHC)-peptide interactions, with signals of higher strength leading to death (negative selection) and signals of intermediate strength leading to differentiation (positive selection). Molecules that regulate T-cell development by modulating TCR signal strength have been described but components that specifically define the boundaries between positive and negative selection remain unknown. Here we show in mice that repression of TCR-induced death pathways is critical for proper interpretation of positive selecting signals in vivo, and identify schnurri-2 (Shn2; also known as Hivep2) as a crucial death dampener. Our results indicate that Shn2(-/-) double-positive thymocytes inappropriately undergo negative selection in response to positive selecting signals, thus leading to disrupted T-cell development. Shn2(-/-) double-positive thymocytes are more sensitive to TCR-induced death in vitro and die in response to positive selection interactions in vivo. However, Shn2-deficient thymocytes can be positively selected when TCR-induced death is genetically ablated. Shn2 levels increase after TCR stimulation, indicating that integration of multiple TCR-MHC-peptide interactions may fine-tune the death threshold. Mechanistically, Shn2 functions downstream of TCR proximal signalling compenents to dampen Bax activation and the mitochondrial death pathway. Our findings uncover a critical regulator of T-cell development that controls the balance between death and differentiation.

[Two Cases of Single-Incision Laparoscopic Ileocecal Resection for Patients over 90 with Colon Cancer].

Single-incision laparoscopic surgery(SILS)is superior to multiport laparoscopic surgery in terms ofcosmetics, but in other terms it is still disputable and needs further investigation. The treatment of SILS for colon cancer has increased, however, the feasibility of single-incision laparoscopic colectomy(SILC)for patients over 90 with colon cancer has not been well examined. We report 2 cases ofsingle -incision laparoscopic ileocecal resection without complications. Case 1: A 104-year-old woman who had been diagnosed with pStage III a obstructive ascending colon cancer. There were no perioperative complications. She was discharged 15 days after the operation. During the 26 months of follow-up, there was no evidence oflocal recurrence or distant metastasis. Case 2: A 90-year-old woman who had been diagnosed with pStage I cecal cancer. There were no perioperative complications. She was discharged 10 days after the operation. Single-incision laparoscopic ileocecal resection for the aged patients is feasible when performed on patients selected by surgeons with extensive SILC experience.

[A Case of Gastrointestinal Stromal Tumor of the Small Intestine Complicated by Hemorrhagic Shock Due to Gastrointestinal and Intraperitoneal Bleedings].

A 44-years-old man presented to our hospital with bloody stool. CT of the abdomen revealed a 90mm mass adjacent to small intestine and high density ascites in lower abdomen. On the day of the admission, he lapsed into hemorrhagic shock caused by gastrointestinal bleedings. So emergency operation was performed. Operative findings showed a solid tumor of small intestine that were 95mm in diameter and a small amount of bloody ascites(100mL). Another tumor was also found in analis small intestine from primary lesion. Small bowel resections were performed for each lesion. Resected specimen showed the solid tumor, 95×70×50mm in size, in the small intestine. Histopathological findings showed outgrowth of spindle cells from the proper muscular layer to the subserosal layer. Immunohistochemical findings revealed positive staining for c-kit and CD34. c-kit positive GIST was thus diagnosed. Chemotherapy with imatinib was administered after surgery and the patient has been free from recurrent disease for 6 months after surgery.

[A Case of Peritoneal Dissemination of Hilar Cholangiocarcinoma Presenting with Hematuria Six Years after Radical Surgery].

A 76-year-old man underwent radical surgery for Stage IV a hilar cholangiocarcinoma in July 2009, and had been followed at an outpatient clinic. Although no apparent recurrent lesion was detected by PET/CT examination, an elevated CA19-9 level was found in January 2014. He was then started on the oral anticancer drug S-1. However, his CA19-9 level increased gradually. The patient presented to a urological department with a complaint of macrohematuria in May 2015. Detailed examination revealed a mass lesion at the top of the urinary bladder, which was suspected to be peritoneal dissemination of the known hilar cholangiocarcinoma invading the urinary bladder wall. Thus, he underwent partial resection of the urinary bladder in July 2015. A histopathological examination of the resected specimen confirmed the diagnosis of recurrence. The patient is nowreceiving chemotherapy with gemcitabine and cisplatin. Detection of recurrences of cholangiocarcinoma is often difficult since the recurrence pattern of cholangiocarcinoma varies widely. However, early detection might enable longterm survival by adequate treatment including chemotherapy. Therefore, thorough multidisciplinary examinations are required when recurrence of cholangiocarcinoma is suspected. In addition, long-term follow-up after radical surgery is required since cholangiocarcinoma sometimes shows slow progression.

[Usefulness of Transumbilical Laparoscopic-Assisted Appendectomy for a Suspected Case of Hydrops Processus Vermiformis].

A-77-year-old man presented to our hospital with high fever and lower abdominal pain. Enhanced CT of the abdomen revealed swelling of the appendix with wall thickening and fluid collection. We diagnosed appendicitis with abscess formation and performed transumbilical laparoscopic-assisted appendectomy after the inflammation improved in response to antibiotics. Operative findings revealed a cystic lesion ofthe appendix and strong adhesion ofthe appendix to the terminal ileum. Based on these operative findings, we changed the operative procedure to a single-incision laparoscopic assisted ileocecal resection because ofthe possibility ofhydrops processus vermiformis. Histopathological findings revealed hyperplasia ofthe glandular epithelium with nuclear enlargement. Mucinous cystadenocarcinoma ofthe appendix was diagnosed. Additional surgery was not performed due to the patient's request. The patient has been free from recurrent disease for approximately 6 months after the surgery. Transumbilical laparoscopic-assisted appendectomy is useful for preventing pseudomyxoma peritonei and easing changes in extended operations for suspected cases of hydrops processus vermiformis.

Efficacy of transumbilical laparoscopic-assisted appendectomy for appendicitis: a four-year experience at a single center.

PURPOSE: To compare the surgical outcomes after transumbilical laparoscopic-assisted appendectomy (TULAA) and open appendectomy (OA) at a single institution. METHODS: We compared the surgical outcomes for 94 consecutive patients who underwent TULAA between April 2010 and March 2014 to those for 91 consecutive patients who underwent OA between April 2006 and March 2010. RESULTS: There were no significant differences in the clinicopathological backgrounds between the two groups. Although the lengths of the operations were similar in both groups, the postoperative hospital stay was significantly shorter in the TULAA group (4.7 days vs. 5.4 days, P = 0.02). The need for abdominal drain insertion was significantly reduced in the TULAA group owing to sufficient intraperitoneal exploration (P = 0.03). The incidence of postoperative complications was also lower in the TULAA group, but the difference was not significant (8.6 % vs. 12.1 %, P = 0.31). In complicated cases, a lower incidence of surgical site infection was confirmed in the TULAA group (6.7 % vs. 20.7 %, P = 0.12). CONCLUSION: Our results demonstrated that TULAA provided better surgical outcomes, especially a faster recovery. TULAA could be an effective procedure incorporating both open and laparoscopic techniques, and can be implemented as a standard procedure for the treatment of appendicitis, regardless of disease severity.

[A Case of Gastritis Cystica Polyposa That Developed Early after Distal Gastrectomy].

We present a case of gastritis cystica polyposa (GCP) that developed early after laparoscopy-assisted distal gastrectomy with BillrothⅠreconstruction. GCP is a chronic inflammatory gastric mucosal lesion that emerges at an anastomotic site usually after a long post-gastrectomy period, which is mainly caused by constant chemical stimulation by duodenal juice. In addition, chronic mechanical stimulation caused by reflux or stasis of gastrointestinal contents may also trigger GCP. Surgeons should ensure a functional and physiologically patent anastomosis during surgery. Hypergastrinemia, caused by persistent Helicobacter pylori infection or continuing administration of proton pump inhibitors, may also contribute to the development of GCP, as GCP is a type of hyperplastic polyp. Therefore, appropriate postoperative follow-up, including pylorus eradication and avoidance of unnecessary administration of proton pump inhibitors, seems to be needed in order to prevent the development of GCP. In our case, many factors exhibited the multiplier effect, resulting in early development of GCP. As GCP also attracts much attention as a precancerous lesion, appropriate prevention and prompt treatment are required.

[The Case of a Long-Surviving Patient with Colorectal Neuroendocrine Carcinoma with Invasion of the Jejunum and Lymph Node Metastases after Operation].

A 44-year-old man presented to our hospital with high fever and right side ache. Laboratory data revealed the presence of inflammation. Enhanced CT of the abdomen revealed a 15 cm mass of the ascending colon, and FDG-PET showed abnormal uptake in the same site. Colonofiberscopy demonstrated an elevated lesion in the ascending colon without malignant findings in biopsies. Enema examination revealed an extrinsic compression of the ascending colon. Although the patient received antibiotic therapy, there were no signs of improvement. Therefore, right hemicolectomy with resection of the invasive lesion of the right abdominal wall and the jejunum was performed. The resected specimen showed a solid tumor, 17×11×8 cm in size, in the ascending colon. The tumor invaded the ileum. Immunohistochemical findings revealed positive staining for NSE, synaptophysin, and chromogranin A. Neuroendocrine carcinoma was thus diagnosed. CPT-11-containing chemotherapy was administered for 1 year after surgery. The patient has been free from recurrent disease for over 7 years after surgery.

SIP1 expression patterns in brain investigated by generating a SIP1-EGFP reporter knock-in mouse.

A loss of function of SIP1 (Smad interacting protein 1) in the mouse as well as in human of Mowat-Wilson syndrome results in severe and multiple defects in neural tissue development, especially in the brain. However, no detailed expression analysis of SIP1 during brain development has been previously reported. In this study, we describe the generation of an EGFP knock-in reporter mouse for the Sip1 locus and our subsequent analysis of SIP1-EGFP fusion protein expression during brain development. SIP1-EGFP expression was observed in the pyramidal neurons of the hippocampus, the dentate gyrus, and the postmitotic neurons in the cerebral cortex. In layer 5 of the cerebral cortex, SIP1-EGFP expression was complementary to the Ctip2-expressing neurons, most of which are thought to be the cortico-spinal neurons. This suggested that SIP1-EGFP expressing cells might have the specific trajectory targets other than the spinal region. We further observed SIP1-EGFP expression in oligodendrocytes of the corpus callosum and fimbria, Bergmann glial cells of the cerebellum, the olfactory bulb, and in the serotonergic and dopaminergic neurons of the raphe nuclei in the brainstem. These findings may help to clarify the unknown roles of SIP1 in these cells and the pathoetiology of Mowat-Wilson syndrome.

Social isolation stress induces ATF-7 phosphorylation and impairs silencing of the 5-HT 5B receptor gene.

Many symptoms induced by isolation rearing of rodents may be relevant to neuropsychiatric disorders, including depression. However, identities of transcription factors that regulate gene expression in response to chronic social isolation stress remain elusive. The transcription factor ATF-7 is structurally related to ATF-2, which is activated by various stresses, including inflammatory cytokines. Here, we report that Atf-7-deficient mice exhibit abnormal behaviours and increased 5-HT receptor 5B (Htr5b) mRNA levels in the dorsal raphe nuclei. ATF-7 silences the transcription of Htr5B by directly binding to its 5'-regulatory region, and mediates histone H3-K9 trimethylation via interaction with the ESET histone methyltransferase. Isolation-reared wild-type (WT) mice exhibit abnormal behaviours that resemble those of Atf-7-deficient mice. Upon social isolation stress, ATF-7 in the dorsal raphe nucleus is phosphorylated via p38 and is released from the Htr5b promoter, leading to the upregulation of Htr5b. Thus, ATF-7 may have a critical role in gene expression induced by social isolation stress.

Thyrotrophin in the pars tuberalis triggers photoperiodic response.

Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.

[Combination of self-expandable metallic stent insertion and laparoscopic surgery as a less invasive treatment of obstructive left-sided colon cancer].

The purpose of this study was to evaluate the outcome of treating obstructive left-sided colon cancer with a combination of self-expandable metallic stent (SEMS) insertion and laparoscopic surgery. Ten patients were included in this study. Two patients had obstructive transverse colon cancer, and eight had obstructive sigmoid colon cancer. The patients had a SEMS inserted preoperatively as a bridge to surgery. Efficient decompression was achieved in all the patients, without any complications. Normal oral intake was possible until the laparoscopic, or laparoscope-assisted, one-stage radical operation. The SEMS insertion did not affect the surgical maneuver or laparoscopic operation at all. None of the patients developed any postoperative complications. After surgery, five patients were diagnosed with Stage II disease and three patients were diagnosed with Stage IIIA disease. The remaining two patients had distant metastasis (para-aortic lymph node and liver) and were diagnosed with Stage IV disease. Chemotherapy was administered to the two patients with Stage IV disease after a comparatively early recovery from a less invasive surgical procedure. SEMS insertion appears to be an effective, less invasive decompression method. When used in combination with laparoscopic surgery, SEMS insertion appears to be a safe and less invasive method of treating obstructive left-sided colon cancer.

Laparoscopic cholecystectomy for patients with accessory liver lobe attached to the wall of the gallbladder: case reports.

BACKGROUND: Laparoscopic cholecystectomy (LC) is one of the most commonly undertaken procedures worldwide for cholecystolithiasis and cholecystitis. Accessory liver lobe (ALL) is a developmental anomaly defined as an excessive liver lobe composed of a normal liver parenchyma. Some ALL exist on the serosal side of the gallbladder. We herein present two cases of ALL incidentally detected during LC. CASE PRESENTATION: The first case was a 69-year-old woman diagnosed with chronic cholecystitis. LC was performed. ALL was observed anterior to the wall of the gallbladder and resected after clipping. Pathological findings revealed liver tissue with Glisson's capsule and a lobular structure in ALL. However, communication between the bile ducts of ALL and the main liver was unclear due to surgical heat degeneration. The second case was a 56-year-old woman diagnosed with acute cholecystitis. LC was performed approximately one month after the attack, and ALL attached to the wall of gallbladder. ALL was clipped and completely resected. Pathological findings showed that the bile ducts of ALL might be connected within the wall of gallbladder. CONCLUSIONS: We presented two cases of ALL attached to the gallbladder encountered during LC. Since ALL contains a normal liver parenchyma, postoperative bleeding or bile leakage may occur if it is inefficiently resected. Therefore, the complete resection of ALL is important to prevent these postoperative complications.

Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Uncoupling of growth plate maturation and bone formation in mice lacking both Schnurri-2 and Schnurri-3.

Formation and remodeling of the skeleton relies on precise temporal and spatial regulation of genes expressed in cartilage and bone cells. Debilitating diseases of the skeletal system occur when mutations arise that disrupt these intricate genetic regulatory programs. Here, we report that mice bearing parallel null mutations in the adapter proteins Schnurri2 (Shn2) and Schnurri3 (Shn3) exhibit defects in patterning of the axial skeleton during embryogenesis. Postnatally, these compound mutant mice develop a unique osteochondrodysplasia. The deletion of Shn2 and Shn3 impairs growth plate maturation during endochondral ossification but simultaneously results in massively elevated trabecular bone formation. Hence, growth plate maturation and bone formation can be uncoupled under certain circumstances. These unexpected findings demonstrate that both unique and redundant functions reside in the Schnurri protein family that are required for proper skeletal patterning and remodeling.

A newly developed oval-shaped port device (E•Z ACCESS Oval type) for use in reduced port surgery: initial clinical experiences with cholecystectomy.

We recently developed an oval-shaped E•Z Access device designed exclusively for use with the LAP PROTECTOR™ Oval type device (Hakko Co. Ltd., Tokyo, Japan). The transverse abdominal opening diameter made by round-shaped (Alexis® Wound Retractor, Applied Medical, Rancho Santa Margarita, CA; and LAP PROTECTOR™ Round type) and oval-shaped (LAP PROTECTOR™ Oval type) wound retractors was measured and compared in 5 patients with cholecystolithiasis. Each device was placed through a single 25-mm longitudinal umbilical incision, and the length of trocar separation was compared. LESS cholecystectomy was then performed using the oval-shaped E•Z ACCESS/LAP PROTECTOR™. The transverse abdominal opening diameter was maximized with the LAP PROTECTOR™ Oval type device. The average distance between the working-ports for the glove method, round-shaped, and oval-shaped E•Z ACCESS/LAP PROTECTOR™ devices in the 25-mm umbilical incisions were 20 ± 0.8 mm, 24 ± 1.5 mm, and 35 ± 0.8 mm, respectively. Wider trocar separation was achieved using the oval-shaped device, making the surgical procedures easier to perform. No perioperative port-related or surgical complications were observed. LESS cholecystectomy using the E•Z ACCESS Oval type device was found to be technically feasible. The Oval type device appears to allow for wider trocar separation, thereby reducing stress on the surgeon, ensuring patient safety, and providing cosmetic benefits.