[A Case of Perforation of Unresectable Esophageal Cancer during Nivolumab Therapy].

A 46-year-old man visited our hospital complaining of dysphagia. He was diagnosed with unresectable esophageal cancer with multiple lung metastases(cStage Ⅳb)and gastric cancer(L, Gre, T3N+M0, cStage Ⅲ). The esophageal lesion and the lung metastatic lesions showed shrinkage initially with 5-FU, CDDP(FP)therapy but then re-grew; therefore, the therapy was changed to nivolumab therapy. After three courses of nivolumab therapy, the patient visited our hospital with a high fever. He was admitted as an emergency patient with a diagnosis of esophageal perforation and mediastinal abscess. CT- guided drainage was performed, and a self-expanding metal stent(SEMS)was placed. He was discharged on the 31st day of hospitalization and nivolumab therapy was resumed. We report the first case of esophageal perforation during immunotherapy with nivolumab therapy for esophageal cancer.

[A Case of Spontaneous Spinal Epidural Hematoma during Chemotherapy with Paclitaxel and Ramucirumab for Advanced Gastric Cancer].

Spontaneous spinal epidural hematomas(SSEH)are rare. The causes of SSEH include hematologic disorders, anticoagulation and antiplatelet therapy, vascular malformations, neoplasms, trauma, or medical interventions, such as epidural catheterization or spinal surgery. However, the cause is usually unclear in most cases. We report a case of SSEH during chemotherapy with paclitaxel and ramucirumab for advanced gastric cancer. A 68-year-old woman was referred to our hospital with a diagnosis of advanced gastric cancer. After 4 courses of neoadjuvant chemotherapy containing S-1 plus oxaliplatin, distal gastrectomy with D2 lymphadenectomy was performed. Postoperative chemotherapy with paclitaxel and ramucirumab was initiated, with a diagnosis of ypStage Ⅲc(T4aN3bM0). She was later transported by ambulance to our hospital with symptoms of sudden onset posterior neck pain and weakness of the extremities. Magnetic resonance imaging(MRI)of her cervical spine showed an epidural hematoma from C2 to C5. The symptoms improved gradually after admission, and the epidural hematoma decreased in size on MRI. Hemorrhagic events such as SSEH should be considered during treatment with angiogenesis inhibitors.

Simple technique of azygos arch division and retraction for minimally invasive esophagectomy.

The azygos arch is usually divided during esophagectomy. To achieve thorough lymphadenectomy up to upper mediastinum, many surgeons prefer to retract the distal stump of the azygos arch by pulling out the thread which ligates the stump to the skin through the dorsal side of the intercostal space. However, the access to the dorsal chest wall near vertebrae for percutaneous puncture is difficult during robot-assisted minimally invasive esophagectomy in the prone position. This paper reports a new simple method of azygos arch division and retraction using a polymer locking ligation system Hem-o-lok (Teleflex, Morrisville, NC, USA) and a barbed suture device. This technique can be easily performed completely as a robotic procedure without extra puncture, and it is also applicable for conventional thoracoscopic procedures with the potential benefits of less trauma and bleeding.

Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.

The spectrum of genetic mutations differs among cancers in different organs, implying a cellular context-dependent effect for genetic aberrations. However, the extent to which the cellular context affects the consequences of oncogenic mutations remains to be fully elucidated. We reprogrammed colon tumor cells in an ApcMin/+ (adenomatous polyposis coli) mouse model, in which the loss of the Apc gene plays a critical role in tumor development and subsequently, established reprogrammed tumor cells (RTCs) that exhibit pluripotent stem cell (PSC)-like signatures of gene expression. We show that the majority of the genes in RTCs that were affected by Apc mutations did not overlap with the genes affected in the intestine. RTCs lacked pluripotency but exhibited an increased expression of Cdx2 and a differentiation propensity that was biased toward the trophectoderm cell lineage. Genetic rescue of the mutated Apc allele conferred pluripotency on RTCs and enabled their differentiation into various cell types in vivo. The redisruption of Apc in RTC-derived differentiated cells resulted in neoplastic growth that was exclusive to the intestine, but the majority of the intestinal lesions remained as pretumoral microadenomas. These results highlight the significant influence of cellular context on gene regulation, cellular plasticity, and cellular behavior in response to the loss of the Apc function. Our results also imply that the transition from microadenomas to macroscopic tumors is reprogrammable, which underscores the importance of epigenetic regulation on tumor promotion.

Optimal Cutoff Values of Skeletal Muscle Index to Define Sarcopenia for Prediction of Survival in Patients with Advanced Gastric Cancer.

BACKGROUND: Sarcopenia, characterized by loss of skeletal muscle mass, is recognized as a prognostic factor in patients with gastric cancer. However, wide variability exists in the cutoff values of muscle mass for defining sarcopenia across previous studies, and the best cutoff values to predict survival remain unknown. This study aimed to determine the optimal cutoff values for sarcopenia to predict survival in patients with advanced gastric cancer. PATIENTS AND METHODS: Patients with clinical stage II/III gastric cancer who underwent gastrectomy at Kyoto University Hospital were included in the study. The cross-sectional area of skeletal muscle at the third lumbar vertebra level was measured using preoperative computed tomography scan. The skeletal muscle index (SMI) was calculated by dividing the area by height in meters squared. Five sex-specific cutoffs of SMI, which were significantly associated with prognosis in patients with gastric and nongastric cancers, were examined as a threshold to define sarcopenia. RESULTS: In the 177 eligible patients, the five cutoffs of SMI resulted in an incidence of sarcopenia between 6 (3%) and 114 (64%). The 5-year overall survival was 48% in patients with sarcopenia based on the cutoffs reported by Martin et al., compared with 68% in those without sarcopenia (p = 0.013). A multivariate regression model demonstrated that sarcopenia based on the cutoffs was significantly associated with overall survival (hazard ratio 2.00, 95% confidence interval 1.24-3.24, p = 0.005). CONCLUSIONS: The cutoff values reported by Martin et al. were optimal to predict survival in patients with advanced gastric cancer.

Reducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell differentiation.

The forced reduction of global DNA methylation suppresses tumor development in several cancer models in vivo. Nevertheless, the mechanisms underlying these suppressive effects remain unclear. In this report, we describe our findings showing that a genome-wide reduction in the DNA methylation levels induces cellular differentiation in association with decreased cell proliferation in Apc (Min/+) mouse colon tumor cells in vivo. Colon tumor-specific DNA methylation at Cdx1 is reduced in the DNA-hypomethylated tumors accompanied by Cdx1 derepression and an increased expression of intestinal differentiation-related genes. Furthermore, a histological analysis revealed that Cdx1 derepression in the DNA-hypomethylated tumors is correlated with the differentiation of colon tumor cells. Similarly, the treatment of human colon cancer cell lines with a hypomethylating agent induces differentiation-related genes, including CDX1. We herein propose that DNA demethylation exerts a tumor suppressive effect in the colon by inducing tumor cell differentiation.

The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.

BACKGROUND: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. METHODS: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. DISCUSSION: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. TRIAL REGISTRATION: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

A case of acute appendicitis incarcerated in obturator hernia.

An 85 year-old woman was transferred with a chief complaint of right thigh pain persisting for 5 days. Abdominal contrast-enhanced computed tomography clearly depicted a swollen appendix incarcerated in the right obturator cavity. She underwent an emergent laparoscopic appendectomy and the simultaneous repair of the obturator hernia. At laparoscopy, appendix was found to be incarcerated in the right obturator canal. The incarcerated appendix was successfully flushed out from the sac by spurting saline into the obturator hernia sac through the catheter inserted into the hernia sac. After a laparoscopic appendectomy, the hernia orifice was repaired using the uterine flap. The patient was discharged from the hospital without any sequelae. This report demonstrates a very rare case of obturator hernia incarcerated with appendix. Although patients with obturator hernia incarcerated with small intestine present with the symptoms related to bowel obstruction, patients with incarceration of appendix do not. Moreover, they would show no typical abdominal symptoms associated with acute appendicitis. Therefore, it is important to perform a radiological evaluation promptly to make a definitive diagnosis when a patient with persisting pain of the right thigh or right ileac fossa with a possibility of obturator hernia with incarceration of the appendix is encountered.

The number of obstructive colorectal cancers in Japan has increased during the COVID-19 pandemic: A retrospective single-center cohort study.

BACKGROUND: The global pandemic of COVID-19 has changed cancer treatment environments. In Japan, cancer screenings were halted and the numbers of endoscopies and surgeries were restricted in some hospitals based on the state of emergency declared. Herein, we investigated the impact of the COVID-19 pandemic on the characteristics of colorectal cancer (CRC) patients in facilities that are on the frontline of both COVID-19 and cancer treatments. PATIENTS AND METHODS: We retrospectively analyzed the cases of all of the CRC patients (n = 123) who underwent surgery at our regional cancer treatment center and tertiary emergency hospital in Japan during a 120-day period ranging from before to after the state of emergency declaration. CRC patients during the corresponding period in the previous year were also examined. RESULTS: Although the number of CRC patients did not show a significant change related to the pandemic, the incidence of obstructive CRCs significantly increased after the pandemic's start. The numbers of outpatients and colonoscopies both decreased, which could have resulted in the decrease of CRC patients detected by cancer screening during the pandemic. The numbers of symptomatic CRC patients and emergency admissions both increased significantly during the pandemic. CONCLUSION: Our findings indicate the possibility that the discovery of CRCs in patients could be delayed due to the halt in screenings caused by the COVID-19 pandemic, resulting in the increase of obstructive CRCs. These results highlight the importance of cancer screening and suggest that the screening system for cancers should be reorganized before future pandemics.

Laparoscopic surgery for ventrally located epiphrenic diverticulum with esophageal achalasia.

Epiphrenic diverticulum is frequently associated with esophageal motility disorder, including esophageal achalasia. Heller's myotomy should accompany diverticulectomy to reduce the bulging pressure in surgery for epiphrenic diverticulum with esophageal achalasia. In such cases, designing myotomy is sometimes difficult, depending on the size and location of the diverticulum. Ventrally located diverticula require special caution to spare some muscular tissue between the longitudinal staple line of the diverticulectomy and myotomy, which is a crucial step to prevent staple-line dehiscence. In this article, we describe a case with ventrally located epiphrenic diverticulum who underwent successful laparoscopic resection and myotomy for esophageal achalasia with an informative surgical video.

Iatrogenic diaphragmatic hernia as a late complication of laparoscopic excisional biopsy of peritoneal nodules: A case report.

INTRODUCTION: Iatrogenic diaphragmatic hernias have been reported as a rare complication of abdominal surgery, and only a few reports have suggested minimal intraoperative injury to the diaphragm as a cause. PRESENTATION OF CASE: We report a rare case of delayed diaphragmatic hernia caused by laparoscopic excisional biopsy of a peritoneal lesion on the diaphragmatic peritoneum. A 70-year-old woman with gastric gastrointestinal stromal tumor underwent laparoscopic partial gastrectomy and excisional biopsy for white nodules on the left diaphragmatic peritoneum using laparoscopic scissors. Slight bleeding that occurred after excisional biopsy was stopped using a soft-coagulation system. Six months after her first surgery, a left diaphragmatic defect and transverse colon migration into the thoracic cavity were detected on computed tomography. The patient subsequently underwent laparoscopic diaphragmatic hernia repair. The site at which the diaphragm defect occurred was consistent with the site of excisional biopsy. The defect was closed with interrupted suturing using non-absorbable threads, following which a composite mesh was applied above the suture site for reinforcement. DISCUSSION: This is the first report of an iatrogenic diaphragmatic hernia after diagnostic laparoscopy for peritoneal excision biopsy of the diaphragmatic surface. In the present case, the coagulation procedure for hemostasis after peritoneal resection was considered to be the cause of the diaphragmatic hernia. The heat generated by soft coagulation might have unexpectedly reached and damaged the deep areas of the diaphragmatic muscle. CONCLUSION: Surgeons performing laparoscopic excisional biopsy of the diaphragmatic peritoneum should consider the potential risk for iatrogenic diaphragmatic hernias.

[Clinicopathological features of young patients with triple negative breast cancer].

This study investigated triple negative diagnoses that occurred in 27 (11%) out of 243 cases of breast cancer analyzed for the presence of estrogen receptor (ER), progesterone receptor( PgR), and human epidermal growth factor receptor 2 (HER 2). In 5 of the triple negative cases of breast cancer, the patients were young, under 35 years of age (average age of 29). In 22 of the cases, the women were 35 years or older (average age of 66). The cancer quickly reoccurred in 4 of the 5 cases of triple negative breast cancer in young women despite various chemotherapy treatments, and in 3 of those cases the women died within 14 months following surgery. Even in statistical analysis, triple negative breast cancer in young women has a significantly poorer prognosis for both disease-free survival rate and overall survival rate, compared with triple negative breast cancer in women 35 and older, and young women without triple negative breast cancer. When basal-like phenotype was defined as being positive for epidermal growth factor (EGFR) and/or cytokeratin (CK)5/6, among the triple negative breast cancer cases of women 35 years and older, the rate for basal-like phenotype, which is said to have a poor prognosis, was 67% (14 out of 21 cases) while in young women with triple negative breast cancer, all cases (5 out of 5) were basal-like phenotype. This suggests that the biological degree of malignancy is extremely high for young women with triple negative breast cancer.

Three-dimensional Stereoscopic Visualization Shortens Operative Time in Laparoscopic Gastrectomy for Gastric Cancer.

Laparoscopic gastrectomy for gastric cancer is now widely accepted and has become a standard surgery. This study investigated the advantages of three-dimensional (3D) stereoscopic visualization for laparoscopic gastrectomy over a conventional two-dimensional (2D) planar screen. The primary outcome of this study was operative time. Ninety-four consecutive cases of gastric cancer patients who underwent laparoscopic total gastrectomy (LTG) (25 cases) or laparoscopic distal gastrectomy (LDG) (69 cases) were enrolled in this study before and after the introduction of the 3D system. Operative time was significantly shorter in the 3D groups for both LTG (351 vs. 406 min, P = 0.026) and LDG (269 vs. 344 min, P < 0.01). During intracorporeal procedures, dissection time was significantly shorter in the 3D groups for both LTG (183 vs. 232 min, P = 0.011) and LDG (161 vs. 213 min, P < 0.01), although the time needed for anastomosis was similar between the groups. However, operators preferred intracorporeal knot-tying as a ligature for anastomosis under 3D (LTG, P = 0.012; LDG, P < 0.01). These data suggest that 3D stereoscopic visualization shortens the operative time of laparoscopic gastrectomy by reducing the intracorporeal dissection time.

Laparoscopic distal gastrectomy for gastric cancer patient with intestinal malrotation: report of a case.

BACKGROUND: Intestinal malrotation, which arises from incomplete rotation of the embryonic midgut, is one of the congenital anomalies usually diagnosed in infancy. On the other hand, intestinal malrotation detected in asymptomatic adults is very rare. It is frequently diagnosed incidentally during abdominal surgery. We report a case of asymptomatic intestinal malrotation diagnosed during laparoscopic distal gastrectomy for gastric cancer. CASE PRESENTATION: A 59-year-old female was diagnosed with early-stage gastric cancer during health screening and admitted to our hospital for radical surgical treatment. Physical examinations and blood tests revealed nothing of note. The type 0-IIc gastric cancer was located in the posterior wall of the mid-body of the stomach. The histological type was poorly differentiated adenocarcinoma. Esophagogastroduodenoscopy and computed tomography (CT) suggested that the depth of tumor invasion was the submucosal layer without regional lymph node swelling. The clinical stage according to the TNM 7th edition was cT1b N0 M0, cStage I. Laparoscopic distal gastrectomy with D1+ lymph node dissection and Billroth-I method reconstruction was planned. During the infrapyloric lymph node dissection, a part of the pancreatic head showed unusual adherence to the first part of the duodenal wall. For safe and accurate lymphadenectomy while avoiding pancreatic injury, we deliberately focused on tracing the dissectible layer between the pancreatic parenchyma and fatty tissues including lymph nodes. Also, we changed the reconstruction procedure from Billroth-I to Roux-en-Y. After distal gastrostomy, we could not find the ligament of Treitz or jejunum on the left side below the transverse colon. Based on a review of the CT image, this patient was diagnosed with intestinal malrotation. Although the detection of malrotation during the operation was incidental, we could complete radical surgery and Roux-en-Y reconstruction safely. The type of malrotation was non-rotation (90°). She was discharged from our hospital without any complications. CONCLUSION: We encountered a case of adult asymptomatic intestinal malrotation with gastric cancer. Even when encountering such a case during laparoscopic gastrectomy, reviewing CT images carefully to reconsider the anatomical anomalies, and tracing the dissectible layer accurately with adequate countertraction can facilitate safe and successful surgery.

Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas.

Clear cell sarcoma (CCS) is a rare soft tissue sarcoma caused by the EWS/ATF1 fusion gene. Here, we established induced pluripotent stem cells (iPSCs) from EWS/ATF1-controllable murine CCS cells harboring sarcoma-associated genetic abnormalities. Sarcoma-iPSC mice develop secondary sarcomas immediately after EWS/ATF1 induction, but only in soft tissue. EWS/ATF1 expression induces oncogene-induced senescence in most cell types in sarcoma-iPSC mice but prevents it in sarcoma cells. We identify Tppp3-expressing cells in peripheral nerves as a cell-of-origin for these sarcomas. We show cell type-specific recruitment of EWS/ATF1 to enhancer regions in CCS cells. Finally, epigenetic silencing at these enhancers induces senescence and inhibits CCS cell growth through altered EWS/ATF1 binding. Together, we propose that distinct responses to premature senescence are the basis for the cell type-specificity of cancer development.

Laparoscopic resection of idiopathic jejunal arteriovenous malformation after metallic coil embolization.

BACKGROUND: Arteriovenous malformations (AVM) developed in the small intestine are rare, and it is sometimes difficult to identify and treat bleeding from small intestinal AVMs endoscopically because of their localization. We present a case of a jejunal AVM successfully treated with the combination of metallic coil embolization and laparoscopic surgery. CASE PRESENTATION: A 50-year-old woman with a history of repetitive gastrointestinal bleeding was admitted to the hospital. Selective angiography revealed a jejunal AVM that was treated with metallic coil embolization. However, the lesion rebled 3 months later, and it was embolized again with metallic coils. Considering the risk of rebleeding, we performed laparoscopic resection of the jejunal AVM. Under laparoscopy alone, it was impossible to detect the lesion of the AVM. We used X-ray fluoroscopy intraoperatively to detect the metallic coils at the AVM. Partial resection of the jejunum with the AVM was performed followed by functional end-to-end anastomosis. The patient was discharged from the hospital without any complications after the surgery. CONCLUSIONS: The combination of metallic coil embolization by angiography and laparoscopic surgery with X-ray fluoroscopy can be effective for patients with repetitive bleeding from jejunal AVM.

Transanal approach for intersphincteric resection of rectal cancer in a patient with a huge prostatic hypertrophy.

The gold standard of surgical technique for rectal cancer is total mesorectal excision (TME). Laparoscopic TME has been proven to provide surgical safety and oncological outcomes equivalent to open TME. However, dissection of the lower rectum has some inherent difficulties related to a narrow pelvic space. The challenge of TME in the lower rectum was confirmed by the Colorectal Cancer Laparoscopic or Open Resection (COLOR) II trial showing a 9% positive circumferential margin (CRM) rate in laparoscopic TME and a 22% positive CRM rate in open TME. Recently, transanal TME has attracted intense attention as a promising alternative to laparoscopic TME. In this video article, we show the performance of a transanal approach for intersphincteric resection (ISR) of rectal cancer in a patient with a huge prostatic hypertrophy.