Association of Preoperative and Postoperative Plasma Syndecan-1 and Colorectal Cancer Outcome.

BACKGROUND/AIM: A three-dimensional network constructed using glycocalyx (GCX) extends throughout the cancer cell nest in human colorectal cancer (CRC). GCX was found to be closely related to cancer. We examined the prognostic correlation and potential of syndecan-1 (SDC1), a representative proteoglycan of GCX, as a biomarker. PATIENTS AND METHODS: We analyzed SDC1 in the transcriptomic profiles of a major publicly available CRC cohort from The Cancer Genome Atlas (TCGA) using a computational algorithm. We investigated serum SDC1 levels preoperatively and on postoperative day seven in 48 patients with stage I-III CRC who underwent surgery during July-December 2019 at Gifu University Hospital. RESULTS: For TCGA, no significant differences existed between the high and low SDC1 expression groups regarding disease-free, disease-specific, and overall survival for stage I-III, and only overall survival for stage IV was significantly different. In our study, among the 48 patients, 17 (no recurrence), 13 (1 recurrence), and 18 (10 recurrences) had stage I-III, respectively. Preoperative and postoperative day 7 SDC1 levels for patients with stage I-III were 10.7±2.3 and 9.9±3.1 ng/ml (p=0.40), 11.1±1.7 and 10.1±0.8 ng/ml (p=0.07), and 10.3±2.0 and 9.5±1.4 ng/ml (p=0.15), respectively. In stage II and III, patients were divided into two groups according to differences between preoperative and postoperative SDC1 levels (SDC1pre-pro). SDC1pre-pro ≤0 group significantly prolonged disease-free survival compared with SDC1pre-pro >0 group (p=0.048). CONCLUSION: Dynamic change in serum SDC1 levels serves as a prognostic biomarker for stage II and III colorectal cancer.

Expression of IZUMO2 in colorectal cancer in association with clinicopathological features.

IZUMO2 belongs to the testis-expressed IZUMO family of proteins, which are characterized by an N-terminal IZUMO domain. Based on integrated analysis of expression profiles and matched DNA methylation data from a public database, IZUMO2 represents a prognosis-related methylation-driven gene in colorectal cancer. However, it remains unclear whether IZUMO2 protein expression is suppressed or overexpressed in colorectal cancer cells. In this study, we aimed to elucidate the expression of the IZUMO2 protein in colorectal cancer, with a focus on the clinicopathological features. Sixty-four colorectal cancer tissue specimens were immunohistochemically stained using specific antibodies against IZUMO2. IZUMO2 immunoreactivity was detected at the invasion front in 30 of the 64 colorectal cancer samples. Kaplan-Meier analysis demonstrated that patients with IZUMO2 immunoreactivity had a relatively shorter overall and progression-free survival (log-rank test, P = 0.046 and 0.019, respectively). IZUMO2 immunoreactivity served as an independent factor predictive of poor progression-free survival in colorectal cancer (P = 0.025) as determined via the Cox proportional hazard regression model. Moreover, IZUMO2 immunoreactivity represented an independent factor for poor overall survival (P = 0.035) and progression-free survival (P = 0.013) in patients with colon cancer. The present findings suggest that IZUMO2 is expressed in many colorectal cancers, especially at the cancer invasion front, and may represent an indicator of poor prognosis in colorectal cancer.

Implication of IZUMO2 in the cell-in-cell phenomenon: A potential therapeutic target for triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by the loss of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The aggressive clinicopathological features and resistance to currently available therapeutics of the disease warrant an urgent need for the development of novel alternate therapeutic options. We have previously reported adiponectin-expressing regulatory T cells (A-Tregs), which can induce apoptosis in TNBC through the cell-in-cell phenomenon. In this study, we aimed to elucidate the molecule that allows TNBC cells to engulf A-Tregs. METHODS: A monoclonal antibody, which repressed the engulfment of A-Tregs by TNBC cells, was developed. Immunoprecipitation followed by mass spectrometry and small interfering RNAs-mediated gene silencing was performed to characterize the antigen. RESULTS: We successfully generated a monoclonal antibody, designated G1D7, which abrogated the engulfment of A-Tregs by TNBC and subsequent A-Treg-mediated apoptosis. G1D7 detected the immunoglobulin-like type I membrane protein IZUMO2, a molecule related to IZUMO1 that is essential for cell-cell membrane binding and fusion of sperm to oocyte. CONCLUSION: The findings highlight the importance of IZUMO2 on TNBC cells in facilitating the cell-in-cell phenomenon by A-Tregs.

Short-term outcomes associated with the use of a new powered circular stapler for rectal reconstructions: a retrospective study comparing it to manual circular staplers using inverse probability of treatment weight analysis.

BACKGROUND: The most common postoperative complication in malignant rectal surgery is anastomotic leakage (AL). AL after anterior or low anterior resection in rectal tumors is a fatal postoperative complication. Recently, the first automated suture circular stapler, which is expected to reduce the incidence of AL, (J&J). MATERIALS AND METHODS: This study included a total of 248 rectal tumor patients who underwent double stapler technique (DST) anastomotic procedures in the department of gastroenterological surgery /pediatric surgery at Gifu University School of Medicine from January 2017 to December 2021. The experience of a single institution utilizing the The Echelon circular™ stapler (ECP stapler:Manual VS Automatic) in rectal surgery cases was evaluated retrospectively from maintained database. RESULT: One hundred thirty-nine patients (58.4%) were performed by manual circular stapling, 99 patients (41.6%) by powerd circular stapling. Diverting stoma was performed in 45 cases (32.4%) by manual circular stapling, 42 patients (42.4%) by powerd circular stapling Postoperative complications were occurred clavien-dindo grade II or higher in 57 cases (23.9%) and grade III or higher in 20 cases (8.4%). Anastomotic leakage occurred in 14 patients (5.9%) within all grades. After IPTW, the variables of patient characteristics was SMD ≤ 0.2 (Table.3), and there was a significant difference in anastomotic leakage (Odds Ratio (OR), 0.57; 95% Confidence Interval(CI), 0.34-0.98; p = 0.041). In addition, there was no significant difference in postoperative complications in grade II or higher (OR, 0.88; 95%CI, 0.65-1.19; p = 0.417) and grade III or higher (OR, 0.46; 95%CI, 0.29-0.74; p = 0.001) were significantly remarkable lower in powered circular stapling group. CONCLUSION: In this IPTW comparison of patients undergoing rectal reconstructions, the ECP trial cohort had lower risks of several surgical complications AL and statistically signifcant lower rates of ileus/bowel obstruction, infection, and bleeding as Clavien-Dindo ≥ grade II and III as compared with for whom manual circular staplers were used.

Adiponectin-expressing Treg-containing T cell fraction inhibits tumor growth in orthotopically implanted triple-negative breast cancer.

BACKGROUND: In our previous study, we identified a population of adiponectin expressing regulatory T cells (Tregs) residing within thymic nurse cell complexes, which were capable of inhibiting the development of breast cancer in vitro. Triple-negative breast cancer (TNBC) with no proper treatment at present is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2. In this study, we aimed to investigate the potential of a cultured T cell fraction comprising adiponectin-expressing Tregs, referred to as A-TregTF (adiponectin-expressing Treg-containing T cell fraction), in inhibiting the progression of TNBC in vivo. METHODS: The efficacy of a spontaneously expanding T cell fraction comprising adiponectin-expressing Treg in inhibiting tumor growth was analyzed in a murine orthotopic 4 T1-Luc TNBC model. RESULTS: The treatment with T cell fraction containing adiponectin-expressing Tregs significantly inhibited the growth and metastasis of orthotopically transplanted 4 T1-Luc tumor cells. Histopathological examination further revealed that the adiponectin-expressing Tregs infiltrated the tumor tissue via a cell-in-cell mechanism and were found to be specifically localized around the necrotic areas. CONCLUSIONS: Based on our findings, the T cell fraction comprising adiponectin-expressing Tregs, represents a potential candidate for adoptive cell therapy against TNBC.

Potential activity of adiponectin-expressing regulatory T cells against triple-negative breast cancer cells through the cell-in-cell phenomenon.

BACKGROUND: A population of regulatory T cells (Treg), which reside within thymic nurse cell complexes, express adiponectin and abrogate breast cancer development in transgenic mice. In this study, we examined whether adiponectin-expressing Treg could impair triple-negative breast cancer, which is defined by a lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2. METHODS: CD4- and CD25-positive cells were sorted from cultured T lymphocytes of a previously characterized experimental thymic tumor model composed of thymic nurse cells and abundant lymphoid stroma. These sorted cells were examined for FOXP3 and adiponectin immunoreactivity and subsequently exposed to triple-negative breast cancer MDA-MB-157 and -231 cells. RESULTS: Adiponectin-expressing Treg were obtained by CD4- and CD25-positive sorting and cell death was induced in triple-negative breast cancer cells through the cell-in-cell phenomenon. CONCLUSIONS: Adiponectin-expressing Treg may be candidates for adoptive cell therapy against triple-negative breast cancer.

Late recurrent gastric carcinoma 12 years after surgery with attenuation of CD44 variant 9 expression.

BACKGROUND: Late recurrence of gastric cancer at 10 years post-gastrectomy is extremely rare, and the underlying mechanism remains unclear. We report a para-aortic lymph node metastasis case that recurred 12 years postoperatively. CASE PRESENTATION: A 44-year-old woman pathologically diagnosed with moderately to poorly differentiated adenocarcinoma with pT2(SS)pN2cM0pStageIIIA according to the Japanese Classification of Gastric Carcinoma (the 13th Edition) underwent laparoscopic distal gastrectomy with D1 + lymph node dissection. She received adjuvant chemotherapy with tegafur-uracil (400 mg/day) for 2 years. At postoperative year (POY) 5, a swollen lymph node was detected in the No.16b1lat lymph node station. However, positron emission tomography (PET) revealed normal uptake, and the levels of tumor markers were within normal limits; hence, the possibility of metastasis was considered low, and the patient was placed under observation. At POY 12, computed tomography revealed an enlargement of the No.16b1lat lymph node station, and PET showed abnormal uptake. Endoscopic ultrasound-guided fine-needle aspiration revealed a moderately differentiated adenocarcinoma. Hence, a diagnosis of recurrence of gastric cancer was made. The patient underwent para-aortic nodal dissection (PAND) of No.16b1lat & int stations. Immunochemical staining results also suggested the recurrence of gastric cancer. However, the expression of CD44 variant 9 (CD44v9), a cancer stem cell marker for gastric adenocarcinoma, was attenuated in the recurrent lesions compared with that in the primary lesions. Postoperatively, she received chemotherapy with tegafur-gimeracil-oteracil (80 mg/day) for 1 year. Bone metastasis was observed at POY 4 after PAND, and the IHC analysis showed a HER2 score of 3 + in a needle biopsy specimen of bone metastasis. The expression of CD44v9 was slightly positive. The patient is being treated with chemotherapy with FOLFOX + trastuzumab. CONCLUSIONS: A defense mechanism against reactive oxygen species has been reported as a mechanism causing recurrence of CD44v9-positive gastric cancer. Consequently, CD44v9-positive gastric cancer grows in metastatic organs, repeatedly self-renews, and proliferates to form recurrent lesions. In the present case, the degree of CD44v9 staining in recurrent lesions was suggested to be related to the recurrence time.

Patient with suspected severe acute respiratory syndrome coronavirus 2 infection with successful emergency surgery for ulcerative colitis-associated toxic megacolon.

BACKGROUND: In patients with acute severe ulcerative colitis with concomitant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the treatment strategy should consider the presence of pneumonia, respiratory status, and the severity of the ulcerative colitis (UC). We report a case of a 59-year-old man with SARS-CoV-2 infection who was diagnosed with toxic megacolon caused by UC. CASE PRESENTATION: Preoperative computed tomography scanning of the chest showed ground-glass opacities. The patient was treated conservatively until the pneumonia improved, but developed bleeding and liver dysfunction associated with UC. As the patient's condition worsened, emergency surgery with subtotal colorectal resection, ileostomy, and rectal mucous fistula creation was performed while undertaking adequate infection control measures. Intraoperatively, contaminated ascites was observed, and the intestinal tract was markedly dilated and fragile. Nevertheless, the postoperative outcome was positive, with no pulmonary complications. The patient was discharged on postoperative day 77. CONCLUSIONS: The COVID-19 pandemic presented challenges in surgical scheduling. Patients with SARS-CoV-2 infection required close monitoring for postoperative pulmonary complications.

Optimizing Treatment Strategy for Oligometastases/Oligo-Recurrence of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC.

Gastric carcinosarcoma with FGFR2 amplification under long-term control with pazopanib: a case report and literature review.

BACKGROUND: Gastric carcinosarcoma is most frequently diagnosed at an advanced stage when the tumor is generally large with invasion into other organs, lymph node metastasis, and distant metastasis. Standard chemotherapy has not been established, and surgery is the only curative treatment. Here, we present a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. CASE PRESENTATION: A 77-year-old man was referred to our hospital because of nausea and vomiting. Computed tomography and upper gastrointestinal endoscopy revealed a type 1 tumor arising from the gastric antrum and extending into the duodenal bulb. He underwent distal gastrectomy (D2) with Roux-en-Y reconstruction. Histopathologically, the tumor had mixed adenocarcinoma and sarcoma components. According to the tumor-node-metastasis classification, the diagnosis was primary gastric carcinosarcoma pT1bN1M0 stage IB. Liver metastasis was detected 2 months after surgery; multiple lung metastases were detected 17 month after surgery. A genomic profiling test was performed using liver specimens as the patient became refractory to chemotherapy commonly used for gastric cancer, and the test revealed FGFR2 amplification along with TP53 R209*, AKT3 N127D, NOTCH1 A2036T, and POLD1 M161I. The patient was treated with pazopanib (800 mg/daily), and the tumor growth was controlled for 11 months. CONCLUSIONS: We report a case of postoperative recurrence of gastric carcinosarcoma under long-term tumor control with pazopanib. This case suggested that pazopanib may be effective in treating gastric carcinosarcoma.

Spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip: A case report.

INTRODUCTION AND IMPORTANCE: Spontaneous esophageal rupture is a life-threatening condition caused by a sudden increase in the intraesophageal pressure. While surgery is the mainstay of management for spontaneous esophageal ruptures, in recent years, an increasing number of patients have been managed with endoscopic interventions. We report a case of spontaneous esophageal rupture managed with endoscopic closure using an over-the-scope clip (Ovesco Endoscopy AG, Tübingen, Germany). CASE PRESENTATION: A 68-year-old female presented with epigastric pain and left-sided back pain following vomiting. A computed tomography scan revealed mediastinal emphysema and an esophagogram showed leakage from the left side of the lower thoracic esophagus into the mediastinum. The patient was diagnosed with spontaneous esophageal rupture localized to the mediastinum and was treated conservatively. However, she had persistent fever and continuing esophageal leakage on the esophagogram. On the 12th day of admission, a gastrointestinal endoscopy was performed, which found a 10-mm full-thickness longitudinal laceration on the left side of the lower esophagus. Endoscopic closure using an over-the-scope clip was performed. The next day, the patient became afebrile. One week later, esophagogram revealed slight residual leakage and an additional endoscopic closure using an over-the-scope clip was performed; the patient subsequently had an uneventful recovery and was discharged on the 44th day of admission. CLINICAL DISCUSSION: Endoscopic closure using an over-the-scope clip led to a good outcome in this patient with spontaneous esophageal rupture. CONCLUSION: Endoscopic closure using an over-the-scope clip is an effective and minimally invasive technique for selected patients with spontaneous esophageal rupture.

Laparoscopic surgery for appendiceal cancer with intestinal malrotation in an adult: A case report.

INTRODUCTION: Intestinal malrotation is a congenital anatomical anomaly resulting from abnormal midgut rotation. Many cases occur during childhood and present with intestinal obstruction and midgut volvulus. Intestinal malrotation rarely occurs in adults and is found incidentally because it is asymptomatic. We herein report a case of intestinal malrotation, and colorectal cancer operated laparoscopically. PRESENTATION OF CASE: A 78-year-old man presented to our Department of Surgical Gastroenterology with fecal occult blood. There were no abnormal findings in the physical examination. Colonoscopy revealed a type 3 tumor in the cecum. Contrast-enhanced computed tomography revealed that the tumor was located in the appendix along the midline of the abdomen. The small intestine and colon occupied the right and left sides of the abdominal cavity, respectively. The diagnosis was appendiceal cancer with nonrotation-type intestinal malrotation. A laparoscopy-assisted ileocecal resection was performed. During surgery, the right-side colon was not fixed to the retroperitoneum, and the right-side colon could be extracted out of the abdominal cavity through the umbilical wound with only adhesive dissection, and mesenteric and lymph node dissection can be performed outside the body. The postoperative course was uneventful. DISCUSSION: Appendiceal cancer with intestinal malrotation is managed with laparoscopic surgery because this method is safe and minimally invasive. CONCLUSION: The laparoscopic approach may be safer and less invasive than laparotomy, and extracorporeal lymph node dissection is safe and reliable for patients with intestinal malrotation.

Spontaneous bacterial peritonitis caused by Edwardsiella tarda: A case report.

INTRODUCTION: Edwardsiella tarda is a member of the Enterobacteriaceae family of gram-negative bacilli isolated from animals. Gastroenteritis is the most common manifestation of E. tarda infection. However, extraintestinal infections can occur in immunocompromised hosts as well as patients with hepatobiliary disease, malignancy, and/or diabetes mellites. The prognosis of sepsis caused by E. tarda is extremely poor, with a mortality rate of 38%. Here we report the occurrence of spontaneous bacterial peritonitis associated with E. tarda infection. PRESENTATION OF CASE: An 87-year-old man with Child-Pugh A cirrhosis secondary to hepatitis C virus infection presented with diarrhea and sudden-onset pain in the abdomen. On arrival, guarding and rebound tenderness were observed over the entire abdomen. Computed tomography revealed circumferential thickening of the cecum and a small volume of ascites in the pelvic cavity. A diagnosis of peritonitis was made, and surgery was performed. Surgical findings included redness and thickening of the cecal wall and purulent ascites without intestinal contents. Peritoneal fluid culture revealed E. tarda as the sole pathogen. The abdominal cavity was washed, a drain was placed in the pelvic cavity, and postoperative intravenous antibiotic therapy was initiated. The postoperative course was uneventful. DISCUSSION: E. tarda infection in the presence of an underlying disease such as hepatobiliary disease, malignancy, and/or diabetes mellitus has a poor prognosis. CONCLUSION: Although E. tarda infection is extremely rare, it is a life-threatening illness that can cause intestinal and extraintestinal infections. If necessary, early surgical intervention should be considered for cases of extraintestinal infection.

Complete resection of rectal cancer with a synchronous solitary adrenal metastasis: A case report.

INTRODUCTION: Solitary adrenal metastasis derived from colorectal cancer is rare. Adrenal metastasis is usually associated with systemic spread of the disease and is considered to be unsuitable for surgical resection. However, it has been reported that an aggressive surgical resection of adrenal metastasis results in improved overall survival in selected patients. We herein report an extremely rare case of complete resection of rectal cancer with a synchronous solitary adrenal metastasis. PRESENTATION OF CASE: A 70-year-old woman who presented with bloody stool was diagnosed with rectal cancer with a synchronous solitary adrenal metastasis and was suspected of having liver invasion. After a total of 2 cycles of chemotherapy with capecitabine and oxaliplatin, an abdominoperineal resection with D2 (proxD3) lymph node dissection and right adrenalectomy was performed and complete resection was possible. According to the TNM classification, the diagnosis was stage IVA (fT3N1bM1a[ADR]). At 18 months after surgery, the patient is alive with no evidence of recurrence and distant metastasis. DISCUSSION: Complete resection of adrenal metastasis may have a possibility of leading to a good prognosis in patients with a synchronous solitary adrenal metastasis. CONCLUSION: Adrenalectomy should be considered in patients who can undergo complete resection, as it may offer a good long-term prognosis.