Splenic rupture after surgical fixation of rib fractures with video-assisted thoracoscopic surgery: A case report.

INTRODUCTION: Recently, the utilization of surgical stabilization of rib fractures (SSRF) with video-assisted thoracoscopic surgery (VATS) has been increasing owing to its effectiveness. The present report describes the case of a patient who underwent SSRF with VATS and subsequently developed a splenic rupture that was speculated to be related to intrathoracic manipulation during surgery. PRESENTATION OF CASE: A 62-year-old male patient sustained injuries from a fallen festival car over his thoracoabdominal zone and was diagnosed with bilateral multiple rib fractures and burst fractures of the twelfth thoracic and first lumbar vertebrae. The patient underwent SSRF with VATS. Following surgery, the patient went into hemorrhagic shock due to a splenic rupture, necessitating an emergency open splenectomy. DISCUSSION: Despite no initial detection of splenic injury on contrast-enhanced CT, it is possible that a slight splenic injury existed at the time of the initial diagnosis. Moreover, during surgery, additional external forces may have been applied to the spleen due to positional changes, such as shifting to the lateral position or retracting the diaphragm using forceps; these manipulations could have potentially caused a slight splenic injury, possibly leading to splenic rupture. CONCLUSION: When performing SSRF through VATS, it is important to recognize that manipulation and traction of the diaphragm could potentially cause splenic rupture, even if a slight force is applied. Therefore, the diaphragm should be evaluated without traction and manipulation whenever possible.

[A Case of the Huge GIST in the Transverse Colon Mesentery with Intra-Tumoral Hemorrhage and Jejunal Infiltration].

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.

[Results of Watch and Wait after Chemoradiotherapy for Locally Advanced Rectal Cancer].

BACKGROUND: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention. PURPOSE: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department. MATERIALS AND METHODS: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up. RESULTS: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months. CONCLUSIONS: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.

An ampullary adenoma presenting with jaundice caused by duodenal intussusception: a case report.

BACKGROUND: Ampullary adenomas are premalignant lesions. However, biliary obstruction causing jaundice is rare. Duodenal intussusception secondary to an ampullary adenoma rarely occurs because of the fixed position of the duodenum in the retroperitoneum. Herein, we have described a rare case of ampullary adenoma with jaundice caused by duodenal intussusception. CASE PRESENTATION: A 40-year-old woman presenting with vomiting and yellowish discoloration of the skin was admitted to another hospital. The patient had experienced recurrent epigastric pain and vomiting for the past 18 months. Blood test results showed elevated levels of bilirubin (3.9 mg/dL), and abdominal computed tomography (CT) showed a 60-mm hypovascular mass in the third part of the duodenum and a left lateral shift of the dilated common bile duct. The patient was referred to our hospital for further evaluation. She recovered from hyperbilirubinemia spontaneously (levels of bilirubin, 1.0 mg/dL), and the CT showed a tumor shift from the third part of the duodenum to the second part and improvement of the dilated common bile duct. Hypotonic duodenography revealed a tumor that moved easily from the second to the third portion of the patient's position. Upper gastrointestinal endoscopy revealed a large papillary tumor occupying the second part of the duodenum, which was diagnosed as an adenoma through biopsy. The possibility of malignancy could not be negated owing to the presence of jaundice and an elevated carbohydrate antigen 19-9 level (76.0 U/mL). Pancreaticoduodenectomy was performed. The resected specimen showed a 60 × 40 × 40-mm pedunculated ampullary mass with submucosal elongation. The pathological examination indicated that the ampullary tumor was a high-grade intestinal adenoma. The postoperative course was uneventful, and the patient was discharged 26 days postoperatively. CONCLUSIONS: This report describes a rare case of a patient with an ampullary adenoma presenting with jaundice resulting from duodenal intussusception. Owing to the possibility of a postoperative cancer diagnosis which may have caused the biliary obstruction and the difficulty in making an accurate preoperative diagnosis, it is imperative to choose the appropriate surgical procedure such as a pancreaticoduodenectomy.

Hyperdry Human Amniotic Membrane as a Protective Dressing for Open Wounds With Exposed Bowel in Mice.

INTRODUCTION: An enteroatmospheric fistula forms when the exposed bowel is perforated with chronic enteric fistula formation. Currently, there is no established preventative method for this condition. Hyperdry (HD) amniotic membrane (AM) can promote early granulation tissue formation on the exposed viscera and is suitable for dressing intractable wounds as it possesses anti-inflammatory, antibacterial, and immunomodulatory properties. This study investigated whether HD-AM promotes early formation of blood vessel-containing granulation tissue for enteroatmospheric fistula treatment. METHODS: An experimental animal model of an open wound with exposed bowel was developed. A 15 × 20 mm wound was prepared on the abdomen of Institute of Cancer Research mice, and the HD-AM was placed. The mice were assigned to one of the following groups: HD-AM group, in which the stromal layer of the HD-AM was placed in contact with the exposed bowel; HD-AM UD group, in which the epithelial layer of the HD-AM was placed in contact with the exposed bowel; and the HD-AM (-) or control group, in which the HD-AM was not used. RESULTS: On postoperative days 7 and 14, granulation tissue thickness significantly increased in the HD-AM and HD-AM UD groups compared with that in the HD-AM (-) group. Macrophages accumulated in the HD-AM epithelium only in the HD-AM group. During HD-AM contact, a subset of invading macrophages switched from M1 to M2 phenotype. CONCLUSIONS: HD-AM is a practical wound dressing with its scaffolding function, regulation of TGF ß-1 and C-X-C motif chemokine 5 (CXCL-5), and ability to induce M1-to-M2 macrophage conversion.

[A Case of Pancreatic Tail Cancer Causing Gastrointestinal Hemorrhage Due to Transverse Colon Invasion].

An 81-year-old woman was admitted to our hospital due to frequent bleeding and hemorrhagic shock. Blood tests revealed anemia and contrast-enhanced abdominal CT revealed a pancreatic tail tumor with a diameter of 60 mm. The boundary between pancreatic tumor and the transverse colon, stomach and spleen was unclear, and invasion of the transverse colon as well as the stomach and spleen was suspected. Hemorrhage due to colon invasion of the pancreatic tail cancer and intra-tumoral hemorrhage were suspected. Due to persistent bleeding, the patient had emergency surgery to control bleeding. The pancreatic tail tumor invaded not only the colon but also stomach and spleen, distal pancreatectomy, partial gastrectomy and splenectomy was performed in combination with resection of the transverse colon, and transverse colon colostomy. We report a case of gastrointestinal bleeding caused by transverse colon invasion of pancreatic tail cancer, which resulted in emergency surgery.

[A Case of Perihilar Cholangiocarcinoma with Postoperative Hepatic Encephalopathy Due to Portosystemic Shunt Treated by Percutaneous Embolization].

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.

Intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm harboring a GNAS mutation: A case report.

BACKGROUND: Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life. They usually occur in the mediastinum or lung, but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity. A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen (CEA), harboring a GNAS mutation, is reported. The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts. CASE SUMMARY: In 2007, a man in his 50s was incidentally found to have an intra-abdominal cystic mass, 8 cm in diameter. Surgical resection was recommended, but he preferred to remain under observation. In 2020, his serum CEA level increased to 26.7 ng/mL, and abdominal computed tomography showed a 15 cm × 12 cm, multifocal, cystic mass located predominantly on the lesser curvature of the stomach. Since malignancy could not be ruled out, he finally underwent surgical resection. Histologically, the cystic wall was lined by ciliated columnar epithelium, accompanied by bronchial gland-like tissue, bronchial cartilage, and smooth muscle. Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5% and positive for CEA. Moreover, a GNAS mutation (p.R201C) was detected in the atypical epithelium, leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm. The patient is currently undergoing outpatient follow-up without recurrence. CONCLUSION: An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.

Successful hepatic resection for invasive Klebsiella pneumoniae large multiloculated liver abscesses with percutaneous drainage failure: A case report.

Background: Invasive Klebsiella-associated liver abscesses can progress rapidly and cause severe metastatic infections such as meningitis and hydrocephalus, which are associated with high morbidity and mortality. In patients with large multiloculated liver abscesses after failure of percutaneous drainage, rapid diagnosis of the abscess followed by hepatic resection is necessary for early recovery and to prevent severe secondary metastatic complications. Case presentation: An 84-year-old woman with a large liver abscess and in septic shock was transferred to our hospital. Abdominal CT showed multiloculated liver abscesses 15 cm in diameter in the right lobe of the liver. We first performed percutaneous liver abscess drainage. The patient was managed in the intensive care unit, as well as treated with intravenous administration of meropenem followed by cefozopran according to the antibiogram. Klebsiella pneumoniae with invasive infection was confirmed by a string test in an isolated colony of K. pneumoniae; the K1 serotype with the rmpA and magA genes was determined by polymerase chain reaction and Sanger sequencing. Additional percutaneous liver abscess drainage was performed due to initial inadequate drainage. Although the abscess had shrunk to a diameter of 8 cm after drainage in 4 weeks, the patient recovered from sepsis, but still had low-grade fever (occasionally 38°C) and continued to have symptoms of chronic inflammation with persistent hyper mucus discharge from the liver abscess. Surgical resection was chosen to prevent prolonged hospitalization and ensure early recovery. A right posterior sectionectomy of the liver, including liver abscess, was performed. The post-operative course was uneventful, with no complications, and she was discharged after 18 days. There were no signs of abscess recurrence 1 year after surgery. Conclusion: We present a case of successful hepatic resection after percutaneous drainage failure in a patient with invasive K. pneumoniae multiloculated liver abscess.

Open abdominal management for perforative peritonitis with septic shock: a retrospective analysis on usefulness of a standardized treatment protocol.

BACKGROUND: Damage control surgery (DCS) with open abdominal management (OAM) has been increasingly expanded to include critically ill non-trauma patients. However, there is limited data regarding the usefulness of this protocol for the treatment of severe perforative peritonitis (PP), especially with septic shock (SS). Here, we retrospectively evaluated the usefulness of our OAM protocol for PP with SS. METHODS: We retrospectively reviewed patients with from June 2015 to September 2018. The proposed protocol was composed of the following steps: (1) rapid control of contamination; (2) temporary abdominal closure; (3) repeated washout of the abdominal cavity; and (4) delayed definitive surgery. For temporary abdominal closure, a negative pressure wound therapy device was used. The end points were the morbidity and 30-day mortality rates. Logistic backward regression was performed to identify factors associated with complications. RESULTS: The mortality rate was 4% (1/25) and the overall morbidity rate of surviving patients was 58.3% (14/24). The mean duration of the first DCS was 67.36 ± 22.83 min. The median durations of ventilation and intensive care unit stay were 5 and 7 days, respectively. Although not significant, morbidity might be associated with age, diabetes mellitus, initial operative time, and OAM duration. CONCLUSIONS: A standardized protocol for OAM may improve the outcomes of patients with SS due to PP. This damage control approach can be applied for the treatment of severe abdominal sepsis.

Timing of indocyanine green injection prior to laparoscopic colorectal surgery for tumor localization: a prospective case series.

BACKGROUND: Accurate identification of tumor sites during laparoscopic colorectal surgery helps to optimize oncological clearance. We aimed to assess the timing of the local injection preoperatively and clarify the usefulness and limitation of tumor site marking using indocyanine green (ICG) fluorescence imaging. METHODS: Consecutive patients who underwent primary colorectal cancer surgery from September 2017 to January 2019 were included. Preoperatively, lower endoscopy was used to inject the ICG solution into the submucosal layer near the tumor. During laparoscopic surgery, ICG fluorescence marking as the tumor site marking was detected using a laparoscopic near-infrared camera system. The detection rate and factors associated with successful intraoperative ICG fluorescence visualization including the interval between local injection and surgery were evaluated. RESULTS: One hundred sixty-five patients were enrolled. Using the laparoscopic near-infrared system, the intraoperative detection rates of ICG marking were 100% for ICG injection within 6 days preoperatively, 60% for injection between 7 and 9 days preoperatively, and 0% for injection earlier than 10 days preoperatively. There were no complications associated with ICG marking. Additionally, this method did not disturb the progress of the surgical procedure because injected ICG in the submucosal layer did not cause any tissue inflammation, and if ICG spilled into the serosa, it was invisible by white light. CONCLUSION: Advantages of ICG fluorescence tumor site marking were high visibility of infrared imaging during laparoscopic colorectal surgery and minimal adverse events of surgery. One of the most important findings regarding practical use was a rapid decrease in fluorescence marking visibility if one week passed from the time of ICG local injection.

Perioperative Factors Associated With Respiratory Complications Following Open Abdomen Management.

BACKGROUND: Postoperative respiratory complications are often severe and associated with a high risk of mortality in patients who undergo open abdomen (OA) management following emergency damage-control surgery. The causes of postoperative respiratory complications remain unknown. Therefore, we evaluated postoperative factors associated with respiratory complications in nontrauma patients who had undergone OA management using propensity score matching, with a focus on OA-related risk factors. METHODS: This retrospective analysis included subjects who underwent OA management during a 4-y study period. Age, body mass index, and smoking history were selected as covariates. After propensity score matching, we compared postoperative factors (ie, first operative time, duration of OA, initial 3-d fluid balance, length of ICU stay, and in-hospital mortality) in 2 groups of subjects: those who had post-OA respiratory complications (PORCs) and those who did not. RESULTS: 60 subjects (33 men and 27 women) were identified; 38.3% of these subjects had PORCs. After propensity score matching, 18 subjects were matched. The 3-d fluid balance was significantly higher in subjects with PORCs than in those without PORCs (3,513 mL vs 1,087 mL; P = .03). CONCLUSIONS: To our knowledge, this is the first study to examine factors associated with respiratory complications following OA in nontrauma subjects. After adjusting for known co-factors associated with postoperative respiratory complications, the 3-d fluid balance was identified as a significant risk factor for PORCs in subjects who had undergone OA. Clinicians should pay attention to the incidence of PORCs in OA subjects with a positive fluid balance after emergency abdominal surgery.

Novel laparoscopic methods for inguinal hernia post pelvic fracture: A case report.

INTRODUCTION: Pelvic fractures can occur in minor injuries, such as falls, in the elderly. Extensive adhesion of preperitoneal space is common after pelvic fracture surgery; hence, surgical interventions for inguinal hernia may be challenging. We treated a case of inguinal hernia after pelvic fracture surgery, using novel laparoscopic methods: iliopubic tract repair (IPTR) and modified intraperitoneal onlay mesh (mIPOM) approach. PRESENTATION OF CASE: This is the case of an elderly male with pelvic fracture. Open reduction and internal fixation were performed. Eighteen months after the procedure, a right inguinal bulge appeared, swelling increased, and he opted for surgery. We chose laparoscopic surgery to determine the status of the hernia and anatomy around the pelvis. He was diagnosed with an indirect inguinal hernia, and the inner inguinal ring was widely open. We chose the mIPOM approach and IPTR. He was discharged on day 3 post-operation. He developed a seroma after surgery, which disappeared after a month. Six months post-operation, no recurrence or neurologic pain observed. DISCUSSION: The transabdominal preperitoneal approach (TAPP) was initiated at first; however, the adhesion inside the inferior epigastric vessels was very strong, challenging to break into the preperitoneal space. We switched to the mIPOM method because the peritoneum was fragile and difficult to suture. Additionally, the internal ring was widely opened; hence, we proceeded with IPTR on confirmation that no tension on the abdominal wall was applied. CONCLUSIONS: Laparoscopic surgery is useful in flexibility of surgical options, such as TAPP, IPTR, IPOM, in addition to hybrid conversion.

Efficacy of indocyanine green fluorescence angiography in preventing anastomotic leakage after laparoscopic colorectal cancer surgery.

PURPOSE: Some recent studies have suggested that fluorescence angiography with indocyanine green (ICG) might be useful for preventing anastomotic leakage (AL) after laparoscopic colorectal surgery. However, its efficacy has not been proven. We evaluated whether intraoperative ICG fluorescence angiography could decrease the AL rate with laparoscopic colorectal cancer surgery. METHODS: This retrospective study included patients with colorectal cancer who underwent laparoscopic surgery at our institution between March 2014 and December 2018. Patients were divided into two groups: with or without ICG fluorescence angiography. The primary outcome was the rate of AL. RESULTS: A total of 488 patients were included: 223 patients in the ICG group and 265 patients in the no-ICG group. In the ICG group, the transection line was changed to a more proximal location in seven patients (3.1%), including one patient with transverse colon surgery and six with rectal surgery. None of these seven patients developed AL. There were 18 ALs (3.7%) overall. The AL rate was 1.8% in the ICG group and 5.3% in the no-ICG group. For colon cancer, there were no significant differences in the AL rate between the groups (p = 0.278). In rectal cancer, the AL rate was significantly lower in the ICG group than in the no-ICG group (3.5% vs. 10.5%, p = 0.041). After propensity score matching, the AL rate was also significantly lower in the ICG group for rectal cancer (p = 0.044). CONCLUSION: ICG fluorescence angiography can potentially reduce the AL rate with laparoscopic rectal cancer surgery.

Patient trends and outcomes of surgery for type A acute aortic dissection in Japan: an analysis of more than 10 000 patients from the Japan Cardiovascular Surgery Database.

OBJECTIVES: To evaluate the background trends and surgical outcomes for more than 10 000 patients with acute type A dissection in Japan in a recent 8-year period. METHODS: Data on replacement of the ascending aorta and/or aortic arch for acute type A dissection were collected from the Japan Cardiovascular Surgery Database from 2008 to 2015. Linear-by-linear association tests or Cuzick's test for trend was used to evaluate group trends over time. The results were calculated for ascending or hemiarch replacement and arch replacement. A multivariable logistic regression model was used to calculate the risk-adjusted operative mortality rate. RESULTS: A total of 11 843 patients were included. The overall 30-day mortality and operative mortality rates were 7.6% and 9.5%, respectively. The number of surgically treated cases increased from 2436 patients in 2008-2009 to 3533 in 2014-2015, a 45.0% increase. A trend analysis revealed significant changes in patient characteristics with time, including increasing age and rate of preoperative renal failure. Despite worsening risk factors, the unadjusted operative mortality rate with arch replacement showed a significant downward trend (P = 0.01; test of trend). The risk-adjusted mortality rate showed a downward trend both in ascending aorta or hemiarch replacement and arch replacement, although the trend was not statistically significant (P > 0.05). CONCLUSIONS: Unadjusted and adjusted operative deaths have shown a decreasing trend, although patients undergoing surgery for acute type A dissection have demonstrated worsening of risk factors, such as age and renal failure. The number of surgeries performed for acute type A dissection significantly increased throughout the study period in Japan.

Validation of the Japanese Version of the Low Anterior Resection Syndrome Score.

BACKGROUND: The low anterior resection syndrome (LARS) score is a patient-reported outcome measure to evaluate the severity of bowel dysfunction after rectal cancer surgery by scoring the major symptoms of LARS. The aim of this study was to translate the English version of the LARS score into Japanese and to investigate the validity and reliability of the LARS score. METHODS: The LARS score was translated in Japanese following current international recommendations. A total of 149 rectal cancer patients completed the LARS score questionnaire and were also asked a single question assessing the impact of bowel function on quality of life (QoL). A total of 136 patients answered the LARS score questionnaire twice. RESULTS: The Japanese LARS score showed high convergent validity, based on its good correlation between the LARS score and QoL (p < 0.001). The LARS score was able to discriminate between patients according to the tumor distance to anal verge (p < 0.001), type of surgery (p < 0.001), and time since surgery (p = 0.001). Patients after ultra-low anterior resection and intersphincteric resection showed especially high scores. The score also had high test-retest reliability (intraclass correlation coefficient: 0.87). CONCLUSION: The Japanese LARS score is a valid and reliable tool for measuring LARS. The LARS score is appropriate for assessments in postoperative bowel function and international comparison. Using this score, patient-reported outcome measures of LARS in Japanese patients can be shared internationally. Additional validation reports from non-English speaking countries can support the LARS score as a worldwide assessment tool for postoperative bowel dysfunction.

Intraluminal Apple as a Rare Cause of Small Bowel Obstruction.

Small bowel obstruction due to ingested foreign bodies is rare in adults. A 48-year-old male visited our hospital with abdominal pain and vomiting. Computed tomography revealed intestinal obstruction by a 3 × 4 cm apple-shaped foreign body. Emergency surgery was performed to clear the obstruction which, upon inspection, was caused by a sexual toy made of rubber. Flexible rubber products that are ingested should be carefully followed after they pass thorough the pylorus. For obstructions related to sexual behavior, the patient's sense of shame often delays the process of seeking medical attention, thereby making preoperative diagnosis difficult.

Transforming Growth Factors α and ß Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model.

To gain insight into the cellular and molecular interactions mediating the desmoplastic reaction and aggressive malignancy of mass-forming intrahepatic cholangiocarcinoma (ICC), we modeled ICC desmoplasia and progression in vitro. A unique three-dimensional (3D) organotypic culture model was established; within a dilute collagen-type I hydrogel, a novel clonal strain of rat cancer-associated myofibroblasts (TDFSM) was co-cultured with a pure rat cholangiocarcinoma cell strain (TDECC) derived from the same ICC type as TDFSM. This 3D organotypic culture model reproduced key features of desmoplastic reaction that closely mimicked those of the in situ tumor, as well as promoted cholangiocarcinoma cell growth and progression. Our results supported a resident liver mesenchymal cell origin of the TDFSM cells, which were not neoplastically transformed. Notably, 3D co-culturing of TDECC cells with TDFSM cells provoked the formation of a dense fibrocollagenous stroma in vitro that was associated with significant increases in both proliferative TDFSM myofibroblastic cells and TDECC cholangiocarcinoma cells accumulating within the gel matrix. This dramatic desmoplastic ICC-like phenotype, which was not observed in the TDECC or TDFSM controls, was highly dependent on transforming growth factor (TGF)-ß, but not promoted by TGF-α. However, TGF-α was determined to be a key factor for promoting cholangiocarcinoma cell anaplasia, hyperproliferation, and higher malignant grading in this 3D culture model of desmoplastic ICC.

ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of colorectal cancer via the Akt pathway.

Colorectal cancer (CRC) is a mortal disease due to treatment resistance, recurrence and distant metastasis. Emerging evidence has revealed that a small sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating cells (CICs) is endowed with high levels of tumor-initiating ability, self-renewal ability and differentiation ability and is responsible for treatment resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is essential to improve current treatments. However, the molecular mechanisms by which CSCs/CICs are maintained are still elusive. In this study, we aimed to determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and increased the sphere-forming ability and resistance to a chemotherapeutic reagent. The opposite phenomena were observed by gene knockdown using siRNA. Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and activation of the pathway was cancelled by gene knockdown of galectin-3. The results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.

Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor Prognosis in Human Esophageal Squamous Cell Carcinoma.

BACKGROUND: The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC). METHODS: We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed. RESULTS: The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor. CONCLUSION: HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.