Patient-derived Organoid Model for Predicting the Chemoresponse in Patients With Colorectal Cancer.

BACKGROUND/AIM: Cancer mortality has decreased due to the contribution of extensive research on cancer treatment, including chemotherapy, radiation, and immunotherapy. However, histopathologically similar tumors originating from the same organ are treated with identical or similar chemotherapeutic regimens regardless of patient characteristics or cancer subtypes. The aim of this study was to evaluate the utility of organoids in predicting responses to chemotherapeutic agents. PATIENTS AND METHODS: This study retrospectively reviewed patient-derived organoids (PDOs) from 10 colorectal cancer patients to compare chemotherapy responses. Drug sensitivities for 5-fluorouracil (5-FU), cisplatin, oxaliplatin, and irinotecan were compared using GI50 (concentration that inhibits cancer cell growth by 50%). RESULTS: When organoids were treated with 5-FU, GI50 was the lowest compared to the other three chemotherapeutic agents (cisplatin, oxaliplatin, and irinotecan). The responsiveness to chemotherapeutic agents differed depending on specific patient characteristics including age, tumor location, stage, and gross type. The response of the patients' organoids to chemotherapeutic agents was consistent with the response to chemotherapy actually performed in those patients with cancer recurrence after surgery. CONCLUSION: PDOs may be useful as a preclinical model in predicting chemotherapy responses in cancer patients.

En-bloc resection including SMV and duodenum in patient of locally advanced colon cancer.

Tumor could directly invade or is adherent to other organs, but superior mesentery vein (SMV) and duodenum invasion are very rare. A 62-year-old woman was diagnosed with abdominal pain for several months. Multiple erythematous brownish skin patches and palpable mass were found at epigastric area. Computed tomography imaging showed focal wall thickening at the transverse colon that invaded to the rectus muscle and anterior abdominal wall. On exploration, we identified tumor invaded or was adherent to the duodenum and superior mesenteric vein and performed en-bloc resection. After surgery, the patient received chemotherapy and was followed up without any recurrence for 16 months. Adhesion and invasion of tumor to surrounding organs can be unexpectedly found during surgery. In our case, we found duodenum and SMV invasion and achieved R0 resection by SMV and duodenum resection, which could improve the patient's prognosis.

Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen.

PURPOSE: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen. METHODS: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks. RESULTS: A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis. CONCLUSION: Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.

Bowel perforation surgery due to fecal impaction immediately after hernia mesh surgery (TAPP).

Inguinal hernia repair using prosthetic mesh is used as a standard treatment in most countries and considered superior to primary suture repair. Although prosthetic mesh has greatly reduced the risk of recurrence, the risk of mesh infection remains. A 71-year-old man was diagnosed with symptomatic bilateral inguinal hernias. He underwent successful laparoscopic transabdominal preperitoneal (TAPP) repair and was discharged the same day. After 3 days, he was diagnosed with small bowel perforation, and underwent emergency surgery. We found perforation of the distal ileum caused by the fecal impaction and severe intra-abdominal contamination. We performed subtotal colectomy and ileosigmoid anastomosis, but did not remove the prosthetic mesh because the previous TAPP site was intact. The patient recovered well post-operatively. Therefore, contaminated or dirty surgery immediately after the hernia mesh surgery could be a feasible treatment.

Absent or impaired rectoanal inhibitory reflex as a diagnostic factor for high-grade (grade III-V) rectal prolapse: a retrospective study.

BACKGROUND: Clinically diagnosing high-grade (III-V) rectal prolapse might be difficult, and the prolapse can often be overlooked. Even though defecography is the significant diagnostic tool for rectal prolapse, it is noticed that rectoanal inhibitory reflex (RAIR) can be associated with rectal prolapse. This study investigated whether RAIR can be used as a diagnostic factor for rectal prolapse. METHODS: In this retrospective study, we evaluated 107 patients who underwent both anorectal manometry and defecography between July 2012 and December 2019. Rectal prolapse was classified in accordance with the Oxford Rectal Prolapse Grading System. Patients in the high-grade (III-V) rectal prolapse (high-grade group, n = 30), and patients with no rectal prolapse or low-grade (I, II) rectal prolapse (low-grade group, n = 77) were analyzed. Clinical variables, including symptoms such as fecal incontinence, feeling of prolapse, and history were collected. Symptoms were assessed using yes/no surveys answered by the patients. The manometric results were also evaluated. RESULTS: Frequencies of fecal incontinence (p = 0.002) and feeling of prolapse (p < 0.001) were significantly higher in the high-grade group. The maximum resting (77.5 vs. 96 mmHg, p = 0.011) and squeezing (128.7 vs. 165 mmHg, p = 0.010) anal pressures were significantly lower in the high-grade group. The frequency of absent or impaired RAIR was significantly higher in the high-grade group (19 cases, 63% vs. 20 cases, 26%, p < 0.001). In a multivariate analysis, the feeling of prolapse (odds ratio [OR], 23.88; 95% confidence interval [CI], 4.43-128.78; p < 0.001) and absent or impaired RAIR (OR, 5.36; 95% CI, 1.91-15.04, p = 0.001) were independent factors of high-grade (III-V) rectal prolapse. In addition, the percentage of the absent or impaired RAIR significantly increased with grading increase of rectal prolapse (p < 0.001). The sensitivity of absent or impaired RAIR as a predictor of high-grade prolapse was 63.3% and specificity 74.0%. CONCLUSIONS: Absent or impaired RAIR was a meaningful diagnostic factor of high-grade (III-V) rectal prolapse. Furthermore, the absent or impaired reflex had a positive linear trend according to the increase of rectal prolapse grading.

Fournier's gangrene in a rectal cancer patient.

INTRODUCTION: Fournier's gangrene (FG) is caused by a variety of causes, but FG led by rectal cancer is rare. PRESENTATION OF CASE: A 62-year-old man presented with perineal pain for several days. Multiple black spots on the scrotum and perineum surrounded by erythema were found on a physical exam. Computed tomography showed diffuse air density with subcutaneous edema in the perineum, scrotum, anus, and left lower abdominal wall and showed 4.1 cm-size mass in anus. He was diagnosed with FG caused by rectal cancer. He underwent extensive debridement of the perineum, scrotum, medial buttocks, and diverting loop colostomy of transverse colon. After repeated debridement of some residual necrotic tissue, abdominal perineal resection was performed after 24 days after initial surgery. The patient received reconstruction surgery of the soft tissue defect and discharged on postoperative day 84. He is being followed up without any recurrence for 10 months. CONCLUSION: Prompt clinical diagnosis and urgent surgical management are crucial for patient's favorable outcome. The patient in our case study could be recovered by a combined modality therapy we provided.

Mechanical intestinal obstruction following laparoscopic inguinal hernia repair in a patient with abdominal cocoon syndrome.

Abdominal cocoon syndrome (ACS) is a rare condition characterized by partial or complete encasement of small intestine by a thick fibro-collagenous membrane. A 65-year-old man presented to the surgical department with left inguinal. He underwent laparoscopic transabdominal preperitoneal inguinal hernia. When we inserted a trocar into the peritoneal cavity, the small intestine was injured and repaired immediately. We identified a fibrotic membrane covering the small intestine, which was found as ACS. Two weeks later after discharge, he presented to the emergency department with mechanical intestinal obstruction. Conservative treatment had no effect on the patient and membrane excision, adhesiolysis and small intestine resection with anastomosis were performed. Unfortunately, the patient was hospitalized for a long time with bowel leakage and discharged on postoperative day 48. The preoperative diagnosis is quite challenging and most cases are diagnosed intraoperatively. When finding the ACS during the operation, careful attention should be needed.

Clinical Potential of Circulating Tumor Cells in Colorectal Cancer: A Prospective Study.

OBJECTIVES: Circulating tumor cells (CTCs) in the blood have been used as diagnostic markers in patients with colorectal cancer (CRC). In this study, we evaluated a CTC detection system based on cell size to assess CTCs and their potential as early diagnostic and prognostic biomarkers for CRC. METHODS: From 2014 to 2015, 88 patients with newly diagnosed CRC, who were scheduled for surgery, and 31 healthy volunteers were enrolled and followed up in Pusan National University Hospital. CTCs were enriched using a centrifugal microfluidic system with a new fluid-assisted separation technique (FAST) and detected by cytomorphological evaluation using fluorescence microscopy. RESULTS: Two or more CTCs were detected using FAST in 74 patients and 3 healthy volunteers. The number of CTCs in the CRC group was significantly higher than that in the healthy volunteers (P < 0.001). When a receiver operating characteristic curve was created to differentiate patients with CRC from healthy volunteers, the sensitivity and specificity were almost optimized when the critical CTC value was 5/7.5 mL of blood. When this value was used, the sensitivity and specificity in differentiating patients with CRC from the healthy controls were 75% and 100%, respectively. In patients with CRC with ≥5 CTCs, vascular invasion was frequently identified (P = 0.035). All patients with stage IV were positive for CTCs. Patients with ≥5 CTCs showed a trend toward poor overall and progression-free survival. DISCUSSION: Our study demonstrated promising results with the use of FAST-based CTC detection for the early diagnosis and prognosis of CRC.

A Prospective Longitudinal Study about Change of Sleep, Anxiety, Depression, and Quality of Life in Each Step of Breast Cancer Patients.

PURPOSE: Quality of sleep (QoS), anxiety, depression, and quality of life (QoL) are common issues among breast cancer patients. Prospective longitudinal studies of QoS, anxiety, depression, and QoL in breast cancer patients are lacking. The aim of this study was to find out whether there is a proper treatment point associated with QoS, anxiety, depression, and QoL during early treatment of breast cancer patients. METHODS: We used 4 self-report questionnaires about QoS, anxiety, depression, and QoL. QoS was measured using the Pittsburgh Sleep Quality Index, anxiety was measured with the Beck Anxiety Inventory, depression was measured with the Beck Depression Inventory, and QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form. Patients were assessed at the time of surgery, at the beginning of chemotherapy, and at the end of chemotherapy. Clinicopathological information was collected for analysis. RESULTS: Fifty-two patients were enrolled in this study, and 29 completed 3 self-report questionnaires. QoS, anxiety, and depression showed no differences during the early treatment period. However, QoL changed during that period (p = 0.004). Type of breast surgery (total mastectomy vs. breast-conserving surgery) showed a relationship with QoS during the entire treatment period, but with anxiety only at the time of surgery (p = 0.002). Although the sample size was too small, the total mastectomy group showed better results. CONCLUSION: Breast cancer patients experience sleep disturbance, anxiety, depression, and loss of QoL. During the period of treatment, these do not change significantly, but these symptoms are often overlooked. Providing sufficient explanations about the treatment and prognosis of breast cancer and mental support for breast cancer patients prior to treatment will help to improve patients' QoS, anxiety, depression, and QoL.

An unusual case of dedifferentiated leiomyosarcoma of the primary mesentery mimicking ovarian cancer.

Dedifferentiated leiomyosarcoma of the primary mesentery is extremely rare. We report a case of dedifferentiated leiomyosarcoma (LMS) of the primary mesentery mimicking ovarian cancer. A 62-year-old woman presented with progressive low abdominal pain. Pelvic magnetic resonance imaging (MRI) revealed a large adnexal mass with carcinomatosis peritonei. Laboratory examination revealed an elevated serum level WBC 46,520/uL (Ref. 4,000~11,000/uL), PLT 687,000/uL (Ref. 140,000~400,000/uL), CA-125 69.1 U/mL (Ref. 0~35 U/mL), and beta-hCG 43.1 mIU/mL (Ref. 0~5 mIU/mL) level. The patient underwent exploratory laparotomy under suspicion of ovarian cancer. We observed a 20-25 cm-sized huge pedunculated subserosal mass arising from the mesentery, and other masses with sizes of 15-20 cm were adherent to peritoneum and ileocecal region. There was a multiple seeding metastasis in the omentum and bowel mesentery. A frozen section revealed malignancy originating from the mesentery, and thus, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissection, and mass excision were performed. Subsequent histopathologic examination resulted in a final diagnosis of dedifferentiated leiomyosarcoma of the mesentery. The patient was transferred to a department of hemato-oncologist for additional managements. Doxorubicin was used for adjuvant chemotherapy.

Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer.

NTRK1 gene fusions, the targets of multikinase inhibitors, are promising therapeutic targets for colorectal cancer (CRC). However, screening methods for detecting NTRK1 gene fusions in CRC tissues have not been reported. In this study, we investigated the potential use of immunohistochemistry (IHC) for detecting NTRK1 gene fusions. We performed and compared IHC with fluorescence in situ hybridization (FISH) in 80 CRC patients. TrkA immunostaining was observed to be both membranous and cytoplasmic and was scored semiquantitatively using staining intensity and proportions. The tumors were observed to be NTRK1 gene fusion-positive when ≥20 out of 100 nuclei in FISH. A significant correlation between the IHC and FISH results for determination of the NTRK1 gene fusions was observed. We measured the cytoplasmic TrkA expression, which showed an area under the receiver operating characteristic (ROC) curve of 0.926 (range: 0.864-0.987, 95% CI, P=.001). By choosing 4.5 (sum of the intensity and proportion scores of cytoplasmic TrkA expression) as the cut-off value for the positive and negative NTRK1 gene fusion groups, the sensitivity and specificity for predicting lymph node metastasis were 100 and 83.8%, respectively (P=.001). Specifically, high cytoplasmic TrkA expression (sum of intensity and proportion scores >4) was associated with the presence of NTRK1 gene fusions (P<.0001, r=0.528). Taken together, our data showed that IHC for TrkA can be used as an efficient screening method for detecting NTRK1 gene fusions in CRC.

The significance of tumor budding in T1 colorectal carcinoma: the most reliable predictor of lymph node metastasis especially in endoscopically resected T1 colorectal carcinoma.

Endoscopic resection is widely recognized as a first-line treatment for T1 colorectal cancers (CRC), although additional surgical intervention may be indicated based on the risk of lymph node (LN) metastasis. However, risk factors for LN metastasis in T1 CRC not fully established. We investigated the clinicopathological features of T1 CRC and evaluated their association with lymph node metastasis in 133 cases of T1 CRC, consisting of 87 cases with first-line endoscopic resection (EMR) followed by additional surgery and 46 cases with primary surgical resection. Among the total 133 cases, 16 cases (12.0%) showed LN metastasis; 13 cases (13/16, 81.25%) were included in endoscopic resection cohort. These were all of the non-pedunculated gross type and most of LN+ tumors invaded submucosa over 1000 µm (surgical cohort versus endoscopic resection cohort; 3 versus 11). However, there was no statistical difference in the depth of submucosal invasion between the LN+ and LN- in both surgical cohort (2799.42 µm ± 401.56 versus 3000.00 µm ± 721.69, P = .897) and endoscopic resection cohort (2066.55 µm ± 142.96 versus 2305.77 µm ± 345.62, P = .520). Conversely, presence of and a higher number of tumor budding foci were associated with an increase in the incidence of LN metastasis in both cohort (P < .0001). Positive resection margins as well as absence of adenoma component were also an independent predictive factor for lymph node metastasis in 87 cases with first-line endoscopic resection followed by additional surgery. We found that tumor budding was the most reliable LN metastasis predictor in T1 CRC in both surgically resected and endoscopic resection specimens.

Necrotizing soft tissue infection: analysis of the factors related to mortality in 30 cases of a single institution for 5 years.

PURPOSE: Necrotizing soft tissue infection is the infection of the soft tissue with necrotic changes. It is rare, but results in high mortality. We analyzed the characteristics of patients, prognosis, and mortality factors after reviewing 30 cases of a single hospital for 5 years. METHODS: From January 2009 to December 2013, 30 patients diagnosed with necrotizing fasciitis or Fournier's gangrene in Pusan National University Hospital were enrolled for this study. The following parameters were analyzed retrospectively: demographics, infection site, initial laboratory finding, initial antibiotics, isolated microorganisms, number of surgeries, time to first operation, length of intensive care unit, and total hospital stays. RESULTS: The overall mortality rate was 23.3%. Mean body mass index (BMI) of the survival group (24.7 ± 5.0 kg/m(2)) was significantly higher than the nonsurvival group (22.0 ± 1.4 kg/m(2), P = 0.029). When BMI was less than 23 kg/m(2), the mortality rate was significantly higher (P = 0.025). Two patients (6.7%) with chronic kidney disease requiring hemodialysis died (P = 0.048). Initial WBC count (>13×10(3)/µL), CRP (>26.5 mg/dL), and platelet (PLT) count (<148×10(3)/µL) were found to have negative impact on the prognosis of necrotizing soft tissue infection. Factors such as potassium level, blood urea nitrogen (>27.6 mg/dL), serum creatinine (>1.2 mg/dL) that reflected kidney function were significant mortality factors. CONCLUSION: Patients with low BMI or abnormal values of WBC count, CRP, and PLT count reflecting the degree of infection or abnormal renal function will need more intensive care.

Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases.

BACKGROUND: Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. METHODS: In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). RESULTS: The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. CONCLUSIONS: The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma.

Distribution and Impact of the Visceral Fat Area in Patients With Colorectal Cancer.

PURPOSE: The purposes of this study were to investigate the distribution of the visceral fat area (VFA) and general obesity and to compare visceral and general obesity as predictors of surgical outcomes of a colorectal cancer resection. METHODS: The prospectively collected data of 102 patients with preoperatively-diagnosed sigmoid colon or rectal cancer who had undergone a curative resection at Pusan National University Yangsan Hospital between April 2011 and September 2012 were reviewed retrospectively. Men with a VFA of >130 cm(2) and women with a VFA of >90 cm(2) were classified as obese (VFA-O, n = 22), and the remaining patients were classified as nonobese (VFA-NO, n = 80). RESULTS: No differences in morbidity, mortality, postoperative bowel recovery, and readmission rate after surgery were observed between the 2 groups. However, a significantly higher number of harvested lymph nodes was observed in the VFA-NO group compared with the VFA-O group (19.0 ± 1.0 vs. 13.5 ± 1.2, respectively, P = 0.001). CONCLUSION: Visceral obesity has no influence on intraoperative difficulties, postoperative complications, and postoperative recovery in patients with sigmoid colon or rectal cancer.

NTRK1 fusions for the therapeutic intervention of Korean patients with colon cancer.

The identification and clinical validation of cancer driver genes are essential to accelerate the translational transition of cancer genomics, as well as to find clinically confident targets for the therapeutic intervention of cancers. Here we identified recurrent LMNA-NTRK1 and TPM3-NTRK1 fusions in Korean patients with colon cancer (3 out of 147, 2%) through next-generation RNA sequencing (RNA-seq). NTRK1 fusions were mutually exclusive oncogenic drivers of colon cancer that were accompanied with in vitro potential of colony formation and in vivo tumorigenicity comparable to KM12, a human colon cancer cell line harboring TPM3-NTRK1 fusion. NTRK1-encoded TrkA protein was prevalent in 11 out of 216 Korean (5.1%) and 28 out of 472 Chinese patients (5.9%) from independent cohorts, respectively. The expression level of TrkA was significantly correlated with NTRK1 fusion (p = 0.0192), which was verified by a fluorescence in situ hybridization (FISH). Korean patients with TrkA-positive colon cancer had a marginal but significant shorter overall survival time than TrkA-negative colon cancer [hazard ratio (HR) = 0.5346, 95% confidential interval (CI) = 0.2548-0.9722, p = 0.0411]. In addition, KM12 cell line was sensitive to selective TrkA inhibitors. These results demonstrate that NTRK1 fusion is granted as a clinically relevant target for therapeutic intervention of colon cancer.

Cardiac mucosa at the gastroesophageal junction: An Eastern perspective.

AIM: To investigate the nature and origin of cardiac mucosa (CM). METHODS: Biopsy samples from sixty-one individuals were included in this study. The specimens were taken "at", "just below", or "just above" the gastroesophageal junction, including the histologic squamocolumnar junction. Clinical data were obtained by reviewing electronic medical records for each patient. Patients with a history of stomach adenoma or carcinoma and esophageal carcinoma were excluded, and cases that were endoscopically suspicious of Barrett's esophagus or a polyp were also ruled out. Histologic and endoscopic reviews were performed blinded to the patient's clinical data. Histologic evaluation was conducted by two pathologists, and endoscopic review was performed by a endoscopist with wide experience in the field. Histologically, the columnar epithelium of squamocolumnar junction, presence and severity of acute and chronic inflammation, atrophy, intestinal metaplasia, and presence of carditis were evaluated. Endoscopically, reflux esophagitis was evaluated by Los Angeles (LA) classification, hiatal hernias were classified by Hill grade, and gastroesophageal flap valves were assessed. RESULTS: Fifty-nine of the 61 (96.7%) patients were Korean; 65.6% (40/61) of the patients underwent endoscopy according to the schedule of the National Health Insurance Program as a screening inspection. Of these, only 20.0% (8/40) of cases had reflux symptoms. CM was present in 41/61 (67.2%) individuals, and its presence was associated with older age compared to oxyntocardiac mucosa/oxyntic mucosa (60.59 ± 2.02 years vs 51.55 ± 3.35 years; P = 0.018). The presence of CM was associated with endoscopic diagnosis of esophagitis according to the LA classification (P = 0.022). CM was associated with mononuclear cell infiltration and neutrophilic infiltration, which were statistically significant (P = 0.001, and P = 0.004, respectively). The inflammation of CM, "carditis", showed a statistically significant association with endoscopic diagnosis of reflux esophagitis according to the LA classification (P = 0.008). CONCLUSION: CM at the gastroesophageal junction is a common histologic finding in biopsy specimens, though not always present, and associated with gastroesophageal reflux disease and carditis severity.

Snail and serpinA1 promote tumor progression and predict prognosis in colorectal cancer.

The role of Snail and serpin peptidase inhibitor clade A member 1 (serpinA1) in tumorigenesis has been previously identified. However, the exact role and mechanism of these proteins in progression of colorectal cancer (CRC) are controversial. In this study, we investigated the role of Snail and serpinA1 in colorectal cancer (CRC) and examined the mechanisms through which these proteins mediate CRC progression. Immunohistochemical analysis of 528 samples from patients with CRC showed that elevated expression of Snail or serpinA1 was correlated with advanced stage, lymph node metastasis, and poor prognosis. Moreover, we detected a correlation between Snail and serpinA1 expression. Functional studies performed using the CRC cell lines DLD-1 and SW-480 showed that overexpression of Snail or serpinA1 significantly increased CRC cell invasion and migration. Conversely, knockdown of Snail or serpinA1 expression suppressed CRC cell invasion and migration. ChIP analysis revealed that Snail regulated serpinA1 by binding to its promoter. In addition, fibronectin mediated Snail and serpinA1 signaling was involved in CRC cell invasion and migration. Taken together, our data showed that Snail and serpinA1 promoted CRC progression through fibronectin. These findings suggested that Snail and serpinA1 were novel prognostic biomarkers and candidate therapeutic targets in CRC.

Histopathological features of the gastroesophageal junction: an Eastern view.

The definition and features of the gastroesophageal junction (GEJ) and the histopathologic features of the cardiac mucosa remain controversial. Most reports originate from western countries, which have different prevalence of GEJ adenocarcinoma and gastroesophageal reflux disease (GERD) compared to eastern countries. Therefore, we investigated GEJ anatomic and histopathologic features by histological mapping in 30 esophagogastrectomy specimens of middle and lower esophageal squamous cell carcinoma. We measured the lengths of the cardiac mucosa, oxyntocardiac mucosa, and esophageal cardiac-type glands. We assessed the presence of intestinal metaplasia, pancreatic acinar cells, Brunner's-like glands, and submucosal esophageal gland beneath cardiac mucosa and the relationship of these features with age and the circumferential location of cardiac mucosa. The lengths of cardiac mucosa and esophageal cardiac-type glands significantly increased with age (<63 years, 2767.86±734.95 µm vs. ≥63 years, 5453.12±839.52 µm, P=0.025 and <63 years, 1151.78±452.81 µm vs. ≥63 years, 2273.44±321.58 µm, P=0.049, respectively) and the presence of circumferential cardiac mucosa (+, 5731.25±721.57 vs. -, 2625.00±356.00 µm, P=0.007; +, 2425.00±326.13 µm vs. -, 400.00±204.80 µm, P<0.0001 respectively). The presence of intestinal metaplasia and irregular GEJ increased with age and the circumferential location of cardiac mucosa. The presence of esophageal submucosal glands beneath the cardiac mucosa, pancreatic acinar cells, and Brunner-like glands were seen in 8/30 (26.7%), 15/30 (50%), and 14/30 (46.7%) cases, respectively. These data indirectly suggest that cardiac mucosa originated from the distal esophagus and that the presence of cardiac mucosa may indicate GERD, in accordance with data from Western countries.

Diffusion-weighted magnetic resonance imaging for non-neoplastic conditions in the hepatobiliary and pancreatic regions: pearls and potential pitfalls in imaging interpretation.

Potentially, diffusion-weighted magnetic resonance imaging (DWI) can assess the functional information on concerning the status of tissue cellularity, because increased cellularity is associated with impeded diffusion. DWI in the hepatobiliary and pancreatic regions has demonstrated the usefulness to detect malignant lesions and differentiate them from benign lesions. However, it has been shown more recently that there is some overlap in ADC values for benign and malignant neoplasms. Moreover, some non-neoplastic lesions in the hepatobiliary and pancreatic regions exhibit restricted diffusion on DWI, because of pus, inflammation, or high cellularity. Focal eosinophilic liver disease, hepatic inflammatory myofibroblastic tumor, granulomatous liver disease, acute cholecystitis, xanthogranulomatous cholecystitis, focal pancreatitis, or autoimmune pancreatitis frequently exhibit restricted diffusion on DWI, which may be confused with malignancy in the hepatobiliary and pancreatic regions. Thus, DWI should not be interpreted in isolation, but in conjunction with other conventional images, to avoid the diagnostic pitfalls of DWI. Nevertheless, the presence of diffusion restriction in the non-neoplastic lesions sometimes provides additional information regarding the diagnosis, in problematic patients where conventional images have yielded equivocal findings. DWI may help differentiate hepatic abscess from malignant necrotic tumors, gallbladder empyema from dense bile or sludge in the gallbladder, and pylephlebitis from bland thrombosis in the portal vein. Therefore, knowledge of DWI findings to conventional imaging findings of diffusion-restricted non-neoplastic conditions in the hepatobiliary and pancreatic regions helps establishing a correct diagnosis.