Clinicopathological features and cancer transcriptomic profiling of poorly cohesive gastric carcinoma subtypes.

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.

Oncological outcomes of large gastrointestinal stromal tumors treated by laparoscopic resection.

BACKGROUND: The resection of large gastric gastrointestinal stromal tumors (GISTs) by laparoscopic has been controversial. Extending from our prior study, the long-term oncological outcome of laparoscopic resection of large (5-8 cm) gastric GISTs was reported. METHODS: From 2002 to 2018, a consecutive 66 patients with gastric GISTs of 5-8 cm were treated at National Taiwan University Hospital. Among them, 30 patients received open surgery, and 36 received laparoscopic surgery. The clinicopathological data, peri-operative and oncological outcomes were compared between groups. RESULTS: The clinical demographics including sex, age, BMI, tumor locations and ratio of wedge resection were similar between groups. The mean tumor size was 6.0 ± 0.83 cm versus 6.3 ± 1.07 cm (Open vs. Laparoscopic, p = 0.3). The operation time, blood loss, and post-operative complications, were also similar. The mean hospital stay was shorter in the laparoscopic group (8.8 ± 2.5 days) than in the open group (12.0 ± 8.9 days), though not significantly different. The median follow-up time was 108 ± 58 months (97 ± 50 in laparoscopic group; 122 ± 64 in open group). All except three patients remain disease-free. One in the open group and two in the laparoscopic group had recurrence of tumor, and they were stable of disease under Imatinib treatment. Eight patients died in non-GIST causes during follow-up. The 5-year recurrence-free survival were 100% for the open and 94.2% for the laparoscopic group (p = 0.2). CONCLUSION: Our data showed that laparoscopic surgery for gastric GIST between 5 and 8 cm was safe and oncologically feasible.

Laparoscopic versus open distal gastrectomy for elderly patients with advanced gastric cancer: a retrospective comparative study.

BACKGROUND: Laparoscopic radical distal gastrectomy (LDG) has been more frequently performed for locally advanced distal gastric cancer (AGC) than open distal gastrectomy (ODG). However, the benefits of LDG for elderly AGC patients (AGC-lap) remain unclear. METHODS: Patients aged ≥ 70 years who underwent D2 distal gastrectomy from July 2014 to July 2021 were enrolled consecutively. Perioperative parameters, pathological features, and oncological outcomes of AGC-lap patients (n = 39) were compared with those of elderly AGC patients receiving ODG (AGC-open; n = 37) and elderly early gastric cancer patients receiving LDG (EGC-lap; n = 41) respectively. RESULTS: The median age of all AGC patients was 77 years, and 28% of them had an Eastern Cooperative Oncology Group score ≥ 2. Most of the perioperative and pathological features (including the number of lymph nodes harvested) were similar between the AGC-lap and AGC-open groups. AGC-lap patients had longer median operative times (215 min versus 192 min) but significantly less surgical complications (10.3% versus 37.8%) and shorter median hospital stays (11 days versus 13 days) than did AGC-open patients (all p < 0.05). The 3-year recurrence-free and overall survival was 66.2% and 88.8% in the AGC-lap group and 51% and 66.3% in the AGC-open group (both p = 0.1). The perioperative features, including operative time, number of lymph nodes harvested, hospital stay, and complication rates, were similar between the AGC- and EGC-lap groups. CONCLUSIONS: LDG was safely and effectively performed in elderly AGC patients, resulting in faster recovery and a lower complication rate than ODG, without compromising oncological outcomes.

Adjuvant tegafur-uracil (UFT) or S-1 monotherapy for advanced gastric cancer: a single center experience.

BACKGROUND: Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated. METHODS: Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups. RESULTS: From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted. CONCLUSIONS: This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Percutaneous embolization for a subacute gastric fistula following laparoscopic sleeve gastrectomy: a case report and literature review.

BACKGROUND: The management for subacute or chronic fistula after bariatric surgery is very complicated and with no standard protocol yet. It is also an Achilles' heel of all bariatric surgery. The aim of this case report is to describe our experience in managing this complication by percutaneous embolization, a less commonly used method. CASE PRESENTATION: A 23-year-old woman with a body mass index of 35.7 kg/m2 presented with delayed gastric leak 7 days after laparoscopic sleeve gastrectomy (LSG) for weight reduction. Persistent leak was still noted under the status of nil per os, nasogastric decompression, and parenteral nutrition for 1 month; therefore, endoscopic glue injection was performed. The fistula tract did not seal off, and the size of pseudocavity enlarged after gas inflation during endoscopic intervention. Subsequently, we successfully managed this subacute gastric fistula via percutaneous fistula tract embolization (PFTE) with removal of the external drain 2 months after LSG. CONCLUSIONS: PFTE can serve as one of the non-invasive methods to treat subacute gastric fistula after LSG. The usage of fluoroscopy-visible glue for embolization can seal the fistula tract precisely and avoid the negative impact from gas inflation during endoscopic intervention.

Derangement of esophageal anatomy and motility in morbidly obese patients: a prospective study based on high-resolution impedance manometry.

BACKGROUND: Morbidly obese patients often suffer from gastroesophageal reflux disease (GERD). High-resolution impedance manometry (HRIM) allows a comprehensive evaluation of esophageal motility and esophagogastric junction (EGJ) morphology and helps to clarify GERD pathophysiology. OBJECTIVE: To evaluate the esophageal function and EGJ anatomy in morbid obesity by HRIM. SETTING: University Hospital, Taiwan. METHODS: We consecutively enrolled 57 morbidly obese patients planning to undergo bariatric surgery and 58 healthy volunteers in this prospective study. All patients responded to validated symptom questionnaires and underwent fasting blood tests, HRIM, and esophagogastroduodenoscopy. We compared anthropometric and HRIM parameters between the 2 groups, and analyzed correlations between the GERD symptom scores and clinical variables in the obese patients. RESULTS: The obese patients, comprising 30 males (53%), had a median age of 35 years and body mass index of 40.5 kg/m2. The 4-second integrated relaxation pressure in the lower esophageal sphincter was significantly higher in the patients than the volunteers (median: 10.8 versus 5.6 mm Hg; P < .001). EGJ outflow obstruction and ineffective esophageal motility were diagnosed in 16% and 11% of the patients, respectively, versus 5% and 28% of the volunteers (P = .022). Manometric hiatal hernia (m-HH) was present in 19 (33%) of the patients and none of the volunteers; all m-HH were associated with erosive esophagitis. Most of the patients were considered as no GERD by the validated questionnaires, regardless of the presence of m-HH and erosive esophagitis. CONCLUSIONS: The obese patients had a higher lower esophageal sphincter 4-second integrated relaxation pressure and higher prevalence of EGJ outflow obstruction and m-HH than the healthy volunteers. The presence of m-HH was strongly associated with erosive esophagitis. The absence of GERD symptoms in morbid obesity was not necessarily suggestive of negative esophagogastroduodenoscopy and HRIM findings, and the discrepancy existed between esophagogastroduodenoscopy and HRIM for diagnosing HH. A comprehensive evaluation of the EGJ anatomy and esophageal function may be considered before bariatric surgery.

Endoscopic submucosal dissection comparing with surgical resection in patients with early gastric cancer - A single center experience in Taiwan.

BACKGROUND/PURPOSE: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan. This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment. METHODS: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan. The primary endpoint was disease specific survival. Recurrence free survival and length of hospital stay were also compared. RESULTS: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p = 0.39), so as the recurrence free survival (cumulative survival 92.31% vs. 94.06%, p = 0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found (cumulative recurrence 7.69% vs. 20%, p = 0.39) and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs. 40%, p < 0.01). However, the shorter duration of hospital stay in ESD group was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p < 0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery. CONCLUSION: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pre-treatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

Circulating Diabetic Candidate Neurotrophic Factors, Brain-Derived Neurotrophic Factor and Fibroblast Growth Factor 21, in Sleeve Gastrectomy.

Recent studies show brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 21 (FGF21) are neurotrophic factors associated with obesity and diabetes mellitus (DM). Laparoscopic sleeve gastrectomy (LSG) can significantly reduce weight and improve DM. In this study, we enrolled 78 patients with obesity and evaluated the change of BDNF and FGF21 6 months after LSG. At baseline, the BDNF level was similar between the preoperative DM (n = 30) (17.1 ± 7.7 ng/ml) and non-DM (n = 48) (17.0 ± 6.9 ng/ml) patients with obesity, but FGF21 was significantly higher in the DM patients (201.5 ± 204.3 versus 107.6 ± 63.8 pg/ml). At 6 months after LSG, most of the preoperative DM patients (96.7%) had DM either resolved (66.7%) or improved (30%). BDNF increased and FGF21 decreased significantly regardless of the preoperative DM status, while FGF21 decreased more prominently in the preoperative DM patients (-92.6 ± 179.8 versus -4.6 ± 63.4 pg/ml). After adjusted for age, sex, and preoperative DM status, FGF21 became significantly and positively related to C-peptide (ß = 18.887), insulin (ß = 2.399), and homeostasis model assessment of insulin resistance index (ß = 8.566) after surgery. In conclusion, diabetic patients with obesity had higher FGF21 and similar BDNF levels compared to non-diabetic obese patients. BDNF increased and FGF21 decreased significantly after LSG. FGF21 became positively associated with several insulin-related profiles after surgery.

The effect of performing two pancreatoduodenectomies by a single surgical team in one day on surgeons and patient outcomes.

BACKGROUND: The centralization of pancreatoduodenectomy (PD) has been shown to improve patient outcomes. The scheduling of two PDs in one day is one option to shorten the waiting time for patients referred to high volume centers. The effect on the surgical team or patient outcomes of such an approach have not previously been explored. This study aimed to investigate the effect of scheduling two PDs in one day on the surgeon's workload and patient outcomes. METHODS: A retrospective review of patients undergoing PD by a single surgeon between 2007 and 2018 was performed. Patients were allocated into: first PD (FIRSTPD group) or second PD (SECONDPD group) according to the position on the surgical operating list. The intraoperative, postoperative outcomes, and workload (the Surgery Task Load Index; SURG-TLX) were assessed between two groups. RESULTS: A total of 967 (91%) and 101 (9%) patients were included in the FIRSTPD and SECONDPD group, respectively. There were no differences in the duration of surgery (coefficient = -9.65; 95% confidence interval: -29.26 to 9.94; P = 0.334), incidence of major complications (odds ratio = 1.08; 95% confidence interval: 0.67-1.73; P = 0.739), or 90-day mortality (odds ratio = 1.03; 95% confidence interval: 0.12-8.53; P = 0.978) for those patients in the SECONDPD group as compared to the FIRSTPD group. The mean scores of two (physical and temporal demand) of the six SURG-TLX subscales of surgical workload were recorded as significantly higher by surgeons following two PD's as compared to one PD. CONCLUSIONS: Although scheduling a second PD in one day shows no association with adverse patient outcomes, there is an increase in the physical and temporal subscales of surgical workload and consideration should be given to how this could be minimized.

Endoscopic Retrograde Biliary Drainage Causes Intra-Abdominal Abscess in Pancreaticoduodenectomy Patients: An Important But Neglected Risk Factor.

BACKGROUND: Patients with periampullary cancer frequently suffer obstructive jaundice and commonly require preoperative biliary drainage (PBD) for relief and to avoid related complications. Although research has established a correlation between PBD and surgical wound infection, the impact of PBD on major infectious complications (intra-abdominal abscess [IAA]) and overall mortality remains debatable. We hypothesized that PBD could lead to IAA and mortality, and evaluated their correlation in patients undergoing pancreaticoduodenectomy (PD). METHODS: We enrolled patients undergoing PD at an Asian academic medical center between 2007 and 2016. The types of PBD included endoscopic retrograde biliary drainage (ERBD) and percutaneous transhepatic cholangiography and drainage (PTCD). The primary outcome was IAA, defined as the presence of pus or infected fluid inside the abdominal cavity and with documented infectious pathogens. RESULTS: There was one (0.1%) 30-day mortality and eight (0.9%) 90-day mortalities among 899 consecutive patients examined. More than one-quarter of patients had PBD (n = 237, 26.4%; 165 ERBD, 72 PTCD). In the ERBD, PTCD, and non-PBD groups, the IAA rates were 37.0%, 16.7%, and 10.6%, respectively. On multivariate analysis, ERBD (odds ratio 3.67; 95% confidence interval 2.22-6.06; p < 0.001) was the only significant factor associated with IAA. No significant factor was found to analyze variables associated with mortality. CONCLUSIONS: ERBD, but not PTCD, is associated with an increased risk of IAA in patients undergoing PD, which suggests that ERBD should be avoided whenever possible to prevent IAA. Further randomized clinical trials should be conducted to validate this relationship.

Late acute pancreatitis after pancreaticoduodenectomy: incidence, outcome, and risk factors.

BACKGROUND: The pancreatoenteric anastomotic stricture (PEAS) is a common long-term complication after pancreaticoduodenectomy (PD), some of which present as acute pancreatitis requiring emergency care. This important topic has never been reported. In this study, we focus on the incidence, radiological features, clinical outcome, and risk factors of late-occurring acute pancreatitis (LAP) after PD. METHODS: We retrospectively reviewed a prospectively collected database of 539 patients who underwent PD at a single tertiary referral center between June 2005 and December 2014. Only patients with at least 3 years of follow-up and available pre- and post-operative images were included. RESULTS: Of the 539 patients, 23 (15 [65%] with and eight [35%] without PEAS) were diagnosed with LAP after PD. The cumulative incidence of LAP was 3.6% (1-year), 4.4% (2-year), and 5.1% (5-year). The median time to the first LAP episode was 22 months (range 8-38 months) after PD. All the first and recurrent LAP events were mild in severity and resolved after conservative treatment. Multivariate analysis showed that a history of acute pancreatitis before PD (P = 0.001, HR 5.24, 95% CI 1.95-14.10) and PEAS (P = 0.047, HR 2.75, 95% CI 1.01-7.49) were two significant risk factors. CONCLUSIONS: We propose using a more conservative treatment for patients who experience LAP after PD.

Laparoscopic distal gastrectomy for clinical stage I gastric adenocarcinoma: Techniques evolution and oncological outcomes of the first 100 cases.

BACKGROUND/PURPOSE: While gaining more acceptance, the use of laparoscopic distal gastrectomy (LDG) to treat gastric cancer were still limited in Taiwan. This study reviewed our experience about the technique evolution and outcome of using LDG for the patients with clinical stage (c-stage) I gastric cancers. METHODS: A retrospective review of the patients undergoing LDG for c-stage I gastric cancers at a medical center of Taiwan was performed. The demographics, peri-operative parameters, reconstruction methods, morbidities, pathologic and oncological outcomes were analyzed. RESULTS: A total of 100 patients with c-stage I gastric cancers between October 2005 and September 2016 were enrolled. Laparoscopy-assisted distal gastrectomy (LADG) was performed in the initial 69 cases. Total laparoscopic distal gastrectomy (TLDG) was done in the following 31 cases. There was no conversion of procedures, nor surgical mortality. The surgical morbidity rate was 13%, including 3 major complications. The ratio of using Billroth I reconstruction (83.9% versus 43.5%, p < 0.01) and the mean number of harvested lymph nodes (38.6 ± 14.8 versus 31.2 ± 15.2, p = 0.02) were both higher in the TLDG group than in the LADG group. The pathologic examination confirmed 78 patients were stage I, while 22 were stage II disease. Seven of the 24 patients with lymph node metastasis received adjuvant chemotherapy. Two patients had recurrence of diseases. The 3-year recurrence-free and overall survival were 93.3% and 95.8% separately. CONCLUSION: These results suggested that laparoscopic gastrectomy could be performed safely and feasibly for patients with early gastric cancers. LADG is recommended for the establishment of the demanding technique.