Short-term outcomes of robotic tumor-specific mesorectal resection of rectal cancer: surgical techniques in mesorectal division using rolling division of the mesorectum.

BACKGROUND: This study aims to report our surgical techniques for robot-assisted laparoscopic anterior resection, specifically focusing on mesorectal division using rolling division of the mesorectum, and to elucidate short-term outcomes at a single institution. Tumor-specific mesorectal excision (TSME) is commonly performed for resection of a tumor located in the upper rectum. However, especially in a narrow pelvis, it is difficult to perform appropriate mesorectal division at an adequate distance from the tumor in robot-assisted laparoscopic anterior resection. METHODS: Retrospective case series of patients with rectal cancer who underwent robot-assisted TSME using rolling division of mesorectum. Patient characteristics, perioperative clinical results, surgical and pathological details were recorded. RESULTS: A total of 198 patients underwent robot-assisted TSME for rectal cancer using rolling division of mesorectum between May 2019 and December 2023.The tumor was located in the upper rectum in 45 patients, middle rectum in 115 patients and lower rectum in 38 patients. The types of resections were 40 high anterior resection and 158 low anterior resections. The median operation time was 175 (range 109-310) min, and median mesorectal division time was 24 (range 15-45) min. Median blood loss was 3 (range 0-20) ml; no patients required blood transfusion. The overall complication rate of Clavien-Dindo classification grades I-IV was 7.1%. Anastomotic leakage was observed in two patients (1.0%) with grade III. There was no surgical mortality in this series. CONCLUSION: This robotic technique for anterior resection is a feasible and reliable procedure for achieving sufficient and safe TSME in this cohort.

Clinical impact of skeletal muscle mass change during the neoadjuvant chemotherapy period in patients with gastric cancer: An ancillary study of JCOG1002.

BACKGROUND: Recent studies have revealed that sarcopenia is associated with postoperative complications and poor prognosis. Although neoadjuvant chemotherapy is a promising treatment for gastric cancer, its toxicity may lead to the loss of skeletal muscle mass. This study investigates the changes in skeletal muscle mass during neoadjuvant chemotherapy and its clinical impact on patients with locally advanced gastric cancer. METHODS: Fifty patients who completed two courses of neoadjuvant chemotherapy followed by surgery were included. Skeletal muscle mass was measured using computed tomography images before and after chemotherapy. The proportion of skeletal muscle mass change (%SMC) during neoadjuvant chemotherapy and its cutoff value was explored using the receiver operating characteristic for the overall survival of patients undergoing R0 resection. Risk factors of skeletal muscle mass loss were also evaluated. RESULTS: Overall, 64% of patients had skeletal muscle mass loss during neoadjuvant chemotherapy (median %SMC -3.4%; range: -18.9% to 10.3%). Multivariable analysis identified older age (≥70 years) as an independent predictor of skeletal muscle mass loss (mean [95% confidence interval]: -4.70% [-8.83 to -0.58], p = 0.026). Among 43 patients undergoing R0 resection, %SMC <-6.9% was an independent poor prognostic factor for overall survival (hazard ratio, 11.53; 95% confidence interval, 2.78-47.80) and relapse-free survival (hazard ratio 4.54, 95% confidence interval 1.50-13.81). CONCLUSIONS: Skeletal muscle mass loss occurs frequently during neoadjuvant chemotherapy for locally advanced gastric cancer and could adversely affect survival outcomes.

Concurrent targeting of GSK3 and MEK as a therapeutic strategy to treat pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies worldwide. However, drug discovery for PDAC treatment has proven complicated, leading to stagnant therapeutic outcomes. Here, we identify Glycogen synthase kinase 3 (GSK3) as a therapeutic target through a whole-body genetic screening utilizing a '4-hit' Drosophila model mimicking the PDAC genotype. Reducing the gene dosage of GSK3 in a whole-body manner or knocking down GSK3 specifically in transformed cells suppressed 4-hit fly lethality, similar to Mitogen-activated protein kinase kinase (MEK), the therapeutic target in PDAC we have recently reported. Consistently, a combination of the GSK3 inhibitor CHIR99021 and the MEK inhibitor trametinib suppressed the phosphorylation of Polo-like kinase 1 (PLK1) as well as the growth of orthotopic human PDAC xenografts in mice. Additionally, reducing PLK1 genetically in 4-hit flies rescued their lethality. Our results reveal a therapeutic vulnerability in PDAC that offers a treatment opportunity for patients by inhibiting multiple targets.

Drosophila Screening Identifies Dual Inhibition of MEK and AURKB as an Effective Therapy for Pancreatic Ductal Adenocarcinoma.

Significant progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) by generating and using murine models. To accelerate drug discovery by identifying novel therapeutic targets on a systemic level, here we generated a Drosophila model mimicking the genetic signature in PDAC (KRAS, TP53, CDKN2A, and SMAD4 alterations), which is associated with the worst prognosis in patients. The '4-hit' flies displayed epithelial transformation and decreased survival. Comprehensive genetic screening of their entire kinome revealed kinases including MEK and AURKB as therapeutic targets. Consistently, a combination of the MEK inhibitor trametinib and the AURKB inhibitor BI-831266 suppressed the growth of human PDAC xenografts in mice. In patients with PDAC, the activity of AURKB was associated with poor prognosis. This fly-based platform provides an efficient whole-body approach that complements current methods for identifying therapeutic targets in PDAC. SIGNIFICANCE: Development of a Drosophila model mimicking genetic alterations in human pancreatic ductal adenocarcinoma provides a tool for genetic screening that identifies MEK and AURKB inhibition as a potential treatment strategy.

Opponent learning with different representations in the cortico-basal ganglia pathways can develop obsession-compulsion cycle.

Obsessive-compulsive disorder (OCD) has been suggested to be associated with impairment of model-based behavioral control. Meanwhile, recent work suggested shorter memory trace for negative than positive prediction errors (PEs) in OCD. We explored relations between these two suggestions through computational modeling. Based on the properties of cortico-basal ganglia pathways, we modeled human as an agent having a combination of successor representation (SR)-based system that enables model-based-like control and individual representation (IR)-based system that only hosts model-free control, with the two systems potentially learning from positive and negative PEs in different rates. We simulated the agent's behavior in the environmental model used in the recent work that describes potential development of obsession-compulsion cycle. We found that the dual-system agent could develop enhanced obsession-compulsion cycle, similarly to the agent having memory trace imbalance in the recent work, if the SR- and IR-based systems learned mainly from positive and negative PEs, respectively. We then simulated the behavior of such an opponent SR+IR agent in the two-stage decision task, in comparison with the agent having only SR-based control. Fitting of the agents' behavior by the model weighing model-based and model-free control developed in the original two-stage task study resulted in smaller weights of model-based control for the opponent SR+IR agent than for the SR-only agent. These results reconcile the previous suggestions about OCD, i.e., impaired model-based control and memory trace imbalance, raising a novel possibility that opponent learning in model(SR)-based and model-free controllers underlies obsession-compulsion. Our model cannot explain the behavior of OCD patients in punishment, rather than reward, contexts, but it could be resolved if opponent SR+IR learning operates also in the recently revealed non-canonical cortico-basal ganglia-dopamine circuit for threat/aversiveness, rather than reward, reinforcement learning, and the aversive SR + appetitive IR agent could actually develop obsession-compulsion if the environment is modeled differently.

Structure of crystalline water ice formed through neon matrix sublimation under cryogenic and vacuum conditions.

Ice I has three forms depending on the stacking arrangements of its layers: hexagonal ice Ih, cubic ice Ic, and stacking disordered ice Isd. Below ∼60 K, amorphous water becomes metastable, and the formation of any form of ice I is often implicitly precluded. Using a newly developed low-temperature reflection high-energy electron diffraction (RHEED) technique, we show that crystalline ice with cubic stacking sequences (i.e., ice Ic) formed through Ne sublimation from a solid H2O/Ne (1:1000 ratio) matrix at 13 K. The extent of stacking disorder (disordered cubic and hexagonal stacking sequences) in the ice formed by Ne matrix sublimation is smaller than that in vapor-deposited ice Isd prepared at 143 K and below the limit of detection of low-temperature RHEED. Dependence of the resulting ice structures on the thickness of the H2O/Ne matrix shows that amorphous water first forms in the early stages of Ne sublimation, and the cubic stacking sequence subsequently takes place. As the cubic ice Ic formed here at a much lower temperature (13 K) than previously observed (typically above 78 K), Ne matrix sublimation represents a novel route to the formation of cubic ice Ic under low-temperature and low-pressure conditions.

Impact of postoperative intra-abdominal infectious complications on survival outcomes in patients with gastric cancer who underwent laparoscopic surgery.

BACKGROUND: Postoperative intra-abdominal infection is known to adversely affect survival outcomes in patients with gastric cancer; however, previous reports have investigated this complication only in open surgery. This adverse effect is expected to be weakened by less invasive surgery, such as a laparoscopic approach, by way of maintaining immune function. METHODS: This study included 1223 patients with gastric cancer who underwent open (n = 439) or laparoscopic (n = 784) curative surgery between 2010 and 2015. For each approach, patients were divided into two groups based on presence or absence of postoperative intra-abdominal infection of Clavien-Dindo grade II or higher (C-group and NC-group, respectively). Survival outcomes were compared in propensity-matched cohorts to evaluate the impact of the complication. RESULTS: The incidences of Clavien-Dindo ≥ grade II postoperative intra-abdominal infectious complications were 9.7% (43/439) in open surgery and 9.8% (70/714) in laparoscopic surgery. After propensity score matching, 86 patients in open surgery and 138 in laparoscopic surgery were extracted for analysis. The 5-year overall survival rate in the open C-group (n = 43) was worse than that in the open NC-group (n = 43) but with no significant difference (70.9% vs. 82.8%, log-rank P = 0.18). The 5-year overall survival rates were equivalent between the laparoscopic C-group (n = 69) and the laparoscopic NC-group (n = 69) (90.5% vs. 90.4%, log-rank P = 0.99). CONCLUSION: In general, postoperative intra-abdominal infection adversely affects survival outcomes; however, its impact may be weakened by less invasive surgery. Further evaluation using larger datasets is necessary before reaching definitive conclusions.

The impact of hiatal hernia on survival outcomes in patients with gastroesophageal junction adenocarcinoma.

Aim: A hiatal hernia (HH) complicates the diagnosis and surgical treatment of gastroesophageal junction (GEJ) cancer. This study aimed to investigate the effect of HH on the survival outcomes of GEJ cancer patients. Methods: This single-center study reviewed clinical data of 78 patients with GEJ adenocarcinoma who underwent R0 resection from 2008 to 2017. The patients were divided into two groups according to whether they presented with or without HH: the HH (+) group (n = 46) and the HH (-) group (n = 32). Results: Patients in the HH (+) group were older than those in the HH (-) group (69.0 vs 67.5 years, P = .018). Regarding surgical outcomes, intra-abdominal infectious complications was more common in the HH (+) group than in the HH (-) group (23.9% vs 9.4%, respectively; P = .089), particularly abscess formation (17.4% vs 3.1%, respectively; P = .036). Neither overall survival (OS) nor relapse-free survival (RFS) differed between the two groups. However, survival rates were significantly worse in a subset of patients with T3-4 disease (OS: log-rank, P = .036) (RFS: log-rank, P = .040) in the HH (+) group. In a multivariate analysis for OS in this cohort, HH was an independent prognostic factor (hazard ratio 3.60; 95% confidence interval 1.06-11.9, P = .032). Conclusion: Hiatal hernia may adversely affect surgical and survival outcomes in patients with GEJ cancer. Thus, surgical strategy must be carefully considered in these patients.

Reduction in postoperative complications by robotic surgery: a case-control study of robotic versus conventional laparoscopic surgery for gastric cancer.

BACKGROUND: Robotic gastrectomy (RG) is being increasingly performed globally; it is considered an evolved type of conventional laparoscopic surgery with excellent dexterity and precision, but higher costs and longer operation time. Thus, there is a need to identify the benefits from RG and its specific candidates. METHODS: This retrospective study analyzed data from a prospectively collected clinical database at our center. Data of patients with primary gastric cancer undergoing either robotic or laparoscopic radical gastrectomy from June 2014 to June 2020 were reviewed. Surgical outcomes were compared between the two groups, and multivariable analyses were performed to elucidate the relevant factors for postoperative complications in several subgroups. RESULTS: A total of 1172 patients were divided into those who underwent RG (n = 152) and those who underwent laparoscopic gastrectomy (LG) (n = 1020). Baseline characteristics were similar in the two groups, except the RG group included more patients undergoing total/proximal gastrectomy (TG/PG) and patients at clinical stage III. Compared with the LG group, the RG group had lower incidences of postoperative complications ≥ Clavien-Dindo grade III (2/152 (1.3%) versus 72/1020 (7.1%); P = 0.004), and intraabdominal complications ≥ grade II (6/152 (3.9%) versus 119/1020 (11.7%); P = 0.004). Multivariable analysis revealed that RG was a significant relevant factor for reducing overall postoperative complications (≥ grade III) (odds ratio (OR) 0.16, P = 0.013), and intraabdominal complications (≥ grade II) (OR 0.29, P = 0.002). Subgroup analyses demonstrated that this tendency was enhanced in patients undergoing TG/PG (OR 0.29, P = 0.021) or at clinical stage II/III (OR 0.10, P = 0.027). CONCLUSIONS: RG reduces the incidence of postoperative complications compared with conventional LG and this tendency may be enhanced in technically complicated procedures with demanding anastomosis or D2 lymphadenectomy. Patients requiring such procedures would most benefit from RG.

Gastric mesenchymal tumor with smooth muscle differentiation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion.

Gastric mesenchymal tumors are relatively rare, and their molecular pathogeneses are poorly understood, except for gastrointestinal stromal tumor, desmoid, and inflammatory myofibroblastic tumors. We report a case of a gastric mesenchymal tumor with prominent smooth muscle cell differentiation and an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. On gross section, the tumor was 26 mm at the largest diameter, well-circumscribed, and located in the submucosal and muscular layers of the stomach wall. Histologically, the tumor comprised intersecting fascicles of spindle cells, non-atypical nuclei, and highly eosinophilic cytoplasm. Myxoid changes were observed focally, but inflammatory infiltrates were only evident in limited areas. Immunochemical staining revealed that the tumor was positive for α-smooth muscle actin and desmin. Diffuse positive staining for h-caldesmon was observed throughout the tumor, which suggested smooth muscle cell differentiation. Intracytoplasmic staining for ALK protein was also observed, and fluorescence in situ hybridization using ALK break-apart probes showed split chromosomal signals. RNA-sequencing analysis identified EML4-ALK fusion transcripts. We concluded that the tumor was a gastric mesenchymal tumor with smooth muscle differentiation based on its distinct differential smooth muscle properties, such as highly eosinophilic cytoplasm and diffuse expression of h-caldesmon. Furthermore, activated ALK may underly the tumor's pathogenesis.

Sex Differences in the Oxygenation of the Left and Right Prefrontal Cortex during Moderate-Intensity Exercise.

INTRODUCTION: Differences in cognitive performance with exercise between men and women have previously been reported. In this study, we evaluated between-sex differences in oxygenation of the prefrontal cortex (PFC) with moderate-intensity aerobic exercise (AE), which could contribute to noted differences in cognitive function. METHOD: The subjects were ten men (age, 21.5 ± 0.5 years; height, 171.7 ± 4.8 cm; weight, 65.6 ± 5.6 kg) and ten women (age, 21.4 ± 0.5 years; height, 157.6 ± 4.9 cm; weight, 51.3 ± 6.5 kg). They completed our AE protocol, consisting of a 30-min leg-ergometer cycling at an intensity of 50% peak oxygen uptake, with an initial 4-min rest period for baseline measurement. Measures of the dynamics of cerebral oxygenation included: oxygenated hemoglobin (O2Hb) in the left and right PFC (LR-PFC) and deoxygenated hemoglobin (HHb). The 30-min exercise period was subdivided into six 5-min phases, with the average and peak values determined in each phase. RESULTS: A significant interaction was found between LR-PFC HHb and sex (p < 0.001), with significantly higher values in men than in women in phases 3-6 (p < 0.05). CONCLUSION: We report a significant sex effect of HHb in the LR-PFC.

Feasibility and quality of life assessment of laparoscopic proximal gastrectomy using double-tract reconstruction.

PURPOSE: As the frequency of cancer in the proximal stomach or around the esophagogastric junction (EGJ) increases worldwide, the use of laparoscopic proximal gastrectomy (LPG) has expanded. This study evaluated the safety of LPG with double-tract reconstruction (LPG-DT) and the resulting quality of life (QOL) of patients. METHODS: In this retrospective cohort study, we reviewed the data of patients who underwent LPG-DT via linear-stapled esophagojejunostomy for gastric or EGJ cancer between 2013 and 2019, and outcomes were compared with those of laparoscopic total gastrectomy with Roux-en-Y reconstruction (LTG-RY) peMME000372rformed over the same period. Surgical outcomes, changes of nutritional parameters, and chronological QOL as evaluated using the Postgastrectomy Syndrome Assessment Scale (PGSAS-37) questionnaire were compared in the propensity-matched cohorts. RESULTS: In total, 289 patients (99 LPG-DT and 190 LTG-RY) were eligible and the outcomes were evaluated in the propensity-matched cohorts (n = 75 each). Operative time and the incidence of complications (≥ grade III) were comparable. Reflux esophagitis was more frequent in the LPG-DT group (8.0% vs. 0%), whereas the incidence of anastomotic stricture did not differ. The percentage rates of body weight loss and hemoglobin reduction were lower in the LPG-DT group at any time point within postoperative 2 years but show no statistical differences. In PGSAS-37 (n = 26, n = 23), the diarrhea and quality of ingestion scores were slightly better in the LPG-DT group. CONCLUSIONS: The present study suggested that our LPG-DT is feasible and safe in appropriately selected patients, and it may provide slightly better outcomes in nutrition and QOL compared with LTG-RY.

Delta-shaped gastroduodenostomy after totally laparoscopic distal gastrectomy for gastric cancer: comparative study of original and modified methods.

BACKGROUND: Delta-shaped anastomosis (DA) has been widely accepted as a standard procedure for intracorporeal Billroth-I reconstruction after laparoscopic distal gastrectomy. We introduced DA in 2010 at our hospital and later developed a modified DA method in which a stapled corner of the duodenal stump was removed simultaneously with closure of an entry hole to reduce postoperative complications. METHODS: The clinical data of 507 patients undergoing laparoscopic distal gastrectomy with DA from October 2010 through December 2018 were retrospectively collected from our in-house database. On the basis of the reviewed data, patients were divided into two groups: the original DA group (org-DA, n = 392) and the modified DA group (mod-DA, n = 115). Surgical outcomes, postoperative nutritional parameters, and endoscopic findings 1 year after surgery were compared between the two groups. RESULTS: Baseline characteristics were similar between the two groups. Anastomotic stricture occurred in three patients (0.8%) in the org-DA group and one patient (0.9%) in the mod-DA group (P = 0.911). Anastomotic leakage was recorded in five patients (1.3%) in the org-DA group and none of the patients (0%) in the mod-DA group (P = 0.593). One year after surgery, the change in body weight in the org-DA group/mod-DA group was - 8.1%/- 7.0% (P = 0.285), and the change in hemoglobin level was - 5.0%/- 3.9% (P = 0.012). Endoscopic examination at the 1-year follow-up in the mod-DA group showed smaller amounts of food residue (P = 0.008) as well as less residual gastritis (P < 0.001) than in the org-DA group. CONCLUSIONS: The modified DA method can be performed safely with a complication rate comparable with the original DA method. Furthermore, better postoperative function is expected because of its more natural anatomy and physiology resulting from the modified method.

Long-term oncological outcomes of laparoscopic versus open transhiatal resection for patients with Siewert type II adenocarcinoma of the esophagogastric junction.

BACKGROUND: Insufficient information is available about the long-term outcomes of patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG) who undergo laparoscopic transhiatal approach (LTH). Here we evaluated the oncological safety of LTH for patients with Siewert type II AEG compared with the open transhiatal approach (OTH). METHODS: Subjects included 79 patients with Siewert type II AEG who underwent gastrectomy combined with lower esophagectomy from 2008 to 2018 at our institution. Overall survival (OS), recurrence-free survival (RFS), status of adjuvant chemotherapy, late-phase complications, and recurrence patterns were compared between the OTH (n = 29) and LTH groups (n = 43). RESULTS: The median observation periods were 60 months (6-120 months) and 36 months (1-88) for the OTH and LTH groups, respectively. The 5-year OS rates were significantly different: 74% (95% CI 71-77%) and 98% (95% CI 97-99) in the OTH and LTH groups (HR 0.10, 95% CI 0.01-0.83), respectively, though the OTH group included more patients with advanced disease. After stratification, according to pathological stage to adjust for selection bias, the 5-year OS and RFS rates were longer, but not significantly different among patients in the LTH group with pStage III (HR 0.42, 95% CI 0.05-3.47; HR 0.47, 95% CI 0.10-2.12, respectively). Recurrence patterns were similar in the both groups. CONCLUSIONS: Long-term outcomes of the LTH group were not inferior to those of the OTH group, suggesting the possibility of LTH as a treatment option for selected patients with Siewert type II AEG.

Can laparoscopic spleen-preserving splenic hilar lymph node dissection replace prophylactic splenectomy for proximal advanced gastric cancers that invade the greater curvature?

BACKGROUND AND OBJECTIVES: Proximal advanced gastric cancer that invades the greater curvature is often treated by prophylactic splenectomy because of a risk for metastasis to the splenic hilar lymph node (station No.10). We evaluated whether laparoscopic spleen-preserving splenic hilar dissection (SPSHD) could be a better approach. METHODS: We reviewed records of patients with proximal gastric cancer who underwent total gastrectomy with No.10 dissection between 2012 and 2018 using our in-house database set. We divided patients by whether they had received SPSHD or splenectomy, first to compare surgical outcomes, and subsequently to analyze survival outcomes among patients with tumors invading the greater curvature. RESULTS: Of 145 patients enrolled in this study, 82 had SPSHDs and 63 had splenectomies. All SPSHDs were laparoscopic; 80% of splenectomies were laparotomic. Morbidity ≥ grade III was seen in 8.5% of the SPSHD group and 11.1% of the splenectomy group. The median number of retrieved No. 10 nodes was three in each group. In multivariable analysis, SPSHD was not an independent prognostic factor among patients whose tumors invaded the greater curvature (n = 73). Among propensity-matched cohorts (n = 25 each), 5-year relapse-free survival rates were 77.6% in the SPSHD group and 49.9% in the splenectomy group. CONCLUSION: Laparoscopic SPSHD can potentially replace prophylactic splenectomy.

Feasibility of laparoscopic total gastrectomy with splenectomy for proximal advanced gastric cancer: A comparative study with open surgery.

INTRODUCTION: Total gastrectomy with splenectomy (TGS) is sometimes performed for treatment of locally advanced gastric cancer invading the greater curvature because metastasis to splenic hilar nodes is expected. Despite the widespread use of laparoscopic procedures, the feasibility of laparoscopic TGS (LTGS) has been scarcely reported because of its technical difficulties. METHODS: This retrospective single-institutional study included 93 consecutive patients with proximal advanced gastric cancer who underwent either LTGS or open TGS (OTGS) from 2010 to 2018. The patients who underwent LTGS (n = 12) were compared with a 1:2 ratio propensity score-matched cohort of patients who underwent OTGS (n = 20). Clinical outcomes were retrospectively reviewed and compared between the two groups. RESULTS: The patients' baseline characteristics were well balanced between the two groups. The operating time was longer (332.5 vs 222.5 minutes, P < .01) but the blood loss volume was smaller (34.5 vs 426 mL, P < .01) in the LTGS than OTGS group. The incidence of postoperative morbidity (≥ Clavien-Dindo grade III) was much lower (0.0% vs 36.8%, P = .02) and the median postoperative hospital stay was shorter (9 vs 11 days, P < .01) in the LTGS than OTGS group. The median number of harvested No. 10 or 11 days lymph nodes was equivalent between the two groups. CONCLUSIONS: Although TGS is not a common procedure, LTGS may be safely performed in selected patients when carried out by an experienced surgical team. The oncological safety remains unclear and needs to be further examined in future trials.

Erratum: Author's Affiliation Correction. Type II human epidermal growth factor receptor heterogeneity is a poor prognosticator for type II human epidermal growth factor receptor positive gastric cancer (World J Clin Cases 2019; Aug 6; 7 (15): 1964-1977).

[This corrects the article on p. 1964 in vol. 7, PMID: 31423428.].

Intramucosal-lymphatic invasion has a slight impact on lymph node metastasis in patients with early gastric cancer.

PURPOSE: Lymphatic invasion (LI) is associated with lymph node metastasis (LNM) and a poor prognosis in patients with early gastric cancer (EGC). Although the impact of the LI volume on LNM has been described, no reports have assessed the impact of its depth on LNM. METHODS: A total of 360 EGC patients with pathologically proven LI who underwent radical gastrectomy with lymphadenectomy between January 2005 and June 2018 at our institution were extracted from our database. Patients were divided into 2 groups: the mLI group, in which LI was limited to the muscularis mucosae (n = 34); and the smLI group, in which LI reached the submucosal region (n = 326). Clinicopathological features, including the LNM incidence, were compared between the groups. RESULTS: LNM was recognized in 3 patients (9%) in the mLI group and 101 (31%) in the smLI group (P = 0.005). In the mLI group, LNM was not recorded in any patients who met the curative criteria of ESD other than mLI. CONCLUSIONS: LI limited to the mucosal region does not seem to be a strong indicator for LNM. When pathological findings of an endoscopic submucosal dissection specimen show only mLI as a non-curative criterion, the probability of LNM may be very low.

HER2 heterogeneity is a poor prognosticator for HER2-positive gastric cancer.

BACKGROUND: The clinical significance of intratumoral human epidermal growth factor receptor 2 (HER2) heterogeneity is unclear for HER2-positive gastric cancer, although it has been reported to be a significant prognosticator for HER2-positive breast cancer, which has received trastuzumab-based chemotherapy. AIM: To clarify the clinical significance of intratumoral HER2 heterogeneity for HER2-positive gastric cancer, which has received trastuzumab-based chemotherapy. METHODS: Patients with HER2-positive unresectable or metastatic gastric cancer who received trastuzumab-based chemotherapy as a first line treatment were included. The patients were classified into two groups according to their intratumoral HER2 heterogeneity status examined by immunohistochemistry (IHC) on endoscopic biopsy specimens before treatment, and their clinical response to chemotherapy and survival were compared. RESULTS: A total of 88 patients were included in this study, and HER2 heterogeneity was observed in 23 (26%) patients (Hetero group). The overall response rate was significantly better in patients without HER2 heterogeneity (Homo group) (Homo vs Hetero: 79.5% vs 35.7%, P = 0.002). Progression-free survival of trastuzumab-based chemotherapy was significantly better in the Homo group (median, 7.9 vs 2.5 mo, HR: 1.905, 95%CI: 1.109-3.268). Overall survival was also significantly better in the Homo group (median survival time, 25.7 vs 12.5 mo, HR: 2.430, 95%CI: 1.389-4.273). Multivariate analysis revealed IHC HER2 heterogeneity as one of the independent poor prognostic factors (HR: 3.115, 95%CI: 1.610-6.024). CONCLUSION: IHC of HER2 heterogeneity is the pivotal predictor for trastuzumab-based chemotherapy. Thus, HER2 heterogeneity should be considered during the assessment of HER2 expression.

Extra-perigastric Extranodal Metastasis is a Significant Prognostic Factor in Node-Positive Gastric Cancer.

BACKGROUND: Extranodal metastasis is an isolated tumor nodule without a residual lymph node structure and has been reported as a poor prognostic factor in gastric cancer. The aim of this study is to assess the prognostic value of extranodal metastasis, especially from the viewpoint of its anatomical distribution. METHODS: A total of 139 consecutive gastric cancer patients who underwent curative surgery with lymph node metastasis between 2008 and 2009 were included. Clinicopathological features and patient survival outcomes were retrospectively assessed. Patients with extranodal metastasis were subdivided into two groups: perigastric extranodal metastasis, located near the perigastric area (#1-#7 according to the Japanese classification of gastric carcinoma 15th edition), and extra-perigastric extranodal metastasis, located alongside the major vessels (#8-#12). RESULTS: Extranodal metastasis was found in 51 patients (37%), and it was more frequent in those with bulky, ≥pT3, and pStage III tumors. All patients with extra-perigastric extranodal metastasis had recurrence, resulting in a 0% 5-year overall survival rate, which was significantly worse than that of patients with perigastric extranodal metastasis (59%), or those without extranodal metastasis (84%; P < 0.001). Multivariable analysis identified the presence of extra-perigastric extranodal metastasis as an independent poor prognostic factor. CONCLUSIONS: Extranodal metastasis, especially extra-perigastric extranodal metastasis, was a pivotal poor prognostic factor in node-positive gastric cancer. Recognizing extra-perigastric extranodal metastasis would help provide optimal therapeutic options to these high-risk patients.