Molecular and pathological analyses of gastric stump cancer by next-generation sequencing and immunohistochemistry.

Gastric stump cancer (GSC) has distinct clinicopathological characteristics from primary gastric cancer. However, the detailed molecular and pathological characteristics of GSC remain to be clarified because of its rarity. In this study, a set of tissue microarrays from 89 GSC patients was analysed by immunohistochemistry and in situ hybridisation. Programmed death ligand 1 (PD-L1) was expressed in 98.9% of tumour-infiltrating immune cells (TIICs) and 6.7% of tumour cells (TCs). Epstein-Barr virus (EBV) was detected in 18 patients (20.2%). Overexpression of human epidermal growth factor receptor 2 and deficiency of mismatch repair (MMR) protein expression were observed in 5.6% and 1.1% of cases, respectively. Moreover, we used next-generation sequencing to determine the gene mutation profiles of a subset of the 50 most recent patients. The most frequently mutated genes were TP53 (42.0%) followed by SMAD4 (18.0%) and PTEN (16.0%), all of which are tumour suppressor genes. A high frequency of PD-L1 expression in TIICs and a high EBV infection rate suggest immune checkpoint inhibitors for treatment of GSC despite a relatively low frequency of deficient MMR gene expression. Other molecular characteristics such as PTEN and SMAD4 mutations might be considered to develop new treatment strategies.

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.

Clinical significance of lymphatic invasion in the esophageal region in patients with adenocarcinoma of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: The lymphatic flow around the esophagogastric junction is complicated. Therefore, it is unclear whether lymphatic invasion in the esophageal region (eLI) and in the gastric region (gLI) in patients with adenocarcinoma of the esophagogastric junction (AEG) equally affect the incidence of lymph node metastases (LNM), and consequently, survival. METHODS: We retrospectively reviewed clinicopathological data of 175 patients with AEG between January 2008 and July 2017. Risk factors for LNM and impacts of eLI or gLI on survival outcomes were investigated. RESULTS: eLI was identified in 34% of the patients (59/175). By multivariate analysis, eLI was associated with an increased risk of both mediastinal LNM (odds ratio [OR] = 2.98, 95% confidence interval [CI]: 1.26-7.05) and abdominal LNM (OR = 5.44, 95% CI: 1.95-15.20). The 5-year overall survival for patients with eLI (53%) was significantly worse than for patients without eLI (76%) (hazard ratio = 2.45, 95% CI: 1.37-10.01). gLI was not selected in either of these analyses. CONCLUSIONS: Positive eLI was strongly associated with mediastinal and abdominal LNM and worse survival in patients with AEG compared with gLI. In the histopathological examination, it seems to make sense to assess eLI and gLI separately.

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.

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.

What are the reasons for a longer operation time in robotic gastrectomy than in laparoscopic gastrectomy for stomach cancer?

BACKGROUND: Many studies have shown that robotic gastrectomy requires a longer operation time than laparoscopic gastrectomy. However, no study has analyzed the exact reason for this difference in detail. We therefore investigated the reasons why more time is needed in robotic gastrectomy. METHODS: Ten consecutive cases of robotic distal gastrectomy (RDG) performed in our institution were selected to measure the operation time in detail. Ten cases of laparoscopic distal gastrectomy (LDG) performed during the same period were chosen for comparison. The operation videos and electronic medical records of these 20 patients were retrospectively reviewed. The overall operation time, operation time in each step, and time required for instrument changes were measured. The number of intraoperative instrument changes and camera cleanings were also counted. RESULTS: The overall operation time (including effective time and junk time) was 56.8 min longer for RDG than LDG (273.7 vs. 216.9 min, respectively; p = 0.000). The effective time was only 15.3 min longer for RDG than LDG (145.9 vs. 130.6 min, respectively; p = 0.094). The time needed for the six technical steps was also not significantly different between the two groups. However, the junk time (instrument setup and docking or positioning of surgical arms) was 41.5 min longer for RDG than LDG (127.8 vs. 86.2 min, respectively; p = 0.001). The number of instrument changes was not different between RDG and LDG (p = 0.277), but the time required for each was longer for RDG than LDG (p = 0.000). The number of camera cleanings was lower for RDG than LDG (10.7 vs. 15.5 times, respectively; p = 0.005). CONCLUSIONS: To reduce the operation time in RDG, a smarter and simpler system for setup should be developed to reduce the junk time. Additionally, a system for swifter instrument changes and more sophisticated energy devices are warranted to reduce the effective time.

Prognostic Factors and Recurrence Pattern of Far-advanced Gastric Cancer with Pathologically-positive Para-aortic Lymph Nodes.

BACKGROUND: The role of para-aortic lymph node (PALN) dissection for far-advanced gastric cancer is controversial in patients with clinical PALN positivity who have responded to chemotherapy. MATERIALS AND METHODS: We retrospectively analyzed long-term outcomes of patients with pathologically-positive PALNs who underwent radical gastrectomy. RESULTS: The 3- and 5-year overall survival (OS) rates of 65 pathologically PALN-positive patients who underwent PALN dissection (n=704) were 33.8% and 21.2%, respectively. Multivariable analysis revealed the following poor prognostic factors: nodal involvement around the celiac axis (hazard ratio (HR)=4.04, 95% confidence interval (CI)=1.55-9.63), tumor diameter of ≥120 mm (HR=3.37; 95% CI=1.18-9.63) and ≥3 PALNs involved (HR=2.24; 95% CI=1.21-4.15). Patients with none of these factors survived significantly longer than those with any of these factors (5-year OS=87.5% versus 9.3%, respectively; p<0.001). CONCLUSION: Pathologically PALN-positive patients achieve long survival; however, the indications for PALN dissection should be carefully considered.

Five-year Survival Associated with Stage I Gastric Cancer after Resection of Early Recurrence at Nodal Station No. 14v: a Case Report.

The role of nodal station No. 14v (along the superior mesenteric vein) in lymphadenectomy for distal gastric cancer remains elusive. A 73-year-old woman underwent endoscopic submucosal dissection for gastric cancer, and was referred to our division for additional surgery because of pathologically non-curative resection. A laparoscopic distal gastrectomy with D1+ dissection was performed, with a final diagnosis of pT1bN1M0, Stage IB (2 nodal metastases to No. 6). Four months post-surgery, abdominal computed tomography revealed a 14-mm solitary nodule along the superior mesenteric vein. The lesion was excised and pathologically identified as a lymph node metastasis. Adjuvant chemotherapy with tegafur-gimeracil-oteracil potassium (S-1) was administered for the metastasis. Presently the patient survives without recurrence, 5.5 years after the second operation. Our findings suggest that there is lymphatic flow from the No. 6 to the No. 14v nodal station. Some patients with a No. 6 metastasis may benefit from a No. 14v lymphadenectomy, even in early-staged disease.

Bronchogenic cyst at esophagogastric junction treated by laparoscopic full-thickness resection and hand-sewn closure: a case report.

BACKGROUND: We herein report a case of a bronchogenic cyst arising from the esophagogastric junction treated by laparoscopic full-thickness extirpation. The full-thickness defect was closed by hand sewing a T-shaped line over the gastroendoscope as a bougie to prevent postoperative deformity or stenosis. Partial fundoplication (Toupet fundoplication) was added to prevent reflux. CASE PRESENTATION: A 32-year-old woman with a body mass index of 43 kg/m(2) was admitted for treatment of a cyst-forming submucosal tumor (60 mm in diameter) on the anterior wall of the esophagogastric junction, which was detected during screening endoscopy before bariatric surgery. The tumor was an extraluminal growing type but exhibited severe erosion at the mucosal site. A cystic tumor such as a duplication cyst, bronchogenic cyst, or cyst-forming gastrointestinal stromal tumor was suspected, and the abovementioned surgery was carried out. The postoperative course was uneventful. The pathological findings revealed the tumor to be a benign bronchogenic cyst. Endoscopic examination 3 months postoperatively showed no deformity or stenosis, and the patient complained of no reflux symptoms. CONCLUSION: This procedure may be an efficient option for treatment of submucosal tumors on the esophagogastric junction to maintain function or avoid excessive surgery.