Precise highlighting of the pancreas by semantic segmentation during robot-assisted gastrectomy: visual assistance with artificial intelligence for surgeons.

BACKGROUND: A postoperative pancreatic fistula (POPF) is a critical complication of radical gastrectomy for gastric cancer, mainly because surgeons occasionally misrecognize the pancreas and fat during lymphadenectomy. Therefore, this study aimed to develop an artificial intelligence (AI) system capable of identifying and highlighting the pancreas during robot-assisted gastrectomy. METHODS: A pancreas recognition algorithm was developed using HRNet, with 926 training images and 232 validation images extracted from 62 scenes of robot-assisted gastrectomy videos. During quantitative evaluation, the precision, recall, intersection over union (IoU), and Dice coefficients were calculated based on the surgeons' ground truth and the AI-inferred image from 80 test images. During the qualitative evaluation, 10 surgeons answered two questions related to sensitivity and similarity for assessing clinical usefulness. RESULTS: The precision, recall, IoU, and Dice coefficients were 0.70, 0.59, 0.46, and 0.61, respectively. Regarding sensitivity, the average score for pancreas recognition by AI was 4.18 out of 5 points (1 = lowest recognition [less than 50%]; 5 = highest recognition [more than 90%]). Regarding similarity, only 54% of the AI-inferred images were correctly differentiated from the ground truth. CONCLUSIONS: Our surgical AI system precisely highlighted the pancreas during robot-assisted gastrectomy at a level that was convincing to surgeons. This technology may prevent misrecognition of the pancreas by surgeons, thus leading to fewer POPFs.

Pterostilbene Induces Apoptosis from Endoplasmic Reticulum Stress Synergistically with Anticancer Drugs That Deposit Iron in Mitochondria.

Anticancer agents are playing an increasing role in the treatment of gastric cancer (GC); however, novel anticancer agents have not been fully developed. Therefore, it is important to investigate compounds that improve sensitivity to the existing anticancer drugs. We have reported that pterostilbene (PTE), a plant stilbene, enhances the antitumor effect of low doses of sunitinib in gastric cancer cells accumulating mitochondrial iron (II) (mtFe) at low doses. In this study, we investigated the relationship between the mtFe deposition and the synergistic effect of PTE and different anticancer drugs. For this study, we used 5-fluorouracil (5FU), cisplatin (CPPD), and lapatinib (LAP), which are frequently used in the treatment of GC, and doxorubicin (DOX), which is known to deposit mtFe. A combination of low-dose PTE and these drugs suppressed the expression of PDZ domain-containing 8 (PDZD8) and increased mtFe accumulation and mitochondrial H2O2. Consequently, reactive oxygen species-associated hypoxia inducible factor-1α activation induced endoplasmic reticulum stress and led to apoptosis, but not ferroptosis. In contrast, 5FU and CDDP did not show the same changes as those observed with PTE and DOX or LAP, and there was no synergistic effect with PTE. These results indicate that the combination of PTE with iron-accumulating anticancer drugs exhibits a strong synergistic effect. These findings would help in developing novel therapeutic strategies for GC. However, further clinical investigations are required.

Subcutaneous emphysema associated with laparoscopic or robotic abdominal surgery: a retrospective single-center study.

BACKGROUND: Subcutaneous emphysema (SCE) is a common complication in laparoscopic surgery. However, its precise incidence and impact on the clinical course are partially known. In this study, the incidence and risk factors of SCE were retrospectively analyzed. METHODS: Patients who underwent laparoscopic/robotic abdominal surgery (e.g., gastrointestinal, hepatobiliary, gynecologic, and urologic surgery) between October 2019 and September 2022 were retrospectively analyzed. The presence of SCE was confirmed by either conclusive findings obtained through chest/abdominal X-ray examination immediately after operation, or intraoperative palpation conducted by nurses. X-ray examination was performed in the operation room before extubation. RESULTS: A total of 2503 patients treated with laparoscopic/robotic abdominal surgery between October 2019 and September 2022 were identified and all of them were included in the analysis. SCE was confirmed in 23.1% of the patients (i.e., 577/2503). SCE was identified by X-ray examination in 97.6% of the patients. Extubation failure was observed in 10 patients; however, pneumothorax was not observed. Female sex (odds ratio [OR]: 2.09; 95% confidence interval [95%CI]: 1.69-2.57), age ≥ 80 years (OR 1.63; 95%CI 1.19-2.22), body mass index < 20 (OR 1.32; 95%CI 1.06-1.65), operation time > 360 min (OR 1.97; 95%CI 1.53-2.54), robotic surgery (OR 2.54; 95%CI 1.91-3.38), maximum intraabdominal pressure with CO2 > 15 mmHg (OR 1.79; 95%CI 1.02-3.16), and endo-tidal CO2 > 50 mmHg (OR 1.32; 95%CI 1.08-1.62)were identified as independent factors of SCE. Regarding the extubation failure due to SCE, age (OR 5.84; 95%CI 1.27-26.8) and maximum intraabdominal pressure with CO2 (OR 21.7; 95%CI 4.76-99.3) were identified as risk factors. CONCLUSION: Although the presence of SCE is associated with a low risk of severe complications, monitoring of the perioperative intraabdominal pressure is essential for performing safe laparoscopic/robotic surgery, particularly in elderly patients.

Treatment strategy for successful conversion surgery in clinical stage IVB gastric cancer.

INTRODUCTION: Recent advances in chemotherapy have resulted in successful conversion surgery (CS) for clinical stage (cStage) IVB gastric cancer (GC). This study aimed to evaluate the success rate of CS in clinical practice and determine optimal treatment strategies. METHODS: Totally, 166 patients with cStage IVB gastric and gastroesophageal junction adenocarcinoma, who underwent chemotherapy at Hyogo Medical University Hospital between January 2017 and June 2022, were included. CS was performed after confirming tumor to be M0 based on imaging and/or staging laparoscopy, except for resectable liver metastases. Preoperative chemotherapy was continued for at least 6 months provided that adverse events were manageable. RESULTS: Of 125 eligible patients, 23 were treated with CS, achieving a conversion rate of 18.4% and an R0 resection rate of 91.3%. The median duration of preoperative chemotherapy was 8.5 months; the median number of cycles was eight. The highest conversion rate was observed in patients receiving first-line treatment (14.4%), followed by those receiving second and third lines (5.8% and 2.3%, respectively). The median survival time in patients who received CS was significantly longer than that in patients who continued chemotherapy alone (56.7 versus 16 months, respectively, P < 0.0001). There was no significant difference in the 3-year overall survival between the patients who achieved CS after first-line treatment (63.2%, n = 18) and those who achieved CS after second- or third-line treatment (66.7%, n = 5). CONCLUSION: Consistent chemotherapy strategies could lead to successful CS and improved prognosis in a greater number of patients with cStage IVB GC, regardless of line of treatment.

Proposal for T3 classification of esophagogastric junction carcinoma based on the interconnection of extramural anatomical structures.

Classification of extramural invasion of esophagogastric junction carcinoma (EGJC) is not yet established. The anatomy surrounding the EGJ alters between the mediastinum and the abdominal cavity. This review proposed a T3 classification of EGJC based on anatomical continuity. Analysis of endoscopic ultrasound images, review of intraoperative images, and detailed observation of surgical specimens were followed by a review of the literature. In the EGJ, the muscularis propria of the esophagus is enclosed in mediastinal adipose tissue called the adventitia, which is surrounded by the diaphragmatic crus and contains the paraesophageal lymph nodes (LNs). After passing through the esophageal hiatus along with the vagus nerves and blood vessels, the adventitia joins the adipose tissue containing the paracardial LNs, which is covered by the peritoneum, and then further divides into the lesser and greater omentum. The connective tissue outside the muscularis propria of the stomach, including the adipose tissue of the omentum, is called the subserosa. According to the TNM classification, T3 esophageal and gastric cancer is defined as invasion of the adventitia and subserosa, respectively. Given that the adventitia is anatomically continuous with the subserosa, T3 tumors of the EGJ can be described as those that extend through the muscularis propria but do not invade the peritoneum or diaphragmatic crus. We propose classifying T3 EGJC as "tumor extends through muscularis propria" rather than using the separate terms "adventitia" and "submucosa". T4 could be "tumor perforates serosa or invades adjacent structures", as per the current gastric cancer classification.

Incidence and risk factors for venous thromboembolism in the Cancer-VTE Registry stomach cancer subcohort.

BACKGROUND: The Cancer-VTE Registry was a large-scale, multicenter, prospective registry designed to investigate real-world data on venous thromboembolism (VTE) incidence and risk factors in adult Japanese patients with solid tumors. This pre-specified subgroup analysis aimed to estimate the incidence of VTE, including VTE types other than symptomatic VTE, and identify risk factors of VTE in stomach cancer from the Cancer-VTE Registry. METHODS: Stage II-IV stomach cancer patients who planned to initiate cancer therapy and underwent VTE screening within 2 months before registration were enrolled. RESULTS: Of 1,896 patients enrolled, 131 (6.9%) had VTE at baseline, but 96.2% were asymptomatic. Female sex, age ≥ 65 years, VTE history, and D-dimer > 1.2 µg/mL were independent risk factors of VTE at baseline. Notably, patients with D-dimer > 1.2 µg/mL at the time of cancer diagnosis had an approximately 20-fold risk of VTE. During follow-up, event incidences were symptomatic VTE, 0.3%; incidental VTE requiring treatment, 1.1%; composite VTE, 1.4%; bleeding, 1.6%; cerebral infarction/transient ischemic attack/systemic embolic events, 0.7%; and all-cause death, 15.0%. The incidence of all-cause death was higher in patients with VTE vs without VTE at baseline (adjusted hazard ratio 1.67; 95% confidence interval 1.21-2.32; p = 0.002). CONCLUSIONS: VTE prevalence at the time of cancer diagnosis was not negligible and was extremely high when the patients had high D-dimer. VTE screening by D-dimer before starting cancer treatment is advisable, even for asymptomatic patients, regardless of whether the patient is undergoing surgery or chemotherapy. TRIAL REGISTRATION: UMIN000024942.

Recurrence patterns after curative gastrectomy for pStage II/III gastric cancer: Exploratory analysis of the randomized controlled JCOG1001 trial.

BACKGROUND: Peritoneal, lymph node, and hematogenous recurrence patterns are common after potentially curative surgery for gastric cancer. However, clinicopathological characteristics associated with each recurrence type have rarely been comprehensively reported among patients who received a unified treatment strategy and follow-up protocol. Understanding these recurrence patterns would help with early detection of recurrence and a personalized follow-up plan. We investigated the initial recurrence patterns after curative gastrectomy using data from the randomized clinical JCOG1001 trial. METHODS: Of 1204 patients enrolled in JCOG1001, 932 pStage II/III patients were included. Initial recurrence dates and patterns were recorded by attending physicians according to the protocol. Risk factors for hematogenous, lymph node, and peritoneal recurrence were determined by univariable and multivariable analyses using the Fine-Gray model. RESULTS: Overall, 253 patients developed recurrence. Hematogenous recurrence was the most frequent pattern (n = 115), followed by peritoneal (n = 104) and lymph node recurrence (n = 70). Differentiated type (p = 0.0028), pT4 (p = 0.0466), and pN3 (p < 0.0001) were associated with hematogenous recurrence; however, D2+ lymphadenectomy reduced it (p = 0.0161). Patients with large (≥5 cm) tumors (p = 0.0312), pT4 (p < 0.0001), pN3 (p = 0.0013), and undifferentiated histologic type (p = 0.0001) had significantly higher rates of peritoneal recurrence. Extended lymph node metastasis (pN3) was the only risk factor (p < 0.0001) for lymph node recurrence. CONCLUSIONS: Clinicopathological features differed according to the recurrence patterns. Vigilant follow-up with an understanding of recurrence patterns might be beneficial for some high-risk patients.

Surgery utilizing artificial intelligence technology: why we should not rule it out.

Recent advances in optical and robotic technologies have given surgeons high-definition eyes and precision hands that perform beyond human capabilities. This has expanded the scope of minimally invasive surgery and increased opportunities for surgery in high-risk situations; however, absolute surgical safety has not yet been achieved. Deficiencies in human performance are associated with surgical adverse events and advanced surgery places stress on surgeons and affect their concentration, causing not only novice surgeons with limited experience, but even skilled surgeons, to make misrecognition and decision-making errors. Therefore, the issue of "surgical comfort" for surgeons cannot be ignored. In recent years, artificial intelligence (AI), which is designed to mimic the function of the human brain, has been developed in various fields to assist humans. Computer vision, a visual assistive technology that uses AI, is being applied to surgery and will become available in the near future. AI-controlled robots cannot be expected to replace surgeons, because surgeons operate with higher brain functions that integrate all their abilities, including the senses of humanity, mission, and ethics. However, if there is a way to reduce the mental and physical burden on surgeons by utilizing AI technology, then it should not be ruled out.

Marked improvement of severe reflux esophagitis following proximal gastrectomy with esophagogastrostomy by the right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion.

Duodenogastroesophageal reflux (DGER) following esophagectomy or gastrectomy can cause severe esophagitis, which impairs patients' quality of life and increases the risk of esophageal carcinogenesis. It is sometimes resistant to medical treatment, and surgical treatment is considered effective in such cases. However, an optimal operative procedure for medical treatment-resistant reflux esophagitis (RE) after proximal gastrectomy (PG) with esophagogastrostomy (EG) has not yet been established. We performed the right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion in a 70-year-old man with medical treatment-resistant severe esophagitis caused by DGER following PG with EG for esophagogastric junction cancer. The postoperative course was uneventful, and esophagogastroduodenoscopy performed on the 19th postoperative day showed marked improvement in the esophageal erosions. The patient reported symptomatic relief. The right gastroepiploic vessels-preserving antrectomy and Roux-en-Y biliary diversion were considered safe and feasible for medical treatment-resistant RE following PG with EG.

Urinary tract diversion with gastric conduit after total pelvic exenteration for Crohn's disease-related anorectal cancer: a case report.

BACKGROUND: In Japan, Crohn's disease (CD)-related cancers occur most frequently in the anal canal. Many patients with advanced CD-related cancer require total pelvic exenteration (TPE) based on their medical history, and choosing the most effective method for urinary diversion is a major concern. We herein report the first case of CD-related cancer treatment with urinary diversion using a gastric conduit after TPE in Japan. CASE PRESENTATION: A 51-year-old man with a 25 year history of CD was referred to our institution after having been diagnosed with fistulae between the rectum and urethra. Sigmoidoscopy revealed stenosis of the anal canal, and histological examination of this lesion led to a diagnosis of mucinous adenocarcinoma. Magnetic resonance imaging showed that the tumor had invaded the prostate and left internal obturator muscle, and TPE with left internal obturator muscle resection was planned. Urinary diversion was performed with a gastric conduit. The gastric conduit was created by trimming a gastric tube to a 1.5 cm width via stapled resection of the greater curvature, and the branches of the right gastroepiploic artery were preserved as feeding vessels. The ureters were raised from the mesentery on the right side of the ligament of Treitz. Ureterogastric anastomosis was performed using the Wallace technique, and the entire anastomosis was then retroperitonealized. The anastomotic site had a bleeding tendency, but hemostasis was obtained by proton pump inhibitor administration and discontinuation of enoxaparin, which had been administered to prevent venous thrombosis. No other major complications occurred, and the patient's quality of life was recovered 6 months after surgery. CONCLUSION: Urinary diversion using a gastric conduit is a feasible treatment option for patients with CD-related anorectal cancer requiring TPE.

Transhiatal lower mediastinal lymph node dissection for esophagogastric junction carcinoma by interconnecting four body cavities.

BACKGROUND: Due to the limited number of landmark structures, it is difficult to standardize the surgical procedures for advanced esophagogastric junction cancer such as Ivor Lewis esophagectomy that require transhiatal lower mediastinal lymph node dissection (TH-LMND). We demonstrate an easily reproducible procedure for TH-LMND, wherein four body cavities, namely, the abdominal cavity, infracardiac bursa (ICB), and left and right thoracic cavities are interconnected. METHODS: First, the dissection between the right crus and the esophagus was used to connect the abdominal cavity to the ICB - a lower mediastinal cavity separated from the omental bursa during embryonic development [1,2]. Second, the right thoracic cavity was opened with the shortest distance by dissecting the cranial side of the ICB. The right pulmonary ligament was dissected from the right lung. Third, the dissection to the contralateral side while exposing the aorta and the pericardium connected the left and right thoracic cavities. Then, the left pulmonary ligament was dissected from the left lung. The dissected tissues, including the lymph nodes, were subsequently peeled from the esophagus. RESULTS: Between April 2018 and August 2021, 14 patients underwent laparoscopic or robotic TH-LMND via the procedure above. The median time required to complete the dissection was 75 min. None of the procedures were converted to open surgery, and none of the patients experienced intraoperative complications such as pericardial injury, lung injury, or massive bleeding. CONCLUSION: The surgical concept of interconnecting four body cavities made the procedure more accessible and reproducible while achieving en bloc TH-LMND.

Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD8.

The use of molecular-targeted drugs in the treatment of gastric cancer is increasing. However, the variety of molecular-targeted drugs in gastric cancer is still limited, and the development of new molecular-targeted therapies is required. The effect of combining sunitinib (SUN) with pterostilbene (PTE) on the human gastric cancer cell lines TMK1 and MKN74 was examined in in vitro and in vivo. Compared with SUN or PTE treatment alone, cotreatment induced pronounced suppression of cell proliferation, with a marked increase in oxidative stress. SUN was associated with a significant retention of mitochondrial Fe2+. SUN-treated cells decreased expression of PDZ domain-containing protein 8 (PDZD8). Knockdown of PDZD8 in both cells induced Fe2+ retention, and siPDZD8+PTE markedly suppressed cell proliferation with suppressed oxidative phosphorylation, as did the combination of SUN+PTE. In a nude mouse tumor model, a pronounced antitumor effect was observed with SUN+PTE treatment compared to SUN alone. PDZD8 may be a newly discovered off-target for SUN, and that the combined use of PTE with SUN significantly promotes antitumor activity in gastric cancer cell lines. The combined use of SUN and PTE might be a new molecular-targeted therapy for gastric cancer.

Survival analysis of a prospective multicenter observational study on surgical palliation among patients with malignant bowel obstruction caused by peritoneal dissemination of gastric cancer.

BACKGROUND: Our previous report showed that surgical palliation maintained quality of life (QOL), improved solid food intake, and had an acceptable surgical safety among patients with malignant bowel obstruction (MBO) caused by advanced gastric cancer. This study performed a survival analysis stratified by the patients' QOL to elucidate its impact on survival. METHODS: Patients who underwent resection or bypass of the small intestine/colon or ileostomy/colostomy for bowel obstruction caused by peritoneal dissemination of gastric cancer were included. Validated instruments (EuroQoL-5 Dimensions) were used to assess QOL at baseline and 2 weeks, 1 month, and 3 months following surgical palliation. Postoperative improvement in oral intake was also evaluated using the Gastric Outlet Obstruction Scoring System (GOOSS). Univariate and multivariate survival analyses were performed using baseline characteristics and changes in QOL and GOOSS scores 2 weeks after surgery to determine prognostic factors. RESULTS: We enrolled 60 patients with a median survival time of 6.64 (95% CI 4.76-10.28) months. Patients who received postoperative chemotherapy and had lower baseline C-reactive protein (CRP) levels, higher baseline albumin levels, better baseline EuroQoL-5 Dimensions (EQ-5D) scores, and improved oral intake after palliative surgery exhibited significantly better survival. Multivariate analysis identified postoperative chemotherapy, lower baseline CRP levels, and improved oral intake as independent prognostic factors. CONCLUSIONS: The current study revealed that baseline QOL and postoperative QOL changes did not affect survival. Moreover, improved oral intake, lower baseline CRP levels, and postoperative chemotherapy were significant prognostic factors in patients who underwent palliative surgery for advanced gastric cancer with MBO.

History of the lymph node numbering system in the Japanese Classification of Gastric Carcinoma since 1962.

The Japanese Classification of Gastric Carcinoma was established by the Japanese Research Society for Gastric Cancer in 1962. The latest 15th edition was published in 2017. One of its main features is that lymph nodes are numbered as stations. The number of groups has increased from 16 to 36 in 55 years. Seven groups (nos. 1, 2, 5, 7, 9, 10, and 15) were retained from the original classification. Nine groups (nos. 3, 4, 6, 8, 11, 12, 13, 14, and 16) were sub-divided into two or more groups. Furthermore, seven groups (nos. 17, 18, 19, 20, 110, 111, and 112) were added in the 6th, 11th, and 12th editions. This numbering system helps surgeons recognize the exact lymph nodes that need to be dissected. However, the numbering system has become extremely complicated. It is necessary to organize the historical background of each lymph node station and share the definitions clearly. This review focuses on nine anatomical zones around the stomach and summarizes the history of lymph node stations in the Japanese Classification of Gastric Carcinoma. Lymph node stations will continue to be modified in the future, and the historical background may be useful in future revisions.

Reducing the risk of postoperative pancreatic fistula in radical gastrectomy: pre-assessment with computed tomography for the diagnosis of pancreatic steatosis.

PURPOSE: To determine whether pancreatic steatosis (PS) is associated with the risk of postoperative pancreatic fistula (POPF) after radical gastrectomy, and if so, to investigate whether pre-assessment by diagnostic imaging can mitigate the risk. METHODS: The clinical records of 276 patients with cStage I gastric cancer who underwent laparoscopic gastrectomy with D1 + lymphadenectomy between 2012 and 2015 were reviewed. In the first phase up to July 2013 (n = 138), PS was classified from computed tomography (CT) findings into type S (superficial fat deposition) or type D (diffuse fatty replacement) and examined for association with POPF. In the second phase (n = 138), the preoperative CT assessment of PS was routinized. Separate samples from pancreatoduodenectomy consistent with each type were histologically examined. RESULTS: In the first phase, the incidence of POPF was significantly higher in group S, but not in group D, compared with normal pancreas (16.3% and 9.1% vs. 3.6%, respectively; P = 0.03). The drain amylase level was lowest in group D, reflecting exocrine insufficiency. Histologically, the loose connective-tissue space between the fat infiltrating the pancreas and the peripancreatic fat containing the lymph nodes was unclear in type D but conserved in type S. In the second phase, surgery was performed with more intention on accurately tracing the dissection plane and significantly lowered incidence of POPF in Group S (16.3% to 2.1%; P = 0.047). CONCLUSION: Peripancreatic lymphadenectomy is more challenging and likely to cause POPF in patients with PS. However, the risk may be reduced using appropriate dissection techniques based on the CT pre-assessment findings.

Potential advantages of robotic total gastrectomy for gastric cancer: a retrospective comparative cohort study.

Laparoscopic total gastrectomy (LTG) is a highly technical surgery that can lead to postoperative complications. Whether the recently introduced robotic surgery overcomes the drawbacks of laparoscopic surgery in total gastrectomy remains controversial. Therefore, we aimed to elucidate the potential benefits of robotic total gastrectomy (RTG) and compare the short-term outcomes of RTG and LTG. We retrospectively analyzed 56 patients with primary gastric or esophagogastric junction cancer who underwent RTG or LTG between June 2017 and July 2021. The groups were compared in terms of operative outcomes and postoperative complications. Potential risk factors associated with postoperative complications were assessed by performing multivariable analysis using logistic regression models via the exact method. Operation time was significantly longer, and postoperative hospital stay was significantly shorter in the robotic group (550 vs. 466 min, P < 0.001; 13 vs. 18 days, P = 0.013, respectively). The incidence of overall postoperative complications of Clavien-Dindo grade ≥ II was 18.5% and 24.1% in the RTG and LTG groups, respectively. Pancreatic fistulas were not observed, but other local complications were observed in 0% and 17.2% of the RTG and LTG groups, respectively (P = 0.052). In the multivariable analysis, the independent risk factors for local complications were laparoscopic surgery (odds ratio [95% confidence interval] 8.542 [1.065-∞], P = 0.045) and esophagogastric junction cancer (16.646 [2.559-∞], P = 0.005). Compared with LTG, RTG was associated with fewer local complications (mainly anastomotic leakage), especially in cases of esophagogastric junction cancer with high anastomotic sites.

A minute primary gastric synovial sarcoma with ulcer: a case report.

BACKGROUND: Synovial sarcomas are a rare type of high-grade sarcomas with unknown cell origin. They arise predominantly in the soft tissues but rarely in the stomach. We recently encountered a rare case of minute gastric synovial sarcoma. CASE PRESENTATION: A 61-year-old Japanese woman was pointed out edematous erosion at the body of the stomach. Biopsy specimen showed dense proliferation of spindle-shaped tumor cells mixed with smooth muscle fibers of the muscularis mucosae. Although the definite histological diagnosis was undetermined, the patient underwent laparoscopic wedge resection of the stomach. Histological examination of the resected sample revealed that the maximum diameter of the tumor was only 6 mm and that dense proliferation of rather uniform spindle tumor cells were observed mainly in the submucosa. Immunohistochemistry showed that they were positive for pan-keratin, CD99 and TLE1. SS18-SSX fusion-specific antibody gave diffuse positive staining to the tumor cells, and analysis using mRNA extracted from paraffin sections revealed that the tumor had SS18-SSX1 fusion gene. Thus, it was diagnosed as gastric synovial sarcoma, monophasic fibrous type. CONCLUSIONS: Primary synovial sarcoma of the stomach is rare and only 47 cases have been reported in the English literature to date. The maximum diameter of the lesion of our case was 6 mm which is the smallest among them.

Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial.

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation.

BACKGROUND: Ectopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation. CASE PRESENTATION: A 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys). CONCLUSION: We finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.