Small gastric synovial sarcoma diagnosed and treatment by laparoscopic-endoscopic cooperative surgery: a case report.

We report a case of small gastric synovial sarcoma (SS) finally diagnosed after laparoscopic-endoscopic cooperative surgery (LECS). A 50 year-old male underwent medical examination for a chief complaint of epigastric pain. Endoscopic examination showed a 20 mm submucosal tumor (SMT) located in the anterior wall which extended to the lesser curvature of the middle stomach. The biopsy tissue did not yield a definitive diagnosis. During 6 months of follow-up for this lesion suspected to be an inflammatory tumor, neither the shape nor the size of the tumor changed. We performed LECS for both diagnosis and treatment. Histologically, the tumor was composed of fascicles of spindle cells. Immunohistochemically, the tumor cells were focally positive for epithelial membrane antigen, cytokeratin (AE1/AE3) and S100 protein, while being negative for desmin, α-smooth muscle actin, CD34, c-kit and DOG1. The expression of INI1 was reduced. Fluorescence in situ hybridization (FISH) detected SS18 rearrangement. The SMT was diagnosed as primary SS. A SMT measuring < 20 mm might be malignant potential tumor such as SS even if there are no typical malignant findings by endoscopy. Surgical resection should be considered for SMT measuring < 20 mm with atypical findings even in the absence of definitive high-risk features.

[A Case of Gastric Submucosal Tumor at Esophagogastric Junction Resected by Endoscopic Intragastric Surgery].

We report a case in which a gastric submucosal tumor at the esophagogastric junction was resected by endoscopic intragastric surgery with minimally invasive and function-preserving. A 30s-year-old man was referred to our hospital because of an abnormal findings pointed by a barium examination at a health check up. Upper gastrointestinal endoscopy and endoscopic ultrasound revealed a submucosal tumor approximately 60 mm in size on the posterior wall of the gastric fundus. Endoscopic ultrasound-fine needle aspiration was carried out and pathological result was a leiomyoma. The tumor was an intraluminal and extraluminal growth extending from the dorsal esophagus to the cardiac region, but considering the patient's young age, we decided to perform endoscopic intragastric surgery to preserve the function of stomach. A 30 mm median incision was made above the umbilicus, and the anterior wall of the gastric body was incised and the intragastric surgery was started using the double protector method. The mucosal surface of the tumor was located at the fundus, but the tumor developed into the dorsal aspect of the lower esophageal muscle layer. The tumor was carefully dissected and resected by intragastric manipulation. Postoperative oral contrast examination revealed no obvious stenosis, and gastric peristalsis was normal.

[Laparoscopic Abdominoperineal Resection with the Trans-Perineal Approach for Anal Canal Cancer in a Patient with Situs Inversus Totalis-A Case Report].

Situs inversus totalis(SIT)is a rare congenital condition that causes complete transposition of thoracic and abdominal viscera. Due to associated anatomical abnormalities and low frequency, surgery for affected patients is considered to be difficult. A 72-year-old man was referred to our hospital with a chief complaint of narrow stools. The diagnosis was anal canal cancer(cT1bN0M0)accompanied by SIT. A trans-perineal minimally invasive surgical procedure with laparoscopic abdominoperineal resection(Tp-APR)was performed. When mobilizing the sigmoid colon, the surgeon changed their position in consideration of anatomical abnormalities. On the other hand, manipulation around the rectum was possible using the same technique as in patients with normal anatomy. The postoperative course was uneventful, and he had no recurrence 18 months after surgery. This is the first case that showed Tp-APR for anal canal cancer with SIT performed safely and feasibly. Preoperative simulation of associated abnormal anatomical structures is considered crucial for a case of SIT.

[A Case of Advanced Gastric Cancer with Distant Lymph Nodes Metastasis Showing a Complete Response to Six-Courses Chemotherapy].

This study reports a 66-year-old female presenting abdominal pain. Gastrointestinal endoscopy showed the presence of a type 3 tumor in the lesser curvature of the stomach, and biopsy revealed poorly differentiated adenocarcinoma. CT images displayed thickening of the stomach wall and enlarged paraaortic lymph nodes, left supraclavicular lymph nodes, and left iliac lymph nodes. FDG-PET/CT scan showed abnormal accumulation at the same site. The patient was diagnosed with unresectable highly advanced gastric cancer(cT4aN2H0P0M1[LYM], Stage Ⅳ). She was treated with combination chemotherapy of S-1 and CDDP(SP). Tumor markers normalized(CA19-9 11,158→20 U/mL)after 3 courses with a marked reduction of lesions. After 5 courses of chemotherapy, the tissue biopsy did not reveal any cancer and a complete response(CR) was achieved. Adverse events of diarrhea and loss of appetite were observed. Subsequently, chemotherapy was discontinued after 6 courses, and CR remained for the next 5 years. Thus, we experienced a rare case of unresectable advanced gastric cancer with distant lymph nodes metastasis, showing long-term recurrence-free survival after receiving 6 courses of SP chemotherapy.

[A Case of Internal Hernia Incarceration of a Mesenteric Defect following Laparoscopic Ileocecal Resection].

A 75-year-old man underwent laparoscopic ileocecal and partial small bowel resections for the management of appendiceal cancer. The pathological diagnosis was cecal cancer(T4b[ileum, abdominal wall],N0[0/13], M0, pStage Ⅱc). After 4 months of surgery, he suddenly experienced abdominal pain and vomiting and was presented to our emergency room. He was diagnosed with bowel obstruction following which, conservative treatment was initiated through a nasogastric ileus tube implantation; however, he did not show any improvement. Subsequently, he underwent experimental laparotomy on the 18th day of the disease. Intraabdominal examination revealed herniated small intestine through a mesenteric defect, which was closed following repositioning of the herniated small intestine. The postoperative course was good, and the patient was discharged on the 10th day after surgery. No recurrence of intestinal obstruction has been observed after 1 year and 6 months. Closure of the mesenteric defect, although not commonly performed in laparoscopic colorectal surgery, is worth considering because of the risk of developing an internal hernia requiring surgical treatment, as in our case.

[Surgical Technique for Prevention of Incisional Hernia in Laparoscopic Small Bowel Resection in the Obese Patient].

A 67-year-old woman reporting lower abdominal pain and anemia was examined. Small intestinal tumor was diagnosed by small intestinal radiographic contrast study and small intestinal endoscopy, and we decided to perform a laparoscopic partial resection of the small bowel. Since she was obese patients(BMI 36.3, abdominal wall 6 cm)at high risk of postoperative incisional hernia, we devised a way to make the wound smaller. We judged thick abdominal wall make umbilical wound larger in single port surgery. We performed multi-port surgery by using one 15 mm trocar, and removed small intestinal tumor from 15 mm port incision. In addition, to prevent incisional hernia, we used a trocar with a wound closure assist function for securely closing the port wound in all layers. Histopathological diagnosis was neuroendocrine tumor. The patient is being followed up without recurrence and without incisional hernia. In partial small bowel resection of obese patient, the use of a 15 mm port to minimize wound site and the use of trocar with a wound closure assist function may lead to prevent incisional hernia.

Extra-gastrointestinal stromal tumor arising in the lesser omentum with a platelet-derived growth factor receptor alpha (PDGFRA) mutation: a case report and literature review.

BACKGROUND: Gastrointestinal stromal tumors (GIST) arising from sites other than the gastrointestinal (GI) tract, termed extra-gastrointestinal stromal tumors (EGIST), are rare. Among EGIST, those with platelet-derived growth factor receptor alpha (PDGFRA) mutations are even rarer, with only a few cases reported. About 80% of GIST has KIT mutations, and 10% of GIST have PDGFRA mutations, which commonly affect the TK2 domain (exon 18). Among the exon 18 mutations, the D842V substitution is limited to gastric GIST. In EGIST, the degree of KIT and PDGFRA mutations varies on where the location of the tumor is, and it is suggested that omental EGIST is similar to gastric GIST. Adjuvant imatinib therapy is recommended for high-risk GIST; however, it is known that imatinib is less effective against GIST with a PDGFRA D842V mutation. CASE PRESENTATION: A 75-year-old man was referred to our hospital with an extrinsic tumor of the lesser curvature of the gastric body. Intraoperative findings showed a tumor located outside of the lesser omentum with no connection between the tumor and the gastric wall. The tumor was subsequently resected. Pathological examination indicated a GIST arising in the lesser omentum measuring 70 mm in its longer dimension. Because the tumor had a PDGFRA mutation (D842V substitution), imatinib was suspected to lack efficacy to the tumor. Thus, although the tumor was considered clinically to have a high risk of recurrence, adjuvant imatinib therapy was not indicated. The patient has been free of recurrence for 29 months since the surgery. CONCLUSION: We described a case of EGIST with a PDGFRA mutation arising in the lesser omentum. And we reviewed 57 cases of omental EGIST and showed that the clinicopathological characteristics and mutation status in omental EGIST were very similar to gastric GIST. In particular, PDGFAR D842V mutation rate in omental EGIST seemed as high as that in gastric GIST. These results suggested that omental EGIST is strongly related to gastric GIST, so the behavior of omental EGIST might be akin to gastric GIST. However, further studies are required to determine the prognosis and the necessity of adjuvant therapy for EGIST with a PDGFRA mutation.

MASTER KEY Project: Powering Clinical Development for Rare Cancers Through a Platform Trial.

For rare cancers, challenges in establishing standard therapies are greater than those for major cancers, and effective methods are needed. MASTER KEY Project is a multicenter study based in Japan, with two main parts: prospective registry study and multiple clinical trials. Advanced rare cancers, cancers of unknown primary origin, and those with rare tissue subtypes of common cancers are targeted. The registry study accumulates highly reliable consecutive data that can be used for future drug development. The multiple trials are conducted simultaneously, targeting either a specific biomarker or a rare tumor type of interest. The first interim data set from the registry part presented here shows the prevalence of genetic abnormalities, response rates, survival rates, and clinical trial enrollment rates. From May 2017 to April 2019, 560 patients (mean age = 53) were enrolled in the project. Frequent cancer types included soft tissue sarcomas, neuroendocrine tumors, and central nervous system tumors. Among the 528 patients with assessable data, 69% (364/528) had next-generation sequencing tests, with 48% (176/364) harboring an "actionable" alteration. Seventy-one (13%) patients have been enrolled in one of the clinical trials, with an accrual rate of 3.94 patients/month. A descriptive analysis of biomarker-directed or non-biomarker-directed treatment survival was performed. This project is expected to accelerate development of treatments for rare cancers and show that comprehensive platform trials are an advantageous strategy.

[Laparoscopic Tumor Resection for Retroperitoneal Leiomyosarcoma-A Case Report].

A 59-year-old man visited our department because of cholecystectomy. Preoperative CT revealed a tumor shadow measuring 50 mm in front of the right iliopsoas muscle. MRI showed a low signal intensity on T1-weighted images and a slightly high signal intensity on the T2-weighted image. PET-CT showed accumulation of FDG(SUVmax 5.39)in the tumor but no other abnormal accumulations. We performed tumor resection for diagnostic purposes because malignancy could not be ruled out owing to the large size of the mass. Intraoperative findings showed a well-circumscribed margin of the tumor without invasion to other tissues. The retroperitoneum was incised circumferentially along the tumor under laparoscopic guidance, and the tumor was resected. Histopathological and immunostaining findings were consistent with leiomyosarcoma. In laparoscopic surgery, the surgical margin is observed in detail through the magnifying effect. Therefore, laparoscopic surgery can be a surgical option for tumors that may be completely excised based on preoperative findings.

Current status of the "enhanced recovery after surgery" program in gastric cancer surgery.

Since the late 1990s, perioperative care through the enhanced recovery after surgery (ERAS, European Society for Clinical Nutrition and Metabolism [ESPEN]) program has spread. ERAS protocols aim to reduce surgical complications, improving postoperative outcomes and thereby saving resources by addressing various clinical elements through a multidisciplinary approach or based on evidence. In the field of gastric cancer, the philosophy of ERAS has gradually become accepted and, in 2014, consensus guidelines for enhanced recovery after gastrectomy were published. These guidelines consist of "procedure-specific" guidelines and "general (not procedure-specific) enhanced recovery items." In this review, we focused on the procedure-specific guidelines and tried to update the contents of every element of the procedure-specific guidelines. The procedure-specific guidelines consist of the following eight elements: "Preoperative nutrition," "Preoperative oral pharmaconutrition," "Access (of gastrectomy)," "Wound catheters and transversus abdominis plane block," "Nasogastric/Nasojejunal decompression," "Perianastomotic drains," "Early postoperative diet and artificial nutrition," and "Audit." On reviewing papers supporting these elements, it was reconfirmed that the recommendations of the guidelines are pertinent and valid. Four meta-analyses concerning the evaluation of ERAS protocols for gastric cancer were included in this review. Every study showed that the ERAS protocol reduced the cost and duration of hospital stay without increasing surgical complication rates, suggesting that ERAS is effective for gastric cancer surgery. However, it cannot be said that ERAS has achieved full penetration in Japan because most evidence is established in Western countries. Future studies must focus on developing a new ERAS protocols appropriate to Japanese conditions of gastric cancer.

Minimally invasive resection of synchronous thoracic esophageal and gastric carcinomas followed by reconstruction: a case report.

We report on a case of synchronous carcinomas of the esophagus and stomach. A 68-year-old man was referred to our hospital for an abnormality found during his medical examination. Further evaluation revealed squamous cell carcinoma in the thoracic lower esophagus and gastric adenocarcinoma located in the middle third of the stomach. Thoracoscopic esophagectomy in the prone position (TSEP), laparoscopic total gastrectomy (LTG) with three-field lymph node dissection, and laparoscopically assisted colon reconstruction (LACR) were performed. The patient did not have any major postoperative complications. His pathological examination revealed no metastases in 56 harvested lymph nodes and no residual tumor. He was followed up for 30 months without recurrence. To our knowledge, this is the first report of esophageal and gastric synchronous carcinomas that were successfully treated with a combination of TSEP, LTG, and LACR. These operations may be a feasible and appropriate treatment for this disease.

Impact of the Japanese gastric cancer screening system on treatment outcomes in gastric gastrointestinal stromal tumor (GIST): an analysis based on the GIST registry.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are found incidentally during gastric cancer screening in Japan. This study investigated whether the Japanese gastric cancer screening system helps to improve treatment outcomes in gastric GIST based on an analysis of the GIST registry conducted by the Kinki GIST Study Group. METHODS: The registry was designed to collect data on background characteristics, treatment methods, pathologic characteristics, and prognosis of GIST from January 2003 through December 2007 at 40 participating institutions. RESULTS: The study enrolled 672 GIST patients, 482 of whom had gastric GIST. According to the modified National Institutes of Health consensus criteria, 22.6 % of the patients were classified as high risk for recurrence, 18.5 % as intermediate risk, 35.9 % as low risk, and 13.9 % as very low risk. After exclusion of the patients inevaluable for treatment outcome, the study included 137 symptomatic patients (symptomatic group) and 147 asymptomatic patients (asymptomatic group). The diagnosis of the asymptomatic patients was determined through gastric cancer screening. The median tumor size in the asymptomatic group was significantly smaller than in the symptomatic group (3.5 vs. 5.3 cm; P < 0.0001). The 5-year recurrence-free survival rate in the asymptomatic high-risk patients (72.4 %) was lower than in their symptomatic counterparts (46.3 %) (P = 0.017). More patients in the asymptomatic group underwent laparoscopic surgery (42.2 vs. 27.2 %; P = 0.0081). CONCLUSIONS: By identifying asymptomatic patients, the Japanese gastric cancer screening system contributes to early detection of gastric GIST and favorable treatment outcomes.

Feasibility study of S-1 and intraperitoneal docetaxel combination chemotherapy for gastric cancer with peritoneal dissemination.

BACKGROUND: Gastric cancer with cancer cells on peritoneal cytology has very poor prognosis because of the existence of simultaneous peritoneal metastasis. Here we performed a dose-escalation study of intraperitoneal docetaxel (DTX) combined with S-1 to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer with peritoneal dissemination. PATIENTS AND METHODS: Twelve gastric cancer patients with positive cytology were enrolled in this study. Peritoneal lavage specimens were obtained under local anesthesia or staging laparoscopy before treatment and the combination chemotherapy was applied in patients with positive cytology. DTX was administered on day 1 intraperitoneally with initial dose of 40 mg/m(2), stepped up to 50 or 60 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day on days 1-14, followed by 7 days of rest. After two cycles of the combination chemotherapy, staging laparoscopy was performed to evaluate the effect of the chemotherapy. Simultaneous gastrectomy was performed in cases without peritoneal deposits at staging laparoscopy. RESULTS: The MTD of intraperitoneal DTX was not determined and the RD was defined as 60 mg/m(2) because dose-limiting toxicity occurred in only one patient at level II (DTX: 50 mg/m(2)). Out of twelve patients given the combination chemotherapy, nine had cytologically negative peritoneal lavage and had no peritoneal metastases at surgery after chemotherapy. CONCLUSION: The combined chemotherapy of S-1 plus intraperitoneal DTX was revealed to be safe and may be effective for gastric cancer with peritoneal dissemination.

Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer.

BACKGROUND: Peritoneal relapse is the most common pattern of tumor progression in advanced gastric cancer. Clinicopathological findings are sometimes inadequate for predicting peritoneal relapse. The aim of this study was to identify patients at high risk of peritoneal relapse in a prospective study based on molecular prediction. METHODS: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly, we constructed a molecular prediction system and validated its robustness and prognostic validity by 500 times multiple validation by repeated random sampling in a retrospective set of 56 (38 relapse-free and 18 peritoneal-relapse) patients. Secondly, we applied this prediction to 85 patients of the prospective set to assess predictive accuracy and prognostic validity. RESULTS: In the retrospective phase, repeated random validation yielded approximately 68% predictive accuracy and a 22-gene expression profile associated with peritoneal relapse was identified. The prediction system identified patients with poor prognosis. In the prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan-Meier analysis of peritoneal-relapse-free survival showed a significant difference between the "good signature group" and "poor signature group" (log-rank p = 0.0017). Multivariate analysis by Cox regression hazards model identified the molecular prediction as the only independent prognostic factor for peritoneal relapse. CONCLUSIONS: Gene expression profile inherent to primary gastric cancer tissues can be useful in prospective prediction of peritoneal relapse after curative surgery, potentially allowing individualized postoperative management to improve the prognosis of patients with advanced gastric cancer.

Induction chemotherapy with docetaxel, 5-FU and CDDP (DFP) for advanced gastric cancer.

BACKGROUND: The aim of this study was to evaluate the feasibility and efficacy of modified triplet chemotherapy with docetaxel, 5-fluorouracil and cisplatin as induction chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: Treatment-naïve patients with AGC were eligible. The regimen consisted of 350 mg/m(2)/day 5-FU by continuous infusion on days 1 to 5, 10 mg/m(2)/day CDDP intravenously on days 1 to 5, and docetaxel at 60 mg/m(2)/day intravenously on day 1. After 2 cycles (each cycle consisted of 4 weeks), surgical resection was attempted, 2-4 weeks after the completion of the regimen. RESULTS: Eighteen patients were enrolled. Adverse events included grade 3 anorexia and nausea in 16.7% and 11.1% and grade 4 leukocytopenia and neutropenia in 5.6% and 27.8%, respectively. The overall response rate was 44.4%. Surgery was conducted in 15 patients. The 1- and 3-year survival rates were 75.6% and 51.1%, respectively. CONCLUSION: The modified triplet combination therapy is effective and well tolerated by patients with AGC.

A suspected [18F]fluorodeoxyglucose positron emission tomography-negative metastatic lymph node successfully diagnosed by laparoscopic staging in esophageal cancer: report of two cases.

An accurate preoperative staging is important for selecting an appropriate therapy for esophageal cancer. In particular, diagnosis of lymph node metastases influences the indication for radical surgery. [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely applied primarily as a useful tool for initial staging of esophageal cancer. However, false-negative cases sometimes make it difficult to select the appropriate treatment. We report two patients with esophageal cancer and PET-negative enlarged lymph node successfully diagnosed by laparoscopic sampling. This procedure did not only allow accurate histopathological staging, but also helped to select the optimal minimally invasive management. This technique can be recommended for patients with esophageal cancer in whom the diagnosis of enlarged lymph node cannot be confirmed by preoperative imaging.

Salvage esophagectomy after definitive chemoradiotherapy for thoracic esophageal cancer.

BACKGROUND AND OBJECTIVES: Although locoregional failure frequently occurs after definitive chemoradiotherapy (CRT), the role of salvage esophagectomy has not been fully evaluated. The aim of this study was to compare the outcome of salvage esophagectomy after high-dose definitive CRT with neoadjuvant CRT. METHODS: From 1994 to 2007, 33 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT, and 115 patients underwent neoadjuvant CRT followed by surgery. RESULTS: The postoperative mortality rate in the salvage group (12%) was higher than in the neoadjuvant group (3.6%, P = 0.059). The rates of postoperative complications were significantly higher in the salvage group than in neoadjuvant group: Anastomotic leakage (39% vs. 22%, respectively, P = 0.049), bleeding (15% vs. 1.7%, respectively, P = 0.002), cardiovascular complications (24% vs. 5.4%, respectively, P = 0.001). Univariate analysis showed that pretherapy T stage, pretherapy lymph node status, pathological T stage, and operative curability were significant prognostic factors affecting survival of patients who underwent salvage esophagectomy. In particular, patients with cT3-T4 tumors or cN1 tumors before definitive CRT showed worse prognosis after salvage esophagectomy. CONCLUSIONS: Salvage esophagectomy after high-dose definitive CRT was associated with higher postoperative mortality and morbidity rates compared with neoadjuvant CRT. Only selected patients can be rescued by salvage esophagectomy.

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy.

BACKGROUND: In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established. METHODS: Studied were 74 patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival. RESULTS: Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high-grade budding in the invasive front. The 5-year survival rate of patients with low-grade budding tumors was 49%, compared with 17% for those with high-grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases. CONCLUSIONS: The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified.