Prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer undergoing neoadjuvant chemotherapy followed by gastrectomy.

PURPOSE: In Japan, gastrectomy with D2 lymph node dissection and postoperative adjuvant chemotherapy are the standard treatments for locally advanced gastric cancer. Neoadjuvant chemotherapy (NAC) is not affected by postgastrectomy syndromes or postoperative complications. This multicenter retrospective study investigated the prognostic factors and significance of postoperative adjuvant chemotherapy in patients with advanced gastric cancer who underwent NAC followed by gastrectomy. METHODS: Consecutive patients (n = 221) with advanced gastric cancer who underwent NAC followed by curative surgery were enrolled in this study. Prognostic factors including postoperative adjuvant chemotherapy were investigated using univariate and multivariate analyses. RESULTS: A multivariate analysis revealed that pathological lymph node metastasis (ypN) status and postoperative adjuvant chemotherapy were independent prognostic factors for the overall and relapse-free survival. Forty-five patients (20.4%) did not receive postoperative adjuvant chemotherapy. There were no significant differences between patients with and without adjuvant chemotherapy for all factors, except age. The most common reason for not undergoing postoperative adjuvant chemotherapy was a poor condition (n = 23). CONCLUSIONS: ypN status and postoperative adjuvant chemotherapy were independent prognostic factors in gastric cancer patients who underwent NAC followed by curative gastrectomy. It is important to maintain the patient's condition during NAC and the perioperative period so that they can receive postoperative adjuvant chemotherapy.

[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.

Inhibitor of protein kinase N3 suppresses excessive bone resorption in ovariectomized mice.

INTRODUCTION: The long-term inhibition of bone resorption suppresses new bone formation because these processes are coupled during physiological bone remodeling. The development of anti-bone-resorbing agents that do not suppress bone formation is urgently needed. We previously demonstrated that Wnt5a-Ror2 signaling in mature osteoclasts promoted bone-resorbing activity through protein kinase N3 (Pkn3). The p38 MAPK inhibitor SB202190 reportedly inhibited Pkn3 with a low Ki value (0.004 µM). We herein examined the effects of SB202190 on osteoclast differentiation and function in vitro and in vivo. MATERIALS AND METHODS: Bone marrow cells were cultured in the presence of M-csf and GST-Rankl to differentiate into multinucleated osteoclasts. Osteoclasts were treated with increasing concentrations of SB202190. For in vivo study, 10-week-old female mice were subjected to ovariectomy (OVX). OVX mice were intraperitoneally administered with a Pkn3 inhibitor at 2 mg/kg or vehicle for 4 weeks, and bone mass was analyzed by micro-CT. RESULTS: SB202190 suppressed the auto-phosphorylation of Pkn3 in osteoclast cultures. SB202190 significantly inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation. SB202190 reduced c-Src activity in osteoclast cultures without affecting the interaction between Pkn3 and c-Src. A treatment with SB202190 attenuated OVX-induced bone loss without affecting the number of osteoclasts or bone formation by osteoblasts. CONCLUSIONS: Our results showed that Pkn3 has potential as a therapeutic target for bone loss due to increased bone resorption. SB202190 is promising as a lead compound for the development of novel anti-bone-resorbing agents.

[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 Gastric Anisakiasis That Required Differentiation from Scirrhous Gastric Cancer].

A 36-year-old woman visited a previous doctor with lower abdominal pain and nausea. Her former doctor's upper gastrointestinal endoscopy and CT scan showed giant folds and wall thickening of the lower body of the stomach, and she was referred on suspicion of scirrhous gastric cancer. Similar findings were found on enhanced CT at our hospital. Endoscopic findings performed several days later showed red and thickened mucosa at the cardia, but no wall thickening and giant fold, and there were no findings suggestive of scirrhous gastric cancer. Biopsy showed no atypical cells, and a large number of eosinophils appeared in the lesion at the cardia. Eosinophilia and anisakis IgE antibody were positive and a diagnosis of gastric anisakiasis was made. She was eating grilled horse mackerel the day before her stomachache. At the same time, pruritus and edema around her right knee also appeared, and a dermatologist diagnosed her with anisakis-related eosinophil edema. One month later, CT scan and endoscopy were almost normal. A young woman referred on suspicion of scirrhous gastric cancer experienced a rare case diagnosed with gastric anisakiasis.

[Radical Resection Was Achieved Using a Liver-First Approach for Simultaneous Liver Metastasis from Rectal Cancer-A Case Report].

The patient was a 70s male. A fecal occult blood test showed a positive reaction, and colonoscopy was performed. Under a diagnosis of rectal cancer, he was referred to our hospital. Detailed examination revealed solitary liver metastasis measuring 60 mm and involving the S4 to S1 areas of the liver. A strategy to perform systemic chemotherapy in advance was adopted. Five courses of FOLFOXIRI therapy were conducted, and a partial response(PR)was achieved, suggesting that the tumor is resectable. Extended left/caudal lobectomy was performed. There was no complication, and the patient was discharged. After 4 months, laparoscopic low anterior resection and temporary ileostomy were conducted. According to the TNM staging, the grade was evaluated as ypT2N0. On histological response evaluation, the grade was evaluated as 1a. The stoma was closed. During the 1.5-year follow-up after initial treatment, there has been no relapse. We encountered a patient with simultaneous liver metastasis from rectal cancer in whom the use of a liver-first approach(LFA)after systemic chemotherapy facilitated radical resection. The present case suggested that the LFA contributes to a rise in the resection rate, further improving the prognosis.

[A Case of Giant Mesenteric Lymphangioma in an Adult].

A 26-year-old man with left inguinal pain and frequent urination was examined. An abdominal ultrasound revealed a cystic lesion. In further examinations, CT and MRI showed a large cystic lesion of about 20 cm in size, connected to mesenteric- derived blood vessels. We suspected a huge mesenteric lymphangioma and decided to perform a laparotomy. A tumor was seen in the mesentery of the jejunum and adhered to the duodenum widely. The tumor could be removed safely without resection of the duodenum by first sucking the contents and shrinking the tumor. The final pathological diagnosis was mesenteric lymphangioma. Adult mesenteric lymphangiomas measuring larger than 20 cm are relatively rare. We review the case in the context of the relevant literature.

[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.

[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.

[Results of Surgical Treatment for Gastric Tube Cancer after Esophagectomy].

Recent improvements in the survival of patients after esophagectomy have led to an increase in the occurrence of gastric tube cancers(GTC). We retrospectively examined 7 patients who were surgically treated for GTC among 13 patients who were diagnosed between April 2004 and December 2018. Partial gastrectomy with regional lymph node dissection was performed in 6 patients while total resection of the stomach was performed only in 1 patient. Postoperative complications included 1 anastomotic leakage and 1 subcutaneous abscess. We performed subtotal gastrectomy with preservation of the upper region of the gastric tube in 3 patients. In these patients, blood flow was confirmed from the remnant esophagus to the upper region of the gastric tube using indocyanine green fluorescence imaging. The pathological stage of the treated GTCs were 4 cases of Stage ⅠA, 2 of Stage ⅠB, and 1 of Stage ⅡA. Median follow-up time and postoperative survival time were 32 months and 46.5 months, respectively. Most of our surgically treated cases were early gastric carcinomas that could be radically resected.

[A Curatively Resected Case of Quadruple Cancer including Synchronous Gastric and Superficial Esophageal Cancers with Metachronous Sigmoid Colon Cancer and Hepatocellular Carcinoma].

A 80s year old man was referred to our hospital with melena. Colonoscopy revealed an elevated lesion in the sigmoid colon. Laparoscopic sigmoidectomy(D2)was performed in August 2011. Postoperative diagnosis was advanced sigmoid colon cancer(pT2N1M0 and pStage Ⅲa, UICC). In January 2015, He suffered from epigastric discomfort after meals. Gastrointestinal endoscopy revealed advanced gastric cancer and superficial esophageal cancer. For esophageal cancer, endoscopic submucosal dissection was performed with a diagnosis of cStage 0-Ⅱa(UICC). Laparoscopic distal gastrectomy with Billroth Ⅰ reconstruction was performed for gastric cancer with a diagnosis of pT1bN0M0 and pStage ⅠA(UICC). Follow up CT and MRI images in October 2016 showed a liver tumor in S4/S5. Laparoscopic partial liver resection was performed. Postoperative pathological diagnosis was hepatocellular carcinoma pT1N0M0, pStage Ⅰ(UICC). We finished following up period of the sigmoid colon cancer. Gastric cancer and esophageal cancer are followed up by gastrointestinal endoscopy once a year. Hepatocellular carcinoma is followed up every 3 months. He has no recurrence until now.

[A Case of Pancreatic Neuroendocrine Tumor(p-NET)with Long-Term Survival with Multidisciplinary Treatment].

Pancreatic neuroendocrine tumor(p-NET)is a relatively rare disease, and treatment is multidisciplinary with resection, local therapy, radiotherapy, and chemotherapy. We report on a case in which long-term survival was achieved by multidisciplinary treatment. The case is a 47-year-old male. He was referred to our hospital because of the diagnosis of pancreatic tail tumor and underwent distal pancreatectomy in May 2008. And he was diagnosed as p-NET G1 by the pathological results. After 3 TACE treatments and 1 partial liver resection for recurrent liver metastasis, multiple liver metastases and lymph node metastases were found in August 2014. As a result of the everolimus treatment, the determination of efficacy to lymph nodes was CR and liver lesions were CR with the addition of TACE treatment. In July 2017, he had multiple liver metastases and right humeral metastases, and has been treated with radiotherapy for bone metastases and has maintained CR. After TACE in November 2017, he received 9 rounds of lanreotide treatment. In December 2018, he again had liver metastases and lymph node recurrence. He has been treated with everolimus treatment again and is maintaining SD in outpatient treatment.

[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.

[A Case of GIST That Recurred More Than 30 Years after Surgery and Could Be Resected].

The patient was a 77-year-old woman. She underwent a partial gastrectomy at the age of 40, and a partial colectomy at the age of 75 following a diagnosis of a carcinoid. In November 2019, a 1.5 cm mass with a clear boundary was found in the pancreatic tail, which was strongly stained uniformly. And furthermore, multiple masses between 2 cm and 3 cm with a clear boundary was found inside liver segment S1 and S6 and S7 and S8 on CT, which was strongly stained at the edge in the early phase and was seen as a low density area in the late phase. At a result of image examination, it was diagnosed as a pancreatic tail neuroendocrine tumor and its multiple liver metastases. The distal pancreatectomy, posterior segmentectomy, and partial S1 lt and S8 liver resection were performed. With postoperative pathological diagnosis, the pancreatic tumor was accessory spleen, and liver tumor were epithelioid type GIST which were positive for CD34 and PDGFRA and negative for c- kit. The pathology specimen of colectomy was re-examined, and the diagnosis from the previous surgery was changed to GIST from a carcinoid. Epithelioid type GIST was associated with a PDGFRA gene mutation and was known to have many gastric origins. Based on the clinical course, it was diagnosed as recurrence of gastric GIST at 40 years after 30 years or more.

[Deviation of Peripherally Inserted Central Catheter(PICC)during Total Parenteral Nutrition(TPN)for a Gastric Cancer Patient-A Case of Report].

A 90s woman was diagnosed as having cT4aN2M0, cStage ⅢA, advanced gastric cancer. As she was severely malnourished owing to pyloric stenosis, a peripherally inserted central catheter (PICC)was placed in her left arm, and total parenteral nutrition(TPN)was initiated. She complained of dyspnea, and radiography revealed right pleural effusion on day 4 of TPN. Contrast computed tomography revealed that the tip of the catheter had perforated the vessel wall of the superior vena cava and had migrated into the mediastinal space. After thoracocentesis, the catheter was removed under fluoroscopic guidance after hemostasis was achieved. Thus, the possibility of catheter deviation should be considered in case of dyspnea and pleural effusion during TPN.

[A Phase â ¡ Study of Systemic Chemotherapy with Capecitabine and Cisplatin Followed by Surgery for Advanced Gastric Cancer with Extensive Lymph Node Metastasis(OGSG1401)].

BACKGROUND: Gastric cancer with extensive lymph node metastasis(ELM)is commonly considered unresectable and has a poor prognosis. We conducted a phase Ⅱ study to evaluate the safety and efficacy of capecitabine and cisplatin(XP)as preoperative chemotherapy for gastric cancer with ELM. METHODS: The patients received 2 21-day cycles of XP therapy(ca- pecitabine at 2,000mg/m2 twice daily for 2 weeks and cisplatin at 80 mg/m2 on day 1)followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was administered for 1 year. The primary end point was response rate(RR). The planned sample size was 30. RESULTS: Between April 2015 and November 2016, 4 patients were enrolled, but the enrollment was terminated because of poor patient recruitment. The clinical RR was 50%, and R0 resection was achieved in 75% of the patients. The common Grade 3 adverse events during XP therapy were leukocytopenia(25%), anemia(25%), and hyperlipidemia(25%). The common Grade 3 surgical morbidity was abdominal abscess(33%)and pancreatic fistula(33%). The pathological RR was 25%. CONCLUSIONS: Preoperative XP therapy was feasible, but its efficacy was difficult to evaluate because of the small sample size.

[A Case of Enterocutaneous Fistula Caused by Cytomegalovirus Enteritis after Gastrectomy Successfully Treated with Antiviral Therapy-A Case Report].

Cytomegalovirus(CMV)infection is a well-recognized complication of immunodeficiency. We present the case of a 90- year-old female admitted due to gastric cancer. Fifty-seven days after gastrectomy, intestinal juice was observed from the umbilical wound, which was suspected of anastomotic failure or gastrointestinal perforation. Abdominal computed tomography didn't reveal gastrointestinal perforation. CMV enteritis was diagnosed by transanal double-balloon endoscopy from the cecum to the oral side 15 cm of the ileum. Enterocutaneous fistula was considered to be caused by CMV enteritis. The intestinal fluid outflow from the wound disappeared treated with ganciclovir, and the ulcer in the intestinal tract disappeared, too. We report this case to reinforce the importance of considering CMV infection as a differential diagnosis in gastrointestinal perforation of compromised patients.

[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.

[Clinical Efficacy and Safety of Nab-Paclitaxel plus Ramucirumab Therapy in Patients with Unresectable Advanced or Recurrent Gastric Cancer].

We retrospectively evaluated the efficacy and feasibility of the combination of nab-paclitaxel plus ramucirumab(nab-PTX plus RAM)for the treatment of unresectable or recurrent gastric cancer. Sixteen patients received nab-PTX plus RAM. The overall response rate was 37.5%, and disease control rate was 87.5%. The median progression-free survival was 5.0 months. Grade 3 or higher adverse events(neutropenia: 62.5%, leukopenia: 18.8%, decrease appetite: 6.3%, hypertension: 6.3%, and proteinuria: 12.5%)were observed. Although dose reduction of nab-PTX was required in 93.8% of the patients, no adverse event that led to the discontinuation of treatment. Nab-PTX plus RAM combination therapy showed promising efficacy and manageable toxicities and could be a viable treatment option for patients with advanced gastric cancer.

[A Case of Robot-Assisted Abdominoperineal Resection for Local Control for Lower Rectal Cancer with Synchronous Liver and Lung Metastases].

The patient was a 70s woman who was referred to our hospital with a complaint of bloody stool. Colonoscopy revealed type 2 tumor at a distance of 1 cm from the dentate line, without obstruction. The pathological diagnosis was adenocarcinoma. Enhanced CT revealed a tumor at the rectum below peritoneal reflection as well as swelling of the mesorectal lymph nodes. Multiple liver and lung metastases were also observed. The diagnosis was lower rectal cancer cT4aN2M1b(H2, PUL2), cStage Ⅳ. Chemotherapy was performed for disease control because of unresectable metastases. She received 7 courses of mFOLFOX plus bevacizumab. Further, as the metastatic lesion was inhibited, the primary lesion was excised for the purpose of symptom control. We judged that sphincter preservation was impossible because it was 1 cm away from the dentate line. She underwent robot-assisted abdominoperineal resection with D3 lymphadenectomy and sigmoid colostomy.