Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

BACKGROUND: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. PATIENTS AND METHODS: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. RESULTS: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. CONCLUSIONS: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

[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.

[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.

[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 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.

[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 Pancreatic Pseudocyst Recurrence after Surgery for Remnant Pancreatic Cancer].

The patient was a 72-year-old man with a history of pancreatic cancer and IPMA treated with distal pancreatectomy. He had recurrence-free period after adjuvant chemotherapy with S-1. But 6 years after the surgery, a diameter of 1 cm mass was noted in the remnant pancreas on MRI examination after hepatocellular carcinoma treatment. The mass was diagnosed as remnant pancreatic cancer, and he had undergone partial pancreatectomy of remnant pancreas. The pathological diagnosis was pancreatic ductal carcinoma with negative margin. However, 6 months after the reoperation, epigastric pain appeared, and CT scan showed a pseudocyst of 10 cm in size. The diagnosis was local recurrence with positive cytology, and then puncture drainage was performed. After repeated drainages, adhesion of the cystic lesion, and chemotherapy, the cytology became negative and the cystic lesion disappeared, but peritoneal dissemination metastasis also appeared. The patient died of the primary disease 7 years and 8 months after the first surgery and 1 year and 11 months after the second surgery. There has been no report of local recurrence in the form of pancreatic pseudocyst after pancreatic cancer surgery, and we report this case with literature discussion.

[A Case of Pancreaticoduodenectomy for Vater Papillary Cancer with Celiac Axis Stricture].

During the follow‒up of Vater papillary adenoma, a 74‒year‒old man was admitted to our hospital with a chief complaint of upper abdominal pain and diagnosed as cholangitis with obstructive jaundice. Cholestasis had been considered to be caused by papillary adenoma, however, EUS exam showed continuous bile duct wall irregularity from papilla of Vater. So we diagnosed as papillary carcinoma with extension to the distal bile duct. Preoperative CT showed the stenosis at the root of celiac artery, and hepatic blood flow was considered to be supplied via the pancreatic head arcade from superior mesenteric artery, so an anastomosis of gastroduodenal artery and inferior pancreaticoduodenal artery was performed during pancreaticoduodenectomy( PD). Like this case, when performing PD with celiac artery stricture, it is important to evaluate hepatic blood flow before and during surgery and prepare for the arterial reconstruction.

[Analysis of 16 Cases of Primary Duodenal Carcinoma in Our Hospital].

Primary duodenal carcinoma is a rare disease among gastrointestinal malignancies and has little evidence. We evaluated retrospectively the treatment status of 16 cases of primary duodenal carcinoma in our hospital between 2010 and 2019. The median age was 72(58-88)years and 63% of patients were male, and Each stage were Stage 0 in 4 cases, Stage Ⅰ in 1 case, Stage ⅢA in 2 cases, Stage ⅢB in 3 cases, and Stage Ⅳ in 6 cases(UICC 8th edition). Initial treatment was endoscopic therapy in 3 cases, surgery in 10 cases, chemotherapy in 1 case, and best supportive care in 2 case. The 2-year survival rate was 51.3% and the MST was 25.4 months in all cases. The Stage 0, Stage Ⅰ cases had all recurrence-free survival, while the Stage ⅢA or higher cases, 2-year survival rate was 33.8% and the MST was 20.0 months. Also, XELOX was often selected as the first-line treatment for chemotherapy regimens including recurrence treatment.

[Case of Gastric Cancer with Para-Aortic Lymph Node Metastases Successfully Treated with S-1/Docetaxel Chemotherapy].

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

[A Long-Survived Case of Gastric Cancer with Multiple Liver Metastases Who Underwent Gastrectomy and Received Chemotherapy].

A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.

[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.

[A Case Report of Hepatocellular Carcinoma with Complete Spontaneous Regression].

This is the case of a 77-year-old man with hepatitis C. AFP was increased by 95.9 ng/mL, and abdominal computed tomography(CT)revealed a 20 mm mass in the S6 segment of the liver. Therefore, the patient was referred to our hospital for further examination. Abdominal echo at our hospital showed a 10 mm, low echoic lesion in S6, which tended to shrink. Similarly, CT showed a low-concentration nodule of 10 mm in S6, but the contrast effect in the arterial phase was not clear. EOB-MRI showed a 10 mm nodule of DWI hyperintensity and hepatocyte phase hypointensity in S6. Based on these, a diagnosis of hepatocellular carcinoma(T1N0M0, StageⅠ)was made, and we decided to perform surgery. Intraoperative findings showed no tumor on the liver surface, and echo did not reveal a reproducible nodule. The tumor site was estimated using a 3-dimensional image analysis system created preoperatively. Laparoscopic partial resection of the liver S6 segment was performed at a position distant from the estimated tumor site. Rapid pathological examination showed no malignant findings, but no significant lesion was found in the residual liver, and the surgery was completed. The postoperative pathological diagnosis revealed no clear tumor. EOB-MRI was performed again postoperatively, but no tumor was found in the residual liver. The tumor site that had been indicated preoperatively was resected, and we hypothesized that the hepatocellular carcinoma had spontaneously regressed. Although several mechanisms have been reported for the spontaneous regression of hepatocellular carcinoma, few cases of spontaneous regression during surgery have been reported. We do not have a definite opinion on the treatment protocol for hepatocellular carcinoma that regresses spontaneously; therefore, we will report on past cases.

[Adjuvant Chemotherapy and the Prognosis of ypStageâ Gastric Cancer].

The efficacy of postoperative chemotherapy for patients with ypStageⅠgastric cancer has not been evaluated. We investigated the characteristics and prognosis of7 patients with ypStage Ⅰgastric cancer. cStages were ⅡA, ⅡB, ⅢB, and Ⅳin 1, 1, 1, and 4 patients, respectively. S-1 plus cisplatin and docetaxel plus cisplatin plus S-1 were administered in 5 and 2 patients, respectively, for 2-8 courses before gastrectomy. Microscopic curative resection was performed for all patients. ypStage was 0, ⅠA, and ⅠB in 1, 2, and 4 patients. All patients received postoperative chemotherapy with S-1 or docetaxel plus S-1(DS). The 5-year recurrence-free survival was 71% and the 5-year overall survival was 68%. Two patients developed recurrence. One patient developed recurrence 1 year and 1 month after gastrectomy in spite of S-1 treatment for 4 months. Another patient developed recurrence 11 months after gastrectomy after DS treatment for 4 months followed by S-1. The other 5 patients received S-1 for 1-5 years and have survived without recurrence. Although the prognosis ofypStage Ⅰgastric cancer was comparatively good, the regimen and courses ofpostoperative chemotherapy should be evaluated in a prospective study.

[Two Cases of Liver Metastasis from Gastric Cancer Achieving Long-Term Survival Successfully Treated with Stereotactic Body Radiotherapy(SBRT)].

We report 2 cases with long-term survival following stereotactic body radiotherapy(SBRT)for liver metastasis from gastric cancer. Case 1 was a 65-year-old man. We performed distal gastrectomy for gastric cancer with liver metastasis prior to chemotherapy due to pyloric stenosis. Postoperative S-1 chemotherapy was administered. Two liver metastases observed before the operation were temporarily reduced in size but subsequently enlarged; therefore, SBRT was performed 13 months postoperatively. The liver metastases showed a complete response(CR)and the patient is alive 4 years and 11 months after SBRT(6 years postoperatively). Case 2 was a 71-year-old woman. After performing distal gastrectomy, liver metastasis emerged during postoperative S-1 adjuvant chemotherapy; therefore, SBRT was performed 11 months postoperatively. She was then administered weekly paclitaxel. However, she underwent a right hepatic lobectomy 13 months after SBRT for suspected remnant or marginal recurrence by abdominal enhanced CT. Histopathological examination showed that the tumors contained fibrotic connective tissue with no viable cancer cell remnants; therefore, the therapeutic effect was determined to be of Grade 3. The patient is alive without recurrence in the remnant liver 4 years and 7 months after SBRT(5 years and 6 months after the operation of gastric cancer). Thus, SBRT for liver metastasis from gastric cancer may be considered an effective local treatment.