Perioperative fluid management influences complication rates and length of hospital stay in the enhanced recovery after surgery (ERAS) protocol for patients with colorectal cancer.

PURPOSE: To evaluate the efficacy and safety of the enhanced recovery after surgery (ERAS) protocol and quantify the impact of each ERAS item on postoperative outcomes. METHODS: We used a generalized linear model to compare 289 colorectal cancer patients treated with the ERAS protocol between June, 2015 and April, 2021, with 99 colorectal cancer patients treated with the conventional colorectal surgery pathway between April, 2014 and June, 2015. RESULTS: The median length of hospital stay (LOHS) was significantly shorter in the ERAS group, at 9 days (range 3-104 days) vs. 14 days (range 4-44 days) (p < 0.001), but the complication rates (Clavien-Dindo grade 2 or more) were similar (16.6% vs. 22.2%; p = 0.227). However, in the ERAS group, the higher the compliance with ERAS items, the lower the complication rate and LOHS (both p < 0.001). Multiple regression analysis demonstrated that "Discontinuation of continuous intravenous infusion on POD1" and "Avoidance of fluid overload" were significantly associated with the LOHS (p < 0.001 and p = 0.008). CONCLUSION: The ERAS protocol is safe and effective for elective colorectal cancer surgery, and compliance with the ERAS protocol contributes to shorter LOHS and fewer complications. Items related to perioperative fluid management had a crucial impact on these outcomes.

[A Case of Conversion Surgery for Gallbladder Cancer with Para-Aortic Lymph Node Metastasis].

The study presents the case of a 71-year-old woman who visited a nearby hospital for epigastric pain and weight loss. A CT scan showed a mass in the gallbladder, and the CEA level was high, so she was referred to our hospital for further investigation. Abdominal US, CT, and MRI suggested gallbladder cancer with para-aortic metastasis, and the histological findings on the EUS-FNA confirmed the diagnosis. Since surgical resection was not indicated, chemotherapy was performed(gemcitabine plus cisplatin). After 10 courses of chemotherapy, CT and MRI showed downsizing of para-aortic lymph nodes, and no accumulation of FDG was found on FDG-PET. Confirming the downstaging of cancer, conversion surgery, comprising an extended cholecystectomy and a lymph node resection, was performed. The pathological diagnosis showed no lymph node metastasis. No recurrence was observed after 12 months of surgery. Initially, unresectable gallbladder cancer with para-aortic lymph node metastasis was indicated to be compatible with preoperative chemotherapy and conversion surgery.

[A Case of HER2-Positive Unresectable Advanced Gastric Cancer Showing Long-Term Complete Response Treated by Only Chemotherapy].

A 78-year-old man was diagnosed as HER2-positive unresectable advanced gastric cancer(cT4aN3M1[LYM], Stage Ⅳ). After 2 courses of first-line chemotherapy(S-1 plus oxaliplatin plus trastuzumab), PR was achieved. The treatment could not be continued due to adverse events after 5 courses, thus second-line chemotherapy was conducted. Corresponding to the physical condition. The third-line chemotherapy was also introduced. However, we clinically judged PD because of amount of ascites and chemotherapy was terminated. After that, he has survived for more than 2 years without chemotherapy, and endoscopy and CT showed the disappearance of the tumor, metastatic lymph nodes, and ascites at 41 months after diagnosis. Looking back on the changes in tumor markers, it was possible that he had already achieved CR at the first-line chemotherapy.

[A Case of Lymph Nodes Metastases of Gastric Neuroendocrine Carcinoma Treated with Nivolumab and Showing Complete Response].

A 78-year-old man was diagnosed with lymph node metastasis 2 months after surgery for gastric neuroendocrine carcinoma. He received chemotherapy(CDDP plus CPT-11)and showed partial response(PR)after 3 courses of the regimen. Serum CEA increased 5 months after surgery, thus nab-paclitaxel plus ramucirumab was administered. Although the lymph node kept shrinked after 2 courses of the regimen, the lymph node was detected 12 cm of the size in CT after 5 courses of the regimen. He started to receive nivolumab. The lymph nodes showed PR after 4 courses, and complete response after 6 courses of the regimen for 1 year and 4 months until now.

[A Case of Cardiac Tamponade during Multimodal Treatment for Mediastinal Lymph Node Metastasis of Gastric Cancer].

A 52-year-old man underwent total gastrectomy for gastric cancer and chemoradiotherapy for thoracic paraaortic lymph node metastasis. He also underwent esophageal stent implantation for stenosis. He was admitted to our hospital with fever and breathing difficulty and was diagnosed with infectious pericarditis. He showed symptoms of shock due to cardiac tamponade. After pericardial drainage, his vital signs improved. When signs of infection are detected in patients with a history of chemoradiotherapy or stent implantation, we should consider infectious pericarditis due to esophageal pericardial fistula and apply immediate drainage of cardiac tamponade.

Enhancement of immune proteins expression in skin mucus of Japanese flounder Paralicthys olivaceus upon feeding a diet supplemented with high concentration of ascorbic acid.

To search immune defense proteins in skin mucus of Japanese flounder fed with a diet containing high concentration of ascorbic acid, we carried out 2D-PAGE and compared the resolved pattern of proteins between control group that fed commercial diet and ascorbic acid supplemented group (AsA group) fed a diet supplemented with high concentration of ascorbic acid (2,000 mg/kg) for 7 days. The results revealed that there were many proteins exhibited distinct increase in AsA group. Among them, 6 regions that showed a dramatic elevation were chosen for protein identification using LC-MS/MS analysis and Mascot database search. Six proteins were identified, i.e. serotransferrin (Sero), transferrin (Trans), warm temperature acclimation-related 65 kDa protein (Wap65), complement component c3 (C3), hemoglobin beta-A chain (Hbß) and apolipoprotein A-1 (Apo). Quantitative RT-PCR analysis showed that the mRNA level of Hbß in epidermis of AsA group gave much higher increase (11.6 folds) than control group; the levels of Sero/Trans, Wap65, C3 and Apo showed no apparent difference between the two groups. The mRNA levels of wap65 and c3 in the liver and Apo in the kidney of AsA group exhibited significant increase in comparison to control group. In the case of secreted immunoglobulin M (IgM) and lysozyme (lyz), no difference of the mRNA levels of IgM in epidermis, gill, kidney, spleen and intestine, and lyz in epidermis, gill, spleen and intestine, was observed. The results of in situ hybridization confirmed the elevation of Hbß mRNA level in the epidermis tissue of AsA group. Our present study provided additional evidence showing the effectiveness of AsA in activating innate immune defense system in skin mucosal tissue of fish.

Propranolol suppresses gastric cancer cell growth by regulating proliferation and apoptosis.

BACKGROUND: Despite improvements in gastric cancer treatment, the mortality associated with advanced gastric cancer is still high. The activation of ß-adrenergic receptors by stress has been shown to accelerate the progression of several cancers. Accordingly, increasing evidence suggests that the blockade of ß-adrenergic signaling can inhibit tumor growth. However, the effect of ß-blockers, which target several signaling pathways, on gastric cancer remains to be elucidated. This study aimed to investigate the anti-tumor effects of propranolol, a non-selective ß-blocker, on gastric cancer. METHODS: We explored the effect of propranolol on the MKN45 and NUGC3 gastric cancer cell lines. Its efficacy and the mechanism by which it exerts anti-tumor effects were examined using several assays (e.g., cell proliferation, cell cycle, apoptosis, and wound healing) and a xenograft mouse model. RESULTS: We found that propranolol inhibited tumor growth and induced G1-phase cell cycle arrest and apoptosis in both cell lines. Propranolol also decreased the expression of phosphorylated CREB-ATF and MEK-ERK pathways; suppressed the expression of matrix metalloproteinase-2, 9 and vascular endothelial growth factor; and inhibited gastric cancer cell migration. In the xenograft mouse model, propranolol treatment significantly inhibited tumor growth, and immunohistochemistry revealed that propranolol led to the suppression of proliferation and induction of apoptosis. CONCLUSIONS: Propranolol inhibits the proliferation of gastric cancer cells by inducing G1-phase cell cycle arrest and apoptosis. These findings indicate that propranolol might have an opportunity as a new drug for gastric cancer.

Clinical significance of surgical intervention for imatinib-resistant gastrointestinal stromal tumors in the era of multiple tyrosine kinase inhibitors.

PURPOSE: Imatinib is the standard treatment for unresectable and metastatic GIST. In the late stages, patients undergoing imatinib show drug resistance. Surgical intervention has been occasionally performed for resistant lesions. However, the clinical significance of such intervention remains unclear. METHODS: Between 2006 and 2015, 37 patients were diagnosed with imatinib-resistant GISTs. We performed surgical intervention only for localized resistant lesions. We retrospectively investigated the background characteristics, data on surgical intervention and subsequent treatment, progression-free survival (PFS), and overall survival (OS). RESULTS: Eighteen patients diagnosed with localized resistance received surgical intervention (S-group) and 19 patients diagnosed with generalized resistance were received other TKIs (M-group). In S-group, no serious complications occurred, and all patients restarted imatinib after resection. The median PFS was 14.5 months. Five patients underwent surgical intervention multiple times followed by the continuation of imatinib, and the median duration of imatinib continuation was 22.2 months. Second-line TKIs were administered to 93% of the patients and the dose-intensity and outcome were similar in both groups. The median OS was 47.2 months after surgery. CONCLUSIONS: Surgical intervention could be performed safely and therefore could be followed by the continuation of TKI therapy. Surgical intervention based on the appropriate criteria of resistance might thus be useful for imatinib-resistant GISTs.

[A Case of Long-Term Progress Control of Unresectable Progressive Gastric Cancer with Nivolumab Introduced during Effective Duration of Secondary Treatment].

A 65-year-old man with 1 month of general malaise was admitted to our hospital. Thoracoabdominal CT showed that the supra-clavicular, sub-carina, and para-aortic lymph nodes were swelling. Upper gastrointestinal endoscopy revealed 2 type 1 tumors at the esophagogastric junction, and the biopsy showed Group 5, well to moderately differentiated adenocarcinoma. The clinical diagnosis was cardiac gastric cancer and cStage Ⅳ(cT3N3M1[LYM]). We started capecitabine plus oxaliplatin as the first-line chemotherapy, and weekly paclitaxel plus ramucirumab was administered as the second-line treatment. The second-line treatment was successful, and the effect of PR was obtained. However, considering the period of TTF, while the therapeutic effect continued, we switched to third-line treatment with nivolumab after 7 courses of the second treatment. With the third-line treatment, PR was maintained for 1 year and 3 months, and good quality of life and performance status were obtained for a long period without irAE. However, after 32 courses, because the tumor marker was elevated and lymph nodes were enlarged, we judged PD and switched to the fourth-line treatment with nab-paclitaxel plus ramucirumab. The tumor marker levels decreased, the lymph nodes shrank, and PR was achieved again with the fourth-line treatment. The treatment is still ongoing 2 year and 8 months after the diagnosis.

[Two Cases of Large Gastrointestinal Stromal Tumors Safely and Completely Resected by Laparoscopic Surgery Followed by Neoadjuvant Imatinib Therapy].

Case 1, the patient was a 51-year-old man. Upper gastrointestinal endoscopy revealed a submucosal tumor with delle at the posterior wall of the gastric body, and the biopsy demonstrated a diagnosis of GIST. Abdominal CT scan showed a tumor at the size of 130×110×90 mm. Six months after administration of 400 mg/day of imatinib, the maximum diameter was reduced to 55 mm, then partial gastrectomy was performed by laparoscopic surgery. He continued to take imatinib after the surgery for 3 years, and he is alive without recurrence 4 years postoperatively. Case 2, the patient was a 68-year-old man. An abdominal CT scan showed a tumor at the size of 160×120×85 mm on the posterior outside of the stomach, but no submucosal tumor could be identified by upper gastrointestinal endoscopy. Gastric GIST was suspected and he started taking imatinib 400 mg/day. Because the Grade 3 generalized eruption was appeared, imatinib was discontinued, and then the dose was reduced. Nine months after the initiation of the treatment, the maximum diameter was reduced to 90 mm, and laparoscopic partial gastrectomy was performed. The patient is followed up without administration of imatinib after the surgery, and is alive without recurrence for 1 year and 6 months postoperatively. We report 2 cases that the large gastric GIST was able to be resected safely and completely due to tumor shrinkage by neoadjuvant imatinib therapy.

[A Case of Hepatocellular Carcinoma with Extrahepatic Growth-A Difficult Preoperative Diagnosis].

A 75-year-old man was admitted to our hospital for breathing difficulty. CT showed a 20 cm mass with clear boundaries and internal non-uniformity, which we suspected to be a gastrointestinal stromal tumor(GIST). Surgical resection was been considered to be risky because the mass was close to surrounding organs, such as the stomach, liver and diaphragm. Thus, we chose imatinib therapy. After 2 months, he was admitted to our hospital for anemia. CT showed the size of mass to be smaller, but the area of low density with internal non-uniformity had increased. We diagnosed intratumoral bleeding, and chose surgical resection. The mass was under the omentum, and had infiltrated the extrahepatic area and lesser curvature of the stomach. We diagnosed the mass derived from the stomach, and performed partial gastrectomy with partial liver resection. Pathological diagnosis was extrahepatically growing hepatocellular carcinoma(HCC, pT3N0M0, pStage Ⅲ).

[Two Cases of Resectable Gastric Cancer with Extensive Nodal Metastasis That Received Preoperative DOS Therapy].

Case 1: A 67-year-old male had a type 1 tumor in the stomach with a lymph node metastasis 50 mm in size. He was diagnosed with cT4aN(+)M0, cStage Ⅲ and received preoperative docetaxel plus oxaliplatin plus S-1(DOS)therapy. After 3 courses of the regimen, the patient underwent laparoscopic total gastrectomy. The final stage was ypT3N1(1/38) M0, ypStage ⅡB, R0, and the pathological response was Grade 2b. Case 2: A 64-year-old male had a type 3 tumor in the abdominal esophagus and a lymph node metastasis 15 mm in size. He was diagnosed with cT3N(+)M0, cStage Ⅲ and received preoperative DOS therapy. After 3 courses, he underwent laparoscopic esophagectomy. The final stage was ypT0N0M0, ypStage 0, R0, and the pathological response was Grade 3. DOS therapy may be effective as a neoadjuvant chemotherapy.

[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.

Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms.

Endoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia.

[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.

[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.