Early enteral nutrition with arginine compensates for negative nitrogen balance in patients undergoing curative total gastrectomy.

The effects of early enteral arginine-rich nutrition (EAN) were analyzed among patients undergoing curative-intent total gastrectomy for gastric cancer. There were 19 patients in this prospective study, all randomly assigned to either a parenteral nutrition (PN) group or an EAN group for the first seven days after surgery. The EAN group received 1.8-fold greater arginine (10.1 g/day) compared with the PN group, which was administered through an enteral tube inserted into the jejunal loop. Both groups were provided almost identical amounts of total amino acids (54 g/day), and the total energy was set at 65% of the total requirement (25 kcal/kg/day). No significant differences were observed between the two groups in postoperative complications, length of hospital stay, oral intake, nutritional status, or body weight. The serum arginine profile was similar in the two groups, as it decreased significantly on postoperative day (POD) 1, and gradually returned to preoperative levels by POD 7. The nitrogen balance remained negative until POD 7 in the PN group, but turned neutral at POD 7 in the EAN group. While we could not confirm body weight loss improvement, these results suggested that early arginine-rich enteral nutrition could improve the nitrogen balance after total gastrectomy. J. Med. Invest. 70 : 325-333, August, 2023.

[Curative Resection of Sigmoid Colon Cancer with Multiple Liver Metastases by Long-Term Multidisciplinary Treatment].

A male patient in his 80s underwent colonic stenting for obstructive sigmoid colon cancer with multiple liver metastases. With systemic chemotherapy for approximately 1 year, the liver metastasis disappeared, so laparoscopic sigmoid colectomy was performed for the primary lesion. No recurrence was observed for a while, although CT revealed liver metastasis in the liver S4, and radiofrequency ablation was performed. Radiation therapy was performed for the liver metastasis of liver S2 that subsequently appeared. After a recurrence-free period of approximately 2 years, a rapid regrowth of liver metastasis in liver S2 was observed. Thus, 4 years and 3 months after the initial diagnosis, lateral segmentectomy of the liver was performed. Five years have passed since the first visit, and he is alive without recurrence. The patient had obstructive colorectal cancer with unresectable liver metastasis, and as the obstruction was released by a colonic stent, systemic chemotherapy was prioritized. Hence, liver metastasis was controlled, and the primary lesion was resected. Furthermore, for the liver metastasis that appeared later, various loco-regional cancer therapies were provided to achieve a cancer-free state.

[A case of gastric perforation that occurred during the incubation period for infectious mononucleosis in an adolescent patient].

A 17-year-old young man visited our hospital because of severe upper abdominal pain and was diagnosed with acute peritonitis caused by gastrointestinal perforation. Emergent surgical treatment was performed, and the perforated lesion of the stomach was repaired. He recovered and was discharged without any complication at 14 days postoperatively. However, he had intermittent fever 2 days after discharge and visited our hospital again. He was diagnosed with infectious mononucleosis (IM), derived from Epstein-Barr virus (EBV) initial infection, on biochemical examination that was positive for anti-EBV VCA-IgG and negative for EBV nuclear antigen, although he was ameliorated conservatively. This pathophysiology raised a possibility that EBV infection had induced acute gastritis or gastric ulcer leading to the penetration of the stomach. Six weeks postoperatively, esophagogastroduodenoscopy showed a gastric ulcer in the vestibular part of the stomach. Pathologic examination of the stomach revealed mucosal erosion with B-cell infiltration into the lamina propria;however, Epstein-Barr viral infection was unclear by EBV-encoded small RNA in situ hybridization. Here, we report a rare case of gastric perforation that occurred during the incubation period of IM with a review of the relevant literature.

[A Case of Duodenal Adenocarcinoma in the Third Portion Treated with Partial Duodenectomy].

A 85-year-old man was admitted due to vomiting. Abdominal CT showed the remarkable expansion of the stomach and the stenotic lesion in the third portion of the duodenum. Duodenal endoscopy showed a circular tumor of the third potion of the duodenum, and biopsy disclosed tubular adenocarcinoma. Operation was performed on the basis of a diagnosis of primary duodenal cancer of the third portion. Liver metastasis, peritoneal dissemination, and apparent lymph node enlargement were not observed. The tumor was present in the third portion of the duodenum and partial duodenectomy was performed. Reconstruction was achieved by side to side anastomosis of the duodenum and the jejunum. Histopathological diagnosis was well differentiated tubular adenocarcinoma, SS, ly1, v1. Primary duodenal cancer is a relatively rare disease, and there are few cases of third portion. If pancreatic invasion and lymph node metastasis are not observed as in this case, it is necessary to examine the indication of partial duodenectomy.

[A Case of Unresectable Recurrent Colorectal Cancer with Regorafenib Treatment and Long-Term Survival].

This paper reports a case in which the patient has survived for 5 years and 6 months after recurrence of colorectal cancer by chemotherapy, and especially in regorafenib as fourth-line therapy has obtained stable disease(SD)for 2 years and 6 months. A man in his 70s underwent left hemicolectomy in the diagnosis of descending colon cancer. Four years and 4 months after the operation, abdominal CT revealed paraaortic lymph node metastasis. When SOX plus bevacizumab was performed as first-line therapy, partial response(PR)was obtained, and PR was maintained for a long time. After progressive disease(PD), IRIS was performed as second-line therapy, but the effect was not obtained. Panitumumab was started as third-line therapy, and PR was temporarily recognized, but since it became PD again, regorafenib was introduced as fourth- line therapy. After regorafenib administration, reduction of paraaortic lymph nodes and lowering of CEA are recognized, and long SD can be maintained. This case can be said to be 1 case in which the usefulness of regorafenib was shown as a salvage- line for unresectable colorectal cancer.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells curatively resected after pembrolizumab therapy for lung metastases: a case report.

BACKGROUND: Therapy targeting programmed death-1 or programmed death-1 ligand-1 (PD-1/PD-L1) has been developed for various solid malignant tumors, such as melanoma and non-small-cell lung cancer (NSCLC), but this approach has little effect in the treatment of pancreatic cancer. Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare pancreatic malignancy having unique morphology and is considered a variant of pancreatic ductal adenocarcinoma (PDAC). Although UCOGC has been reported to have better prognosis than conventional PDAC, the optimal treatment for UCOGC with distant metastases has not been determined. CASE PRESENTATION: A 66-year-old man was initially diagnosed with NSCLC with multiple intrapulmonary metastases and abdominal lymph node metastasis in the tail of the pancreas, and bronchial biopsy and diagnostic imaging were performed. Pathologic examination of the lung showed poorly differentiated adenocarcinoma cells expressing epithelial marker and PD-L1. Therefore, pembrolizumab monotherapy for NSCLC was given. The pulmonary lesions shrank markedly and were in complete remission after 8 months of anti-PD-1 therapy, though no therapeutic effect was observed in the pancreatic site. Distal pancreatectomy was then performed, and histopathological examination showed that the tumor was UCOGC originating from the pancreas. The histologic findings of the resected specimen mimicked those of the lung biopsy specimen, leading to the final assessment that the lung tumors were metastatic foci that migrated from the UCOGC, and only the metastatic lesions benefited from pembrolizumab therapy. CONCLUSION: Immune checkpoint inhibitors have limited therapeutic effects on primary lesions of pancreatic cancer, but they may exert antitumor effects on pulmonary metastases of UCOGC.

[A Case of Intraductal Papillary Mucinous Carcinoma of the Pancreas Extending Widely within the Pancreas Resected by Total Pancreatectomy].

A 78-year-old woman visiting our hospital with the chief complaint of abdominal pain was diagnosed with ischemic colitis. CT pointed out pancreatic enlargement, so detailed pancreatic examination was conducted in parallel with treatment. In enhanced CT and MRI, the main pancreatic duct significantly extended over the entire length, and mural nodules scattered in the main pancreatic duct were observed. It was diagnosed with main duct intraductal papillary mucinous neoplasm (IPMN), which is likely to be intraductal papillary mucinous carcinoma(IPMC), and total pancreatectomy was performed. Pathological findings showed diffuse dilation of the main pancreatic duct, non-invasive IPMC progressed over approximately the entire length of the main pancreatic duct, mucinous carcinoma-tubular adenocarcinoma was widely infiltrated in pancreatic tissues around mural nodules. The cancer remained in the pancreas and was eventually diagnosed with IPMC, invasive, pT2, pN0, and pStage ⅠB. This case was an IPMN with high-risk stigmata, and it was an adaptive case of total pancreatectomy because mural nodules extended to the entire pancreas. In recent years, total pancreatectomy has come to be expected good results by the progress of diabetes treatment and the development of pancreatic enzyme agents, it is necessary to carefully judge each case for adaptation.

[Multimodal Therapy for Stage â £ Gallbladder Carcinoma Achieved Long-Term Survival-A Case Report].

A 75-year-old man with a chief complaint of abdominal pain visited our hospital and was diagnosed with Stage Ⅳ gallbladder carcinoma that infiltrated the transverse colon with distant lymph node metastases. He received gemcitabine plus cisplatin chemotherapy, which led the primary lesion to shrink. However, transverse colon obstruction occurred, and semi- urgent right hemicolectomy and extended cholecystectomy were performed. A year and 2 months after first diagnosis, an inferior pancreatic head lymph node swelling was detected. Chemoradiotherapy was performed using S-1, and the lymph node swelling was reduced. Despite continuous S-1 therapy, the lymph node gradually started to swell again, which led to duodenum obstruction by compression. He underwent gastrojejunal bypass; however, his general condition gradually worsened, and he died 2 years and 6 months after the first diagnosis. Even in cases of unresectable gallbladder carcinoma, multimodal therapy, such as surgery, chemoradiotherapy, and palliative gastrointestinal bypass, may archive a long prognosis of 2 years and 6 months.

[A Case of Resection of Intraductal Papillary Mucinous Carcinoma Detected Due to Acute Pancreatitis].

A 67-year-old man visiting our hospital with the chief complaint of sudden upper abdominal pain was diagnosed with acute pancreatitis. Based on computed tomography findings, intraductal papillary mucinous neoplasm(IPMN)was suspected as the cause of the pancreatitis and detailed examination was conducted following its alleviation. Endoscopic retrograde and magnetic resonance cholangiopancreatography showed marked dilation of the main pancreatic duct, with a mural nodule inside the main pancreatic duct at the pancreatic head. Main duct IPMN was diagnosed and pancreaticoduodenectomy was performed 3 months after the onset of acute pancreatitis. The histopathological findings showed a tumor proliferating in a mold pattern in the lumen of the dilated main pancreatic duct, resulting in a diagnosis of intraductal papillary mucinous carcinoma(IPMC). The presence of IPMN should be considered as a cause of acute pancreatitis; if findings suggestive of IPMN are found on imaging, detailed examinations and treatment are needed in consideration of the potential for malignancy following alleviation of pancreatitis.

[Short-Term and Long-Term Outcomes of Colonic Stenting as a Bridge to Surgery for Obstructive Colorectal Cancer].

We examined the short-term and long-term outcomes in 50 patients who underwent stenting as a bridge to surgery(BTS) for obstructive colorectal cancer. The patients comprised 30 men and 20 women, with a mean age of 74.0 years. Stenting and decompression were successful in all patients, and the mean time to oral intake after stenting was 2.4 days. No serious complications related to stenting occurred. Colonoscopy after stenting was important for the preoperative diagnosis of coexisting lesions and planning of the extent of resection. Elective and one-stage surgeries could be performed in all patients after stenting. Regarding long-term outcomes, the 5-year overall survival rate and disease-free survival rate in the BTS patients with Stage Ⅱ plus Ⅲ cancer were 73.1% and 55.7%, respectively. The results of this study suggest that BTS for obstructive colorectal cancer is an effective treatment strategy for not only short-term but also long-term outcomes.

[A Case of Advanced Gallbladder Cancer with Paraaortic Lymph Node Metastases Successfully Treated by Chemotherapy and Conversion Surgery].

The patient was a 76-year-old man who was admitted to our hospital with a diagnosis of ileus. A gallbladder tumor was found incidentally on CT, and it was diagnosed as gallbladder cancer. Enlargement of multiple lymph nodes, including the paraaortic lymph nodes, was observed, and PET-CT further showed FDG uptake in the lymph nodes. Based on these findings, the patient was diagnosed with Stage ⅣB gallbladder cancer with paraaortic lymph node metastases. Since surgical resection was not possible, chemotherapy with gemcitabine and cisplatin(GEM plus CDDP)was started. After completion of 4 courses of GEM plus CDDP, the enlarged lymph nodes were decreased in size on CT, and there was no FDG uptake on PET-CT. These findings indicated downstaging to Stage Ⅱ; thus, conversion surgery with extended cholecystectomy and lymph node dissection was performed. The pathological diagnosis confirmed that the patient had Stage Ⅱ cancer(pT2N0M0). A case of unresectable gallbladder cancer that was treated with GEM plus CDDP and subsequent conversion surgery is reported, along with a literature review.

[Four Cases of Ileocolic Intussusception Associated with Malignant Lymphoma of the Ileum].

We report the cases we encountered in our department involving 4 patients with malignant ilial lymphoma that caused ileocolic intussusception. The patients were 2 male and 2 female, aged 65-76 years. All patients' chief complaint was abdominal pain. Computed tomography revealed target signs characteristic of intussusception. Colonoscopy showed a tumor that escaped into the colon, leading to the diagnosis of ileocolic intussusception due to an ileal tumor. However, definitive diagnosis could not be achieved from biopsy. Thus, ileocecal resection or right hemicolectomy was performed. Macroscopically, all tumors were polypoid type and were present within 25 cm from the valve of Bauhin. Histological diagnoses were diffuse large B-cell lymphoma(DLBCL)in 2 patients, T-cell lymphoma in one, and follicular lymphoma in one. Postoperative chemotherapy was performed in patients with DLBCL and T-cell lymphoma. Tumors are commonly the cause of intussusception in adults; therefore, emergent surgery is imperative. When malignant lymphoma is diagnosed, a multidisciplinary approach that includes postoperative chemotherapy is necessary.

[A case of locally advanced sigmoid colon cancer invading the bladder and seminal vesicle effectively treated with preoperative mFOLFOX6].

A 77-year-old male was admitted to our hospital complaining of dyschezia. Computed tomography (CT) and colonoscopy (CF) revealed a huge sigmoid colon cancer invading the bladder and seminal vesicle. Chemotherapy with mFOLFOX6 was initiated preoperatively, and the tumor shrunk markedly after seven courses of treatment. Pelvic exenteration with negative margins was carried out. The patient is still alive and disease-free 16 months after surgery. It was suggested that mFOLFOX6 may be useful for advanced colon cancer invading other organs when used as neoadjuvant chemotherapy.

Metachronous multiple adenocarcinomas of the pancreas.

We report a rare case of metachronous multiple adenocarcinoma of the pancreas. A 59-year-old Japanese man visited our institute for a routine workup as a hepatitis C virus carrier, resulting in detection of a 3-cm tumor in the pancreatic body by screening echogram. Results from several imaging modalities were consistent with pancreatic carcinoma. Distal pancreatectomy along with dissection of partial gastrectomy, transverse colectomy, and lymph node dissection were performed in November 2003. Histological examination confirmed a pancreatic ductal adenocarcinoma with a clear surgical margin and negative lymph node metastases. Gemcitabine was administered for 5 years, then suspended because no recurrent signs were found. The patient returned to our hospital in March 2009, with obstructive jaundice along with a 2-cm tumor in the head of the remnant pancreas. The condition of the patient was carefully investigated and extra-pancreatic metastatic lesions were not found; a pancreaticoduodenectomy was then carried out. Histological examination revealed a diagnosis of pancreatic adenocarcinoma arising from the remnant pancreas gland.

[Gastric emphysema, a critical condition accompanied by eating disorders: a case report].

Gastric emphysema encompasses a broad spectrum of diseases. A 31-year-old woman presented with severe vomiting and epigastric pain. She had lost body weight for several months, and was later diagnosed as having anorexia nervosa. A radiological study demonstrated intramural gas with huge gastric dilatation and portal venous gas. She underwent total gastrectomy and was rescued from extensive gastric necrosis. Her clinical findings suggest that extraordinary dilation of the stomach increased the intraluminal pressure, thereby resulting in perfusion disturbance and extensive gastric necrosis. There are five other case reports of gastric emphysema associated with eating disorders in the literature. All but one were young women, and one of 4 patients with massive gastric necrosis died due to septic shock. Eating disorders cause gastric emphysema through several unique mechanisms, including gastric muscular atrophy, occlusion of the gastroesophageal junction, and delayed gastric emptying. Gastric emphysema in relation to eating disorders carries a risk of life-threatening complications and requires urgent diagnosis and treatment.

Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease.

BACKGROUND: In human blood, two monocyte populations exist, CD14(++)CD16(-) classical monocytes and CD14(+)CD16(+) proinflammatory monocytes, which account for about 10% of total monocytes, but can expand to promote inflammatory conditions. CD14(+)CD16(+) monocytes produce large amounts of inflammatory cytokines including TNF-alpha and IL-1. Adacolumn adsorptive carriers adsorb from the blood in the column most of the monocytes/macrophages and granulocytes and this has been associated with clinical efficacy in patients with active inflammatory bowel disease (IBD). This study was to investigate the CD14(+)CD16(+) monocyte profile in patients with IBD and the impact of Adacolumn on this proinflammatory phenotype. METHODS: A total of 58 patients with ulcerative colitis (UC, N = 37) or Crohn's disease (CD, N = 21) together with 11 healthy controls were included in this study. Peripheral blood CD14(+)CD16(+) monocytes were determined by three-color immunofluorescence and flow cytometry. RESULTS: The percentage of CD14(+)CD16(+) monocytes in patients with active CD was significantly (P= 0.0089) higher than the level in the control group, in patients with quiescent CD (P= 0.0419) or quiescent UC (P= 0.0063). Further, the percentage of CD14(+)CD16(+) monocytes in patients with active UC who were on prednisolone (PSL) was less than the level in those not on PSL (P < 0.0001), thus PSL might have a suppressive effect on CD14(+)CD16(+) monocytes. Patients with active IBD were each given up to 10 Adacolumn granulocye/monocyte adsorption (GMA) sessions over an 8-wk period. The percentage of CD14(+)CD16(+) monocytes decreased dramatically (P= 0.0077 in UC and P= 0.0117 in CD) compared with entry levels. CONCLUSIONS: A significant reduction in peripheral CD14(+)CD16(+) monocytes by GMA should mitigate the inflammatory drive and contribute to the clinical efficacy of this procedure. Reduction of CD14(+)CD16(+) monocytes by corticosteroids was also seen. Hence, corticosteroids should enhance the efficacy of GMA. This is the first report on CD14(+)CD16(+) monocytes being decreased by Adacolumn GMA in patients with IBD.

Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Curcumin is a biologically active phytochemical substance present in turmeric and has pharmacologic actions that might benefit patients with ulcerative colitis (UC). The aim in this trial was to assess the efficacy of curcumin as maintenance therapy in patients with quiescent ulcerative colitis (UC). METHODS: Eighty-nine patients with quiescent UC were recruited for this randomized, double-blind, multicenter trial of curcumin in the prevention of relapse. Forty-five patients received curcumin, 1g after breakfast and 1g after the evening meal, plus sulfasalazine (SZ) or mesalamine, and 44 patients received placebo plus SZ or mesalamine for 6 months. Clinical activity index (CAI) and endoscopic index (EI) were determined at entry, every 2 months (CAI), at the conclusion of 6-month trial, and at the end of 6-month follow-up. RESULTS: Seven patients were protocol violators. Of 43 patients who received curcumin, 2 relapsed during 6 months of therapy (4.65%), whereas 8 of 39 patients (20.51%) in the placebo group relapsed (P=.040). Recurrence rates evaluated on the basis of intention to treat showed significant difference between curcumin and placebo (P=.049). Furthermore, curcumin improved both CAI (P=.038) and EI (P=.0001), thus suppressing the morbidity associated with UC. A 6-month follow-up was done during which patients in both groups were on SZ or mesalamine. Eight additional patients in the curcumin group and 6 patients in the placebo group relapsed. CONCLUSIONS: Curcumin seems to be a promising and safe medication for maintaining remission in patients with quiescent UC. Further studies on curcumin should strengthen our findings.

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis.

AIM: To investigate the relationship between ulcerative colitis (UC) clinical activity index (CAI) and circulating levels of IL-1ra, IL-10, IL-6 and IL-18. METHODS: Blood levels of IL-1ra, IL-10, IL-6 and IL-18 were measured in 31 patients with active UC, the mean CAI was 11.1, ranging from 5-25; and 12 healthy individuals as controls. Patients were given granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn. Leucocytes which bear the FcgammaR and complement receptors were adsorbed to the column leucocytapheresis carriers. Each patient could receive up to 11 GMA sessions over 8 wk. RESULTS: We found strong correlations between CAI and IL-10 (r = 0.827, P < 0.001), IL-6 (r = 0.785, P < 0.001) and IL-18 (r = 0.791, P < 0.001). IL-1ra was not correlated with CAI. Following GMA therapy, 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls. Further, blood levels of IL-1ra and IL-10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that adhered to the carriers.

Platelet-activating factor, a critical mediator in the pathogenesis of dextran sulfate sodium-induced colitis in rats.

PURPOSE: Disorder of mucosal immunity based on an imbalance between proinflammatory and anti-inflammatory cytokines is believed to be a major factor in the pathogenesis of ulcerative colitis. Platelet-activating factor potentially stimulates the production of proinflammatory cytokines and recruits inflammatory cells. The aim of this study was to determine whether and to what extent platelet-activating factor plays a role in the pathogenesis of ulcerative colitis. METHODS: Using dextran sulfate sodium-induced colitis in rats as a model of ulcerative colitis, we analyzed the composition of cellular infiltrates and the local tissue expression of messenger ribonucleic acid for cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha. To directly assess the impact of platelet-activating factor on the development of colitis, we also determined the efficacy of a specific platelet-activating factor receptor antagonist for preventing dextran sulfate sodium-induced colitis. RESULTS: The activity of colitis was well correlated with the upregulation of cytokine-induced neutrophil chemoattractant and tumor necrosis factor-alpha messenger ribonucleic acid in local tissues and infiltration of cytokine-induced neutrophil chemoattractant-positive neutrophils and ED1-positive macrophages. The platelet-activating factor receptor antagonist effectively ameliorated colitis, along with causing a decrease in the tissue cytokine-induced neutrophil chemoattractant messenger ribonucleic acid level and a decline in neutrophil and macrophage infiltration. However, the antagonist did not alter tissue levels of tumor necrosis factor-alpha messenger ribonucleic acid. CONCLUSION: Platelet-activating factor plays a critical role in the pathogenesis of dextran sulfate sodium-induced colitis through recruitment of cytokine-induced neutrophil chemoattractant-positive neutrophils and macrophages and/or stimulation of cytokine-induced neutrophil chemoattractant release from activated neutrophils. The tissue level of tumor necrosis factor-alpha messenger ribonucleic acid does not closely reflect the activity of colitis.