[A Case of Late Recurrence of Gastric Cancer Over Ten Years Post Gastrectomy].

A 72-year-old woman underwent a low anterior resection of the rectum and a total hysterectomy with a bilateral salpingo- oophorectomy simultaneously for rectal and ovarian cancer, respectively. The pathological diagnosis was a moderately differentiated adenocarcinoma of the rectum with some poorly differentiated components signet-ring cell components. A mucinous adenocarcinoma, with similar characteristics as that in the rectum, was found in the ovary. Intraoperative findings revealed no direct invasion between the rectum and ovaries, with no peritoneal dissemination. She was, therefore, diagnosed with synchronous double cancer. The rectal cancer was pT3N0M0, Stage Ⅱ and the ovarian cancer pStage Ⅰ. Adjuvant chemotherapy with capecitabine was performed for high-risk Stage Ⅱ rectal cancer. At 3.5 years after surgery, her CA19-9 level was high and pleural dissemination and para-aortic lymph node metastasis were confirmed on thoracoabdominal CT. Twelve years after the gastrectomy for gastric cancer, a comparison of the pathological specimens of her stomach at that time with the current pathological specimens revealed that the rectal and ovarian tumors were metastases of gastric cancer and that the current recurrence was a late recurrence of this disease. Late recurrence after gastrectomy, especially 10 years or more after surgery, is extremely rare.

A Prospective Multicenter Observational Study of Venous Thromboembolism after Gastric Cancer Surgery (SHISA-1601).

INTRODUCTION: This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery. METHODS: This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded. RESULTS: A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92-1.0) and 0.87 (95% CI 0.74-1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05). CONCLUSION: VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE.

A Second Attack of Anisakis: Intestinal Anisakiasis Following Gastric Anisakiasis.

A 50-year-old man presented with epigastric pain after eating raw mackerel. Abdominal computed tomography revealed submucosal edema of the gastric antrum and pelvic ileum. Gastroscopy revealed an Anisakis simplex in the gastric antrum. His epigastric pain resolved after endoscopic removal of the Anisakis; however, he developed right lower quadrant pain the following day. Abdominal computed tomography showed submucosal edema of the terminal ileum involving different ileal loops, which was not present on admission. The patient developed delayed intestinal anisakiasis. A serving of raw fish may contain more than one Anisakis. After gastric anisakiasis, a second Anisakis may cause intestinal anisakiasis.

[Laparoscopic Distal Gastrectomy for Elderly Patients with Advanced Gastric Cancer and Gastric Outlet Obstruction - A Case Report].

A 90-year-old female patient was admitted to our hospital with a chief complaint of vomiting.Gastroscopy revealed type 3 gastric cancer and gastric outlet obstruction(GOO).Abdominal computed tomography revealed thickening of the antral wall and suggested the presence of 3 perigastric lymph node metastases, but there was no ascitic fluid or distant metastasis.The clinical diagnosis was T4a(SE)N2H0CYXP0M0, Stage III B, according to the Japanese Classification of Gastric Carcinoma.Her general conditions including kidney and cardiac function were good, we considered that she was able to tolerate radical distal gastrectomy.We planned laparoscopic distal gastrectomy(LDG)and D2 lymphadenectomy after getting sufficient informed consent.The patient experienced an uneventful post-operative recovery, and was discharged in good health 11 days after surgery.

[Early Liver Metastases after Curative Surgery for Stageâ Gastric Cancer with Neuroendocrine Differentiation-A Case Report].

An 87-year-old male patient was admitted to our hospital with a chief complaint of vomiting. Gastroscopy revealed Type 0-Ⅱc+Ⅱa tumor at the posterior wall in the middle third of the stomach. A biopsy indicated moderately differentiated adenocarcinoma. Abdominal CT revealed no lymph node or distant metastases. The clinical diagnosis was cT2(MP), N0, M0, cStage Ⅰ. Laparoscopic distal gastrectomy with D2 lymphadenectomy was performed. The pathological findings revealed moderately differentiated adenocarcinoma containing synaptophysin, chromogranin A, and CD56-positive tumor cells. He was then diagnosed with adenocarcinoma with neuroendocrine differentiation. The pathological diagnosis was pT2(MP), pN0, M0, pStage ⅠB. MRI revealed multiple liver metastases 5 months postoperatively. S-1 alone chemotherapy was started, and the patient showed partial response(PR)after 3 courses, according to the Response Evaluation Criteria in Solid Tumor (RECIST).

[Invasive Micropapillary Carcinoma of the Colon That Was Difficult to Diagnose Preoperatively].

A 73-year-old man was admitted with sigmoid colon diverticulitis. Although a biopsy did not indicate malignancy, the sigmoid colon was completely obstructed following conservative treatment. After sigmoidectomy, the histopathological findings revealed a well-differentiated adenocarcinoma localized to the mucosal surface; invasive micropapillary carcinoma (IMPC)accounting for>95% of the tumor volume spread extensively below the submucosal layer. IMPC is highly malignant and difficult to diagnose preoperatively, possibly due to the presence of poorly differentiated histological sub-types in the deepest portions of the tumor.

Spontaneous external biliary fistula arising from an intrahepatic duct.

A spontaneous external biliary fistula is most commonly a cholecystocutaneous fistula secondary to acute cholecystitis. A fistula arising from an intrahepatic duct is extremely rare. An 87-year-old man presented with swelling of the epigastric region and right upper quadrant abdomen. He had a history of cholecystectomy and endoscopic sphincterotomy. After antibiotic treatment and surgical opening of both lesions, abdominal computed tomography demonstrated a soft tissue mass cephalad to the umbilicus. We excised the mass, and found it to be associated with a fistula through the linea alba. Fistulography showed an abscess cavity communicating with the intrahepatic duct in segment III. Histopathological examination of the mass showed an abscess without malignancy. The fistula closed spontaneously without laparotomy. In this case, the underlying pathology was considered to be associated with a subcapsular hepatic cyst in segment III.

[Esophagogastric Junction Cancer Resection with Bilateral Adrenal Metastasis - A Case Report].

The patient was a 64-year-old man with esophagogastric junction cancer. We performed right thoracotomy-laparotomy for lower esophageal and cardiac gastric resection, D2 lymphadenectomy, and reconstruction of a gastric tube in October 2011. Histopathology confirmed T4aN1M1(LYM), Stage IV cancer(Japanese Classification of Gastric Carcinoma, 14th edition) with R0 resection. Because of preexisting alcoholic cirrhosis, postoperative chemotherapy was not an option. In March 2014, we performed left adrenalectomy for left adrenal metastasis, and in December 2014, we performed right adrenalectomy for metastasis to the right adrenal gland. The patient was prescribed 20mg/day of hydrocortisone postoperatively. Survival from the right adrenalectomy was 2 years and 2 months, and survival from the first operation was 5 years and 4 months, without recurrence. This case of esophagogastric junction cancer resection with bilateral adrenal metastasis is rare, with only one previously reported case in Japan.

Association between reduction of plasma adiponectin levels and risk of bacterial infection after gastric cancer surgery.

BACKGROUND AND PURPOSE: Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities. METHODS: We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ(2) test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility. RESULTS: Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively. CONCLUSION: T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection.

[A case of amelanotic anorectal malignant melanoma mimicking gastrointestinal stromal tumor].

A 56-year-old female patient was admitted, complaining of hematochezia. She was preoperatively diagnosed with poorly-differentiated carcinoma of anorectum with metastases in the lung and mesorectal lymph nodes, and underwent abdominoperineal resection of the rectum. The immunohistochemistry of the rectal tumor showed positive for vimentin and c-kit, and negative for AE1/AE3, S-100, a-SMA, LCA and CD34, which was compatible with gastrointestinal stromal tumor (GIST). Regardless of the administration of imatinib mesylate, multiple metastases in the brain, bone, adrenal glands and inguinal lymph node proceeded in a short term. An excisional biopsy of the inguinal lymph node was performed and immunohistochemistry of the specimen showed positive for S-100, melan-A, HMB45 and tyrosinase. Therefore, we concluded that amelanotic anorectal melanoma (AMM) metastasized to the lymph node, and rechecked the immuno histochemistry of the anorectal tumor. The anorectal tumor showed positive for melan-A, HMB45 and tyrosinase, but negative for S-100. As far as we know, there are few reports of AMM with S-100 negative and c-kit positive. In such cases, making a differential diagnosis between AMM and GIST of the anorectal region can be very confusing.

[A case of advanced gastric cancer with rhabdomyolysis].

We report a patient with advanced gastric cancer with rhabdomyolysis. A 29-year-old man consulted a local doctor complaining of dysphagia and heartburn. He developed rhabdomyolysis that was considered to be caused by administered proton pump inhibitor (PPI). The patient has remained without recurrence for 18 months after operation.

[A case of solitary splenic metastasis from an ovarian cancer 12 years after primary resection].

A 57-year-old woman underwent total hysterectomy and bilateral salpingo-oophorectomy for bilateral ovarian tumors (T1b, N0, M0; Stage I b, serous cystoadenocarcinoma) in May 1994. She received 4 courses of CAP (cyclophosphamide 500 mg/m2+epirubicin 50 mg/m2+cisplatin 60 mg/m2) therapy as adjuvant chemotherapy. An increase of the serum CA125 was detected in December 2006, and abdominal CT revealed a mass in the spleen. Since whole-body FDG-PET-CT showed no evidence of local recurrence of the ovarian cancer or multiple organ metastases, a solitary splenic metastasis from ovarian cancer, even though very rare, was strongly suspected. Splenectomy with distal pancreatectomy was undertaken in December 2007. Histopathological examination revealed poorly-differentiated adenocarcinoma, suggesting the final diagnosis of solitary splenic metastasis from ovarian cancer. Periodic CA125 measurements are considered very important even over 10 years after surgery for ovarian cancer. Once solitary splenic metastasis is diagnosed, surgical resection would be the treatment of choice.

Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis.

BACKGROUND: Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, which increases the plasma APN concentration. MATERIALS AND METHODS: Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone. RESULTS: APN deficiency resulted in significant increases in the plasma levels of TNF-alpha, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-alpha, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis. CONCLUSION: These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.

Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality.

BACKGROUND: Adiponectin, a key substance in metabolic syndrome, is known to have anti-inflammatory properties. The relationship between adiponectin and sepsis in vivo is unclear. In this study, the possible involvement of adiponectin in polymicrobial sepsis was investigated using adiponectin-knockout (APN-KO) mice that underwent cecal ligation and puncture (CLP) and received the peroxisome proliferator-activated receptor gamma (PPAR-gamma) that increases the plasma adiponectin concentration. METHODS: APN-KO and wild-type (WT) mice underwent either CLP or a sham operation. The plasma adiponectin, endotoxin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were determined before and at 2, 4, 6, 8, 12, 16, and 24 hours after the procedures, and the survival rates were compared. Mice were injected with rosiglitazone, a selective PPAR-gamma agonist, and compared survival rates after CLP with those without rosiglitazone. RESULTS: After CLP, APN-KO mice had a significantly higher mortality than WT mice. The plasma endotoxin, TNF-alpha, and IL-6 levels in APN-KO mice were significantly higher than those in WT mice 24 hours after CLP. Within 4 hours after CLP, the plasma adiponectin level in WT mice decreased to half of the initial levels. Pre-CLP treatment with PPAR-gamma was shown to increase the plasma adiponectin level and to improve significantly mortality of WT mice during sepsis; mortality among APN-KO mice did not improve. CONCLUSION: These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis.

Postprandial hyperglycemia after a gastrectomy and the prediabetic state: a comparison between a distal and total gastrectomy.

PURPOSE: Postprandial hyperglycemia is recognized as an important risk factor for developing type 2 diabetes; it is also common in patients after a gastrectomy and is likely to become exacerbated after a total gastrectomy rather than after a distal gastrectomy. In this study, we investigated the glucose and insulin responses after oral glucose tolerance test (OGTT), and compared the incidence of postchallenge hyperglycemia after OGTT in patients after a distal and total gastrectomy. METHODS: Forty-six patients, including 18 patients after a distal gastrectomy and 28 after a total gastrectomy, underwent a 75-g OGTT, and the plasma concentrations of glucose and insulin were measured after OGTT. RESULTS: Glucose peaked at 30 min in the distal gastrectomy patients and 60 min in the total gastrectomy patients, and there were significant differences in the 1-h plasma glucose (PG) and 1.5-h PG levels between the distal and total gastrectomy patients. Insulin peaked at 60 min in both the distal and total gastrectomy patients, and there were significant differences in insulin levels at 60 min between the distal and total gastrectomy patients. The incidence of postchallenge hyperglycemia in the patients after a total gastrectomy (57.1%) was higher than in those after distal gastrectomy (27.8%). Moreover, significant positive correlations were found between 1-h PG and hemoglobin antigen HbA1c after a total gastrectomy but not after a distal gastrectomy. CONCLUSIONS: These results suggest that postchallenge hyperglycemia after OGTT may become more exacerbated after a total gastrectomy than after a distal gastrectomy. Postprandial hyperglycemia, especially after a total gastrectomy, may therefore be involved in the development of diabetes.

Edaravone improves the survival of rats subjected to hemorrhagic shock without resuscitation.

Our aim in this study was to find out whether edaravone (3-methyl-1-phenyl-pyrazolin-5-one, MCI-186), a novel free radical scavenger, improved the survival rate in a rat hemorrhagic shock (HS) model. Fifty male Sprague-Dawley rats were divided randomly into an edaravone group and a saline group. Both groups were subjected to HS by inducing a mean arterial pressure of 30 mmHg for 60 min without resuscitation. The edaravone group was divided into four subgroups based on when edaravone was given: 0, 15, 30, or 60 min after HS. The saline group was given saline immediately after HS. We evaluated the 24-h survival rate in each group. The survival rate of the edaravone subgroup given edaravone immediately after HS was significantly better than that of the saline group. Edaravone improved the survival rate in a rat HS without resuscitation model. Edaravone was most effective when given immediately after HS.

Transient receptor potential vanilloid 1 antagonist, capsazepine, improves survival in a rat hemorrhagic shock model.

OBJECTIVE: To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ). SUMMARY BACKGROUND DATA: TRPV1, distributed within the sensory nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be involved in the cardiovascular responses to HS. METHODS: Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 micromol/kg) was administered at 30 minutes after the shock induction, and the 24-hour survival rates were assessed. The MAP, heart rate, and shed blood volume (SBV) were recorded throughout the experiment. Arterial blood gas analysis and the plasma catecholamines levels were measured before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain. RESULTS: CPZ significantly improved the 24-hour survival rates, which was accompanied by the increase in the MAP and the SBV, a decrease of the plasma catecholamines levels, and attenuation of the severe metabolic acidosis. Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH in the RVLM of the rat brain. CONCLUSIONS: TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.

Endotoxin apheresis for sepsis.

The principle use of apheresis in the treatment of sepsis may be summarized as the removal of toxic substances and the restoration of normal organs function. It is ideal to control the early phases of inflammatory cascade when treating sepsis by removing microbial components, such as endotoxin or peptidoglycan. This review discusses endotoxin apheresis with particular emphasis on treatment using polymyxin B immobilized fiber columns (Toraymyxin) which are used widely in Japan for endotoxin removal therapy in patients with septic shock. Lixelle and CTR which have recently been shown to remove circulating bacterial components are also included in this review.

Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis.

BACKGROUND: Adiponectin is an anti-inflammatory cytokine that is specifically and abundantly produced by adipocytes as a secretory protein. A direct interaction between adiponectin and lipopolysaccharide (LPS) is not fully understood. To elucidate the effects of adiponectin on LPS, we first investigated interactions between recombinant adiponectin and LPS. MATERIALS AND METHODS: Various concentrations of LPS (50, 500, and 5000 pg/ml) and recombinant adiponectin (1, 10, and 100 microg/ml) were incubated for 1 h. The limulus amoebocyte lysate (LAL) activities in the mixture were measured. Interactions between adiponectin (100 microg/ml) and LPS (100 and 300 microg/ml) were also analyzed in Western blotting. Next, we determined plasma adiponectin, tumor necrosis factor-alpha (TNF-alpha), and endotoxin levels at 1.5, 3, and 24 h after onsets of rodent polymicrobial sepsis induced by cecal ligation and puncture (CLP). RESULTS: The incubation with adiponectin significantly and dose-dependently suppressed LAL activity in the mixture compared to control. Western blotting revealed that adiponectin incubated with LPS shifted to a higher mass. In the animal model of sepsis, both plasma endotoxin and TNF-alpha levels after CLP gradually increased and were significantly higher at 3, 24 h compared to those after sham operation. On the contrary, plasma adiponectin levels after CLP gradually decreased and were significantly lower at 3, 24 h compared to those after sham operation. Plasma adiponectin levels were negatively correlated with plasma endotoxin levels (r = -0.77, P < 0.01). CONCLUSIONS: Our results indicate that adiponectin might neutralize LPS in vitro and diminish LPS activity in rats with polymicrobial sepsis. These findings suggest that the anti-inflammatory effects of adiponectin are in part likely because of neutralization of LPS activity.

A possible role of GLP-1 in the pathophysiology of early dumping syndrome.

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.