Effective treatment of gallbladder neuroendocrine carcinoma with nivolumab.

An 89-year-old patient with gallbladder neuroendocrine neoplasms (GB-NENs) and lung cancer metastasis underwent nivolumab monotherapy, resulting in tumor shrinkage. Surgery and adjuvant nivolumab showed efficiency despite low expression of PD-L1.

Comparison of Gastric Emptying Time after the Ingestion of Whisky with Isocalorically Adjusted Glucose Solution.

Previous studies have shown that the liquid gastric emptying mainly depended on energy content, regardless of compositional differences. But the gastric emptying of alcoholic beverages remains unclear. Therefore, we performed the present study to compare gastric emptying times between whisky mixed with water and glucose solution with uniform energy contents and volumes. As a crossover study, 10 healthy male volunteers ingested one of 3 test solutions with a uniform volume of 150 ml, i.e., whisky with water-containing whisky 30 ml (67 kcal), sugar water containing glucose 16.8 g (67 kcal), and water (0 kcal), and the gastric emptying time of each beverage was then assessed by ultrasound measurements of the gastric antral cross-sectional area. The gastric emptying pattern of whisky with water was faster than that of isocaloric sugar water, but slower than that of water. Each antral cross-sectional area 20, 30, and 40 min after the ingestion of sugar water was significantly larger than that of whisky with water. Antral cross-sectional areas 10 and 20 min after the ingestion of water were significantly smaller than those of whisky with water. In conclusion, the gastric emptying time of whisky would be faster than that of isocaloric glucose solution and slower than that of water. Unlike the other beverages, the gastric emptying time of alcohol drinks does not purely depend on the energy content because alcohol itself has no calorie before absorption. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000034443).

Ascending colon stenosis caused by repeated diverticulitis that clinically mimicked advanced colon cancer: A case report.

INTRODUCTION: We experienced a rare case of right-sided large bowl obstruction (LBO) of the colon caused by chronic diverticulitis, which was challenging to diagnose. PRESENTATION OF CASE: A young male was admitted to our department with a fever, diarrhea, and right-sided lateral abdominal pain for several days. CT showed a thickened ascending colon wall with stenosis and adjacent retroperitoneal inflammation without marked diverticula. The next day, he developed severe abdominal pain, and perforation was suspected. We chose the "interval definitive surgery"; at that time, intestinal decompression and laparoscopic drainage. Colonoscopy showed an edematous membrane, but no cancerous lesions or diverticula. Hemi-colectomy was performed after 10 days' nutritional therapy. No postoperative complication occurred. The histopathology showed that the pathogenesis was chronic diverticulitis. DISCUSSION: There have been few reported cases of right-sided LBO caused by diverticulitis, but it is important to be aware that benign disease, such as chronic diverticulitis, can cause LBO. Initial conservative therapy and nutritional therapy produced a correct diagnosis and good outcomes. CONCLUSION: Performing "interval surgery" allowed us to make an accurate diagnosis and may help to prevent surgical complications in rare cases of right-sided LBO due to diverticulitis.

Two cases of splenic neoplasms with differing imaging findings that required laparoscopic resection for a definitive diagnosis.

INTRODUCTION AND IMPORTANCE: Splenic tumors are rare and are sometimes found incidentally. In such cases, laboratory tests and imaging studies should be performed based on the diagnostic algorithm to determine whether the tumor is benign or malignant. However, we clinicians sometimes encounter challenging cases. Herein we experienced two challenging cases of splenic tumor which we could not correctly diagnosis preoperatively. CASE PRESENTATION: Case 1: A female in her 80s presented to our surgical department to undergo follow-up examinations for Stage IIIa ascending colon cancer. A follow-up CT scan showed marked enlargement of the splenic tumor which suggested metastatic cancer. We performed laparoscopic splenectomy. Case 2: A healthy female in her 50s presented to our internal medicine department to undergo a workup after multiple splenic tumors. A follow-up CT scan showed that the tumors had grown slightly. We could not completely rule out a malignant tumor. She rejected further follow-up study and chose splenectomy. CLINICAL DISCUSSION: We experienced two cases of splenic hemangioma with different clinical presentations and imaging findings. Although some studies have reported that biopsying a splenic tumor is a safe and effective way of distinguishing among splenic tumors, in our country splenic biopsies are seldom performed due to fears of causing intraabdominal bleeding or tumor dissemination. Clinicians should consider whether it would be better to perform follow up with a biopsy or splenectomy as a definitive treatment on a case-by-case basis. CONCLUSION: Laparoscopic splenectomy can be used for definitive management in cases involving malignancy or an uncertain etiology.

A case of a pulmonary artery sling misdiagnosed as refractory asthma for 20 years.

We report the case of a 25-year-old woman with a pulmonary artery sling who was misdiagnosed as having childhood-onset refractory asthma for approximately 20 years. The use of computed tomography may be useful for diagnosing this rare condition.

What is the manner of gastric emptying after ingestion of liquids with differences in the volume under uniform glucose-based energy content?

BACKGROUND & AIMS: We previously demonstrated that the gastric emptying rate of liquids chiefly depended on the total amount of calories (energy content) in a uniform volume. The aim of the present study was to examine the effects of different volumes of liquids with a uniform energy content on gastric emptying. METHODS: Three types of test solutions were prepared with a uniform amount of calories (200 kcal provided by glucose) and step-wise increments in volume (200 ml, 400 ml, and 600 ml). The gastric volume of each solution was determined by ultrasound measurements of the gastric antral cross-sectional area after their ingestion by 8 healthy volunteers. RESULTS: The mean gastric volume decreased exponentially to nearly 0 ml 70 min after ingestion in the 200 ml group, 90 min in the 400 ml group, and 100 min in the 600 ml group. Each gastric emptying curve converged with identical slopes on the graph when the points at which the gastric emptying curves of the 200 ml and 400 ml groups reached the zero point on the Y-axis (mean gastric volume) were shifted toward 110 min on the X-axis (time scale). CONCLUSIONS: The volume of liquid ingested with a uniform glucose-based energy content is a critical determinant of liquid gastric emptying. The gastric emptying time may be predicted following the ingestion of an isocaloric liquid with any volume over a predefined range once a gastric emptying curve following the ingestion of a liquid has been plotted on a graph. TRIAL REGISTRY NUMBER: UMIN000014930.

The first case of POEMS syndrome with synchronous breast cancer: What are the associated diagnostic challenges?

Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes (POEMS) syndrome is a rare plasma cell disorder that causes a paraneoplastic syndrome. We report the first case of POEMS syndrome with synchronous breast cancer. The patient was at risk of being misdiagnosed with metastatic cancer, and it is important to emphasize that physical examinations provided vital diagnostic clues.

[EFFECTS AND LIMITATIONS OF PREOPERATIVE CARBOHYDRATE LOADING: A REVIEW FROM THE VIEWPOINT OF ITS MECHANISM OF ACTION].

Preoperative carbohydrate loading has been adopted as an integral part of many enhanced-recovery or fast-track surgery programs. The main aim is to reduce postoperative insulin resistance (IR), thereby allowing for effective postoperative nutrition with more anabolic properties and less risk of hyperglycemia, which may improve postoperative outcomes. Based on the mechanism underlying postoperative IR, preoperative carbohydrate loading can inhibit only the exacerbating peripheral IR caused by excessive circulating concentrations of free fatty acids secondary to starvation but not the peripheral and central IR induced by stress hormones and inflammatory cytokines released as part of the surgical stress response, suggesting that preoperative carbohydrate loading may have only limited benefit. The Cochrane review of the effects of preoperative carbohydrate treatment (published in 2014) provided results that were completely consistent with the legitimate expectation described above, i.e., a small reduction of uncertain clinical significance in the length of hospital stay and little or no effect on postoperative complications or other important clinical outcomes, despite increased postoperative peripheral insulin sensitivity. Because preoperative carbohydrate loading has only limited benefit both theoretically and clinically, we should complement its effect through the introduction of a less-invasive approach capable of attenuating surgical stress-mediated IR.

A long-term follow-up result of pouch plasty for severe dysfunction of jejunal pouch reconstruction after total gastrectomy: a case report.

A 78-year-old woman with malignant lymphoma of the stomach underwent total gastrectomy with a jejunal-pouch (J-pouch) reconstruction in 1994. Twelve years after surgery the patient began to suffer epigastric distress and reflux symptoms. Eventually, she was unable to take anything by mouth. A series of diagnostic images seemed to indicate that the main cause of the dysfunction was flaccidity of the J-pouch and deformity of the outflow route induced by chronic excessive dilatation of the pouch wall. Because all conservative managements only led to temporary improvement and ended in failure, she hoped to receive the operation. We designed "pouch plasty" capable of ameliorating the pouch dysfunction. The aim of pouch plasty was to improve uneven tension of the pouch wall and repair deformity of the outflow route of the food. After the operation, the J-pouch resumed adequate drainage and had good reservoir function. More than 7 years later, the patient had no further complications.

Primary rectal diffuse large B-cell lymphoma associated with ulcerative colitis: a case report.

We need to be aware of primary intestinal lymphoproliferative disease (PILD) associated with ulcerative colitis (UC). We should carefully monitor UC patients, particularly patients who meet the following conditions; a previous Epstein-Barr virus infection, treatment duration ≧4 years, male, and age ≧50 years.

Proton beam therapy combined with concurrent chemotherapy for esophageal cancer.

BACKGROUND/AIM: The aim of the present study was to evaluate the outcomes of proton beam therapy (PBT) concurrently combined with chemotherapy consisting of cisplatin and 5-fluorouracil for esophageal cancer. PATIENTS AND METHODS: Forty consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE) in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when residual tumors were suspected. The median follow-up time was 24 months (range=7-66 months). RESULTS: No cardio-pulmonary toxicities of grade 3 or higher were observed. Recurrences were observed in 16 patients, and the 2-year rates of disease-specific survival and locoregional control were 77% and 66%, respectively. CONCLUSION: Irrespective of the small sample size and short follow-up time of the study, proton beam therapy combined with chemo therapy seems to be feasible for esophageal cancer.

The negative impact of insulin therapy for acute hyperglycemia secondary to glucose load on plasma amino acid profiles in a rat model of sepsis.

BACKGROUND: In critical illnesses, insulin therapy under overfed conditions with an excessive glucose infusion may cause metabolic disturbances in skeletal muscle mainly through muscle cell glucose uptake and the inhibition of physiological protein breakdown. The aim of this study was to examine the potential negative aspects of insulin therapy in a rat model of sepsis. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham surgery. A pre-established continuous intravenous glucose infusion was initiated immediately after surgery. Rats with sepsis were divided into four groups (n = 7 in each group) based on target blood glucose (BG) levels: a no glucose (NG) group (100-150 mg/dl), moderate glucose (MG) group (200-300 mg/dl), high glucose (HG) group (>300 mg/dl), and the hyperinsulinemia (HI) group, which received the same glucose infusion as the HG group with the insulin infusion (200-300 mg/dl). The sham group underwent sham surgery and received the same glucose infusion as the HG group. All rats were sacrificed 9 h after surgery, and blood samples were collected to measure plasma amino acid (AA) profiles. To examine survival rates in the 48 h following CLP, the HG, MG, and HI groups were newly prepared according to the aforementioned experimental design. RESULTS: Plasma levels of the branched-chain AAs, glutamine, arginine, citrulline, and alanine among the septic groups slightly and inversely decreased with the amount of glucose infused, and HI had significantly lower values (p < 0.01). A strong correlation was observed among the AAs. Plasma 3-methylhistidine concentrations were the highest in the HI group. The survival rate of the HI group was greater than that of the HG, but did not reach the level of the MG group. CONCLUSION: In critical illnesses, insulin therapy under overfed conditions may impair the physiological supply of AAs and conditionally essential AA starvation, such as glutamine and arginine, and may have an adverse impact on the prognosis of patients.

The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis.

BACKGROUND: The aim of the study was to investigate both the inflammation-boosting effect and the metabolic stress induced by acute hyperglycemia secondary to overfeeding with excessive glucose infusion and the effects of insulin therapy on those events in a rat model of sepsis. MATERIALS AND METHODS: Sprague-Dawley rats underwent cecal ligation and puncture (CLP) or sham operation. Preestablished continuous intravenous glucose infusion was initiated immediately after surgery. First, rats with CLP-inducing sepsis were divided into three groups on the basis of the target blood glucose (BG) levels: high glucose (HG) group (overfed, >300 mg/dL), moderate glucose group (moderate hyperglycemia, 200-300 mg/dL), and no glucose group (100-150 mg/dL). The sham group received the same glucose infusion as that of the HG group. BG and plasma interleukin (IL) 6 levels were monitored over time. All rats were sacrificed 9 h after surgery to evaluate lung histology and measure hepatic total glutathione and malondialdehyde contents. Based on the results, the high glucose and insulin (HI) group was added to septic groups as a model of insulin therapy, in which insulin with the same HG dose as that in the HG group was administered to maintain moderate hyperglycemia. RESULTS: BG level in all groups remained in the preestablished target range throughout the experiment. Plasma IL-6 level in all septic groups increased in a time-dependent manner, whereas that in the sham group with moderate hyperglycemia hardly increased. Nine hours after CLP, plasma IL-6 level in the HG group rose to 7407.5 ± 1987.3 pg/mL, which was three times higher than that in the other septic groups. There was no significant difference among moderate glucose, no glucose, and HI groups, in which BG level remained constant at <300 mg/dL. The HG group showed the worst consequences of lung injury and oxidative stress in the liver, which were completely stable in HI group. CONCLUSIONS: Acute severe hyperglycemia in critical illness might excessively boost the existing systemic inflammatory response in a threshold-based manner. Insulin therapy under overfeeding could strongly inhibit such a boosting effect and oxidative stress in the liver.

A stand-alone synbiotic treatment for the prevention of D-lactic acidosis in short bowel syndrome.

Synbiotics are combinations of probiotics and prebiotics that have recently been used in the context of various gastrointestinal diseases, including infectious enteritis, inflammatory bowel disease, and bowel obstruction. We encountered a patient with recurrent D-lactic acidosis who was treated successfully for long periods using synbiotics. The patient was diagnosed as having short bowel syndrome and had recurrent episodes of neurologic dysfunction due to D-lactic acidosis. In addition to fasting, the patient had been treated with antibiotics to eliminate D-lactate-producing bacteria. After the failure of antibiotic treatment, a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction. Synbiotics allowed the reduction in colonic absorption of D-lactate by both prevention of D-lactate-producing bacterial overgrowth and stimulation of intestinal motility, leading to remission of D-lactate acidosis.

Effects of platelet-rich plasma on intestinal anastomotic healing in rats: PRP concentration is a key factor.

BACKGROUND: Few studies have examined the effects of platelet-rich plasma (PRP) on intestinal anastomotic healing. The applied preparation methods and PRP concentrations used in the few studies that have been carried out varied markedly. Therefore, the positive effects of PRP on the anastomotic healing process remain unclear. The aim of this study is to examine the effects of different concentrations of PRP on intestinal anastomotic healing. MATERIAL AND METHODS: From SD rat blood, three different concentrations of plasma were prepared: high-concentrated PRP (H-PRP: platelet count 5 × 10(6)/mm(3)), low-concentrated PRP (L-PRP: 2 × 10(6)/mm(3)), and platelet-poor plasma (PPP). Male SD rats underwent proximal jejunal anastomosis and central venous catheterization. Rats were divided into four groups (n = 12 for each group): control, PPP, L-PRP, and H-PRP groups. Two types of PRP and PPP (0.21 mL) were applied to each anastomosis line, with the exception of the control group. Total parenteral nutrition (TPN) solutions were administered (151 kcal/kg/d). Five days after surgery, anastomotic bursting pressure (ABP) in situ and hydroxyproline concentration (HYP) in anastomotic tissue were evaluated. RESULTS: The ABP values of control, PPP, L-PRP, and H-PRP groups were 171 ± 20, 174 ± 23, 189 ± 17, and 148 ± 25 mmHg, respectively. The HYP values of each group were 516 ± 130, 495 ± 123, 629 ± 120, and 407 ± 143 µg/g dry tissue. Compared with the other groups, the L-PRP group exhibited a significant increase in both ABP and HYP, while the H-PRP group exhibited a significant decrease in these two variables. As a result, L-PRP was considered to promote anastomotic wound healing, but H-PRP was considered to inhibit it. There was no significant difference between the PPP group and the control group. CONCLUSIONS: PRP concentration plays a crucial role in the efficacy of PRP. PRP might exert positive effects on intestinal anastomotic healing in a dose-dependent manner up to a certain level, but adverse effects occur when it is highly concentrated. The essential PRP action appears to be driven by the platelets themselves.

Hyperfractionated concomitant boost proton beam therapy for esophageal carcinoma.

PURPOSE: To evaluate the efficacy and safety of hyperfractionated concomitant boost proton beam therapy (PBT) for patients with esophageal cancer. METHODS AND MATERIALS: The study participants were 19 patients with esophageal cancer who were treated with hyperfractionated photon therapy and PBT between 1990 and 2007. The median total dose was 78 GyE (range, 70-83 GyE) over a median treatment period of 48 days (range, 38-53 days). Ten of the 19 patients were at clinical T Stage 3 or 4. RESULTS: There were no cases in which treatment interruption was required because of radiation-induced esophagitis or hematologic toxicity. The overall 1- and 5-year actuarial survival rates for all 19 patients were 79.0% and 42.8%, respectively, and the median survival time was 31.5 months (95% limits: 16.7- 46.3 months). Of the 19 patients, 17 (89%) showed a complete response within 4 months after completing treatment and 2 (11%) showed a partial response, giving a response rate of 100% (19/19). The 1- and 5-year local control rates for all 19 patients were 93.8% and 84.4 %, respectively. Only 1 patient had late esophageal toxicity of Grade 3 at 6 months after hyperfractionated PBT. There were no other nonhematologic toxicities, including no cases of radiation pneumonia or cardiac failure of Grade 3 or higher. CONCLUSIONS: The results suggest that hyperfractionated PBT is safe and effective for patients with esophageal cancer. Further studies are needed to establish the appropriate role and treatment schedule for use of PBT for esophageal cancer.

Early postoperative oral intake accelerates upper gastrointestinal anastomotic healing in the rat model.

BACKGROUND: In our previous study, we reported that early postoperative oral feeding accelerated upper gastrointestinal anastomotic healing in rats. To investigate its underlying mechanism, we performed in vivo and in vitro experiments. MATERIALS AND METHODS: Rats that received proximal jejunal anastomosis were divided into four groups: the enteral nutrition (EN) group were fed via gastrostomy, the total parental nutrition (TPN alone) group were fed via a venous catheter, the TPN + saline group received an additional administration of normal saline solution via gastrostomy, and the TPN + water group received an additional administration of distilled water via gastrostomy. The anastomotic bursting pressure (ABP) and the hydroxyproline content of the anastomotic tissue were measured 5 d postoperatively. In an in vitro setting, the rat gastrointestinal fibroblasts were subjected to uniaxial stretching for 60 min, and the expression of type I and type III collagen mRNA was evaluated. RESULTS: The ABP and hydroxyproline content in the EN group, the TPN + saline group, and the TPN + water group were significantly higher than those in the TPN alone group (ABP; 214.6 ± 42, 199.4 ± 36, and 187.3 ± 29 versus 149.5 ± 49 mmHg; P < 0.01, hydroxyproline; 63.5 ± 10, 67.8 ± 13, and 64.1 ± 14 versus 50.5 ± 12 µmol/g dry tissue; P < 0.01). The mRNA levels of type I and type III collagen were increased by stretch stimulation. CONCLUSIONS: These results suggest that mechanical loading plays a key role in anastomotic healing. Further investigations are necessary to confirm this suggestion.

Clinical results of proton-beam therapy for locoregionally advanced esophageal cancer.

PURPOSE: To evaluate the efficacy and safety of proton-beam therapy for locoregionally advanced esophageal cancer. PATIENTS AND METHODS: The subjects were 51 patients with esophageal cancer who were treated between 1985 and 2005 using proton beams with or without X-rays. All but one had squamous cell carcinoma. Of the 51 patients, 33 received combinations of X-rays (median 46 Gy) and protons (median 36 GyE) as a boost. The median total dose of combined X-rays and proton radiation for these 33 patients was 80 GyE (range 70-90 GyE). The other 18 patients received proton-beam therapy alone (median 79 GyE, range 62-98 GyE). RESULTS: Treatment interruption due to radiation-induced esophagitis or hematologic toxicity was not required for any patient. The overall 5-year actuarial survival rate for the 51 patients was 21.1% and the median survival time was 20.5 months (95% confidence interval 10.9-30.2). Of the 51 patients, 40 (78%) showed a complete response within 4 months after completing treatment and seven (14%) showed a partial response, giving a response rate of 92% (47/51). The 5-year local control rate for all 51 patients was 38.0% and the median local control time was 25.5 months (95% confidence interval 14.6-36.3). CONCLUSION: The results suggest that proton-beam therapy is an effective treatment for patients with locally advanced esophageal cancer. Further studies are required to determine the optimal total dose, fractionation schedules, and best combination of proton therapy with chemotherapy.