[A Case of Adenocarcinoma of Pancreatic Head of Liver Disfunction after Pancreaticoduodenectomy with Celiac Artery Stenosis Treated by Urgent Median Arcuate Ligament Release].

This patient visited our hospital for the purpose of detailed examination of prostate cancer in his seventies. Abdominal contrast-enhanced computed tomography(CT)revealed a low-density mass of 2 cm in the pancreatic head. He was diagnosed with pancreatic cancer. Pancreaticoduodenectomy was performed after 2 courses of gemcitabine and S-1 therapy were performed as neoadjuvant chemotherapy. An intraoperative clamp test of the gastroduodenal artery showed that the pulsation of the common hepatic artery and the proper hepatic artery was weak but sufficient, so the gastroduodenal artery was cut and the operation was completed as planned. A blood test on the 1st day after the operation showed elevated levels of AST 537 U/L, ALT 616 U/L, and 7 hours later blood sampling showed further increases in AST 1,455 U/L, ALT 1,314 U/L. After a detailed review of the preoperative CT, celiac artery stenosis due to compression of the arcuate ligament was suspected, and urgent median arcuate ligament release was performed on the same day. Dissection of the arcuate ligament significantly improved the pulsation of the common hepatic artery and proper hepatic artery. Postoperatively, hepatic enzymes improved and ISGPS showed Grade B pancreatic juice leakage, but the patient was discharged from the hospital on the 49th postoperative day without any other complications. He took S-1 as adjuvant chemotherapy, and no signs of recurrence have been observed 9 months after the operation.

Caldomycin, a new guanidopolyamine produced by a novel agmatine homocoupling enzyme involved in homospermidine biosynthesis.

An extreme thermophilic bacterium, Thermus thermophilus produces more than 20 unusual polyamines, but their biosynthetic pathways, including homospermidine, are not yet fully understood. Two types of homospermidine synthases have been identified in plants and bacteria, which use spermidine and putrescine or two molecules of putrescine as substrates. However, homospermidine synthases with such substrate specificity have not been identified in T. thermophilus. Here we identified a novel agmatine homocoupling enzyme that is involved in homospermidine biosynthesis in T. thermophilus. The reaction mechanism is different from that of a previously described homospermidine synthase, and involves conjugation of two molecules of agmatine, which produces a diamidino derivative of homospermidine (caldomycin) as an immediate precursor of homospermidine. We conclude that there is a homospermidine biosynthetic pathway from agmatine via caldomycin synthase followed by ureohydrolase in T. thermophilus. Furthermore, it is shown that caldomycin is a novel compound existing in nature.

Putrescine Biosynthesis from Agmatine by Arginase (TtARG) in Thermus thermophilus.

In the three domains of life, three biosynthetic pathways are known for putrescine. The first route is conversion of ornithine to putrescine by ornithine decarboxylase (ODC: SpeC), the second route is the conversion of arginine to agmatine by arginine decarboxylase (ADC: SpeA), followed by the conversion of agmatine to putrescine by agmatine ureohydrolase (AUH: SpeB), and the third route is the conversion of agmatine to N-carbamoylputrescine by agmatine deiminase (agmatine iminohydrolase, AIH), followed by the conversion of N-carbamoylputrescine to putrescine by N-carbamoylputrescine amidohydrolase (NCPAH). An extreme thermophile, Thermus thermophilus produces putrescine, although this bacterium lacks homologs for putrescine synthesizing pathways, such as ODC, AUH, AIH and NCPAH. To identify genes involved in putrescine biosynthesis in T. thermophilus, putrescine biosynthesis was examined by disruption of a predicted gene for agmatinase (agmatine ureohydrolase), or by using purified enzyme. It was found that arginase (TTHA1496) showed an agmatinase activity utilizing agmatine as a substrate. These results indicate that this bacterium can use arginase for putrescine biosynthesis. Arginase is a major contributor to putrescine biosynthesis under physiological conditions. The presence of an alternative pathway for converting agmatine into putrescine is functionally important for polyamine metabolism supporting survival at extreme environments.

[A Case of Strangulated Bowel Obstruction after a Laparoscopic Hartmann's Operation for Rectal Cancer].

A 98-year-old woman presented with hematochezia and a circumferential type 2 tumor in the rectum Rb identified on fiberoscopy. We a performed laparoscopic Hartmann's operation and D2 lymphadenectomy for advanced rectal cancer. A sigmoid colostomy was created via the intraperitoneal route. On the postoperative day 12, the patient experienced abdominal pain. Computed tomography showed that the small intestine formed a closed loop in the pelvic space. The patient was diagnosed with a strangulated bowel obstruction of the small intestine for which an emergency exploratory laparotomy was performed. The small intestine, which had passed through a defect between the lifted sigmoid colon and the left abdominal wall, was strangulated by the lifted sigmoid colon. We performed partial resection of the small intestine. The patient died on postoperative day 32 of acute deterioration of aortic valve stenosis. There have been few reports of strangulated bowel obstruction resulting from internal hernia associated with colostomy. These findings demonstrate that it is important to select the appropriate route for colostomy creation in each case.

Alkaline Stress Causes Changes in Polyamine Biosynthesis in Thermus thermophilus.

An extreme thermophile, Thermus thermophilus, produces 16 different polyamines including long-chain and branched-chain polyamines. The composition and content of polyamines in the thermophile cells change not only with growth temperature but also with pH changes. In particular, cell growth decreased greatly at alkaline medium together with significant changes in the composition and content of polyamines. The amounts of tetraamines (spermine and its homologs) markedly decreased at alkaline pH. Thus, we knocked out the speE gene, which is involved in the biosynthesis of tetraamines, and changes of composition of polyamines with pH changes in the mutant cells were studied. Cell growth in the ΔspeE strain was decreased compared with that of the wild-type strain for all pHs, suggesting that tetraamines are important for cell proliferation. Interestingly, the amount of spermidine decreased and that of putrescine increased in wild-type cells at elevated pH, although T. thermophilus lacks a putrescine synthesizing pathway. In addition, polyamines possessing a diaminobutane moiety, such as spermine, decreased greatly at high pH. We assessed whether the speB gene encoding aminopropylagmatine ureohydrolase (TtSpeB) is directly involved in the synthesis of putrescine. The catalytic assay of the purified enzyme indicated that TtSpeB accepts agmatine as its substrate and produces putrescine due to the change in substrate specificity at high pH. These results suggest that pH stress was exacerbated upon intracellular depletion of polyamines possessing a diaminobutane moiety induced by unusual changes in polyamine biosynthesis under high pH conditions.

[A Case of Liver Metastasis Complete Resection for Concurrent Overlapping Cancer of the Transverse Colon and Renal Cell Carcinomas that were Difficult to Differentiate from Hepatocellular Carcinoma].

A 79-year-old man visited the hospital because of constipation. Colonoscopy showed a transverse colon carcinoma. Dynamic CT showed a renal neoplastic lesion and 2 lesions in the liver with early staining and late wash out, and the liver lesions showed ring enhancement on EOB-MRI. The preoperative diagnosis was either transverse colon cancer, renal cell carcinoma, hepatocellular carcinoma, or metastatic liver cancer. The patient underwent partial transverse colon resection, partial right nephrectomy, and partial hepatic resection. Additional to the 2 liver lesions in S6, an intraoperative ultrasound showed 1 tumor in S5; therefore, 3 partial hepatectomies were performed. Histopathological findings revealed that the tumors in S5 and S6 were liver metastases of transverse colon cancer and renal cell carcinoma, respectively. The final diagnosis was transverse colon cancer, pT4a, pN0, pM1, pStage Ⅳa and papillary renal cell carcinoma, pT1a, pN0, pM1, pStage Ⅳ. For 9 months postoperatively, there was no apparent recurrence.

[A Case of Retroperitoneal Leiomyosarcoma Resected Radically by Pancreaticoduodenectomy with Vascular Resection].

A 54-year-old woman visited to a doctor nearby medical clinic complaining of loss of appetite. She was diagnosed with right hydronephrosis on abdominal ultrasonography, and referred to our hospital for further examination. Contrast abdominal computed tomography(CT)revealed that a 6.2 cm tumor with a contrast-enhancing effect inside in the retroperitoneum near the lower pole of the right kidney. She was diagnosed with hydronephrosis due to infiltration of the right kidney of a retroperitoneal tumor. The tumor was suspected of invading the duodenum and inferior vena cava, but no obvious lymph node or distant metastasis was observed. Abdominal MRI revealed a tumor showed hyperintensity on T2-weighted and diffusion-weighted images. We performed pancreaticoduodenectomy with inferior vena cava resection and right nephrectomy. The pathological diagnosis was leiomyosarcoma originating from retroperitoneum and pT2, pN0, pM0, pStage ⅢA. The postoperative course was good, and she was discharged 10 days after the operation. Thoracoabdominal CT showed a tumor 4 cm at the hepatic hilum three months after surgery, and EOB-MRI showed many tumors other than the same site, so multiple liver metastases were diagnosed as recurrence. Doxorubicin has been started and is still being treated.

APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation.

BACKGROUND: Mutations in p53, identified in 90% of oesophageal squamous cell carcinoma (ESCC), are associated with unfavourable prognosis and chemo-resistance. APR-246 induces apoptosis by restoring transcriptional ability of mutant p53, and may be a promising therapeutic agent to overcome chemo-resistance in ESCC. METHODS: In ESCC cell lines differing in p53 status, we performed in vitro cell viability and apoptosis assays, evaluated reactive oxygen species (ROS) generation, and assessed signal changes by western blot after APR-246 administration with/without chemo-agent. Antitumour effects and signal changes were evaluated in in vivo experiments using xenograft and patient-derived xenograft (PDX) mouse models. RESULTS: APR-246 administration induced significant apoptosis by upregulating p73 and Noxa via ROS induction in ESCC cell lines harbouring p53 missense mutations. Moreover, APR-246 plus chemotherapy exerted combined antitumour effects in ESCC with p53 missense mutations. This effect was also mediated through enhanced ROS activity, leading to massive apoptosis via upregulation of p73 and Noxa. These findings were confirmed by xenograft and PDX models with p53 mutant ESCC. CONCLUSION: APR-246 strongly induced apoptosis by inducing ROS activity and p73-Noxa signalling, specifically in ESCC with p53 missense mutation. This antitumour effect was further enhanced by combination with 5-FU, which we first confirmed in ESCC preclinical model.

Postoperative pneumonia in the acute phase is an important prognostic factor in patients with esophageal cancer.

BACKGROUND: The impact of pneumonia on prognosis is controversial, and no report has focused on its onset. This study aimed to examine the impact of pneumonia according to its onset on prognosis and its associated risk factors after esophagectomy. METHODS: In total, 484 patients who underwent curative resection for esophageal squamous cell carcinoma were retrospectively reviewed. Patients with pneumonia were divided into two groups by the date of onset: pneumonia in the acute phase within 7 days after surgery (n = 59) and pneumonia in the subacute phase 8 days after surgery (n = 49). RESULTS: The disease-free survival of patients with acute pneumonia was significantly lower than that of those without pneumonia (P = .0002), whereas the disease-free survival of patients with subacute pneumonia was similar to that of patients without pneumonia (P = .5363). In multivariate analysis for disease-free survival, P-stage III to IV (hazard ratio [HR], 3.344; P < .0001), transfusion (HR, 1.4078; P = .0291), and acute pneumonia (HR, 1.8463; P = .0009) were independent prognostic factors. Multivariate analysis revealed that age >75 years (odds ratio [OR], 2.1746; P = .0232), respiratory disease comorbidity (OR, 4.3869; P = .0002), cT3-4 (OR, 2.0143; P = .0477), extended surgery duration (OR, 2.3406; P = .0152), and posterior mediastinal reconstruction (OR, 0.1432; P = .0439) were independent risk factors for acute pneumonia. CONCLUSION: Post-esophagectomy pneumonia in the acute phase was an independent prognostic factor, whereas advanced age, respiratory disease comorbidity, and extended surgery duration were risk factors for acute pneumonia.

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.

Determination of Polyhexamethylene Biguanide Hydrochloride Using a Lactone-Rhodamine B-Based Fluorescence Optode.

A new determination method for polyhexamethylene biguanide hydrochloride (PHMB) using a lactone-rhodamine B (L-RB) based fluorescence optode has been developed. The optode membrane consists of 2-nitrophenyl octyl ether as a plasticizer, L-RB, and poly (vinyl chloride). The optode responds to tetrakis (4-fluorophenyl) borate, sodium salt (NaTPBF) in the µM range. The fluorescence intensity of the L-RB film for PHMB solution containing 20 µM NaTPBF decreased linearly as the concentration of the PHMB solution increased in the concentration range from 0 to 8.0 µM, which shows that PHMB with a concentration range of 0 to 8.0 µM is determined by the L-RB film optode. The concentration of PHMB in the contact lens detergents by the proposed method was in accord with its nominal concentration.

Successful Stenting Followed by Surgery for Perforated Esophageal Cancer Due to Chemotherapy.

Perforation of esophageal cancer solely due to preoperative chemotherapy is extremely rare, but can be associated with pyothorax and can be difficult to treat. Here, we report the case of a successfully treated patient with thoracic esophageal cancer who had esophageal perforation during docetaxel, cisplatin, and 5-fluorouracil chemotherapy. A 73-year-old patient had esophageal perforation on the fourth day of the first docetaxel, cisplatin, 5-fluorouracil cycle. The second docetaxel, cisplatin, 5-fluorouracil cycle was administered after insertion of esophageal stenting and subtotal esophagectomy. Early drainage and stent placement were crucial for achieving infection control and allowing for a subsequent complete resection.

[A Case Report - A Case of a Rapidly Growing Anal Canal Origin Malignant Melanoma].

An 85-year-old woman presented to her local physician in early August 2015 with a new-onset "swelling" of the anal region and was referred to our department for evaluation and treatment at the beginning of September. At our initial evaluation, the rectal examination showed a black mass lesion, approximately 3.0×1.5 cm in size, in the anal canal by November, the mass had grown to approximately 7.0×3.5 cm in size. The lesion was diagnosed as malignant melanoma by colonoscopic biopsy. Abdominal cystography computed tomography showed an area of lymphadenopathy around the rectum, but no distant metastasis was detected. The patient underwent abdominoperineal resection of the rectum in December. Her postoperative course was good, and she was discharged on the 30th postoperative day. Arecurrent lesion was detected at a recent follow-up examination(approximately 5 months post-discharge), and the patient has been scheduled for immunotherapy. Malignant melanoma of the anal canal has a poor prognosis, and no standard therapy has been established. This report includes a brief review of current literature about the disease.

[A Case of Angioimmunoblastic T-Cell Lymphoma Merged with Colorectal Cancer That We Were Able to Resect after a Chemotherapy Response].

The patient was 77-year-old man. He visited our hospital with the chief complaint of an abdominal mass in March 2015. We diagnosed the patient with transverse colon cancer and he was suspected of having malignant lymphoma. In March 2016, we attempted to perform right hemicolectomy for the transverse colon cancer, but it was difficult because swollen lymph nodes had formed a large mass with the surrounding tissue, including vessels of the mesentery. We could only complete the surgery after mesenteric lymph node biopsy. On the basis of the results of this biopsy, we diagnosed angioimmunoblastic Tcell lymphoma. At first, we administered THP-COP therapy for malignant lymphoma. However, after 3 courses of this therapy, the patient suddenly developed ileus due to the aforementioned colon cancer. According to enhanced CT performed at the onset of intestinal obstruction, chemotherapy dramatically reduced the size of the intraperitoneal lymph nodes. We therefore concluded that it was able to treat the colon cancer. We performed right hemicolectomy in June 2015. Angioimmunoblastic T-cell lymphoma comprises only 2-3% of all malignant lymphoma cases. We experienced a rare case of complications from angioimmunoblastic T-cell lymphoma and colorectal cancer.

[Successful Treatment of Local Recurrence of Advanced Gastric Cancer Using Curative Gastrectomy via Distal Pancreatectomy after Chemoradiotherapy].

The patient was a 65-year-old woman. She was diagnosed with advanced gastric cancer with liver invasion. After receiving systemic chemotherapy(S-1 plus PTX)for 3 months, she underwent total gastrectomy and partial hepatectomy in May 2008. Because she developed celiac artery circumference lymph node recurrence in November 2010 during postoperative adjuvant chemotherapy consisting of S-1 plus PTX, we changed her chemotherapy regimen to CPT-11 plus CDDP. We observed an increase in the size of the lymph nodes in August 2013 and the response was poor even after switching to DOC. However, the lymph nodes continued to increase in size and we administered radiotherapy of 60.4 Gy/33 Fr that resulted in shrinkage of the nodes. We observed an increase in lymph node size and pancreas invasion in September 2015, including an expansion of the mid pancreatic duct. We performed distal pancreatectomy without identifying the recurrence observed in November 2015 assuming it was an exacerbation. Six months after the surgery, the recurrence was not apparent. We report an example of long-term survival that was achieved for Stage IV gastric cancer. The patient underwent combined modality therapy for 8 years, and local recurrence was controlled via a primary operation.

[Two Cases of Small Intestinal Metastasis of Lung Cancer].

Case 1: A 66-year-old man who had undergone upper right lobe resection for large cell lung carcinoma 2 months earlier presented with abdominal pain and vomiting. Computed tomography showed intussusception of the small intestine. Partial resection of the small intestine was performed. The tumor was pathologically diagnosed as lung cancer metastasis to the small intestine. The patient died 30 days after surgery. Case 2: A 57-year-old man was admitted to hospital due to appetite loss. Computed tomography showed a large intestinal tumor and a small lung tumor, as well as multiple liver metastases and lymph node metastases. We diagnosed perforation of the small intestine tumor, and partial resection of small intestine was performed. Pathological examination and immunohistochemical staining revealed that the tumor was a metastatic adenocarcinoma, and the patient was diagnosed with small intestine metastasis of lung cancer. He died 75 days after surgery. Although small intestine metastasis of lung cancer is rare, the incidence is increasing. The prognosis of lung cancer metastasis of the small intestine is poor, and therefore, we must urgently decide the appropriate treatment.

[A Case in Which a Patient Was Operated for Intra-Abdominal Desmoid Tumors after Total Colectomy in FAP].

The patient was a 22-year-old woman with FAP, who had undergone laparoscopic total colectomy 3 years previously. She presented to our hospital with a high fever and abdominal pain. Large hard tumors were palpated in the right lower abdomen and pelvis. Blood examination showed an inflammatory response. CT scan revealed 17 cm diameter solid tumors. At surgery, 2 tumors arising from the mesentery of the small intestine were found, neither of which invaded any organs. We performed tumor extirpation with partial resection of the duodenum, ileum, right fallopian tube and rectum. A jejunal stoma was formed, leaving a length of remnant intestine of about 120 cm. The histopathological diagnosis was given as desmoid tumor with infection. The patient was discharged from the hospital on the 9th postoperative day. Desmoid tumor is the second most common cause of death in FAP patients. Although desmoids can also occur in the extremities, most FAP patients develop intra-abdominal tumors. Despite being histologically benign, they are locally infiltrative and can cause death through invasion and destruction of adjacent vital structures and organs. Here, we report a case of desmoid tumors with FAP with reference to the literature.

[Intraluminal Type Gastrointestinal Stromal Tumor Resected by Single-Incision Percutaneous Endoscopic Intragastric Surgery--A Case Report].

We report a patient with gastric gastrointestinal stromal tumor (GIST) who underwent single-incision percutaneous endoscopic intragastric surgery. The patient was a 70-year-old man. Esophagogastroduodenoscopy and abdominal computed tomography revealed the presence of an intraluminal type gastric submucosal tumor, 4 cm in diameter, in the posterior wall of the gastric body. Laparoscopic partial gastrectomy was performed via a single incision made in the epigastric region. The postoperative course was uneventful. The pathological diagnosis was a low-risk GIST. This method is easy and safe to perform; therefore, we consider it to be an important option for the treatment of intraluminal type gastric GIST.

[Clinical evaluation of the risk factors for liver abscess after TACE or RFA].

Radiofrequency ablation(RFA)and transcatheter arterial chemoembolization (TACE) are widely enforced as a standard combined therapy for liver cancer. Liver abscess occurs occasionally as a complication. This clinical study was conducted to determine risk factors for liver abscess. We investigated the clinical background of 10 cases complicated by liver abscess in 957 cases of patients who underwent TACE or RFA for liver cancer at Minoh City Hospital between April 2002 and March 2012. Risk factors for liver abscess were analyzed statistically in comparison to a control group without liver abscess. Diabetes and a history of biliary tract organic disease were statistically significant independent risk factors determined by multivariate analysis. We consider patients with a history of biliary tract organic disease, or who have a potential biliary tract infection, and diabetes, to be susceptible to infection. A case presenting with diabetes and a history of biliary tract disease is in a high-risk group, so treatment with TACE or RFA for such cases should be considered carefully.

Neuferricin, a novel extracellular heme-binding protein, promotes neurogenesis.

We identified a novel extracellular heme-binding protein and named it neuferricin. The recombinant mouse neuferricin produced in High Five cells was secreted efficiently into the culture medium. Mouse neuferricin mRNA was expressed mainly in the brain at the embryo stage and gradually increased during development. At postnatal stage, it was widely expressed in the brain, heart, adrenal gland, and kidney. Mouse neuferricin has 263 amino acids. It has a cytochrome b5-like heme/steroid-binding domain and appeared to bind hemin because neuferricin solution, but not a solution of neuferricinDeltaHBD (a mutant lacking the heme-binding domain), was tinged with brown and had an absorbance peak at 402 nm. In addition, the experiment with anti-neuferricin antibody using heme-affinity chromatography proved that the endogenous neuferricin detected in the culture medium of Neuro2a cells was associated with hemin. Inhibition of endogenous neuferricin by RNA interference excessively promoted cell survival and proliferation and suppressed neurite outgrowth during the induction of differentiation in Neuro2a cells. Addition of recombinant mouse neuferricin, but not neuferricinDeltaHBD, suppressed survival of Neuro2a cells and rescued from the effects of neuferricin RNAi. In primary cultured mouse neural precursor cells, recombinant mouse neuferricin exhibited the ability to promote neurogenesis. The identification of neuferricin, a novel extracellular heme-binding protein with cytochrome b5-like heme/steroid-binding domain and its neurogenic activity, provide new insights not only into brain development but also the function of heme-binding proteins as extracellular signal transmitters.