Early measurement of urinary N-acetyl-ß-glucosaminidase helps predict severe hyponatremia associated with cisplatin-containing chemotherapy.

BACKGROUND: Although cisplatin is a widely used anticancer drug for treating various types of cancer, its clinical application is limited by severe systemic toxicities, such as nephropathy, hematologic toxicity, and gastrointestinal toxicity. There are no reliable and validated biomarkers to predict adverse events caused by cisplatin. METHODS: Sixty-six patients who underwent cisplatin-containing first-line chemotherapy between June 2010 and November 2013 were retrospectively analyzed. Data on urinary N-acetyl-ß-glucosaminidase activities measured 24-48 h after cisplatin infusion were retrieved, and adverse events during the first course of chemotherapy were recorded according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Patient characteristics were: male/female 60/6, median age 65 (range 36-78) years, esophageal/gastric/other cancer 60/4/2, chemotherapy regimen docetaxel-cisplatin-fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/8/4, cisplatin dose (mg/sm) 60/70/80 16/43/7. Grade 3/4 adverse events were leukopenia (40.9%), neutropenia (54.4%), febrile neutropenia (37.9%), hyponatremia (28.8%), and acute kidney injury (37.9%). Patients with 20 units/gram creatinine or higher urinary N-acetyl-ß-glucosaminidase developed statistically lower minimum serum sodium concentration (median 126 vs. 134 mEq/L, p = 0.0053). There were no significant correlations between urinary N-acetyl-ß-glucosaminidase and the development of other severe adverse events. CONCLUSION: Early significant increase in urinary N-acetyl-ß-glucosaminidase predicts subsequent development of severe hyponatremia after cisplatin-containing chemotherapy.

Laparoscopic resection of a metachronous secondary lymph node metastasis in the mesentery of the ileum after surgery for sigmoid colon cancer with ileum invasion: a case report.

BACKGROUND: Extended excision of the permeation organ neighborhood is often performed in locally invasive colon cancer, and it is reported to have a survival benefit. In addition, some cases of secondary lymph node metastases in a permeation organ were reported. However, they are reports of synchronous secondary lymph node metastases, not metachronous secondary lymph node metastases. To the best of our knowledge, there are no cases of metachronous secondary lymph node metastases after the resection of a primary colorectal cancer in PubMed. CASE PRESENTATION: The case was a 67-year-old man who underwent colonoscopy because of weight loss. Sigmoid colon cancer with all circumference-related stenosis was found by examination, and the patient was transferred to our hospital for the purpose of scrutiny and treatment. The small intestine ileus caused by the invasion of sigmoid colon cancer developed after the transfer. Laparoscopic high anterior resection and extended excision of small intestine segmental resection was performed after the intestinal tract decompression with a nasal ileus tube. Histopathological analysis revealed a pathological diagnosis of pT4b (ileal submucosal invasion) N0 (0/11) M0 f Stage II, tub2, ly1, v2, PN0. Although adjuvant chemotherapy with capecitabine after the operation was planned for half a year, treatment was suspended in the first course by the patient's self-judgment. No recurrence was observed for a year after the operation, but metastasis recurrence in the para-aortic lymph node was found by a computed tomography (CT) one and a half years after the operation. 18 F-fluorodeoxyglucose (FDG) positron emission tomography revealed that FDG was accumulated only in the para-aortic lymph node. Laparoscopic metastasis lymphadenectomy was performed due to the diagnosis of metachronous metastasis to the para-aortic lymph node alone. Intraoperative findings revealed that lymph node metastasis occurred in the mesentery of the ileum. No adjuvant treatment was done after the secondary operation, and he is still alive with no recurrence 1 year and 9 months after the operation. CONCLUSIONS: We report a rare case of a laparoscopic resection of a metachronous secondary lymph node metastasis in the mesentery of the ileum after surgery for sigmoid colon cancer with ileum invasion.

Evaluation of the Outcome of Local Surgery for Stomal Prolapse.

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors' and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Laparoscopic resection of a neuroendocrine tumor that almost fully replaced tailgut cysts: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) originate from neuroendocrine cells, which are found throughout the body. NETs occur principally in the gastrointestinal tract (approximately 65%) and bronchopulmonary tract (approximately 25%) but rarely occur in the presacral space. Aside from primary and metastatic lesions, there have been reports of NETs occurring in the presacral space arising from tailgut cysts, teratomas, and imperforate anus. We herein report a rare case of laparoscopic resection of a NET in the presacral space, which almost fully replaced tailgut cysts. CASE PRESENTATION: A 68-year-old woman was referred to our hospital for surgery of a right inguinal hernia, but preoperative computed tomography revealed an asymptomatic 43-mm mass in the presacral space. Magnetic resonance imaging showed a multilocular solid mass with clear boundaries and a slightly high signal intensity on T1- and T2-weighted images. Positron emission tomography showed 18F-fluorodeoxyglucose uptake. Thus, we suspected a malignant tumor and performed laparoscopic resection to obtain a definitive diagnosis. Macroscopically, the tumor was 43 mm in size with clear boundaries, and the cut surface was a gray-white solid component. Histopathological findings revealed that the tumor was composed of relatively uniform cells with fine chromatin, with round to oval nuclei arranged in solid, trabecular, or rosette-like growth patterns. Small cysts lined with stratified squamous epithelium and columnar epithelium were observed along with solid components of the tumor, which is a feature of tailgut cysts. Therefore, the final diagnosis was NET Grade 1 arising from tailgut cysts. No recurrence was observed within 1 year after surgery. CONCLUSIONS: We performed en bloc laparoscopic resection of a NET arising from tailgut cysts in the presacral space without injury. In cases of a solid lesion in the presacral space, not only the primary disease but also the pathological condition with tissue transformation and replacement should be considered, as in this case.

Preoperative Neutrophil-Lymphocyte Ratio Is a Predictor of Bowel Obstruction Due to Colorectal Cancer Growth.

BACKGROUND: Bowel obstruction is commonly encountered in patients with advanced colorectal cancer; however, the cause of obstruction remains unknown. This study aimed to clarify a predictor of bowel obstruction due to colorectal cancer growth. MATERIALS AND METHODS: Between January 2005 and December 2013, the medical records of 140 patients with T3 or T4 colorectal cancer who underwent curative resection (R0) at our Hospital were investigated retrospectively. This study consisted of 26 patients with obstructive colorectal cancer (OCC) and 114 patients with non-obstructive colon cancer (non-OCC). RESULTS: Significant differences in clinicopathological factors including age, gender, T category, stage, primary tumor site, tumor diameter, macroscopic type, pathological type, lymphatic invasion, venous invasion, and lymph node metastasis were not observed between the two groups. Preoperative hematological/biochemical parameters including leukocyte count (p=0.004), neutrophil count (p=0.003), C-reactive protein (CRP) level (0.001), and neutrophil-to-lymphocyte ratio (NLR) (p=0.001) were significantly higher in the OCC group than in the non-OCC group. However, a significant difference in lymphocyte count was not observed between the two groups (p=0.634). Significant differences in the levels of the serum tumor markers CEA and CA19-9 were not observed between the two groups. CONCLUSION: Preoperative NLR seems to be a useful predictor of bowel obstruction due to colorectal cancer growth.

Duration of Preoperative Biliary Drainage as a Prognostic Factor After Pancreaticoduodenectomy for Pancreatic Head Cancer.

BACKGROUND/AIM: Preoperative biliary drainage (PBD) is often performed for jaundiced patients. However, the optimal duration of PBD remains unknown. The aim of this study was to investigate whether duration of PBD influenced the prognosis of patients after pancreaticoduodenectomy (PD) for pancreatic head cancer. PATIENTS AND METHODS: Twenty-five patients who underwent PD for pancreatic head cancer with obstructive jaundice between 2007 and 2013 were included. Tumor and host factors were analyzed to evaluate their potential prognostic effects and patients' characteristics between the two groups according to the duration of PBD were analyzed. RESULTS: In multivariate analysis, overall survival, duration of PBD ≥21 days and tumor-node-metastasis (TNM) stage III or IV were significant predictors. Duration of PBD ≥21 days was positively correlated with higher level of serum C-reactive protein (CRP), modified Glasgow prognostic score (mGPS) and neoadjuvant therapy. CONCLUSION: Duration of PBD is an independent prognostic factor after PD for pancreatic head cancer with obstructive jaundice.

Antibacterial activity of peptides derived from the C-terminal region of a hemolytic lectin, CEL-III, from the marine invertebrate Cucumaria echinata.

Several synthetic peptides derived from the C-terminal domain sequence of a hemolytic lectin, CEL-III, were examined as to their action on bacteria and artificial lipid membranes. Peptide P332 (KGVIFAKASVSVKVTASLSK-NH(2)), corresponding to the sequence from residue 332, exhibited strong antibacterial activity toward Gram-positive bacteria. Replacement of each Lys in P332 by Ala markedly decreased the activity. However, when all Lys were replaced by Arg, the antibacterial activity increased, indicating the importance of positively charged residues at these positions. Replacement of Val by Leu also led to higher antibacterial activity, especially toward Gram-negative bacteria. The antibacterial activity of these peptides was correlated with their membrane-permeabilizing activity toward the bacterial inner membrane and artificial lipid vesicles, indicating that the antibacterial action is due to perturbation of bacterial cell membranes, leading to enhancement of their permeability. These results also suggest that the hydrophobic region of CEL-III, from which P332 and its analogs were derived, may play some role in the interaction with target cell membranes to trigger hemolysis.

C-type lectin-like carbohydrate recognition of the hemolytic lectin CEL-III containing ricin-type -trefoil folds.

CEL-III is a Ca(2+)-dependent hemolytic lectin, isolated from the marine invertebrate Cucumaria echinata. The three-dimensional structure of CEL-III/GalNAc and CEL-III/methyl alpha-galactoside complexes was solved by x-ray crystallographic analysis. In these complexes, five carbohydrate molecules were found to be bound to two carbohydrate-binding domains (domains 1 and 2) located in the N-terminal 2/3 portion of the polypeptide and that contained beta-trefoil folds similar to ricin B-chain. The 3-OH and 4-OH of bound carbohydrate molecules were coordinated with Ca(2+) located at the subdomains 1alpha, 1gamma, 2alpha, 2beta, and 2gamma, simultaneously forming hydrogen bond networks with nearby amino acid side chains, which is similar to carbohydrate binding in C-type lectins. The binding of carbohydrates was further stabilized by aromatic amino acid residues, such as tyrosine and tryptophan, through a stacking interaction with the hydrophobic face of carbohydrates. The importance of amino acid residues in the carbohydrate-binding sites was confirmed by the mutational analyses. The orientation of bound GalNAc and methyl alpha-galactoside was similar to the galactose moiety of lactose bound to the carbohydrate-binding site of the ricin B-chain, although the ricin B-chain does not require Ca(2+) ions for carbohydrate binding. The binding of the carbohydrates induced local structural changes in carbohydrate-binding sites in subdomains 2alpha and 2beta. Binding of GalNAc also induced a slight change in the main chain structure of domain 3, which could be related to the conformational change upon binding of specific carbohydrates to induce oligomerization of the protein.

Crystal structure of the hemolytic lectin CEL-III isolated from the marine invertebrate Cucumaria echinata: implications of domain structure for its membrane pore-formation mechanism.

CEL-III is a Ca(2+)-dependent and galactose-specific lectin purified from the sea cucumber, Cucumaria echinata, which exhibits hemolytic and hemagglutinating activities. Six molecules of CEL-III are assumed to oligomerize to form an ion-permeable pore in the cell membrane. We have determined the crystal structure of CELIII by using single isomorphous replacement aided by anomalous scattering in lead at 1.7 A resolution. CEL-III consists of three distinct domains as follows: the N-terminal two carbohydrate-binding domains (1 and 2), which adopt beta-trefoil folds such as the B-chain of ricin and are members of the (QXW)(3) motif family; and domain 3, which is a novel fold composed of two alpha-helices and one beta-sandwich. CEL-III is the first Ca(2+)-dependent lectin structure with two beta-trefoil folds. Despite sharing the structure of the B-chain of ricin, CEL-III binds five Ca(2+) ions at five of the six subdomains in both domains 1 and 2. Considering the relatively high similarity among the five subdomains, they are putative binding sites for galactose-related carbohydrates, although it remains to be elucidated whether bound Ca(2+) is directly involved in interaction with carbohydrates. The paucity of hydrophobic interactions in the interfaces between the domains and biochemical data suggest that these domains rearrange upon carbohydrate binding in the erythrocyte membrane. This conformational change may be responsible for oligomerization of CEL-III molecules and hemolysis in the erythrocyte membranes.