Potential therapeutic targets discovery by transcriptome analysis of an in vitro human gastric signet ring carcinoma model.

BACKGROUND: Loss of E-cadherin expression is frequently observed in signet ring carcinoma (SRCC). People with germline mutations in CDH1, which encodes E-cadherin, develop diffuse gastric cancer at a higher rate. Loss of E-cadherin expression is thus assumed to trigger oncogenic development. METHODS: To investigate novel therapeutic targets for gastric SRCC, we engineered an E-cadherin-deficient SRCC model in vitro using a human gastric organoid (hGO) with CDH1 knockout (KO). RESULTS: CDH1 KO hGO cells demonstrated distinctive morphological changes similar to SRCC and high cell motility. RNA-sequencing revealed up-regulation of matrix metalloproteinase (MMP) genes in CDH1 KO hGO cells compared to wild type. MMP inhibitors suppressed cell motility of CDH1 KO hGO cells and SRCC cell lines in vitro. Immunofluorescent analysis with 95 clinical gastric cancer tissues revealed that MMP-3 was specifically abundant in E-cadherin-aberrant SRCC. In addition, CXCR4 molecules translocated onto the cell membrane after CDH1 KO. Addition of CXCL12, a ligand of CXCR4, to the culture medium prolonged cell survival of CDH1 KO hGO cells and was abolished by the inhibitor, AMD3100. In clinical SRCC samples, CXCL12-secreting fibroblasts showed marked infiltration into the cancer area. CONCLUSIONS: E-cadherin deficient SRCCs might gain cell motility through upregulation of MMPs. CXCL12-positive cancer-associated fibroblasts could serve to maintain cancer-cell survival as a niche. MMPs and the CXCL12/CXCR4 axis represent promising candidates as novel therapeutic targets for E-cadherin-deficient SRCC.

Metastatic breast carcinoma simulating linitis plastica of the colon: report of a case.

A 48-year-old woman developed a mobile abdominal mass in the course of treatment for recurrent breast cancer. Imaging studies indicated linitis plastica of the colon. She underwent surgery because of the stenosis of the transverse colon. An examination of the resected specimen revealed a segmental stricture, thickening of the entire wall, and a granular mucosa resembling cobblestones. Microscopic findings of the colon lesion were very similar to those of her primary, invasive lobular carcinoma of the breast. Atypical cells showed immunoreactivity for cytokeratin-7, but not for cytokeratin-20. These findings suggested that the lesion of the colon was a colonic metastasis of breast cancer. Metastatic gastrointestinal diseases originating from breast carcinoma are unusual, and colonic metastases are especially rare. Although colon cancer may occur in patients with a history of breast cancer, metastatic colon cancer should be suspected if linitis plastica is detected.

Laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons: A case report.

Persistent mesocolon is an embryological anomaly of the colon resulting from failure of the primitive dorsal mesocolon to fuse with the parietal peritoneum. We herein present a case of laparoscopic high anterior resection for triple colorectal cancers with persistent ascending and descending mesocolons and a right-bound inferior mesenteric artery. Preoperative 3-D CT demonstrated that the sigmoid colon had shifted to the right abdomen and was located under the ascending colon. Moreover, the inferior mesenteric artery and vein traveled toward the right abdomen accompanied by the mesentery of the descending colon. Adhesiolysis between the ascending and sigmoid colon was initially performed, and the sigmoid colon was placed in its normal position. The inferior mesenteric artery was then divided with lymph node dissection using a medial approach, and high anterior resection was completed. An understanding of the anatomical characteristics of persistent mesocolon is important to ensure safe laparoscopic surgery.

S100A6 is increased in a stepwise manner during pancreatic carcinogenesis: clinical value of expression analysis in 98 pancreatic juice samples.

There are few reports describing the diagnostic significance of S100A6 expression in clinical samples obtained from patients with pancreatic disease. In the present study, we measured S100A6 expression in pancreatic tissues and juice to evaluate its involvement in pancreatic carcinogenesis. We did quantitative real-time reverse transcription-PCR to measure mRNA expression in microdissected cells and pancreatic juice samples. Microdissected invasive ductal carcinoma and intraductal papillary mucinous neoplasm (IPMN) cells expressed significantly higher levels of S100A6 than did microdissected pancreatitis-affected epithelial and normal cells (all comparison; P < 0.008). Median levels of S100A6 in invasive ductal carcinoma were higher than those in IPMN, and those in pancreatitis-affected epithelial cells tended to be higher than those in normal cells, although these differences were not statistically significant. In analyses of pancreatic juice, IPMN and pancreatic cancer samples expressed significantly higher levels of S100A6 than did chronic pancreatitis samples (both; P < 0.017), but levels in pancreatic cancer and IPMN samples did not differ form each other. Receiver operating characteristic (ROC) curve analysis revealed that measurement of S100A6 was useful for discriminating cancer (area under the ROC curve, 0.864) or IPMN (area under the ROC curve, 0.749) from chronic pancreatitis. The present data suggest that expression of S100A6 is increased in a stepwise manner during pancreatic carcinogenesis and may be a biomarker for evaluating malignant potential. Measurement of S100A6 in pancreatic juice may be useful to detect early pancreatic cancer or identify individuals with high-risk lesions that may progress to pancreatic cancer.

S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic carcinogenesis.

PURPOSE: Recent microarray analyses revealed that expression of S100A11 is up-regulated in pancreatic cancer. The aim of the present study was to evaluate the association of S100A11 with pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We measured S100A11 mRNA expression in various clinical samples related to pancreatic cancer and its precursor lesions, intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia, by quantitative reverse transcription-PCR. RESULTS: Levels of S100A11 were significantly higher in pancreatic cancer (n=22) and IPMN (n=18) bulk tissues than in nonneoplastic bulk tissues (n=22; P<0.0001 for both). Levels of S100A11 did not differ between pancreatic cancer and IPMN bulk tissues. In microdissection analyses, however, IPMN cells (n=21) expressed significantly higher levels of S100A11 than did cancer cells (n=23; P=0.003). The median level of S100A11 expression was higher in pancreatic intraepithelial neoplasia cells (n=6) than in cancer cells. In pancreatic juice analyses, cancer-related (n=24; P=0.004) and IPMN-related (n=18; P=0.001) juice expressed significantly higher levels of S100A11 than did chronic pancreatitis-related juice (n=23). CONCLUSIONS: The present data suggest that expression of S100A11, a putative tumor suppressor gene, is increased in the early stage of pancreatic carcinogenesis and decreased during subsequent progression to cancer. Analysis of the S100A11 level in pancreatic juice may be an effective tool for screening of patients with high-risk lesions that could progress to pancreatic cancer or detecting early-stage pancreatic cancer.

Quantitative analysis of human telomerase reverse transcriptase in pancreatic cancer.

Although telomerase activity is a promising diagnostic marker, clinical introduction of this marker for cancer diagnosis is still problematic due to the lack of means of evaluating sample quality. Human telomerase reverse transcriptase (hTERT), one of the subunits of telomerase, is also a promising diagnostic marker. In the present study, we did large-scale analysis of 88 pancreatic juice samples to determine the feasibility of quantitative analysis of hTERT mRNA for diagnosis of pancreatic cancer. We found significant differences in hTERT expression among carcinoma-derived, intraductal papillary mucinous neoplasm (IPMN)-derived, and chronic pancreatitis-derived juice samples. Results showed that quantitative analyses of hTERT mRNAs are more useful in discriminating carcinoma from IPMN than from chronic pancreatitis. When the specificity was set at 100%, the sensitivity for differentiation between carcinoma and IPMN was 43.5%, whereas the sensitivity of cytologic examination was 22.0%. There were significant differences in hTERT expression among carcinoma cells, IPMN cells, and normal ductal cells isolated from pancreatic tissues by microdissection. Lymphocytes and hyperplastic epithelial cells isolated from tissues with the histologic appearance of pancreatitis showed various expression levels of hTERT. Our results suggest that quantitative analysis of hTERT mRNA in pancreatic juice is advantageous over cytologic analysis for differentiation between carcinoma and IPMN but probably not for differentiation between carcinoma and chronic pancreatitis.

S100P is an early developmental marker of pancreatic carcinogenesis.

PURPOSE: Our goal was to clarify the involvement and clinical significance of S100P in pancreatic carcinogenesis. EXPERIMENTAL DESIGN: We examined S100P expression in 45 bulk pancreatic tissues; in microdissected cells, including invasive ductal carcinoma (IDC) cells (20 sections), pancreatic intraepithelial neoplasia (PanIN) cells (12 sections), intraductal papillary mucinous neoplasm (IPMN) cells (19 sections), and normal epithelial cells (11 sections); and in pancreatic juice samples from 99 patients with pancreatic diseases (32 cancer, 35 IPMN, and 32 chronic pancreatitis samples). We used quantitative real-time reverse transcription-PCR with gene-specific priming to measure S100P in these various types of samples. RESULTS: In bulk tissue analyses, pancreatic cancer and IPMN expressed significantly higher levels of S100P than did nonneoplastic pancreas (P<0.017 and P=0.0013, respectively). Microdissection analyses revealed that IPMN expressed significantly higher levels of S100P than did IDC (P<0.0001) and PanIN (P=0.0031), although S100P expression did not differ between IDC and PanIN (P=0.077). In pancreatic juice analyses, cancer and IPMN juice expressed significantly higher levels of S100P than did pancreatitis juice (both P<0.0001). Receiver operating characteristic curve analyses revealed that measurement of S100P in pancreatic juice was useful for discriminating neoplastic disease from chronic pancreatitis (area under the curve=0.837; 95% confidence interval, 0.749-0.903). CONCLUSION: S100P may be an early developmental marker of pancreatic carcinogenesis, and measurement of S100P in pancreatic juice may be useful for early detection of pancreatic cancer or screening of early pancreatic carcinogenesis.

Pylorus-preserving pancreatoduodenectomy: preoperative pancreatic function and outcome.

BACKGROUND/AIMS: To investigate the effects of preoperative pancreatic function on gastric emptying, body weight, and quality of life after pylorus-preserving pancreatoduodenectomy. METHODOLOGY: Thirty-one patients who underwent pylorus-preserving pancreatoduodenectomy were divided into 2 groups according to preoperative pancreatic exocrine and endocrine function (normal vs. abnormal). Gastric emptying, body weight, and quality of life were evaluated before surgery, 1-2 months after surgery (short-term), and 6-12 months after surgery (long-term). RESULTS: Short-term body weight was significantly decreased in comparison to preoperative body weight regardless of preoperative exocrine and endocrine pancreatic function. Body weight returned to the preoperative level by 12 months after surgery in patients with normal preoperative pancreatic function but not in patients with abnormal pancreatic function. In both groups, gastric emptying was delayed at 1-2 months after surgery and then returned to the preoperative value by 12 months. Short-term quality of life did not differ from preoperative quality of life in either group, but long-term quality of life improved to beyond the preoperative level in both groups. CONCLUSIONS: Preoperative pancreatic function appears to significantly influence long-term body weight after pylorus-preserving pancreatoduodenectomy.

Stage IV gastric cancer successfully treated by multidisciplinary therapy including chemotherapy, immunotherapy, and surgery: a case report.

BACKGROUND: The prognosis of stage IV gastric cancer (GC) still remains unfavorable. Multidisciplinary approaches should therefore be considered to improve the survival of patients with stage IV GC. We report here a case of primary GC with potentially unresectable metastasis, successfully treated by a multidisciplinary approach including chemotherapy, immunotherapy, and surgery. CASE PRESENTATION: A 74-year-old man presented with multiple left neck masses. Abdominal computed tomography showed a thickened gastric wall and multiple lymphadenopathies including left supraclavicular lymph node. Gastroenterological endoscopy revealed tumor lesions in the gastric cardia. Tumor biopsy indicated a pathological diagnosis of poorly differentiated adenocarcinoma. Open left cervical lymph node biopsy showed histological features identical with the gastric tumor, indicating left clavicle lymph node metastasis of GC. After 2 years of chemo-immunotherapy with S-1/CDDP, paclitaxel, and cytokine-activated killer cells, lesions other than the stomach lesion had regressed to undetectable on imaging studies. The patient then underwent laparoscopy-assisted total gastrectomy with Roux-en-Y reconstruction followed by adjuvant chemo-immunotherapy with paclitaxel and S-1 for 1 year, and immunotherapy with tumor lysate-pulsed dendritic cell-activated killer cells for 5 years. The patient remained well after 5 years and 6 months of follow-up, with no signs of recurrence. CONCLUSION: Therapeutic combinations including immunotherapy may thus allow surgery to be performed in patients previously considered unsuitable for surgical intervention, potentially leading to a clinical cure, as in the current case.

Long-term results of treatment for pancreaticobiliary maljunction without bile duct dilatation.

HYPOTHESIS: Resection of the gallbladder together with the dilated bile duct is the preferred treatment for pancreaticobiliary maljunction (PBM) with bile duct dilatation, whereas this treatment for PBM without bile duct dilatation is still controversial. DESIGN: Retrospective study of 196 patients from January 1979 to November 2004. SETTING: Two university hospitals. PATIENTS: One hundred ninety-six patients with PBM, 152 (78%) with and 44 (22%) without bile duct dilatation, formed the basis of this study. MAIN OUTCOME MEASURES: The effects of cholecystectomy on long-term results in the patients without bile duct dilatation. RESULTS: Significant differences were observed in patients without bile duct dilatation: patients were older, carcinoma of the gallbladder was more prevalent (19 patients [43.2%] without dilatation vs 9 patients [5.9%] with dilatation), and pancreatic cancer and pancreatitis were also more frequent. Most of their gallbladder carcinomas were found at stage IV (63%). The outcome was very poor in stage IV, whereas 5 patients in stage I and II lived for more than 5 years after surgery. Of the 44 patients without bile duct dilatation, 23 with carcinoma of the gallbladder or pancreas died and the other 2 were lost to follow-up. The remaining 19 patients were alive at the study's conclusion after cholecystectomy without bile duct resection. None of them had bile duct carcinoma at the time of surgery or during the mean follow-up period of 9 years after surgery. CONCLUSIONS: Prophylactic cholecystectomy without bile duct resection is the best treatment option for patients with PBM without bile duct dilatation. Possible association of gallbladder carcinoma should be kept in mind at the time of treatment of patients with PBM when the bile duct is not dilated.

The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target.

Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease. Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.

[A case of primary gastric malignant lymphoma perforated immediately after administration of chemotherapy].

A 77-year-old man was admitted to our hospital with complaints of abdominal pain and body weight loss. Esophagogastroduodenoscopy on admission revealed large ulcerative tumor in the entire region from upper to lower body of the stomach. We diagnosed gastric malignant lymphoma, diffuse large B-cell type and determined stage IV according to the Lugano International Conference classification. Due to gastric perforation occurred on day 4 of chemotherapy, total gastrectomy and partial resection of the transverse colon were performed. Complete remission was achieved by 2 cycles of postoperative chemotherapy together with rituximab.

A Feasibility Study of Neoadjuvant XELOX Without Radiotherapy for Locally Advanced Lower Rectal Cancer.

AIM: This study was planned to evaluate the efficacy and safety of preoperative capecitabine and oxaliplatin (XELOX) without radiation in patients with locally advanced lower rectal cancer. PATIENTS AND METHODS: Patients with clinical stage II/III lower rectal cancer underwent three cycles of XELOX followed by radical surgery. The primary end-point was the R0 resection rate. RESULTS: Thirty-one patients were recruited between February 2012 and August 2014. The completion rate of neoadjuvant chemotherapy was 96.5% among the 29 patients who received it; the remaining two refused chemotherapy and underwent immediate surgery. Grade 3-4 adverse events occurred in nine patients (31%). All 29 patients who received chemotherapy underwent radical resection. The R0 resection rate was 96.5% among these 29 patients. Pathological complete responses were achieved in three patients (10.3%) and downstaging occurred in 13 (44.8%). CONCLUSION: This pilot study found that neoadjuvant XELOX for locally advanced lower rectal cancer is feasible and safe. This neoadjuvant treatment improved resection margin status.

Duodenum is important for the sphincter of Oddi motor response to cholecystokinin octapeptide in conscious dogs.

BACKGROUND: We investigated the role of the duodenum in the sphincter of Oddi response to cholecystokinin-octapeptide (CCK-OP), using conscious dogs. METHODS: In controls, a cannula was inserted into the duodenum opposite the papilla for retrograde manometry. In the duodenectomy group, the entire duodenum was resected, while preserving the papilla, which was implanted into the jejunum, and the cannula was placed. Sphincter motility was recorded after bolus injections of 20 and 100 ng/kg of CCK-OP. RESULTS: CCK-OP at 20 ng/kg produced sphincter relaxation followed by contraction in the controls, but produced no changes after duodenectomy. CCK-OP at 100 ng/kg caused strong contractions followed by relaxation in the controls, but caused only contractions after duodenectomy. CONCLUSIONS: (1) Relaxation and delayed contraction of the sphincter induced by 20 ng/kg of CCK-OP require the presence of the duodenum; (2) early contractions of the sphincter induced by 100 ng/kg of CCK-OP do not require the duodenum; (3) the duodenum plays an important role in the actions of CCK-OP on sphincter motility.

Total pancreatectomy for intraductal papillary-mucinous tumor of the pancreas: reappraisal of total pancreatectomy.

BACKGROUND/AIMS: Total pancreatectomy is rarely performed as the treatment of pancreatic carcinoma because of markedly impaired quality of life and poor prognosis. Intraductal papillary-mucinous tumor (IPMT) of the pancreas is characterized by extensive intraductal spread and favorable outcome even in its invasive stage. The role of total pancreatectomy was reappraised in the treatment of IPMT. METHODOLOGY: A total of five Japanese patients with IPMT underwent total pancreatectomy and their clinical follow-up data were reviewed. RESULTS: Total pancreatectomy was performed due to massive involvement of the entire pancreas in two patients, positive surgical margins on frozen section in one, benign IPMT with concomitant pancreatic cancers in one and recurrent IPMT in the remnant pancreas after distal pancreatectomy for IPMT in the other. Three of them underwent total pancreatectomy of the Whipple type, another underwent total gastrectomy and the other underwent the pylorus-preserving method. Surgical margins were negative by histology and no lymph node metastases were evident. Two patients had severe infection including liver abscess in one and pneumonia in the other. The former died on postoperative day 82 and the latter was controlled by medical treatment and discharged on postoperative day 73. The other three patients had an uneventful postoperative course and were discharged from 29 to 62 days after the operation. Long-term follow-up of the four patients revealed that three patients had hypoglycemic attacks, two diabetic retinopathy and two fatty liver. The four patients were doing well from 683 to 4,140 days after the operation without signs of recurrence. CONCLUSIONS: Total pancreatectomy would be indicated as a treatment of benign or malignant IPMT with extensive involvement when patients' condition permits and gives a chance of cure, although careful long-term medical care and follow-up are essential.

ERT following IORT improves survival of patients with resectable pancreatic cancer.

BACKGROUND/AIMS: The clinical course of patients with pancreatic carcinoma remains dismal despite the recent advances of diagnostic and therapeutic procedures. One of the main causes is residual carcinoma cells, especially at the retroperitoneal aspect after pancreatectomy. Radiation therapy (RT) [intraoperative radiation therapy (IORT) and external radiation therapy (ERT)] is a therapeutic strategy to conquer the remaining cancer cells. METHODOLOGY: Effects of RT were retrospectively examined in 81 patients with pancreatectomy for pancreatic cancer together with early and late complications. RESULTS: Preoperative clinical data were not different between the RT(+) and RT(-) groups excluding peripheral lymphocyte counts. Postoperative early complications equally occurred including pancreatic fistula. Regarding late complications (>2 months after operation), stomal ulcer, vertebral fracture, pseudoaneurysm, intraabdominal hemorrhage, and liver abscess were present only in patients with RT. Glucose intolerance tended to be more frequent in the RT (+) group, i.e. 12 (63%) of the 19 with RT examined and 14 (42%) of the 33 without RT examined. Follow-up imaging showed recurrence in 27 (71%) of the 38 patients without RT and 13 (52%) of the 25 patients with RT. The sites of the recurrence were not different by the presence or absence of RT. One-year, 3-year and 5-year cumulative survival rates were similar between the RT (-) group (100%, 39%, 21%, respectively) and IORT (+) alone group (100%, 29% and 17%, respectively). The rates in the IORT (+) and ERT (+) group were 100%, 54% and 28%, respectively, which tended to be better than those in the other two groups, but the differences were not statistically significant. CONCLUSIONS: These findings suggest that only the combination of IORT and ERT somewhat improves the short-term clinical course of patients with resectable pancreatic cancer, although there are some RT-related late complications. It is recommended that ERT be added to IORT after pancreatectomy for pancreatic cancer to improve the clinical course, once IORT has been performed.

[Recent advances in diagnosis of pancreatic cancer].

The clinical course of patients with pancreatic cancer remains dismal. This may be because the pancreas is a retroperitoneal organ, the symptoms are non-specific, occur late, and pancreas cancer has an invasive nature. Screening for asymptomatic or symptomatic patients using serum tumor markers and ultrasonography is not cost-effective. However, the clinical course of small carcinomas less than 1 cm or 1 cm in size is favorable. Thus, the detection of small pancreatic carcinoma is essential to improve the clinical outcome. Possible discovery of pancreatic carcinoma as a diagnostic clue to diabetes mellitus, and intraductal papillary-mucinous neoplasm are introduced based on our clinical experience.

Characterization of circular muscle motor neurons of the duodenum and distal colon in the Australian brush-tailed possum.

The motor innervation of the duodenum and distal colon remains uncharacterized within the same species. Our aim was to compare the projections and neurochemical properties of duodenal and distal colon circular muscle motor neurons. Circular muscle motor neurons were retrogradely traced by using a neural tracer in vitro, processed for choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity and then visualized by using indirect immunofluorescence. A mean of 372 +/- 64 and 156 +/- 23 neurons (mean +/- SEM) were tracer-labeled within the duodenum and colon, respectively. The ChAT+/NOS- neurons comprised 57.6 +/- 6.6% and 39.6 +/- 4.4% of all labeled cells in the duodenum and colon, respectively, and projected mainly in the oral direction. Of all labeled cells, the ChAT-/NOS+ neurons comprised 8.5 +/- 2.3% in the duodenum and 46.6 +/- 5.0% in the distal colon and projected mainly in the anal direction. Of the remainder, 20.6 +/- 5.0% and 8.2 +/- 2.4% were ChAT+/NOS+ and 13.2 +/- 0.9% and 5.6 +/- 1.4% were ChAT-/NOS- in the duodenum and distal colon, respectively. Within both regions, the distribution of the ChAT+/NOS- and ChAT-/NOS+ neurons are consistent with the ascending excitatory and descending inhibitory reflexes. The proportion of ChAT-/NOS+ neurons is greater within the colon in comparison with the duodenum. A considerable proportion of duodenal motor neurons were ChAT+/NOS+ and ChAT-/NOS-. These two classes may underlie nonperistaltic motor patterns, which predominate within the duodenum. These findings demonstrate regional differences in the innervation of intestinal circular muscle.

Second-generation recombinant hemoglobin molecules do not stimulate sphincter of Oddi, gallbladder or duodenal motility in the Australian brush-tailed possum.

BACKGROUND: Several studies have investigated the effects of hemoglobin-based oxygen carriers on gastrointestinal motility. Diaspirin cross-linked hemoglobin reduces sphincter of Oddi trans-sphincteric flow and increases duodenal motility in the Australian brush-tailed possum, effects attributed to nitric oxide (NO) scavenging. Recently, second-generation recombinant hemoglobin molecules with reduced NO scavenging ability have been developed. AIM: To determine the effects of two second-generation recombinant hemoglobin solutions and the prototype recombinant hemoglobin with high NO binding, on duodenal and biliary motility in the Australian brush-tailed possum. METHOD: Blood pressure; duodenal, sphincter of Oddi and gallbladder motility; and trans-sphincteric flow were recorded. The effects of recombinant hemoglobin or human serum albumin (control) solutions on these parameters were investigated. Each solution was infused intravenously at 1 mL/kg/min to deliver 250 mg/kg or 500 mg/kg. RESULTS: Duodenal contraction frequency was stimulated by the high dose of prototype recombinant hemoglobin, but not by a comparable dose of second-generation recombinant hemoglobin. The induced duodenal activity occurred in the later phase of the experimental period. In contrast, biliary motility and trans-sphincteric flow were not altered by any hemoglobin solution. The high dose of all the hemoglobin solutions elevated blood pressure, whereas the low dose solutions did not alter any parameter measured. CONCLUSION: At the doses studied, the second-generation recombinant hemoglobin with reduced NO binding capacity did not significantly alter duodenal and biliary motility, supporting the need for further studies to evaluate their potential usefulness as blood substitutes.

Spleen-preserving laparoscopic distal pancreatectomy after division of the splenic vessels.

A 37-year-old woman with a history of syncope was hospitalized with a diagnosis of hypoglycemia due to insulinoma. Computed tomography (CT) and magnetic resonance imaging revealed an enhanced solid mass, 1.5 cm in diameter, at the tail of the pancreas. Angiography via the splenic artery revealed a hypervascular mass. Because the tumor was located deep in the pancreatic parenchyma, laparoscopic distal pancreatectomy was performed. The pancreas was exposed by dissecting the greater omentum, and the tumor was located by intraoperative ultrasonography. After division of the splenic artery, the pancreas, main pancreatic duct, and splenic vein were transected with an endoscopic linear stapler. The pancreatic pedicle was divided at the splenic hilum to preserve the spleen. The postoperative course was uneventful except for the appearance of splenic infarction on a CT scan 2 weeks after surgery but without any overt symptoms. Spleen-preserving laparoscopic distal pancreatectomy by division of splenic vessels is a feasible treatment option for benign pancreatic disease.