Laparoscopy-Assisted Spleen-Preserving Distal Pancreatectomy for Living-Donor Pancreas Transplantation.

BACKGROUND: Living pancreas transplantation plays an important role in the treatment of patients with severe type 1 diabetes. However, pancreatectomy is very invasive for the donor, and less-invasive surgical procedures are needed. Although some reports have described hand-assisted laparoscopic surgery for distal pancreatectomy in living-donor operations, less-invasive laparoscopy-assisted (LA) procedures are expected to increase the donor pool. We herein report the outcomes of four cases of LA spleen-preserving distal pancreatectomy (Warshaw technique [WT]) in living pancreas donors. PATIENTS AND METHODS: Four living pancreas donors underwent LA-WT at our institution from September 2010 to January 2013. All donors fulfilled the donor criteria established by the Japan Society for Pancreas and Islet Transplantation. RESULTS: The median donor age was 54 years. Two donors underwent left nephrectomy in addition to LA-WT for simultaneous pancreas-kidney transplantation. The median donor operation time for pancreatectomy was 340.5 minutes. The median pancreas warm ischemic time was 3 minutes. The median donor blood loss was 246 g. All recipients immediately achieved insulin independence. One donor required reoperation because of obstructive ileus resulting from a port-site hernia. Another donor developed a pancreatic fistula (International Study Group of Pancreatic Fistula grade B), which was controlled with conservative management. After a maximum follow-up of 73 months, no clinically relevant adverse events had occurred. These results were comparable with those of previous studies concerning living-donor pancreas transplantation. CONCLUSION: The LA-WT is a safe and acceptable operation for living-donor pancreas transplantation.

Effect of cell permeable peptide of c-Jun NH2-terminal kinase inhibitor on the attenuation of renal ischemia-reperfusion injury in pigs.

The outcomes of organ transplantation have improved due to better immunosuppressive drugs, surgical techniques, and management of complications. However, ischemia-reperfusion injury remains a challenge affecting graft survival. In this study, we employed injection of a protein transduction domain (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was administered into the renal artery, allowing it to be taken into various elements including vascular endothelial cells by endocytosis via the PTD. Serum creatinine and blood urea nitrogen concentrations were lower among PTD-JNKI than controls. In addition, renal tissue blood flow was maintained in the PTD-JNKI group, resulting in less tissue injury and fewer apoptotic cells. These results suggested that the PTD technique improved renal transplantation outcomes.

Laparoscopic splenectomy using pneumoperitoneum or gasless abdominal wall lifting: a 15-year single institution experience.

INTRODUCTION: Laparoscopic splenectomy using pneumoperitoneum has been performed since 1992. The gasless abdominal wall-lifting method for laparoscopic splenectomy was introduced as an alternative. This retrospective study was undertaken to compare results using the two techniques. METHODS: Between 1995 and 2010, 54 patients underwent laparoscopic splenectomy at a single institution; 30 underwent the procedure using the gasless technique and 24 using pneumoperitoneum. There were no significant differences between the two groups regarding age, sex or BMI, but more patients underwent concurrent operations in the pneumoperitoneum group. The abdominal wall-lift system with subcutaneous K-wires was used for the gasless method. RESULTS: Intraoperative blood loss was similar in the two groups (193.0 ± 196.7 mL gasless, 217.3 ± 296.6 mL pneumoperitoneum; P > 0.05), but operative time (182.1 ± 92.1 min, 135.1 ± 46.1 min; P < 0.05), and resected spleen weight (306.1 ± 297.7 g, 138 ± 81.0 g; P < 0.05) were significantly different. In the gasless group, additional procedures included conversion (n = 1), mini-laparotomy (n = 2), and CO(2) insufflation (n = 2). Excluding the concurrent living-related kidney donor patients, hospital stay was similar (6.9 ± 2.5 days, 6.3 ± 2.0 days, P > 0.05). CONCLUSION: Although gasless laparoscopic splenectomy is feasible, there are disadvantages, particularly the restricted operative working space in some patients. These results suggest that either technique may be used on an individual basis in patients undergoing laparoscopic splenectomy.

Effect of milrinone on ischemia-reperfusion injury in the rat kidney.

BACKGROUND: Milrinone (MIL), a phosphodiesterase (PDE) 3 inhibitor, exhibits cardiotonic and angioectatic effects. Various PDE inhibitors have been shown to suppress inflammatory cytokines. In this study, we evaluated the angioectatic and anti-inflammatory cytokine effects of MIL on renal function after warm ischemia in a rat ischemia-reperfusion (I-R) injury model. MATERIALS AND METHODS: MIL or control solution was perfused from the left renal artery to the right kidney, and the left kidney was excised. The right renal artery, vein, and ureter were clamped and then released after 50 minutes to produce warm ischemia. We evaluated control (n = 7), MIL (n = 7), and sham operation (n = 7) groups for serum creatinine, blood urea nitrogen (BUN), blood flow, expression of tumor necrosis factor (TNF)-α mRNA, apoptosis index, and histological evidence of acute tubular necrosis. RESULTS: Serum creatinine and BUN concentrations peaked at 24 hours after reperfusion. MIL treatment significantly reduced serum creatinine (control group 1.27 ± 0.45 mg/dL vs MIL group 0.77 ± 0.19 mg/dL, P < .05; sham 0.35 ± 0.2 mg/dL) and BUN (control 67.6 ± 13.6 mg/dL vs MIL 51.0 ± 8.8 mg/dL, P < .05; sham 23.0 ± 4.2 mg/dL) levels at 24 hours. Thereafter, serum creatinine and BUN concentrations in the MIL group remained significantly lower compared with the control group for 120 hours (P < .05). MIL group exhibited significantly higher tissue blood flow, less acute tubular necrosis, lower expression of TNF-α mRNA in renal tissue, and lower apoptotic index (P < .05). CONCLUSIONS: MIL maintained renal tissue blood flow by its vasodilatory effect, suppressed expression of TNF-α mRNA by increasing intracellular cyclic adenosine monophosphate, and ultimately decreased tubular cell apoptosis, thus protecting renal function after warm I-R injury.

Living donor renal transplantation using grafts with multiple arteries procured by laparoscopic nephrectomy.

OBJECTIVE: Kidney grafts with multiple renal arteries (MRAs) are not uncommon, but they do make transplantation more difficult. Laparoscopic graft nephrectomy has become the standard; however, the safety and reliability must be maintained for both a donor and a recipient even in case of MRAs. This study evaluated the short-term outcomes of living donor renal transplant using grafts with MRAs procured by laparoscopic nephrectomy. PATIENTS AND METHODS: This study reviewed all living donor kidney transplantations performed from January 2008 to June 2009, which were divided into 3 groups according to the number of renal graft arteries. The serum creatinine level, warm ischemic time (WIT), rewarming time, total ischemic time (TIT), operative time, acute rejection episodes, and complications in each group were evaluated. RESULTS: The serum creatinine level showed no difference among the groups. Longer TIT was observed in the MRAs group, but WIT and rewarming time did not differ. The acute rejection rate was not different. There were no vessel complications in any donors and recipients. CONCLUSION: Harvesting kidney grafts with MRAs by laparoscopic nephrectomy requires a longer TIT; however, transplantation can be performed safely and reliably for both donors and recipients.

Availability of pancreatic allograft biopsies via a laparotomy.

OBJECTIVE: The aim of this study was to evaluate the availability of a pancreatic allograft biopsy via a laparotpmy. PATIENTS AND METHODS: From September 2004 to November 2007, 17 pancreas transplantations were performed: 15 simultaneous pancreas and kidney transplantations (SPK), 1 pancreas transplant alone (PTA), and one pancreas after kidney transplantation (PAK). Thirteen pancreatic allograft biopsies were obtained via an open laparotomy. This study evaluated the complications associated with this procedure, the rate of obtaining an adequate sample, and the relationship between biopsy-proven rejections and laboratory markers. In SPK cases we evaluated the synchronization between pancreas and kidney rejection. The pancreatic samples were diagnosed according to the Drachenberg classification. RESULTS: No complications resulted from the procedure. The rate of obtaining adequate samples was 84.6%. Pancreas rejection correlated with elevation of the laboratory markers in 71.4%. Simultaneous pancreas and kidney rejection occurred in 62.5%, only kidney in 25%, and only pancreas in 12.5%. CONCLUSION: A pancreas graft biopsy was absolutely imperative to improve the outcome in PTA, and even in SPK cases. A pancreatic allograft biopsy via a laparotomy was a safe, necessary and easy procedure to obtain an accurate diagnosis of rejection among pancreas transplantation patients.

Retroperitoneal hand-assisted laparoscopic surgery for endoscopic adrenalectomy.

Although hand-assisted laparoscopic surgery (HALS) is very common in various laparoscopic procedures, it is rarely used for retroperitoneal endoscopic adrenalectomy because of the small working area. The authors evaluate HALS in endoscopic adrenalectomy with respect to its use as a rescue procedure in complicated cases. In their department, 47 patients underwent endoscopic adrenalectomies between 1998 and 2004. Mainly because of complicated anatomy, three primary aldosteronism cases were converted to retroperitoneal HALS. This involved making an additional 6 cm skin incision, into which the surgeon's left hand was inserted, with the palm used to create a sufficient visual field and working area. The fingers were used for tactile sensation and blunt resection. For these three cases, successful retroperitoneal HALS in endoscopic adrenalectomy resulted in no mortality or morbidity. These findings indicate that this procedure is a feasible technique for complicated benign adrenal tumor cases.

CT virtual pancreatoscopy: a new method for diagnosing intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

BACKGROUND: We sought to validate computed tomographic virtual pancreatoscopy (CT-VP) created by multidetector row CT (MD-CT) in the clinical diagnosis of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Five cases of pancreatic IPMNs were included in this study. A nasopancreatic drainage tube was inserted and the pancreatic duct was filled with contrast medium, after which an upper abdominal scan was performed by MD-CT. CT-VP and three-dimensional (3D) CT pancreatographic images were created using a workstation and compared with images by conventional diagnostic techniques. All cases were evaluated by endoscopic retrograde pancreatography (ERP) and three cases of main duct type were assessed by intraoperative real pancreatoscopy (RP). RESULTS: In the main duct cases, papillary projections in the main pancreatic duct and branch orifices were clearly detected by CT-VP. These lesions and structures were confirmed by intraoperative RP, and the CT-VP images were clearer than RP images. In branch cases, a surface-rendering method allowed protruding lesions to be clearly detected in the dilated branches. CONCLUSION: Compared with conventional ERP or RP, CT-VP and 3D-CT pancreatographic images were finer in quality, and the procedures were less invasive, faster, and less expensive. The potential shown by CT-VP with 3D-CT pancreatography in the clinical diagnosis of pancreatic IPMNs suggests that this approach may replace ERP in the near future.

Squamous metaplasia induced by transfection of human papillomavirus DNA into cultured adenocarcinoma cells.

BACKGROUND/AIM: It has been reported previously in cases of adenosquamous carcinoma of the lung in Okinawa, a subtropical island 2000 km south of mainland Japan, that the squamous cell carcinoma components were positive for human papillomavirus (HPV) by non-isotopic in situ hybridisation (NISH). The adenocarcinoma cells adjacent to the squamous cell carcinoma components were enlarged and also positive for HPV. This is thought to indicate that after adenocarcinoma cells are infected with HPV, they undergo morphological changes, and that "squamous metaplasia" follows. In this present study, the effects of HPV transfection into adenocarcinoma cells were examined. The relation between the region expressing the HPV gene and squamous metaplasia was also studied. METHODS: Plasmid pBR322 containing HPV type 16 (HPV-16) was transfected into cultured colonic adenocarcinoma (DLD-1) and lung adenocarcinoma (PC-14) cells using the calcium phosphate method. Neomycin was used as a selection marker. The presence of HPV E1, E2, E4, E5, E6, E7, L1, and L2 mRNAs and also transglutaminase 1, involucrin, cyclin dependent kinases (CDKs), cyclins, caspases, apoptosis inducing factor, DNase gamma, Fas, and Fas ligand mRNAs in HPV transfected cells was investigated by means of reverse transcription polymerase chain reaction (RT-PCR). The G0-G1 cell population was analysed by flow cytometry. Morphological examination under light and electron microscopes was also carried out. RESULTS: The virus transfected cells showed squamous metaplasia when they were injected into severe combined immunodeficient mice, expressing the high molecular weight keratin (Moll's number 1 keratin) and involucrin molecules immunohistochemically, and involucrin and transglutaminase I mRNAs by RT-PCR. The squamous metaplasia was most conspicuous in the HPV transfected DLD-1 cell when compared with HPV transfected PC-14 cells. Squamous metaplasia was most clearly demonstrated in one HPV transfected DLD-1 cell clone, which expressed not only E2 but also E6-E7 fusion gene mRNA. Viral L1 mRNA expression was absent in HPV transfected cell clones, and was not related to squamous metaplasia. The growth rate of HPV transfected cells was reduced. Transfection of the virus into the cultured adenocarcinoma cells increased the G0-G1 cell population greatly, as assessed by flow cytometer analysis. Furthermore, in the virus transfected cells, apoptosis was also observed by means of the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labelling method. CONCLUSION: HPV transfection into adenocarcinoma cells induced clear squamous metaplasia. One of the HPV transfected cell clones that expressed E2 and E6-E7 fusion gene mRNA showed the squamous metaplasia particularly clearly, and apoptosis was also demonstrated.

Role of ATP in the sensitivity to heat and the induction of apoptosis in mammalian cells.

Heat-induced cell death and apoptosis were studied with respect to intracellular ATP. Studies on the relationship between hyperthermic cell-killing at 44 degrees C and cellular ATP levels in four cell lines grown as monolayers and six cell lines grown in suspension showed good correlations between cellular ATP levels and the sensitivity to heat. D(0) values (the dose required to reduce survival in the linear portion of the response by 63%) linearly increased with an increase in cellular ATP levels. No such changes in sensitivity to heat were observed between the cells cultured at different cell densities, regardless of the change in the cellular ATP level. These results suggest that cellular intrinsic ability to supply ATP rather than the level of pooled ATP per se is responsible for the thermal response. Heat-induced apoptosis in L5178Y cells was observed following treatment at 42 degrees C for 70 min, 44 degrees C for 20 min or 47 degrees C for 3 min, which corresponded to surviving fractions of 25, 0.6 and 0.8%, respectively, but not at 47 degrees C for 20 min, indicating that mild heat shock induced apoptosis. 2-deoxyglucose (2DG) and 2,4-dinitrophenol (DNP) increased the sensitivity to heat and affected the mode of cell death. Cells treated with 2DG and DNP (2DG/DNP) were heated at 42 degrees C for 20 min, and then incubated at 37 degrees C for up to 2h in the presence or absence of 2DG/DNP. In the absence of 2DG/DNP, the cellular ATP level recovered to 76% of the control level and DNA ladder formation was observed, whereas in the presence of 2DG/DNP, the cellular ATP level was further decreased (3-7% of the control) and no DNA fragmentation was detected. These results suggest that the inhibition of ATP synthesis is closely associated with the enhancement of sensitivity to heat and that ATP is required for the induction of apoptosis.

Fungal metabolites, PF1092 compounds and their derivatives, are nonsteroidal and selective progesterone receptor modulators.

The potential of new nonsteroidal progesterone receptor ligands, the derivatives of PF1092C ((4aR,5R,6R,7S)-6,7-dihydroxy-4a,5,6,7-tetrahydro-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one) discovered from fungal metabolites, was evaluated. PF1092A ((4aR,5R,6R,7S)-6-acetoxy-7-hydroxy-4a,5,6,7-tetrahydro-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one) showed good and moderate affinity for porcine and human progesterone receptors in in vitro receptor binding assays, respectively, and partial agonist activity for the progesterone receptor, as determined in assays of two types of progesterone-dependent enzymes in human mammary carcinoma T47D cells. The derivative of PF1092C, CP8481, ((4aR,5R,6R,7S)-6-(2-furancarbonyloxy)-7-hydroxy-4a,5,6,7-tetrahydro-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one) possessed better affinity for both progesterone receptors and showed less cross-reactivity for other steroid receptors, such as rat androgen receptor, human glucocorticoid receptor, and human estrogen receptor, and was a more potent modulator of the progesterone receptor than PF1092A. CP8400 ((4aR,5R,6R,7S)-6,7-diacetoxy-4a,5,6,7-tetrahydro-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one) and CP8401 ((4aR,5R,6R,7S)-6,7-dipropionyloxy-4a,5,6,7-tetrahydro-3,4a,5-trimethylnaphtho[2,3-b]furan-2(4H)-one), other derivatives, were indicated to be progesterone receptor antagonists. These results suggest that PF1092 compounds can serve as a new pharmacophore for potent and specific nonsteroidal progesterone receptor modulators.

[Evaluation of non-surgical therapy for the malignant lymphomas located mainly in the stomach and duodenum].

We evaluated the effects of the conservative treatment to 29 patients with non-Hodgkin lymphomas located mainly in stomach and duodenum. We could induce complete remission in all the cases of stage I, II, and III including MALT lymphomas by the combination therapy of Helicobacter pylori (H. pylori) eradication, chemotherapy, and radiation, and the complete remission persisted in all except for the three cases who died of other causes. Even in stage IV lymphomas mainly located in stomach and duodenum, we could induce complete remission in 50% of them. Considering the quality of life of patients with lymphomas located mainly in stomach and duodenum, the conservative treatment may be of benefit more than the surgical approach.

Long-term survival after surgical resection for pancreatic cancer.

BACKGROUND/AIMS: Pancreatic cancer remains one of the most formidable tumors defying early detection and effective treatment. Long-term survivors, however, do exist after resection. We investigated the clinicopathologic features of patients with pancreatic cancer who survived more than 5 years to draw out some suggestions concerning the indication of surgical treatment. METHODOLOGY: We studied the clinicopathologic features of 13 patients with pancreatic cancer who survived more than 5 years after resection. We reviewed their clinical records to investigate preoperative symptoms, serum tumor markers, operative findings, postoperative adjuvant therapy, and modes of recurrence and survival periods. Information on the location, size, histology and spread of the primary tumors were mainly obtained from pathology reports. RESULTS: Histologic types of the long survivors included ductal adenocarcinoma of common type in 4 patients, mucinous noncystic adenocarcinoma in 2, intraductal papillary-mucinous carcinoma (invasive) in 4, undifferentiated carcinoma in 1, endocrine tumor (islet cell carcinoma) in 1 and acinar cell carcinoma in 1. All 4 cases of ductal adenocarcinoma of the common type showed a moderate invasion either to the retroperitoneum, the portal vein or the duodenum. Two patients with mucinous noncystic carcinoma attained a long survival despite extensive invasion of the pancreatic stroma, although one died of peritoneal carcinomatosis. Two of 4 patients with intraductal papillary-mucinous cancer (invasive) died of peritoneal dissemination 6 and 11 years after resection, respectively. Three patients with cancer of other special histologic types, i.e., undifferentiated, well-differentiated endocrine carcinoma and acinar cell carcinoma, showed invasion of the portal vein and splenic artery, involvement of the retroperitoneum and a metastatic tumor in the liver, respectively. CONCLUSIONS: Whereas special histologic types including ductal variants tended to predispose to long-term survival, ductal adenocarcinoma of the common type had some chance of long survival even with invasion of the surrounding tissues.

Esophageal inflammatory pseudotumor mimicking malignancy.

A 54-year-old man with a complaint of dysphagia was found to have a prominent stricture in the proximal esophagus. A biopsy of the stenotic area indicated sarcoma, leading to subtotal esophagectomy. The surgically removed esophagus demonstrated a well-defined intramural mass, consisting of a mixture of fibroblastic cells with bland cytological appearances and inflammatory cells. Reflux esophagitis which was present distal to the stricture seemed to play a role in the development of this inflammatory pseudotumor.

Histologic and immunohistologic findings and prognosis of 40 cases of gastric large B-cell lymphoma.

It has been considered that gastric large B cell lymphoma mainly consists of mucosa-associated lymphoid tissue lymphoma (MALToma) with large cell transformation. However, debate continues about the cell lineage. We analyzed 61 operated cases of gastric B cell lymphoma, mainly focusing on 40 cases of diffuse large cell lymphoma (DLCL). Immunohistologically, two cases were classified as CD10-positive follicular lymphoma, 19 cases were low-grade MALToma, 11 CD10-negative DLCL with a component of low-grade MALToma (high-grade MALToma), 12 CD10-positive DLCL, and 17 CD10-negative DLCL without MALToma (pure DLCL). Lymphoepithelial lesion (LEL) was found in all -cases of high-grade MALToma, and in eight of these its invasion was confined to the mucosa and submucosa. Expression of Bcl-6 was detected in two cases of high-grade MALToma. Only two cases of CD10-positive DLCL had large cell LEL, and seven cases showed tumor invasion beyond the submucosa. All 12 cases were positive for Bcl-6, and a delicate meshwork of CD35 (Ber-MAC-DRC)-positive follicular dendritic cells was detected in eight cases. Pure DLCL of all 17 cases reached the proper muscle layer or more, and expression of Bcl-6 was detected in 10 cases. For patients with pure DLCL, overall survival was significantly (p <0.05) worse than those of high-grade MALToma and CD10-positive DLCL by Kaplan-Meier and log-rank methods. Clinical staging and Bcl-6 expression were also good prognostic factors in patients with DLCL. Three groups of gastric DLCL each had unique histologic findings, immunohistologic characteristics, and prognosis.

[A case of Lemmel's syndrome with serious jaundice exacerbated by eating].

An 86-year old woman rapidly developed serious jaundice (T-Bil 18.3 mg/dl 12.3 mg/dl). Her jaundice was exacerbated by eating, and improved by fasting. Abdominal CT showed a giant diverticulum in the second part of the duodenum and dilation of the proximal common bile duct. Endoscopic findings confirmed juxtapapillary duodenal diverticulum in contact with the distal common bile duct. MRCP revealed extrinsic compression of the distal common bile duct by the diverticulum. Lemmel's syndrome was diagnosed. Jaundice did not recur after surgery. We speculated that in this case the diverticulum filled by duodenal contents easily compressed the distal common bile duct after eating.

Nuclear localization of immunoreactive beta-catenin is specific to familial adenomatous polyposis in papillary thyroid carcinoma.

Thyroid carcinoma is the first symptom in some patients with familial adenomatous polyposis (FAP). We evaluated the cellular localization of beta-catenin in thyroid carcinomas associated (n = 4) or not associated (n = 173) with FAP, since loss of functional protein of the adenomatous polyposis coli (APC) gene leads to nuclear accumulation of beta-catenin in adenomas and carcinomas of the FAP colon. Immunoreactive beta-catenin was demonstrated at the cell membrane of glandular cells of the non-neoplastic thyroid and non-FAP carcinomas. On the other hand, cytoplasmic and nuclear accumulation of beta-catenin is specific to FAP-associated papillary carcinomas. The abnormality in the APC / beta-catenin pathway is thus also important in FAP-associated thyroid carcinoma, and beta-catenin immunohistochemistry is a feasible screening method to identify occult FAP in young patients with thyroid tumors.