Functional roles of graft-infiltrating lymphocytes during early-phase post-transplantation in mouse cardiac transplantation models.

Immunological behavior of graft-infiltrating lymphocytes (GILs) determines the graft fate (i.e., rejection or acceptance). Nevertheless, the functional alloreactivity and the phenotype of GILs at various times during the early post-transplantation phase have not been fully elucidated. We examined the immunological activities of early-phase GILs using a murine model of cardiac transplantation. GILs from 120-h allografts, but not 72-h allografts, showed robust activation and produced proinflammatory cytokines. In particular, a significant increase in CD69+ T-bet+ Nur77+ T cells was detected in 120-h allografts. Furthermore, isolated GILs were used to reconstitute BALB/c Rag2-/- γc-/- (BRG) mice. BRG mice reconstituted with 120-h GILs displayed donor-specific immune reactivity and rejected donor strain cardiac allografts; conversely, 72-h GILs exhibited weak anti-donor reactivity and did not reject allografts. These findings were confirmed by re-transplantation of cardiac allografts into BRG mice at 72-h post-transplantation. Re-transplanted allografts continued to function for >100 days, despite the presence of CD3+ GILs. In conclusion, the immunological behavior of GILs considerably differs over time during the early post-transplantation phase. A better understanding of the functional role of early-phase GILs may clarify the fate determination process in the graft-site microenvironment.

The Efficacy of the Hepatocyte Spheroids for Hepatocyte Transplantation.

The safety and short-term efficacy of hepatocyte transplantation (HCTx) have been widely proven. However, issues such as reduced viability and/or function of hepatocytes, insufficient engraftment, and lack of a long-term effect have to be overcome for widespread application of HCTx. In this study, we evaluated hepatocyte spheroids (HSs), formed by self-aggregation of hepatocytes, as an alternative to hepatocytes in single-cell suspension. Hepatocytes were isolated from C57BL/6 J mice liver using a three-step collagenase perfusion technique and HSs were formed by the hanging drop method. After the spheroids formation, the HSs showed significantly higher mRNA expression of albumin, ornithine transcarbamylase, glucose-6-phosphate, alpha-1-antitrypsin, low density lipoprotein receptor, coagulation factors, and apolipoprotein E (ApoE) than 2 dimensional (2D)-cultured hepatocytes (p < 0.05). Albumin production by HSs was significantly higher than that by 2D-cultured hepatocytes (9.5 ± 2.5 vs 3.5 ± 1.8 µg/dL, p < 0.05). The HSs, but not single hepatocytes, maintained viability and albumin mRNA expression in suspension (92.0 ± 2.8% and 1.03 ± 0.09 at 6 h). HSs (3.6 × 106 cells) or isolated hepatocytes (fSH, 3.6 × 106 cells) were transplanted into the liver of ApoE knockout (KO-/-) mice via the portal vein. Following transplantation, serum ApoE concentration (ng/mL) of HS-transplanted mice (1w: 63.1 ± 56.7, 4w: 17.0 ± 10.9) was higher than that of fSH-transplanted mice (1 w: 33.4 ± 13.0, 4w: 13.7 ± 9.6). In both groups, the mRNA levels of pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α, MCP-1, and MIP-1ß) were upregulated in the liver following transplantation; however, no significant differences were observed. Pathologically, transplanted HSs were observed as flat cell clusters in contact with the portal vein wall on day 7. Additionally, ApoE positive cells were observed in the liver parenchyma distant from the portal vein on day 28. Our results indicate that HS is a promising alternative to single hepatocytes and can be applied for HCTx.

Short-term and Long-term Outcomes Following Laparoscopic Gastrectomy for Advanced Gastric Cancer Compared With Open Gastrectomy.

INTRODUCTION: To investigate the oncological feasibility and technical safety of laparoscopic gastrectomy with D2 lymphadenectomy for advanced gastric cancer. METHODS: A total of 186 advanced gastric cancer patients treated by gastrectomy with D2 lymphadenectomy were eligible for inclusion including those with invasion into the muscularis propria, subserosa, and serosa without involvement of other organs, and stages N0-2 and M0. We retrospectively compared the short-term and long-term outcomes between laparoscopic gastrectomy and open gastrectomy. RESULTS: We analyzed short-term outcomes by comparing distal with total gastrectomy results. We found no significant difference for distal gastrectomy for postoperative morbidity [laparoscopic vs. open: n=4 (4.6%) vs. n=1 (3.6%); P=1.00]. We also found no significant difference in postoperative morbidity for total gastrectomy [laparoscopic vs. open: n=2 (4.0%) vs. n=1 (4.0%); P=1.00]. No deaths occurred in any group.The entire cohort analysis revealed no statistically significant differences in overall-free or recurrence-free survival between the laparoscopic and open groups. For overall survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.29 and 0.27, respectively), and for pathologic stage II or III (P=0.88 and 0.86, respectively). For recurrence-free survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III (P=0.63 and 0.60, respectively), and for pathologic stage II or III (P=0.98 and 0.72, respectively). CONCLUSION: Laparscopic gastrectomy for advanced gastric cancer compared favorably with open gastrectomy regarding short-term and long-term outcomes.

Pediatric fitz-hugh-curtis syndrome diagnosed by magnetic resonance imaging.

A 17-year-old girl, who had a sexual intercourse history, presented with fever and right upper quadrant pain. On physical examination, tenderness and percussion tender were identified at that quadrant point, but cervical motion tenderness was not identified. Plane X-ray, abdominal ultrasonography, and nonenhanced abdominal computed tomography, because of contrast agent allergy, showed no specific findings. Nonenhanced magnetic resonance imaging (MRI) demonstrated the high-intensity area in the surface and subcapsule of the liver. From vaginal discharge, polymerase chain reaction for Chlamydia trachomatis was positive. Considered physical and MRI findings, Fitz-Hugh-Curtis syndrome was diagnosed. After Azithromycin administering (1000 mg/day), she got better and discharged.

Correlation between port-to-target distance and procedural difficulty in single-incision laparoscopic cholecystectomy: An observational study.

INTRODUCTION: Single-incision laparoscopic cholecystectomy (SILC) is more challenging than conventional (multiport) laparoscopic cholecystectomy (CLC) because of the increased likelihood of instrument collision and the limited surgical workspace. In SILC, procedural difficulties may increase when the port-to-target distance is long. We aimed to assess the correlation between port-to-target distance and procedural difficulty. METHODS: Thirty-six consecutive patients who underwent SILC at our hospital were included in this study. The umbilicus-to-Calot's triangle distance (UCD) was measured intraoperatively. The correlations between the UCD and operative time were analyzed, and for comparison, CLC cases during the same period (n = 28) were similarly analyzed. Moreover, UCD was estimated from preoperative CT (UCD-CT), and the usefulness of UCD-CT was assessed during SILC and CLC. RESULTS: Thirty-four patients successfully underwent SILC. There were positive correlations between the UCD and pneumoperitoneum time. Multivariate linear regression analysis, including BMI and height, which were previously reported to have a correlation with longer operative time in SILC, showed that UCD is an independent predictive factor for prolonged operative duration. However, BMI and height were not independent predictive factors. UCD and UCD-CT had a very strong positive correlation; therefore, UCD was estimated from CT. UCD-CT had a strong positive correlation with operative time in SILC, but not in CLC. CONCLUSIONS: A longer UCD is an important predictive factor for difficult cases of SILC, but this finding is not applicable in CLC. The usefulness of UCD is specific to SILC.

Rare case of idiopathic sclerosing cholangitis, which was difficult to distinguish from cholangiocarcinoma: A case report.

It is often difficult to correctly diagnose patients who present with dilation of the bile duct. Cholangiocarcinoma, primary sclerosing cholangitis (PSC) and immunoglobulin (Ig)G4-related sclerosing cholangitis must be considered as potential diagnoses for these cases. The current study presents a 73-year-old female patient who presented with a high fever and abdominal pain. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography revealed stenosis and dilation of the intrahepatic bile duct without solid components. It was suspected that the patient had intrahepatic cholangiocarcinoma. A left liver lobectomy, cholecystectomy and distal gastrectomy combined with a D2 lymph node dissection were performed. A pathological examination of the liver revealed increased fibrosis in the stroma, irregular bile duct dilation and clusters of inflamed lymph cells. No carcinoma or IgG4-positive plasma cells were observed and the typical findings of PSC were not detected. Based on these clinical and pathological results, the diagnosis was idiopathic sclerosing cholangitis, which is particularly rare. It is often difficult to preoperatively differentiate between cholangiocarcinoma and benign bile duct stenosis.

Optimal resection area for superior mesenteric artery nerve plexuses after neoadjuvant chemoradiotherapy for locally advanced pancreatic carcinoma.

Recently, several reports demonstrated the efficacy of neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT) for patients with borderline resectable (BRPC) and locally advanced unresectable pancreatic carcinoma (LAPC). The aim of this study was to evaluate the treatment response after NACRT, especially for nerve plexuses, and the optimal resection area for superior mesenteric artery nerve plexuses in BRPC and LAPC patients after NACRT.A total of 17 patients with BRPC and LAPC received preoperative gemcitabine-based NACRT. The numbers of BRPC and LAPC patients were 13 and 4, respectively. We evaluated nerve plexus invasion by CT before and after NACRT, decided on the resection area of plexus invasion in SMA before NACRT, and compared the preoperative evaluation and clinicopathological findings.In the plexus of the supra-mesenteric artery (pl-SMA), arterial nerve plexus invasion, in cases <90°, all patients showed the absence of residual cancer in the resected specimen after NACRT. In cases between 90° and 180°, 1 of 2 patients (50%) showed nerve plexus invasion. In cases over 180°, all patients showed nerve plexus invasion. We could perform R0 resection in all 10 cases, and pl-SMA invasion disappeared in 6 of 7 BRPC patients.We demonstrated the relationship between the angle of nerve plexus tumor invasion and treatment effect after NACRT. We could perform R0 resection in all pl-SMA invasion cases, deciding on the resection area of pl-SMA based on CT before NACRT.

Carcinoma in the residual rectum of a long-standing Crohn's disease patient following subtotal colectomy: A case report.

The development of colorectal cancer in long-standing Crohn's disease (CD) patients has become a major complication. Therapeutic guidelines for CD-associated cancer (CDAC) have already been established in Western countries; however, specific guidelines are not currently available in Japan. Surveillance of the residual intestine for cancer screening is important for long-standing CD patients. The present case report describes the occurrence of rectal carcinoma in a patient with a 25-year history of CD. A 37-year-old male with a 17-year history of CD underwent semi-emergent subtotal colectomy and ileostomy for bowel obstruction secondary to the transverse colon stenosis, and multiple severe stenosis and inflammation. Postoperatively, the patient resumed pharmacological treatment and underwent follow-up colonoscopies at ~1-2-year intervals. Despite continued pharmacological treatment, inflammation continued in the residual rectum. A total of 8 years following the primary operation, colonoscopy revealed inflammatory polyposis at the remnant rectum, which was diagnosed as adenocarcinoma. The interval between the last colonoscopy was 16 months. The patient then underwent laparoscopic abdominoperineal resection, and remained without recurrence for 12 months following resection. Thus, in long-standing CD patients, annual colonoscopy of the residual intestine may be considered for cancer screening, and specific surveillance guidelines for CDAC should be established.

Pancreaticoduodenectomy with Preservation of Collateral Circulation or Revascularization for Biliary Pancreatic Cancer with Celiac Axis Occlusion: A Report of 2 Cases.

BACKGROUND In cases of celiac axis occlusion requiring pancreaticoduodenectomy for malignancy, both oncologic curability and control of hepatic arterial flow must be considered, but the operative strategy is undeveloped. CASE REPORT Case 1: A 74-year-old man was diagnosed with hilar cholangiocarcinoma with celiac axis stenosis. The collateral from the superior mesenteric artery ran through the pancreas head but no invasion was observed in preoperative imaging. Hepatopancreatoduodenectomy with preservation of a collateral was performed. Case 2: A 69-year-old woman was diagnosed with pancreas head cancer with celiac axis occlusion. The collateral from the superior mesenteric artery ran through pancreas head and tumor invasion was observed. Pancreaticoduodenectomy with bypass revascularization using a vein graft was performed. Both operations were performed safely oncologically under preoperative planning that was based on computed tomographic angiography. The operative procedure was ultimately determined by evaluation of perioperative blood flow under Doppler ultrasonography after clamping the gastroduodenal artery. CONCLUSIONS Preoperative simulations of arterial revascularization and perioperative evaluation of blood flow are necessary for the success of this procedure.

L-Carnitine supplementation reduces the general fatigue of cancer patients during chemotherapy.

L-Carnitine (LC) plays an important role in the metabolism of fatty acids, and LC deficiency is associated with a feeling of weakness or general fatigue. Cancer patients receiving chemotherapy often develop LC deficiency, which is considered to be a factor contributing to general fatigue. The aim of the present study was to evaluate the efficacy of LC supplementation as a treatment for general fatigue in cancer patients during chemotherapy. A total of 11 cancer patients who were suffering from general fatigue during chemotherapy in our hospital between September 2014 and December 2015 were examined (6 cases involved adjuvant chemotherapy and 5 cases involved chemotherapy for unresectable or recurrent disease). The patients were administered 1,500 mg/day of levocarnitine per os, and the change in mean daily fatigue from the baseline to 8 weeks was assessed using the Brief Fatigue Inventory. The change in the plasma levels of albumin and the lymphocyte counts from the baseline to 8 weeks were also assessed. LC supplementation reduced general fatigue in all cases. Moreover, LC supplementation maintained the plasma levels of albumin and lymphocyte counts during chemotherapy, and enabled patients to continue chemotherapy sequentially without dose reduction. Therefore, LC supplementation improved general fatigue in all the examined cancer patients during chemotherapy. This treatment may make improve the tolerability of chemotherapy in cancer patients by reducing general fatigue and improving the nutritional status.

Curative resection of pancreatic ductal adenocarcinoma developing in the remnant pancreas 13 years after distal pancreatectomy for intraductal papillary mucinous neoplasms: A case report.

Intraductal papillary mucinous neoplasms (IPMNs) are characterized by the papillary proliferation of atypical mucinous epithelial cells in the pancreatic ductal system. There are two recurrence patterns following resection of IPMNs: Metachronous multifocal occurrence of IPMNs, and distinct pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. Several recent studies investigated the development of distinct PDAC during follow-up evaluation of IPMNs and the incidence rate ranged from 4.5 to 8%. Thus, IMPNs may be a good predictor for the early detection of PDAC during observation or after the resection of IPMNs. We herein report the rare case of a patient who underwent resection of PDAC that developed in the remnant pancreas 13 years after distal pancreatectomy with splenectomy for IPMNs. PDAC may develop in the remnant pancreas after pancreatectomy for IPMNs; thus, careful long-term follow-up with periodic surveillance, at least every 6 months, is warranted.

Laparoscopic total gastrectomy for advanced gastric cancer in a patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare congenital anomaly. Generally, laparoscopic surgery is difficult to perform in patients with SIT because of both the potential challenges associated with unexpected vascular anomalies and the lack of standardized strategy for handling such cases. This is the first report of laparoscopic total gastrectomy with lymph node dissection for advanced gastric cancer in a patient with SIT. A 79-year-old man with SIT was diagnosed with advanced gastric cancer. We performed laparoscopic total gastrectomy with modified D2 lymph node dissection (D2 without splenectomy) and esophagojejunal anastomosis using an overlap method involving retrocolic Roux-en-Y reconstruction. The total operating time was 232 min, and blood loss was 110 mL. There were no postoperative complications. In summary, laparoscopic total gastrectomy for gastric cancer can be performed safely, even in a patient with SIT.

Laparoscopic Cholecystectomy in a Child Using Slender Forceps.

Laparoscopic procedures in children are technically demanding because of reduced working space with careful monitoring of pneumoperitoneum pressure. We report a case of laparoscopic cholecystectomy performed in a 9-year-old boy using slender forceps which addressed all the above mentioned concerns. This shows a possibility of needlescopic surgery in children.

Long-term survival and prognosis associated with conversion surgery in patients with metastatic gastric cancer.

In gastric cancer, primary systemic chemotherapy is the standard approach for the management of patients with initially unresectable metastasis, and it occasionally leads to a reduction in the size of the lesion, which facilitates surgical resection. The aim of this study was to examine the prognosis of patients who were able to undergo complete resection following chemotherapy. A total of 10 patients who underwent radical surgery for stage IV primary gastric cancer after chemotherapy between 2009 and 2015 at the Department of Surgery of Hokkaido Social Work Association Obihiro Hospital (Obihiro, Japan) were retrospectively investigated. Three regimens were used (S-1, n=1; S-1 + cisplatin, n=8; and S-1 + docetaxel, n=1). The mean time from chemotherapy to surgery was 210 days. One total gastrectomy + splenectomy + colectomy, one total gastrectomy + splenectomy, four total gastrectomies and three distal gastrectomies were performed. There were two cases of pancreatic fistula formation postoperatively. All the patients survived for >1 year. Of the 10 patients, 5 survived without recurrence. The median survival time was 871.1 days after diagnosis. Therefore, curative resection after chemotherapy is associated with a better prognosis in stage IV gastric cancer patients.

Comparison of the invasiveness between reduced-port laparoscopy-assisted distal gastrectomy and conventional laparoscopy-assisted distal gastrectomy.

It is unknown whether reduced-port gastrectomy has a less invasive nature than conventional laparoscopy-assisted distal gastrectomy (C-LADG). So we compared 30 cases of dual-port laparoscopy-assisted distal gastrectomy (DP-LADG; using an umbilical port plus a right flank 5-mm port) as a reduced-port gastrectomy with 30 cases of C-LADG alternately performed by a single surgeon. No significant differences were observed in blood loss, intraoperative complications, the number of dissected lymph nodes, postoperative complications, the day of first defecation, analgesic agents required, changes in body temperature, heart rate, white blood cell count, serum albumin level, or lymphocyte count between the 2 groups. The amounts of oral intake in the DP-LADG group were significantly higher on postoperative days 9 and 10. We concluded that the amount of oral intake in the DP-LADG group was superior to that in the C-LADG group; however, no other evidence of DP-LADG being less invasive than C-LADG was obtained.

[A resected case of recurrent intrahepatic cholangiocellular carcinoma with a cholangiocellular carcinoma component after transcatheter arterial embolization and radiofrequency ablation].

We report a resected case of intrahepatic cholangiocarcinoma (ICC) with a cholangiolocellular carcinoma (CoCC) component. A 77-year-old man had been followed up regularly for chronic hepatitis C for 20 years. In April 2008, a hepatic tumor of 30-mm diameter was detected in segment 2 by computed tomography scan. The tumor was enhanced in the early phase and the enhancement was prolonged. He was treated with transcatheter arterial embolization following the diagnosis of hepatocellular carcinoma (HCC). He had a local recurrence in the same segment (S2) in March 2009, and transcatheter arterial embolization and radiofrequency ablation were performed. In March 2011, abdominal dynamic computed tomography and magnetic resonance imaging showed a sectoral lesion in S2/4 with early and prolonged enhancement. Following the preoperative diagnosis of local recurrence of HCC, he underwent left lobectomy of the liver. Histopathologically, strongly atypical glandular epithelial cells and mucin production were observed, and these cells grew invasively into the liver parenchyma. Furthermore, tumor cells in the peripheral area grew and replaced adjacent hepatic cells, and anastomosing cavities of glands were found on the gitter stein. For these reasons, the histopathological diagnosis was ICC with a CoCC component.

[A case in which a mucin-producing papillary adenocarcinoma of the gallbladder was resected].

An 81-year-old man complaining of abdominal pain underwent ultrasonography at another hospital that revealed gallbladder swelling, and he was admitted to our hospital for further examination. CT and ERCP revealed a papillary tumor extending from the body to the fundus, leading to the diagnosis of gallbladder cancer. Other examinations showed no sign of invasion or lymph node metastases. We performed full-thickness cholecystectomy. The histopathological diagnosis was mucin-producing papillary adenocarcinoma(T1N0M0, Stage I) of the gallbladder.

[A case report of goblet cell carcinoid tumor of the appendix].

Goblet cell carcinoid (GCC) tumor of the appendix is rare, and the prognosis is considered poor compared to classical carcinoid tumor. We present a case of a 60-year old woman who underwent appendectomy for acute appendicitis. Histopathological studies revealed a GCC tumor with submucosal invasion. Based on the malignancy of this tumor and the possible risk of regional lymph node metastases, we performed laparoscopic ileocecectomy with lymph node dissection. Histologically, no residual tumor or lymph node metastases were found. The patient remains well without any sign of recurrence.

Effect of shorter term of intravenous infusion for reduction of catheter-related bloodstream infection after gastrectomy.

After gastrectomy, a longer period of intravenous alimentation is required than for other digestive surgeries, portending a higher risk of catheter-related bloodstream infection (CRBSI). From assessment of CRBSI occurring between 2004 and 2007 (preintervention group), the duration of intravenous infusion between 2008 and 2010 (postintervention group) was changed to shorter-term (6-day) infusion. To verify the effect of changes in injection schedule on the incidence of CRBSI, the occurrence of CRBSI was studied comparatively among preintervention and postintervention cases, excluding cases requiring intravenous infusion preoperatively, and cases requiring long-term intravenous infusion postoperatively due to postoperative complications. The rate of CRBSI in the postintervention group (0%; 0 of 298) was significantly lower than that in the preintervention group (1.7%; 8 of 477; P = 0.026). There was no significant difference between preintervention and postintervention groups in postoperative complications. Six-day infusion decreased the incidence of CRBSI after gastrectomy significantly, without increasing postoperative complications.