Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected.     

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Background/Purpose Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs. Methods Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct’s largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations. Results Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2–8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2–5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323). Conclusions The incidence of K-ras mutation may be associated with the hypersecretion of mucin.     

Follicular lymphoma of the extrahepatic bile duct mimicking cholangiocarcinoma

We report a case of a 33-year old man who presented with symptoms and signs of an acute biliary tract obstruction with jaundice and abdominal pain. Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence, and a mass at the hepatic hilum which obstructed the extrahepatic bile duct from the outside. At laparotomy, there was 3-cm-size nodule at the hilum which presented with a rubbery consistency. We performed extrahepatic bile duct resection and right and left hepaticojejunostomy. Histological examination of the resected specimen revealed follicular lymphoma, which consisted of medium cleaved follicle-like cells, grade 1 of 3 according to the revised European-American classification of lymphoid neoplasms proposed by International Lymphoma Study Group. Postoperative follow-up of more than 1 year has been completely uneventful, without any symptoms or signs of disease recurrence. This is the second case report of follicular lymphoma of the extrahepatic bile duct.     

Small Bowel Perforation Caused by Metastasis from an Extra-Abdominal Malignancy: Report of Three Cases

Small bowel perforation is rarely caused by metastasis from an extra-abdominal malignancy. This report describes three cases of small bowel perforation that occurred secondary to a metastatic tumor. The first case involved a 72-year-old man with malignant lymphoma of the larynx that had been treated with chemo- and radiation therapy; the second involved a 70-year-old man with rhabdomyosarcoma of the mediastinum that had been treated with radiation therapy; and the third involved a 41-year-old man with lung carcinoma that had been treated with surgery 10 months prior to perforation. Each patient presented with acute abdominal pain, had X-ray findings of free air in the abdomen, and underwent limited emergency surgery. Wedge resection and closure of the ileum was performed for the first patient and partial bowel resection with the creation of an intestinal stoma was performed for the second and third patients. In each case, the histologic findings of the resected specimens were consistent with the extra-abdominal primary tumors. Although the patients recovered sufficiently to begin eating and moving about, all three died of cancer or cancer-related complications within 45 days of surgery. We conclude that surgeons should be aware of the poor prognosis of such patients and perform only the minimal surgery required. Received: April 7, 2000 / Accepted: September 26, 2000     

The original hole-in-one guide for atlantoaxial transarticular screw fixation

Atlantoaxial fusion by transarticular screw fixation provides firm fixation, and good results have been reported. However, there are also problems, such as injury of the vertebral artery at the time of screw insertion. For accurate facet fusion, we developed a new hole-in-one guide for screw fixation and obtained good results with its use. In 60 adult subjects, we measured the antero-posterior and transverse axes and determined the center of the atlantoaxial surface and the insertion point of the screw in three dimensions on computed tomography scans. Based on these values, we measured the optimum screw insertion angle on sagittal and coronal planes, and the distance between the center and the posterior margin of the joint surface; our new hole-in-one guide was produced with these data. When the guide tip is determined to be located at the center posterior margin of the axial joint surface, and the guidewire insertion point is determined to be located at the center of the axial inferior facet immediately above the C2/3 joint, the guidewire is passed through the axial pedicle and the center of the atlantoaxial joint. Since April 1997, we have used this hole-in-one guide technique in eight patients with atlantoaxial instability. The screws passed the pars interarticularis and the center of the atlantoaxial joint in all patients with safety and accuracy. No complications associated with this technique occurred. Received: December 24, 1999 / Accepted: August 25, 2000     

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma: a case report

We report a case of primary mucosa-associated lympoid tissue (MALT) lymphoma of the urinary bladder associated with left renal pelvic carcinoma. A 84-year-old woman showed microscopic hematuria during follow up for hypertention. Left renal pelvic tumor was found and she was referred to our hospital for further evaluation and managemant. She showed pyuria and Escherichia coli was detected by urine culture. Intravenous pyelography and computed tomography revealed the left renal pelvic tumor and solid bladder tumor. Transurethral resection of bladder tumor and left total nephroureterectomy were performed. Histologically, the left renal pelvic tumor was urothelial carcinoma > > adenocarcinoma, G2, pT2 and the bladder tumor was MALT lymphoma. Ga-scintigraphy showed no hot uptake suspicious of metastatic lesion. Then, external beam radiotherapy (36 Gy) was performed to the urinary bladder. She has been alive for 14 months with neither renal pelvic tumor nor MALT lymphoma showing any evidence of disease progression.     

Case of spontaneous bilateral VA dissecting aneurysm presenting with SAH

We report a case of bilateral vertebral artery (VA) dissecting aneurysm presenting subarachnoid hemorrhage (SAH). It was difficult to decide which side was responsible for SAH because the patient's symptom and head CT suggested that the left VA aneurysm had ruptured, but angiography and MRA showed an irregular pearl and string sign on the right side. He was successfully treated by trapping of the right VA dissecting aneurysm and we confirmed by intraoperative evaluation that the right VA dissecting aneurysm had ruptured. The left unruptured aneurysm decreased its size spontaneously. In the treatment of the bilateral VA dissecting aneurysms, angiography needs to be performed over and over again because contralateral unruptured aneurysm may grow or rupture due to increased hemodynamic stress. Various combinations of direct sugery with or without arterial reconstruction and endovascular treatment should be considered when treating bilateral VA dissecting aneurysms.     

Clinical outcome of surgical management for patients with renal cell carcinoma involving the inferior vena cava

BACKGROUND: The objective of this study was to evaluate the clinical outcome after surgical management of renal cell carcinoma (RCC) extending to the inferior vena cava (IVC). METHODS: This study included a total of 55 patients (41 men and 14 women; mean age, 59.3 years) with RCC (39 right- and 16 left-sided tumors) involving the IVC, who underwent radical nephrectomy and tumor thrombectomy between 1983 and 2005 at a single institution in Japan. The level of thrombus was classified as follows: level I, infrahepatic; level II, intrahepatic; level III, suprahepatic; and level IV, extending to the atrium. Clinicopathological data from these patients were retrospectively reviewed to identify factors associated with survival. RESULTS: There were 11 and 18 patients who were diagnosed as having lymph node and distant metastases, respectively. Twenty-two patients had tumor thrombus in level I, 20 in level II, 10 in level III, and 3 in level IV. Pathological examinations demonstrated that 34 and 21 patients had clear cell carcinoma and non-clear cell carcinoma, respectively, 42, 9 and 4 were pT3b, pT3c and pT4, respectively, and 6, 35 and 14 were Grades 1, 2 and 3, respectively. Cancer-specific 1-, 3- and 5-year survival rates of these 55 patients were 74.5%, 51.4% and 30.3%, respectively. Among several factors examined, clinical stage (P = 0.047), lymph node metastasis (P = 0.016), histological subtype (P = 0.034) and tumor grade (P < 0.001) were significantly associated with cancer-specific survival by univariate analysis. Furthermore, multivariate analysis demonstrated clinical stage (P = 0.037) and tumor grade (P < 0.001) as independent predictors of cancer-specific survival irrespective of other significant factors identified by univariate analysis. CONCLUSIONS: In patients with RCC involving the IVC, biological aggressiveness characterized by tumor grade rather than tumor extension would have more potential prognostic importance; therefore, more intensive multimodal therapy should be considered in patients with high grade RCC with tumor thrombus extending into the IVC.     

Involvement of the programmed death-1/programmed death-1 ligand pathway in CD4+CD25+ regulatory T-cell activity to suppress alloimmune responses

BACKGROUND: Immune regulatory CD4+CD25+ T (regulatory T; Treg) cells play a vital role in the induction and maintenance of self-tolerance. They are essential for the homeostasis of T cells, the prevention of autoimmunity, and the induction of tolerance to allogeneic donor grafts. However, the underlying mechanism of their functions remains mostly elusive. Therefore, we investigated here a crucial role of Treg cells in their response to alloantigen via the programmed death (PD)-1/PD-1 ligand (PD-L1) pathway. METHODS: In vitro mixed lymphocyte reaction (MLR) assay, graft-versus-host disease (GvHD) and a skin transplantation model were used to evaluate the mechanisms of PD-1/PD-L1 pathway. RESULTS: Blockade of the PD-1/PD-L1 pathway using anti-PD-L1 monoclonal antibodies (mAb) is found to inhibit Treg cell's ability to suppress and restore CD4+CD25-T-cell proliferation in vitro. GvHD was lethal after adoptive transfer of allogeneic C57BL/6 (H-2K) spleen cells to NOD/SCID (H-2K) mice unless CD25+ T cells were also included. Strikingly, the suppression of GvHD by CD25+ cells was abrogated by anti-PD-L1 mAb administration. The abrogation of Treg-cell-mediated suppression could also be demonstrated in a Balb/c (H-2K) to B6/Rag-2KO (H-2K) skin-allograft model. CONCLUSIONS: The blockade of the PD-1/PD-L1 pathway abrogates Treg-mediated immunoregulation, thus suggesting that the PD-1/PD-L1 pathway is required for Treg suppression of the alloreactive responses of CD4+CD25-T cells. This finding has important implications for clarifying the mechanisms of allograft rejection and GvHD.     

Comparative biomechanical analysis of an improved novel pedicle screw with sheath and bone cement

STUDY DESIGN: A human cadaveric biomechanical study of fixation strength of an improved novel pedicle screw (NPS) with cement and a conventional screw. OBJECTIVE: To clarify whether the NPS has adequate fixation strength without leakage in vertebrae with low bone quality. SUMMARY OF BACKGROUND DATA: The fixation strength of pedicle screws decreases in frail spines of elderly osteoporotic patients. Augmentation of screw fixation with bone cement must be balanced against increased difficulty of screw removal and risk of cement leakage. We developed the NPS consisting of an internal screw and an outer sheath to mitigate the disadvantages of cement augmentation. METHODS: The T12 and L1 vertebrae obtained from 18 formalin preserved cadavers (11 males and 7 females; mean age, 82.7 y) were used. The mean bone mineral density was 0.39 +/- 0.14 g/cm2. The NPS was inserted into one pedicle of each vertebra and the control screw, a Compact CD2 screw, was inserted into the contralateral pedicle. Both screws were 6mm in diameter and 40 mm in length. Pull-out tests were performed at a crosshead speed of 10 mm/min. Cyclic loading tests were performed with a maximum 250 N load at 2 Hz until 30,000 cycles. RESULTS: Cement leakage did not occur in any of the specimens tested. The mean maximum force at pull-out was 760 +/- 344 N for the NPS and 346 +/- 172N for the control screw (P < 0.01). Loosening of 50% of the screws was observed after 17,000 cycles of the NPS and after 30 cycles of the control screw. The hazard ratio of loosening was 19.6 (95% confidence interval 19.3-19.9) (P < 0.001). CONCLUSIONS: The NPS showed a significantly higher mechanical strength than the control screw in both pull-out tests and cyclic loading tests. The NPS showed more than adequate strength without cement leakage.