Intraductal papillary mucinous neoplasms of the pancreas: an updated experience

OBJECTIVE: To update the authors' experience with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. BACKGROUND DATA: IPMNs are intraductal mucin-producing cystic neoplasms of the pancreas with clear malignant potential. Since the authors' 2001 report, the number of IPMNs resected at our institution has more than doubled, providing an opportunity to define the clinical features of this distinct neoplasm. METHODS: All patients undergoing pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and March 2003 were evaluated. Noninvasive IPMNs were classified as "adenoma," "borderline," or "carcinoma-in situ" (CIS) depending on the degree of dysplasia within the specimen. Invasive cancers were classified as tubular, colloid, mixed, or anaplastic types. Pathology was retrospectively reviewed to identify main-duct or branch-duct origin of the tumors. Long-term overall survival for patients having IPMNs with invasive cancer was compared with those patients having IPMNs without an invasive component. RESULTS: Between January 1987 and March 2003, inclusive, 136 pancreatic resections were performed for patients with IPMNs, with 78 resections performed since January 2001. The mean age of the patients was 66.8 +/- 1.1 years, with 57% being male and 89% white. Pancreaticoduodenectomy was performed in 71% of patients, total pancreatectomy in 15%, distal pancreatectomy in 12%, and central pancreatic resection in 2%. IPMNs without evidence of invasive cancer were identified in 62% (n = 84) of patients (17% adenoma, 28% borderline, or 55% CIS). The remaining 38% (n = 52) of patients had IPMNs with associated invasive cancer (60% tubular, 27% colloid, 7% mixed, and 6% anaplastic). The mean age of patients with IPMN adenoma was 63.2 years, 66.7 years for those with borderline/CIS IPMNs, and 68.1 years for those with invasive cancer (P = 0.08, adenomas vs. invasive cancer). In those patients with invasive cancers, 15% had invasive cancer at the final surgical margin, 23% had IPMN without invasive cancer at the margin, and 54% had lymph node metastases. Residual IPMN was identified at the neck or uncinate margin in 24% of patients with noninvasive IPMNs. The overall 5-year survival for patients having IPMNs without invasive cancer was 77% (several deaths secondary to metachronous invasive cancer), compared with 43% in those patients with an invasive component (P < 0.0001). There were no differences in survival when comparing adenomas, borderline neoplasms, and CIS. Similarly, there were no statistically significant differences in survival when comparing branch-duct, main-duct, and combined variants; however, the branch-duct variants were more often noninvasive. For those patients with invasive IPMNs, 2-year survival was 40% when margins were positive for invasive cancer or for IPMN without invasive cancer, and 60% when margins were tumor-free (P = 0.15). Those patients with colloid carcinomas (n = 14) had improved survival compared with those with tubular carcinomas (n = 31), with 5-year survival rates of 83% and 24%, respectively. IPMN recurrences and deaths from cancer occurred in patients with both invasive and noninvasive IPMNs at initial resection. CONCLUSIONS: IPMNs continue to be recognized with increasing frequency. Five-year survival for those patients following resection of IPMNs with invasive cancer (43%) is improved compared with those patients with resected pancreatic ductal adenocarcinoma in the absence of IPMN (averages 15%-25%). Survival following resection of IPMNs without invasive cancer (regardless of degree of dyplasia) is good, but recurrent disease in the residual pancreas suggests that long-term surveillance is critical. Based on the age at resection data, there appears to be a 5-year lag time from IPMN adenoma (63.2 years) to invasive cancer (68.1 years).     

Nevoid Basal cell carcinoma syndrome with medulloblastoma and meningioma--case report

A 35-year-old man presented with a rare case of nevoid basal cell carcinoma syndrome, or Gorlin's syndrome, associated with both medulloblastoma and meningioma, manifesting as visual field constriction due to multiple parasellar tumors. He had undergone resection of a medulloblastoma at the age of 1 year 9 months, followed by adjunctive irradiation with a total dose of 40 Gy. He presented with multiple subcutaneous nodules on his face and neck. Histological examination of biopsy specimens established the diagnosis of nevoid basal cell carcinoma syndrome. Tuberculum sellae meningioma was removed through a craniotomy, and his symptoms improved. Meningioma is known to occur in the field of therapeutic irradiation, so chemotherapy may be a better option for medulloblastoma associated with nevoid basal cell carcinoma syndrome.     

Modification of the education system for organ procurement coordinators in Japan after the revision of the Japanese Organ Transplantation Act

Background

From October 1997 to July 2010, only 86 brain-dead (BD) organ donations were obtained and no organs were retrieved from children under 15 years of age because of the strict Japan Organ Transplantation Act. The Act was revised on July 17, 2010, allowing organs to be donated after BD with family consent.

Objective

To manage the increased donations after the revision, the Japan Organ Transplant Network (JOT) employed 10 organ procurement coordinators (OPCs) and modified its education systems. We retrospectively reviewed the modified education programs to evaluate whether they were effective and whether the processes of organ donation were promptly performed after the revision of the Act.

Methods

The modifications of education program were: changing OPC to guideline manuals to correspond to the revised Transplant Act; OPCs were taught the new organ procurement system; and a special education program was provided for the 10 newcomers for 2 months.

Results

After 12 months of the revision, 58 BD organ donations were accomplished, whereas they had averaged 6.6 in a year before the revision. Two pediatric BD organ donations were accomplished without problem. One priority organ donation to a relative was performed uneventfully. After applying the modified education program, skilled JOT OPCs and leader JOT OPCs increased.

Conclusions

To manage increased organ donations after the revision of the Act, the educational system was modified and 58 brain dead organ donations were performed safely.     

Professional education and hospital development for organ donation

Because of the strict Organ Transplantation Act, only 81 brain dead (BD) organ donations had been performed in Japan for 13 years since 1997. The Act was revised on July 17, 2010, allowing, organs to be donated after BD with consent from the family, if the subject had not denied organ donation previously. This act has lead to an expectation of a 6-7-fold increase in BD donation. The 82 organ procurement coordinators (OPC) in Japan include 32 belonging to the Japanese Organ Network (JOT) and the others to each administrative division. JOT has guideline manuals of standard roles and procedures of OPC during organ procurement from BD and cardiac death donors.To manage the increased organ donations after the revision of the act, we have modified the education system. First, we modified the guideline manuals for OPC to correspond to the revised Transplant Act and governmental guidelines. Second, all OPC gathered in a meeting room to learn the new organ procurement system to deal with the revised Transplant Act and guidelines. Third, a special education program for 2 months was provided for the 10 newcomers. Last, the practical training in each donor case for newcomers was performed by older OPC.Topics of the education program were the revised transplant act and guidelines, family approach to organ donation, BD diagnosis, donor evaluation and management, organ procurement and preservation, allocation system, hospital development and family care.In the future, each OPC will be divided into special categories, such as the donor family OPC, the donor management OPC, and the operating room OPC. Therefore, we need to construct separate special education programs for each category.     

Prostate biopsy in patients with long-term use of indwelling bladder catheter: What is the rationale?

ObjectiveAcute urinary retention (AUR) is expected to occur in 2% to 39% men with benign prostatic hyperplasia. To date, no study has elucidated the effect of long-term use of indwelling bladder catheter on serum prostate specific antigen (PSA) levels and on the incidence of prostate cancer (CaP). The aim of the present study is to analyze the incidence of CaP in patients with long-term use of indwelling bladder catheter and determine some practice patterns on this issue.Materials and methodsThe study comprised a retrospective analysis of data from 1,651 patients who had undergone transrectal ultrasound (TRUS)-guided prostate biopsy from July 2004 to June 2009. Among these patients, 198 (12%) were using an indwelling bladder catheter during the biopsy for at least 1 month. The incidence of CaP was recorded according to total PSA levels. Other variables such patient age, free/total PSA rate, PSA density, prostate volume, and duration of catheter use was also analyzed. Men with a digital rectal examination suspicious for cancer were not considered for analysis.ResultsMedian patient age was 71 years (37 to 89 years). Overall, 25% of patients presented a CaP diagnosis. CaP incidence according to the PSA levels was 0%, 18.9%, 24.5%, and 40.6% for patients with PSA ≤4.0, 4.1–10.0, 10.1–20.0, and >20.0 ng/ml, respectively. When prostate volume was analyzed together, we demonstrated that only 1 (2.4%) patient with PSA below 10.0 ng/ml and prostate volume >60 g had CaP. Median total PSA, PSA density, and prostate volume were statistically different between patients with and without CaP.ConclusionsProstate biopsy should not be indicated for all patients with diagnosis of BPH and AUR who present an elevated PSA level. Patients with PSA below 10.0 ng/ml, and prostate volume >60 g should only undergo biopsy in selected cases. Patients with PSA >20.0 ng/ml and a prostate volume ≤60 g are at higher risk of CaP diagnosis.     

Induction of 11beta-hydroxysteroid dehydrogenase type 2 and hyperaldosteronism are essential for enhanced sodium absorption after total colectomy in rats

BACKGROUND: Patients who undergo total colectomy with ileopouch anal reconstruction often have persistent diarrhea and frequent bowel movements. Analysis of the intestinal adaptation after total colectomy may lead to developing novel therapies for postoperative diarrhea. METHODS: Sprague-Dawley rats underwent total colectomy with ileoanal reconstruction and were sacrificed 4 and 8 weeks later. Mucosal response to aldosterone was evaluated with the use of ileal mucosa in an Ussing chamber by measuring short circuit current after in vitro stimulation with aldosterone. We investigated the expression of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD 2) in intestinal epithelial cells. To examine the role of hyperaldosteronism, we also evaluated rats treated with a sodium-deficient diet or subcutaneous aldosterone infusion. RESULTS: Aldosterone levels increased 80-fold after total colectomy. A comparable amount of aldosterone dramatically increased aldosterone-mediated, amiloride-sensitive short circuit current in the mucosa from colectomized rats, but not in control rats. We measured an increase in 11beta-HSD 2 messenger RNA and protein in the distal ileum from colectomized rats. Circulating aldosterone appears to be essential for these functional and molecular changes because similar results were obtained by using the mucosa from both dietary sodium-depleted and aldosterone-infused rats. CONCLUSIONS: Induction of 11beta-HSD 2 is essential for enhanced mineralocorticoid action in the remnant ileum after total colectomy in rats.     

Granular cell tumor of the neurohypophysis with optic tract edema

Granular cell tumor of the neurohypophysis is a rare disease entity. To our knowledge, this is the first report concerning a granular cell tumor of the neurohypophysis associated with optic tract edema. A 55-year-old man underwent brain magnetic resonance imaging (MRI) for a medical check-up, and a suprasellar tumor was detected. Brain computed tomography (CT) demonstrated a well delineated, homogenous, slightly hyperdense suprasellar tumor. MRI detected a lobular tumor that was isointense on T1-weighted images, hypointense on T2-weighted images, and showed homogeneous enhancement after administration of a gadopentetate dimeglumine. T2-weighted images and fluid-attenuated inversion recovery (FLAIR) images demonstrated a hyperintense region in the optic tract. Subtotal tumor resection was performed, and histological examination confirmed the diagnosis of granular cell tumor. Postoperative MRI showed that the tumor volume was reduced and optic tract edema diminished compared with the preoperative findings. We also review the literature focusing on radiographic findings, and compare the effectiveness of MRI and CT for diagnosing granular cell tumor of the neurohypophysis.     

Absolute myocardial flow quantification with 82Rb PET/CT: comparison of different software packages and methods

Purpose

In clinical cardiac ⁸²Rb PET, globally impaired coronary flow reserve (CFR) is a relevant marker for predicting short-term cardiovascular events. However, there are limited data on the impact of different software and methods for estimation of myocardial blood flow (MBF) and CFR. Our objective was to compare quantitative results obtained from previously validated software tools.

Methods

We retrospectively analyzed cardiac ⁸²Rb PET/CT data from 25 subjects (group 1, 62?±?11 years) with low-to-intermediate probability of coronary artery disease (CAD) and 26 patients (group 2, 57?±?10 years; P?=?0.07) with known CAD. Resting and vasodilator-stress MBF and CFR were derived using three software applications: (1) Corridor4DM (4DM) based on factor analysis (FA) and kinetic modeling, (2) 4DM based on region-of-interest (ROI) and kinetic modeling, (3) MunichHeart (MH), which uses a simplified ROI-based retention model approach, and (4) FlowQuant (FQ) based on ROI and compartmental modeling with constant distribution volume.

Results

Resting and stress MBF values (in milliliters per minute per gram) derived using the different methods were significantly different: using 4DM-FA, 4DM-ROI, FQ, and MH resting MBF values were 1.47?±?0.59, 1.16?±?0.51, 0.91?±?0.39, and 0.90?±?0.44, respectively (P?<?0.001), and stress MBF values were 3.05?±?1.66, 2.26?±?1.01, 1.90?±?0.82, and 1.83?±?0.81, respectively (P?<?0.001). However, there were no statistically significant differences among the CFR values (2.15?±?1.08, 2.05?±?0.83, 2.23?±?0.89, and 2.21?±?0.90, respectively; P?=?0.17). Regional MBF and CFR according to vascular territories showed similar results. Linear correlation coefficient for global CFR varied between 0.71 (MH vs. 4DM-ROI) and 0.90 (FQ vs. 4DM-ROI). Using a cut-off value of 2.0 for abnormal CFR, the agreement among the software programs ranged between 76 % (MH vs. FQ) and 90 % (FQ vs. 4DM-ROI). Interobserver agreement was in general excellent with all software packages.

Conclusion

Quantitative assessment of resting and stress MBF with ⁸²Rb PET is dependent on the software and methods used, whereas CFR appears to be more comparable. Follow-up and treatment assessment should be done with the same software and method.     

Coronary Vascular Bed Perfusion with a Polyethylene Glycol-Modified Hemoglobin-Encapsulated Liposome, Neo Red Cell, in Rats

Whether hemoglobin (Hb) encapsulated liposomes have vasoconstrictive activity remains controversial. We therefore examined the vascular activity of a liposome Hb, Neo red cell (NRC), in a simple in vitro model of Langendorff perfusion of the rat heart using Krebs-Henseleit (KH) solution as the perfusate. In the KH solution, NRC (Hb at 1 mg/ml), however, induced an immediate and abnormal increase in perfusion pressure. Histological examinations revealed that embolisms were the likely cause of this disturbance. Inorganic crystals formed by the mixing of NRC with the perfusate were a possible source of the embolisms. We found that the addition of bovine serum albumin to the perfusate was effective in avoiding embolic events. This protocol was used to compare the vasoconstrictive properties of unmodified bovine Hb and NRC. Unmodified bovine Hb (1 mg/ml) caused an increase in perfusion pressure and a decrease in the duration of bradykinin-induced relaxation. In contrast, NRC (Hb at 1 mg/ml) had no such vasoconstrictive effects. These results provide the first information regarding perfusion of the circulatory vascular bed by NRC and further evidence that the encapsulation of Hb into liposomes is an effective approach to modulate Hb-related vasoconstrictive activity.     

Implications of Popliteal Lymph Node Detected by Sentinel Lymph Node Biopsy

BACKGROUND: Although there is lymphatic flow into the popliteal fossa from a skin tumor located in the lower leg, popliteal metastasis is extremely rare. Recently, sentinel lymph nodes outside traditional nodal basins have been identified. This study investigated the incidence of sentinel nodes in the popliteal region and the indication for biopsy. METHODS: Fourteen patients with various skin cancers involving the lower extremities (nine melanomas, four squamous cell carcinomas, and one sweat gland carcinoma) underwent lymphoscintigraphy and excision with sentinel lymph node biopsy. RESULTS: In all 14 patients, hot spots showed accumulation in the groin region. Five of 14 patients (36%) demonstrated popliteal sentinel nodes in addition to the inguinal nodes. Three of five popliteal sentinel nodes were histologically studied. A patient with acral melanoma demonstrated micrometastasis of melanoma cells in a popliteal node but not in the groin node. CONCLUSION: This study demonstrates that sentinel lymph nodes located in the popliteal fossa are frequently detected by lymphoscintigraphy and that biopsy should be performed if popliteal nodes are identified.