Pheochromocytoma as the first manifestation of MEN2A with RET mutation S891A: report of a case

We report a rare case with pheochromocytoma as the first manifestation of multiple endocrine neoplasia type 2A with RET mutation S891A. Bilateral pheochromocytomas were identified in a 54-year-old woman. Screening for RET revealed a rare S891A mutation located in the intracellular tyrosine kinase domain. This mutation was previously recognized as one of the mutations only in cases manifesting solely medullary thyroid carcinomas (MTCs). Since calcitonin stimulation test indicated positive result, total thyroidectomy was performed 1 year after the bilateral adrenalectomy, and C-cell hyperplasia was diagnosed by histopathological examination. Our report suggests that cases with S891A mutation, akin to those with other RET mutations, require screening for pheochromocytoma. In addition, it is indicated that calcitonin stimulation test should be performed even in the unaffected elder cases with S891A mutation although the mutation is classified as lowest risk group on MTC in guidelines.     

Current status of countermeasures for infectious diseases and resistant microbes in the field of urology

A worldwide increase in antimicrobial‐resistant microbes due to the improper use of antimicrobial agents, along with a lack of progress in developing new antimicrobials, is becoming a societal problem. Although carbapenem‐resistant Enterobacteriaceae, which are resistant to carbapenem antimicrobials, first appeared in 1993, treatment options remain limited. Mechanisms behind antimicrobial resistance involve changes to microbial outer membranes, drug efflux pump abnormalities, β‐lactamase production and the creation of biofilms around cell bodies. Genetic information related to these forms of antimicrobial resistance exists on chromosomes and plasmids, and when located on the latter can easily be transmitted to other strains, no matter the species, which creates a risk of antimicrobial resistance spreading exceptionally rapidly. To prevent the spread of antimicrobial resistance, the World Health Organization in 2015 published an action plan on antimicrobial resistance, based on which World Health Organization member countries have laid out specific policies and targets. Urinary tract infections are a type of healthcare‐associated infection, and the sexually transmitted disease pathogen, Neisseria gonorrhoeae, has been included in a list of microbes that pose a risk to human health published by the US Centers for Disease Control and Prevention. Urologists face numerous problems when attempting to use antimicrobials properly, which is one method of dealing with antimicrobial resistance. Therefore, this article describes the current state of resistant microbes associated with urinary tract infections and countermeasures for antimicrobial resistance, including new antimicrobials.     

Comparison of the Loss of Renal Function after Cold Ischemia Open Partial Nephrectomy,Warm Ischemia Laparoscopic Partial Nephrectomy and Laparoscopic Partial Nephrectomy Using Microwave Coagulation

Purpose

Nephron sparing surgery is an effective surgical option in patients with renal cell carcinoma. Laparoscopic partial nephrectomy involves clamping and unclamping techniques of the renal vasculature. This study compared the postoperative renal function of partial nephrectomy using an estimation of the glomerular filtration rate (eGFR) for a Japanese population in 3 procedures; open partial nephrectomy in cold ischemia (OPN), laparoscopic partial nephrectomy in warm ischemia (LPN), and microwave coagulation using laparoscopic partial nephrectomy without ischemia (MLPN).

Materials and Methods

A total of 57 patients underwent partial nephrectomy in Yokohama City University Hospital from July 2002 to July 2008. 18 of these patients underwent OPN, 17 patients received MLPN, and 22 patients had LPN. The renal function evaluation included eGFR, as recommended by The Japanese Society of Nephrology.

Results

There was no significant difference between the 3 groups in the reduction of eGFR. eGFR loss in the OPN group was significantly higher in patients that experienced over 20 minutes of ischemia time. eGFR loss in LPN group was significantly higher in patients that experienced over 30 minutes of ischemia time.

Conclusion

This study showed that all 3 procedures for small renal tumor resection were safe and effective for preserving postoperative renal function.Key Words: eGFR, Partial nephrectomy, Renal function, Laparoscopic partial nephrectomy     

Feasibility of laparoscopic gastrectomy for advanced gastric cancer with positive peritoneal cytology

Purpose

The role of gastrectomy for patients with positive peritoneal cytology, but a negative macroscopic peritoneal implant (P?/cy+), remains unclear. The aim of this study was to evaluate laparoscopic gastrectomy for P?/cy+ patients.

Methods

This study reviewed a prospectively maintained gastric cancer database of gastric-cancer patients those underwent surgical resection. P?/cy+ gastric cancer that had invaded the subserosa, or deeper layers, of the stomach wall without distant organ metastases was considered operable in this institution. P?/cy+ patients underwent either open or laparoscopic gastrectomy with D2 lymphadenectomy. The short-term results were examined to assess differences in outcome between the two groups.

Results

Eighteen P?/cy+ patients without distant organ metastases underwent surgery between 2000 and 2010. Laparoscopic gastrectomy was performed in nine patients and open gastrectomy in nine patients. The estimated blood loss was significantly smaller, the resumption of food intake earlier, and the length of postoperative hospital stay shorter in the patients that underwent laparoscopic gastrectomy than in the patients that underwent open gastrectomy. There were no significant differences in the 2-year survival rates between the groups.

Conclusion

Laparoscopic gastrectomy for P?/cy+ patients is a minimally invasive and safe oncologic procedure with good short-term results.     

Hyperactive Transforming Growth Factor‐β1 Signaling Potentiates Skeletal Defects in a Neurofibromatosis Type 1 Mouse Model

Dysregulated transforming growth factor beta (TGF‐β) signaling is associated with a spectrum of osseous defects as seen in Loeys‐Dietz syndrome, Marfan syndrome, and Camurati‐Engelmann disease. Intriguingly, neurofibromatosis type 1 (NF1) patients exhibit many of these characteristic skeletal features, including kyphoscoliosis, osteoporosis, tibial dysplasia, and pseudarthrosis; however, the molecular mechanisms mediating these phenotypes remain unclear. Here, we provide genetic and pharmacologic evidence that hyperactive TGF‐β1 signaling pivotally underpins osseous defects in Nf1^flox/?;Col2.3Cre mice, a model which closely recapitulates the skeletal abnormalities found in the human disease. Compared to controls, we show that serum TGF‐β1 levels are fivefold to sixfold increased both in Nf1^flox/?;Col2.3Cre mice and in a cohort of NF1 patients. Nf1‐deficient osteoblasts, the principal source of TGF‐β1 in bone, overexpress TGF‐β1 in a gene dosage–dependent fashion. Moreover, Nf1‐deficient osteoblasts and osteoclasts are hyperresponsive to TGF‐β1 stimulation, potentiating osteoclast bone resorptive activity while inhibiting osteoblast differentiation. These cellular phenotypes are further accompanied by p21‐Ras–dependent hyperactivation of the canonical TGF‐β1–Smad pathway. Reexpression of the human, full‐length neurofibromin guanosine triphosphatase (GTPase)‐activating protein (GAP)‐related domain (NF1 GRD) in primary Nf1‐deficient osteoblast progenitors, attenuated TGF‐β1 expression levels and reduced Smad phosphorylation in response to TGF‐β1 stimulation. As an in vivo proof of principle, we demonstrate that administration of the TGF‐β receptor 1 (TβRI) kinase inhibitor, SD‐208, can rescue bone mass deficits and prevent tibial fracture nonunion in Nf1^flox/?;Col2.3Cre mice. In sum, these data demonstrate a pivotal role for hyperactive TGF‐β1 signaling in the pathogenesis of NF1‐associated osteoporosis and pseudarthrosis, thus implicating the TGF‐β signaling pathway as a potential therapeutic target in the treatment of NF1 osseous defects that are refractory to current therapies. © 2013 American Society for Bone and Mineral Research.     

Incidence and therapeutic outcome of pouchitis for ulcerative colitis in Japanese patients

AIM: The aim of this study was to examine the cumulative risk of pouchitis following restorative proctocolectomy for UC and FAP in Japanese patients, and to assess the response to medical treatment and its outcome. PATIENTS AND METHODS: 521 patients with UC and 117 FAP patients underwent proctocolectomy and received a J-shaped IPAA at our department of surgery. We investigated these patients using PDAI for the diagnostic criteria of pouchitis. RESULTS: Pouchitis occurred in only 32 UC patients (6.1%). The cumulative risk of developing pouchitis for a UC patient was 7% at 5 years after and 12% at 10 years after surgery. The medical treatment of acute pouchitis was usually oral metronidazole (250 mg twice daily) for 2 weeks or oral ciprofloxacin (200 mg thrice daily) in patients who could not tolerate metronidazole. Single episodes of pouchitis occurred in 21 patients (65.6%) and chronic or frequent relapses of pouchitis in 11 patients (34.4%). Three patients (9.4%) required re-ileostomy. Two patients (6.3%) required pouch excision. There were no patients with complicated dysplasia. CONCLUSION: The cumulative risk of pouchitis in Japanese UC patients is lower than that of western countries.     

Interposed autologous nerve segment stimulates nerve regeneration in peripheral nerve allografts in a rat model

The ability of autologous nerve segments interposed between allografts, to increase the total nerve-gap distance, was studied. Sciatic nerve allografts were carried out in a rat model. A 15-mm nerve gap was repaired with a 25-mm nerve graft (interposed group: allo-auto-allograft; control group: allo-allo-allograft). Cyclosporin was given for 12 weeks. Nerve regeneration was evaluated using the weight of the anterior tibial muscle and histologic, morphometric and immunohistochemical analyses at 12, 13, 14, 15, 16, 20, and 24 weeks. Nerve regeneration in the interposed group was statistically significantly better than that in the control group. The authors concluded that a nerve allograft with interposed autograft may enhance nerve regeneration in this model, because of the migration of host-derived Schwann cells into the graft from not only the proximal and distal host nerve stumps, but also the interposed autograft.     

Preoperative parameters expanding the indication of sphincter preserving surgery in patients with advanced low rectal cancer

OBJECTIVE: To clarify the preoperative parameters of the required distal margin that can be applied to the criteria of sphincter-preserving surgery in rectal cancer. SUMMARY BACKGROUND DATA: Although aggressive sphincter-preserving surgery, including intersphincteric resection, is beginning to be applied to low rectal tumors, unexpected distal cancer spread might undermine local control in patients undergoing such a procedure. The 'two-centimeter rule' of distal clearance is predominant at present, whereas preoperative criteria to determine the individual required distal margin have not yet been established. METHODS: First, by reviewing 556 rectal cancers, promising risk parameters of intramural distal spread (IM) were selected and, subsequently, such parameters were examined in regard to whether they could be evaluated preoperatively. Furthermore, 80 patients with lower rectal cancers located above the anal canal who were undergoing abdominoperineal resection were reviewed as to whether IM risk factors could be used as criteria to identify the low rectal cancer with or without anal canal involvement. RESULTS: IM was observed in 10.6% (IM >or= 10 mm: 2.3%) of the patients examined, and the incidence was higher in tumors with certain unfavorable histologic characteristics, including tumor "budding," in their submucosal region at the distal edge (24.4%) than in those with no such histology (5.3%). Regarding such unfavorable histology as IM risk factor, together with 3/4 or more annularity and type 3 gross appearance, IM rates were 3.3% (IM >or= 10 mm: 0.5%) in the no-risk group, 9.1% (IM >or= 10 mm: 1.7%) in the one-risk group, and 29.1% (IM >or= 10mm: 7.8%) in the multiple-risks group. These results were reproduced well even if such risk factors were evaluated endoscopically or histologically on preoperative biopsy specimens. Furthermore, no anal canal involvement was observed in 32 tumors without IM risk; however, microscopic cancer spread down to the anal canal, including that into outside of the internal sphincter muscle, was observed in 9.1% of tumors with one IM risk and in 26.7% of multiple-risk tumors. CONCLUSIONS: The preoperative evaluation of particular parameters related to IM enabled the accurate selection of rectal cancer to which the one-centimeter rule of distal clearance can be applied. This could allow us to expand the indication of sphincter preservation for very low rectal cancer patients.     

Predictors of extrahepatic recurrence after resection of colorectal liver metastases

BACKGROUND: It is important to identify patients at high risk of extrahepatic recurrence after surgery for liver metastases, in order to maximize the survival benefit obtained by prophylactic regional chemotherapy. METHODS: Data from 68 patients who underwent resection of colorectal liver metastases but who did not receive hepatic arterial chemotherapy or intravenous systemic chemotherapy were collected. Twenty-two variables were examined by univariate and multivariate analyses to determine which factors were relevant to extrahepatic recurrence. A scoring system was developed that included the most relevant factors. RESULTS: The extrahepatic recurrence rate at 3 years after hepatectomy was 57.8 per cent. Three variables were independently associated with extrahepatic recurrence including raised serum level of carcinoembryonic antigen after hepatectomy (relative risk (RR) 5.4, P < 0.001), venous invasion of the primary tumour (RR 4.0, P = 0.001) and high-grade budding of the primary tumour (RR 3.1, P = 0.006). Patients with none of these risk factors had a 3-year extrahepatic recurrence rate of 7.1 per cent, compared with 61.6 per cent for those with one risk factor and 100 per cent for those with two or three risk factors. CONCLUSION: It was possible to identify patients at high risk of disease relapse at extrahepatic sites. This system might be used on an individual basis to select patients with colorectal liver metastases for regional chemotherapy or systemic chemotherapy after surgical intervention.     

Skip mediastinal nodal metastases in non-small cell lung cancer

Objective: To reveal the incidence and clinical significance of mediastinal nodal metastases without N1-station nodal metastases (‘skip-N2 metastases’) in non-small cell lung cancer (NSCLC). Methods: A total of 450 NSCLC patients who underwent tumor resection with a systemic mediastinal nodal dissection were retrospectively reviewed. p53 status and proliferative activity represented as proliferative index (PI) were also examined immunohistochemically. Results: Skip-N2 metastases were documented in 49 (13%) patients of all 450 patients; among 334 patients without N1-nodal involvement, 18% patients had skip-N2 metastases. The postoperative survival of skip-N2 patients was almost same as that for patients with metastases to both N1 and N2 nodes. Skip-N2 metastases were significantly more frequent in male patients and squamous cell carcinoma patients. In addition, the mean PI for tumor with skip-N2 metastases was significantly higher than that for any other pathologic nodal (pN)-status diseases. Combined with histologic type and PI, the incidences of skip-N2 metastases for adenocarcinoma showing lower PI were only 5% (7/137) of all patients and 7% (7/94) of patients without N1-nodal involvement. Conclusions: N1 nodal status is not a useful predictor of N2 nodal status in NSCLC, because skip-N2 metastases were documented in 18% patients showing no N1-nodal involvement. However, N1 node-guided dissection might be performed in patients with adenocarcinoma showing lower PI, because the incidence of skip-N2 metastases was extremely low.