Martin K. Walz

Endoscopic treatment of large primary adrenal tumours.

Endoscopic adrenalectomy has become the treatment of choice for small benign adrenal tumours but should not be used for malignant lesions. It is debatable whether large and therefore potentially malignant primary adrenal tumours should be removed by minimally invasive techniques.

Long term prognosis of patients with pediatric pheochromocytoma

A third of patients with paraganglial tumors, pheochromocytoma, and paraganglioma, carry germline mutations in one of the susceptibility genes, RET, VHL, NF1, SDHAF2, SDHA, SDHB, SDHC, SDHD, TMEM127, and MAX. Despite increasing importance, data for long-term prognosis are scarce in pediatric presentations. The European-American-Pheochromocytoma-Paraganglioma-Registry, with a total of 2001 patients with confirmed paraganglial tumors, was the platform for this study. Molecular genetic and phenotypic classification and assessment of gene-specific long-term outcome with second and/or malignant paraganglial tumors and life expectancy were performed in patients diagnosed at <18 years. Of 177 eligible registrants, 80% had mutations, 49% VHL, 15% SDHB, 10% SDHD, 4% NF1, and one patient each in RET, SDHA, and SDHC. A second primary paraganglial tumor developed in 38% with increasing frequency over time, reaching 50% at 30 years after initial diagnosis. Their prevalence was associated with hereditary disease (P=0.001), particularly in VHL and SDHD mutation carriers (VHL vs others, P=0.001 and SDHD vs others, P=0.042). A total of 16 (9%) patients with hereditary disease had malignant tumors, ten at initial diagnosis and another six during follow-up. The highest prevalence was associated with SDHB (SDHB vs others, P<0.001). Eight patients died (5%), all of whom had germline mutations. Mean life expectancy was 62 years with hereditary disease. Hereditary disease and the underlying germline mutation define the long-term prognosis of pediatric patients in terms of prevalence and time of second primaries, malignant transformation, and survival. Based on these data, gene-adjusted, specific surveillance guidelines can help effective preventive medicine.

Immunohistochemical Determination of Somatostatin Receptor Subtypes 1, 2A, 3, 4, and 5 in Various Adrenal Tumors

While octreotide binds with high affinity to sst2a only, the new analogue SOM230 demonstrates high affinity for sst1, 3, and 5, in addition. We examined the immunohistochemical expression of somatostatin receptor subtypes (sst) in 7 pheochromocytomas (PHEO), 5 Conn adenomas (CONN), 9 Cushing adenomas (CUSH), 7 nonfunctioning tumors (NFA), and 4 adrenal carcinomas (CA). About one third of the PHEO were positive for sst1, 2a, and 5. Less than 30% of cells were stained in the majority of these tumors. Each of the PHEO expressed sst3 with more than 60% of cells stained. Two thirds of the NFA revealed positive staining for sst1, 2a, and 3 with less than 30% of cells affected. Sst5 was expressed in nearly all of the NFA with positive staining in 30–60% of tumor cells. Nearly all CUSH and CONN were positive for the subtypes evaluated. In the majority of these tumors, less than 30% of cells were positively stained. Fifty percent of CA expressed sst2a and 3 with positive staining in 30–100% of cells. None of them expressed sst1. Somatostatin receptors are expressed in adrenal tumors with a tumor‐specific distribution pattern. This may offer new diagnostic and therapeutic possibilities.

A randomized controlled bicenter trial of yoga for patients with colorectal cancer.

The aim of this trial was to evaluate the effects of yoga on health‐related quality of life in patients with colorectal cancer.

Safe introduction of a new surgical technique: remote telementoring for posterior retroperitoneoscopic adrenalectomy

Posterior retroperitoneoscopic adrenalectomy (PRA) is a safe and effective approach to adrenalectomy, offering less pain and faster recovery than open or laparoscopic surgery. Although the popularity of PRA is increasing, few surgical centres have extensive experience with the procedure. The ideal approach to achieve proficiency with any new technique involves on‐site observation of an experienced surgeon‐mentor, followed by mentored hands‐on experience of the surgeon‐learner. However, it is not always feasible for a surgeon‐mentor to offer on‐site supervision to the surgeon‐learner in his or her home institution. Advances in Internet applications have made remote telementoring a viable alternative to on‐site mentoring in selected situations.

Bioinformatic Challenges in Clinical Diagnostic Application of Targeted Next Generation Sequencing: Experience from Pheochromocytoma

Background Recent studies have demonstrated equal quality of targeted next generation sequencing (NGS) compared to Sanger Sequencing. Whereas these novel sequencing processes have a validated robust performance, choice of enrichment method and different available bioinformatic software as reliable analysis tool needs to be further investigated in a diagnostic setting. Methods DNA from 21 patients with genetic variants in SDHB, VHL, EPAS1, RET, (n=17) or clinical criteria of NF1 syndrome (n=4) were included. Targeted NGS was performed using Truseq custom amplicon enrichment sequenced on an Illumina MiSEQ instrument. Results were analysed in parallel using three different bioinformatics pipelines; (1) Commercially available MiSEQ Reporter, fully automatized and integrated software, (2) CLC Genomics Workbench, graphical interface based software, also commercially available, and ICP (3) an in-house scripted custom bioinformatic tool. Results A tenfold read coverage was achieved in between 95-98% of targeted bases. All workflows had alignment of reads to SDHA and NF1 pseudogenes. Compared to Sanger sequencing, variant calling revealed a sensitivity ranging from 83 to 100% and a specificity of 99.9-100%. Only MiSEQ reporter identified all pathogenic variants in both sequencing runs. Conclusions We conclude that targeted next generation sequencing have equal quality compared to Sanger sequencing. Enrichment specificity and the bioinformatic performance need to be carefully assessed in a diagnostic setting. As acceptable accuracy was noted for a fully automated bioinformatic workflow, we suggest that processing of NGS data could be performed without expert bioinformatics skills utilizing already existing commercially available bioinformatics tools.

A new anastomotic leakage model in circular double stapled colorectal anastomosis after low anterior rectum resection in pigs.

ABSTRACT Background: A high incidence of anastomotic leakage (37.5%) is reported after low anterior rectal resection (LAR) and circular double-stapled anastomosis without protective ileostoma. Since the pathomechanism of anastomosis leakage is still unclear, a suitable animal model would be most desirable. Methods: The objective was to assess the incidence of clinically apparent and inapparent leakage after LAR in pigs (n = 20). Endpoints were radiological, clinical, macroscopic, and histologic proof of anastomotic leakage on the 9th postoperative day. Integrity of anastomosis was assessed by double-contrast barium examination on 9th postoperative day. Animals were sacrificed and anastomoses were resected for histopathological investigation. In case of earlier clinical apparent anastomotic leakage, radiologic double-contrast barium was performed immediately. Results: LAR with a circular double-stapled anastomosis without protective ileostoma was performed in 20 pigs (m:f = 8:12). Length of resection was 10–20 cm, anastomosis was performed 7 cm ab ano. Five animals (25%) developed clinical apparent anastomotic leakage (no appetite, fever, inactivity, tachypnea, discomfort, pain) between the 6th (n = 1) and 9th (n = 4) postoperative day, proven by double-contrast barium radiographs. Additionally in 1 animal clinical inapparent anastomotic insufficiency was observed radiologically. Total rate of leakage was 30% (n = 6). These results were confirmed by leucocytosis, low potassium levels, in two cases high ALT and AST and local peritonitis in all cases. Conclusion: Including one additional case of clinical inapparent leakage, total rate of anastomotic leakage was 30% (6/20). Thus we managed to establish a new experimental model of anastomotic leakage after low rectal resection comparable to the human situation.

Minimally Invasive Video-Assisted Thyroidectomy

The minimally invasive video-assisted approach was first described in 1996 for parathyroid (Miccoli et al. 1997) and few years later for thyroid surgery (Bellantone et al. 1999; Miccoli et al. 1999). In the same period following the enthusiastic results of laparoscopic abdominal surgery, a purely endoscopic parathyroidectomy and thyroidectomy with multiple trocars placement and CO2 insufflation were also performed (Gagner 1996; Huscher et al. 1997). The innovation of the video-assisted technique consisted of a gasless procedure performed through a single 1.5–2 cm central access and use of an endoscope for magnification. Because of its similarity to conventional surgery, this method gained quickly a quite large acceptance (Miccoli et al. 2002). Moreover, the attraction of the mini-incision has been supposed in earlier studies to be coupled with an advantage in terms of postoperative pain and cosmetic result in favour of MIVAT when compared to conventional thyroidectomy (Miccoli et al. 2001; Bellantone et al. 2002). Our experience with MIVAT is based on more than 1,500 procedures performed over more than 10 years experience in a tertiary referral centre for endocrine surgery.

Energy Devices in Minimally Invasive Thyroidectomy

An accurate haemostasis is essential during any surgical procedure. This problem is well known for thyroid surgery since over one century when Billroth, considered one of the best surgeons in Europe, reported a mortality of 40% on a series of 20 patients in 1869. Few decades later, in the hands of Theodor Kocher, thyroidectomy developed into a safe operation with a mortality rate of 0.5% by 1898 (Richard 1990). The key for these extraordinary results was the technique he introduced which first ligated the major arteries and veins followed by identifying and isolating the recurrent laryngeal nerve (Kocher 1883). Since that time, suture ligation has continued to be the gold standard of obtaining haemostasis. The introduction of the minimally invasive thyroid surgery poses the problem to break this 100-year-old rule. The impossibility to ligate is obvious for the purely endoscopic operations such as the endoscopic neck, thoracic and axillary approach (Henry and Segab 2006; Strik et al. 2007; Kang et al. 2009), but also the video-assisted operation due to the limited working space permits conventional ligatures only after the extraction of the thyroid lobe through the skin incision (Miccoli et al. 2006). Many instruments are now available for this use and have been demonstrated to be at least as safe as the knot-and-tie technique.

Safe introduction of a new surgical technique

Posterior retroperitoneoscopic adrenalectomy (PRA) is a safe and effective approach to adrenalectomy, offering less pain and faster recovery than open or laparoscopic surgery. Although the popularity of PRA is increasing, few surgical centres have extensive experience with the procedure. The ideal approach to achieve proficiency with any new technique involves on‐site observation of an experienced surgeon‐mentor, followed by mentored hands‐on experience of the surgeon‐learner. However, it is not always feasible for a surgeon‐mentor to offer on‐site supervision to the surgeon‐learner in his or her home institution. Advances in Internet applications have made remote telementoring a viable alternative to on‐site mentoring in selected situations.