Clinical Exome Gene Panel Analysis of a Cohort of Urothelial Bladder Cancer Patients from Sri Lanka.

BACKGROUND: Bladder cancer has a high rate of recurrence and high mortality rates in those who progress to muscle invasive disease. Biomarkers and molecular sub classification of tumours beyond standard histopathology has been proposed to address therapeutic dilemmas. The Cancer Genome Atlas project and other studies have contributed to the enhanced knowledge base of the mutational landscape of urothelial bladder cancer. Once again, these are mostly from Caucasian and Chinese patients, with data from the rest of Asia and Sri Lanka being sparse. The objective of this study was to assess the genomic variations of a cohort of urothelial bladder cancer patients in Sri Lanka. METHODS: The molecular genetic study was conducted on formalin fixed paraffin embedded tumour samples of 24 patients, prospectively enrolled from 2013 to 2017. The samples were sequenced and variant distribution performed based on a 70-gene panel. RESULTS: Total number of filtered mutations in the 24 patients was 10453. Median mutations per patient were 450 (range 22-987). The predominant mutational change was C>T and G>A. The top 5 mutated genes in our cohort were SYNE1, SYNE2, KMT2C, LRP2, and ANK2. The genes were clustered into 3 groups dependent on the number of mutations per patient per gene. The genes of cluster 1 and 2 mapped to Chromatin modifying enzymes and Generic Transcription Pathway. The chromatin remodelling pathway accounted for the largest proportion (22%) of mutations. CONCLUSIONS: Clinical exome sequencing utilising a gene panel yielded a high mutation rate in our patients. The predominant mutational change was C>T and G>A. Three clusters of genes were identified. SYNE1 was the gene with the most mutations. The mutations comprised predominantly of genes of the chromatin remodelling pathway.

Anatomic description of the distal great saphenous vein to facilitate peripheral venous access during resuscitation: a cadaveric study.

The distal great saphenous vein is a popular site for venous access by means of percutaneous cannulation or venous cutdown in a hemodynamically unstable patient. The aim of this study was to precisely define the surface anatomy and dimensions of the distal part of the great saphenous vein to facilitate the aforementioned procedures. Cross-sectional anatomy of the distal saphenous vein was studied in 24 cadaveric ankles sectioned at a horizontal plane across the most prominent points of the medial and lateral malleoli. The curvilinear distance from the most prominent point of the medial malleolus to the center of the saphenous vein, its widest collapsed diameter and skin depth were obtained. The great saphenous vein was located at a mean distance of 24.4 ± 7.9 mm anterior to the medial malleolus. The mean widest collapsed diameter was 3.8 ± 1.5 mm. The mean distance from the skin surface to the vein was 4.1 ± 1.2 mm. These measurements could be used to locate the saphenous vein accurately, particularly in hemodynamically unstable patients with visually indiscernible veins.

Demographics, pathological characteristics and survival in urothelial bladder cancer in a cohort of Sri Lankan patients.

Introduction: Bladder cancer has the 9th highest incidence among Sri Lankan males. This study describes the demographic profiles and survival in bladder cancer patients at two tertiary care centres in Sri Lanka. Methods: A group of patients with urothelial bladder cancer, presenting for the first time for definitive treatment, were prospectively enrolled from 2013 to 2017. Results: There were sixty-six patients, with median age of 65 years and male to female ratio of 7:1. Histopathologically pTa 24%, pT1 47% and pT2 29%. Of the pT1 tumours 61% were low grade (LG). The majority (71%) of non-muscle invasive bladder cancer (NMIBC) patients underwent transurethral resection of bladder tumour only. For the entire cohort the 5-year overall survival was 59% and cancer specific survival (CSS) was 65%. CSS in NMIBC was 75% and 30% in muscle invasive bladder cancer (MIBC). The 5-year female CSS (22%) was significantly lower than in males (71%). Conclusion: Our cohort has a high male to female ratio. The percentage of MIBC was lower than reported in previous Sri Lankan studies. Of the pT1 tumours there is a higher percentage of pT1 LG patients in comparison to Western reports. There is low utilisation of intravesical mitomycin / bacillus Calmette-Guérin (BCG) in the treatment of NMIBC. The 5-year CSS in the Sri Lankan (lower middle-income economy) cohort lies between the values of high-income economies and upper middle-income economies in Asia. The reasons for poor CSS among Sri Lankan women with bladder cancer needs to be further investigated.

Giant Cell Urothelial Carcinoma of Bladder.

Giant cell urothelial carcinoma is a rare variant of bladder cancer recognized by the current World Health Organization classification of urologic tumours. It is an aggressive tumour with a poor prognosis that usually presents at an advanced stage. It is characterized histologically by pleomorphic giant cells. We discuss a case of giant cell urothelial carcinoma presenting at an early stage in a previously well 62-year-old woman. Histology showed a tumour comprising pancytokeratin positive bizarre mononuclear and multi-nuclear giant cells admixed with areas of conventional urothelial carcinoma and carcinoma in situ. Three-month follow-up cystoscopy and magnetic resonance imaging showed no evidence of recurrence or pelvic lymphadenopathy.

Morphology of ejaculatory ducts: A systematic review.

The morphology of human ejaculatory ducts has not been well established. The objective of this study was to describe macroscopic and microscopic anatomy of ejaculatory ducts. We conducted a systematic review using MEDLINE, Scopus, PubMed, and Cochrane databases. Search terms were: "ejaculatory ducts," "seminal colliculus," "prostatic utricle," "anatomy," "histology," "radiology," and "embryology." We only included studies assessing adult (>18 years) humans published before November 1, 2019. We excluded studies describing pathological ducts and case reports. Independent authors extracted data using predefined criteria. Fourteen studies were included in the qualitative synthesis. Usually, the ejaculatory ducts entered the prostate by piercing the central part of its base. Most studies identified an anteromedial curve of the ducts at the outset within the prostate, their subsequent course being a straight path towards the seminal colliculus, their terminal parts diverging immediately before joining the prostatic urethra. However, the morphology of the terminal part of the ducts was inconsistent. The mean length of the ducts ranged from 1.4 to 2.2 cm. In conclusion, the luminal diameter gradually decreased as the ducts traveled towards the seminal colliculus. Ejaculatory ducts angulate anteromedially at their onset within the prostate and travel straight towards the seminal colliculus. Their terminal parts diverge immediately before joining the prostatic urethra. However, the reported dimensions of the ducts differ among studies.

Pigmented border as a new surface landmark for digital nerve blocks: a cross sectional anatomical study.

The purpose of this study was to identify surface anatomy of digital nerves in relation to the pigmented border of digits. Three-hundred and sixty digital nerves in 36 preserved adult cadaveric hands were dissected under magnification. The digital nerves were constantly located anterior to the pigmented border. The median curvilinear distance along the skin from the pigmented border to the digital nerves of the index, middle, ring and little fingers was 1.4 mm. In the thumb, this distance was 2.4 and 3.7 mm on the radial and ulnar sides, respectively. The digital nerve was located 2.4 mm deep to the skin in all fingers. The median angle to the nerve from the skin at the pigmented border was 30°. These dimensions differed in the thumb compared with the rest of the fingers. We conclude that the pigmented border of digits is a reliable anatomical landmark to locate digital nerves.

Preserving the marginal mandibular branch of the facial nerve during submandibular region surgery: a cadaveric safety study.

BACKGROUND: The marginal mandibular branch of the facial nerve is vulnerable to iatrogenic injuries during surgeries involving the submandibular region. This leads to significant post-operative morbidity. Studies assessing accurate anatomical landmarks of the marginal mandibular branch are sparse in South Asian countries. Present study was conducted to assess the relationship between the marginal mandibular branch and the inferior border of the body of mandible. METHODS: Twenty-two preserved cadavers of Sri Lankan nationality were selected. Cadavers were positioned dorsal decubitus with necks in extension. The maximum perpendicular distance between the inferior/caudal most ramus of the marginal mandibular branch and the inferior border of the body of the mandible was recorded on both hemi faces. RESULTS: Recorded maximum distance was 17.65 mm on left side and 10.80 mm on right side. Mean maximum distance, was 7.12 ± 2.97 mm. There was no statistically significant difference in the maximum deviation on left (7.84 ± 3.41 mm) and right sides (6.44 ± 2.37 mm). CONCLUSION: Course of the marginal mandibular nerve is complex. If the distance of the incision in the posterior submandibular approach is less than 2 cm from the inferior border of the mandible, there is a high probability of damaging the inferior ramus of the marginal mandibular branch of the facial nerve.

An improved technical trick for identification of the thoracodorsal nerve during axillary clearance surgery: a cadaveric dissection study.

BACKGROUND: Accurate anatomical landmarks to locate the thoracodorsal nerve are important in axillary clearance surgery. METHODS: Twenty axillary dissections were carried out on ten preserved Sri Lankan cadavers. Cadavers were positioned dorsal decubitus with upper limbs abducted to 900. An incision was made in the upper part of the anterior axillary line. The lateral thoracic vein was identified and traced bi-directionally. The anatomical location of the thoracodorsal nerve was studied in relation to the lateral border of pectoralis minor and from a point along the lateral thoracic vein, 2 cm inferior to its confluence with the axillary vein. RESULTS: The lateral thoracic vein was invariably present in all the specimens. All the lateral thoracic veins passed lateral to the lateral border of pectoralis minor except in one specimen, where the lateral thoracic vein passed along its lateral border. The thoracodorsal nerve was consistently present posterolateral to the lateral thoracic vein. The mean distance to the lateral thoracic vein from the lateral border of pectoralis minor was 28.7 ± 12.6 mm. The mean horizontal distance, depth, and displacement, from a point along the lateral thoracic vein, 2 cm inferior to its confluence with the axillary vein to the thoracodorsal nerve were 14.5 ± 8.9 mm, 19.7 ± 7.3 mm and 25 ± 5 mm respectively. The thoracodorsal nerve was found in a posterolateral direction, at a 540 ± 120 angle to the horizontal plane, 95% of the time. CONCLUSIONS: The lateral thoracic vein is an accurate guide to the thoracodorsal nerve. We recommend exploring for the thoracodorsal nerve from a point 2 cm from the confluence of the lateral thoracic vein and the axillary vein for a distance of 25 ± 5 mm in a posterolateral direction, at a 540 ± 120 angle to the horizontal plane.

Morphological variations of the human ejaculatory ducts in relation to the prostatic urethra.

Loss of ejaculation can follow transurethral resection of the prostate (TURP). Periverumontanal prostate tissue is preserved in ejaculation-preserving TURP (ep-TURP). Knowledge of ejaculatory duct anatomy in relation to the prostatic urethra can help in ep-TURP. This was evaluated in cross-sections of the prostate using a 3 D model to determine a safe zone for resecting the prostate in ep-TURP. A 3 D reconstruction of the ejaculatory ducts was developed on the basis of six prostate gland cross-sections. The measurements obtained from the 3 D model were standardized according to the maximum width of the prostate. Simple linear regressions were used to predict the relationships of the ejaculatory ducts. The maximum widths of the prostates ranged from 22.60 to 52.10 mm. The ejaculatory ducts entered the prostate with a concavity directed posterolaterally. They then proceeded toward the seminal colliculus in a fairly straight course, and from that point they angulated anteromedially. As they opened into the prostatic urethra they diverged. Significant regression models predicted the relationships of the ejaculatory ducts to the prostatic urethra based on the sizes of the prostates. The 3 D anatomy of ejaculatory ducts can be predicted on the basis of prostate width. The ejaculatory ducts can be preserved with 95% accuracy if a block of tissue 7.5 mm from the midline on either side of the seminal colliculus is preserved, up to 10 mm proximal to the level of the seminal colliculus, during TURP. Clin. Anat. 31:456-461, 2018. © 2017 Wiley Periodicals, Inc.

Extra and Intramuscular Distribution of the Thoracodorsal Nerve with Regard to Nerve Reconstruction Surgeries.

Background The lateral branch of the thoracodorsal nerve (LBTN) is used for nerve transfer in facial, musculocutaneous, axillary nerve injuries and for irreparable C5, C6 spinal nerve lesions and accessory nerve defects. For a successful surgical outcome, the nerve to be used in nerve transfer should be of adequate length and thickness for nerve coaptation. Aim Our objective was to evaluate the length of the LBTN that could be obtained as a donor nerve, externally and within the muscle. Method Eight (8) cadavers with intact upper limbs and thorax which could be positioned in the anatomical position were selected for the study. Cadavers with dissected axillae, brachial plexus or upper limbs were excluded. The thoracodorsal neurovascular bundle was dissected and the number of branches of the thoracodorsal nerve was identified along with its lateral branch. The lateral branch was dissected up to the latissimus dorsi muscle and further intramuscularly. All lengths were measured using a vernier caliper. Results The mean length of the LBTN, up to its first intramuscular branch, is 8.14 cm (range 5.99-12.29 cm). Beyond this, the intramuscular nerve branched further and was of very minute diameter. The mean unbranched intramuscular length of the nerve is 3.36 cm (range 1.3-7.71 cm) which is 41.28% of the total length of the LBTN. Conclusion A significant proportion of the LBTN is found within the latissimus dorsi muscle. This length could potentially be used for direct nerve coaptation by intrafascicular dissection.

Anatomical landmarks for safer carpal tunnel decompression: an experimental cadaveric study.

BACKGROUND: Carpal tunnel syndrome is a common presentation to surgical outpatient clinics. Treatment of carpal tunnel syndrome involves surgical division of the flexor retinaculum. Palmar and recurrent branches of the median nerve as well as the superficial palmar arch are at risk of damage. METHODOLOGY: Thirteen cadavers of Sri Lankan nationality were selected. Cadavers with deformed or damaged hands were excluded. All selected cadavers were preserved with the conventional arterial method using formalin as the main preservative. Both hands of the cadavers were placed in the anatomical position and dissected carefully. We took pre- determined measurements using a vernier caliper. We hypothesized that the structures at risk during carpal tunnel decompression such as recurrent branch of the median nerve and superficial palmar arch can be protected if simple anatomical landmarks are identified. We also hypothesized that an avascular area exists in the flexor retinaculum, identification of which facilitates safe dissection with minimal intra operative bleeding. Therefore we attempted to characterize the anatomical extent of such an avascular area as well as anatomical landmarks for a safer carpal tunnel decompression.Ethical clearance was obtained for the study. RESULTS: In a majority of specimens the recurrent branch was a single trunk (n =20, 76.9%). Similarly 84.6% (n = 22) were extra ligamentous in location. Mean distance from the distal border of the TCL to the recurrent branch was 7.75 mm. Mean distance from the distal border of TCL to the superficial palmar arch was 11.48 mm. Mean length of the flexor retinaculum, as measured along the incision, was 27.00 mm. Mean proximal and distal width of the avascular area on TCL was 11.10 mm and 7.09 mm respectively. CONCLUSION: We recommend incision along the radial border of the extended ring finger for carpal tunnel decompression. Extending the incision more than 8.16 mm proximally and 7.75 mm distally from the corresponding borders of the TCL should be avoided. Incision should be kept to a mean length of 27.0 mm, which corresponds to the length of TCL along the above axis. We also propose an avascular area along the TCL, identification of which minimizes blood loss.

Angiokeratoma of Fordyce simulating recurrent penile cancer.

Penile cancer requires careful clinical follow-up. Therefore, when a patient presented with a florid papillary lesion at his penectomy site, it was immediately biopsied. The histologic examination, however, revealed a benign angiokeratoma with no evidence of recurrent cancer. Angiokeratoma on the scrotum after treatment for carcinoma of the penis has only been documented once. To our knowledge, this is the first description of it causing a diagnostic dilemma with recurrence. A radiotherapy association has only been documented in vulval lesions. Symptomatic treatment is laser vaporization. This emphasizes the importance of histologic assessment before any oncologic surgery intervention.