Specialist Dermatologist, Aster Hospital, 9 A Street, Al Qusais Industrial 2, PO Box 119428, Dubai-UAE

Dr Ramachandran Rajagopal

Primary syphilis is a form of early syphilis developing 9 to 90 days after exposure. It usually takes typical, easily-recognizable clinical forms, including non-tender and non-itchy chancres on the genitals, which may be accompanied by regional lymphadenopathy. However, different presentations are being seen, which could cause diagnostic misses if a clinician lacks full awareness of these forms. Two cases are reported with different presentations, one mimicking innocuous balanitis and the other a probable herpetic genital eruption. The serology for both was positive and led to the correct treatment.

Sexually-transmitted diseases are commonly encountered in present-day society due to varying lifestyle habits and the modern-day stresses of life. Despite education on safe sex practices, individuals at times engage in promiscuous and high-risk behaviour, resulting in the resurgence of sexually transmitted diseases. Of late, the clinical appearance of sexually transmitted disorders have been changing, and cases may not necessarily conform to typically known forms. 

A 23-year-old circumcised male reported with a mildly painful reddish lesion on the glans penis, appearing about a week before presentation. He had used fucidin ointment, following which it became red all over with mild discomfort. Friction with undergarments gave rise to mild pain in the area. He did give a history of exposure to his ‘girlfriend’ one month prior to onset of symptoms, which was unprotected. The history of exposure was forthcoming only during the second review visit. 

A clinical examination revealed uniformly erythematous erosive balanitis, which was mildly tender (Fig 1). No induration, chancre or discharge was present. No significant regional lymphadenopathy was present. No lesions were seen on other areas of the body. The initial appearance mimicked allergic contact dermatitis to fucidin ointment. The patient did not respond to treatment with mild topical steroid for suspected allergic contact dermatitis. 

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During the review of the case, when there was no response to topical steroid and the positive exposure history was forthcoming, serological screening for syphilis was requested.  The serology for syphilis was reactive with a titre of 1:512. A confirmatory test for syphilis by TPHA revealed a positive titre of 1:5120. 

A diagnosis of Syphilitic balanitis of Follmann (SBF) was made, and the patient treated with a single dose of Inj Benzathine Penicillin 2.4 Mega units, with good recovery. 

A 41-year-old male presented with a mildly painful nodular eruption on the ventral aspect of penis near the frenulum of one-week duration. He gave a history of unprotected exposure three months prior, to his steady girlfriend. 

Clinical examination revealed a firm, indurated nodule on the ventral aspect of the penis, with pseudo-vesiculation on the surface of the nodule (Fig 2). There was mild tenderness near the frenum of the penis, probably due to associated lymphangitis. There was no significant regional lymphadenopathy. 

The patient was initially treated for probable herpes genitalis, due to the pseudo-vesicular lesions on the penile lesion. There was no significant improvement in the lesion from the antiviral therapy. On review, a serological test for syphilis was ordered, which showed reactive serology with a titre of 1:266. A diagnosis of early primary syphilis was made. The patient was treated with Inj Benzathine Penicillin 2.4 mega unit IM single dose, with subsequent subsidence of the lesion. 

Eugène Follmann first described syphilitic balanitis as a manifestation of primary syphilis in 1948. Since then, it has been known as syphilitic balanitis of Follmann (SBF). Follmann recorded an incidence of balanitis in cases of primary syphilis of 0.3–0.5% (1). Thus, SBF should be considered an uncommon condition. Cardboard-like induration of the glans penis is described as a hallmark of SBF in a series of cases by Abdennader et al (2). However, this was not noted in the cases by Follmann. A chancre was also associated with one of their cases, and has been said to occur before, simultaneously with, or after balanitis.  There was no induration or chancre in the present case with associated balanitis. Hence, a syphilis serology is warranted in all cases of atypical balanitis. 

Syphilis can mimic many other diseases, and in the second case it resembled herpes genitalis, with some pseudovesicles on the skin surface of an indurated nodule on the ventral aspect of the penis. The indurated nodule can be explained by lymphangitis associated with the infection. Awareness of such presentation can facilitate early diagnosis of primary syphilis, especially if the genital lesion is atypical, as it was in this case. 

In conclusion, syphilis serology is warranted for all indurated genital lesions, irrespective of clinical appearance, and in cases which do not respond to other treatments. Syphilis should also be suspected in cases of erythematous balanitis which are not itchy and are associated with a history of exposure.  

Follmann E. Le problème de la balanitesyphilitique. Ann Dermatol Syph. 1948;8:470–483.

Abdennader S, Janier M, Morel P. Syphilitic Balanitis of Follmann: Three Case Reports. Acta Dermato-Venereologica [Internet]. 2011;ISSN 0001-5555. Available from: https://www.medicaljournals.se/acta/content_files/files/pdf/91/2/3328.pdf.

Interesting Presentations of Primary Syphilis

#111827

Amal P Upadhyay

Parwej Khan

Sameah Mirajan

Abhay R Khadke

NMC Specialty Hospital, Al Nahdha, Dubai.

Piyush Somani

The presence of pancreatic tissue away from its normal location, in various places throughout the gastrointestinal tract, is known as ectopic pancreas, or pancreatic rest. It is usually an incidental finding and clinically silent. Rarely, an ectopic pancreas can become inflamed or develop bleeding, obstruction or cancer. At times it may be challenging to diagnose. We would like to present two cases that demonstrate how variable the clinical presentation can be. 

Ectopic pancreas, gastrointestinal stromal tumor (GIST), Leiomyoma.

Ectopic pancreatic rest was first reported associated with an ileal diverticulum in 1727

It is defined as pancreatic tissue with no anatomic or vascular connection with the main pancreas. The stomach and small intestine are the most common sites, but it has been reported at other sites as well. It is usually asymptotic unless it becomes inflamed or obstructed, or there is bleeding or malignant change[4]. We report two cases with contrasting presentations in this article.

A 28 year-old male presented with melena, dizziness and intermittent abnormal pain of 3 day duration. The patient had moderately severe anaemia secondary to blood loss. The physical examination was normal. A blood test showed Hb of 8.7 mg/dl on CBC, but other routine blood tests including a liver function test and abdominal ultrasound were unremarkable.

Esophagogastroduodenoscopy (figure 1) revealed a globular polyploid mass in the distal corpus along the greater curvature, with a firm stalk; the overlying mucosa looked normal except for an ulcerated punctum. This was initially thought to be GIST/Leiomyoma.

A biopsy revealed lobules of pancreatic exocrine and endocrine components in the submucosa, with no evidence of malignancy.

As the lesion presented with a significant upper GI bleed, a decision was made to transfuse 1 unit of blood PRBC and to proceed with laparoscopic surgery. During surgery, a gastric lesion was located through endoscopic transillumination. Gastrotomy was performed including a wide excision of the polyp with a 1 cm margin. Hemostasis was achieved and the gastrotomy closed. The patient had no postoperative complications and was discharged 4 days later. Surgical pathology was consistent with an ectopic pancreatic rest. The patient appeared well and asymptomatic during follow up.

A 34 year-old male presented to the GE clinic with a 9 month history of recurrent dyspepsia. The physical examination was clinically normal, and all routine blood tests including lipase, ultrasound abdomen, ECG, stress ECHO and TMT were unremarkable.

Esophagogastroduodenoscopy (figure 2) revealed one polypoidal lesion of around 1.5 cm at the D1/D2 junction, with normal overlying mucosa. The minor papilla appeared prominent but otherwise normal.

Endoscopic ultrasound (Figure 3) showed a 15.76 mm x 10.31 mm heterogeneous, predominantly hypo-echoic, polypoidal, regular, oval shaped lesion, probably arising from the muscularis propria. The mucosa/ muscularis mucosae/submucosa/serosa appeared to be normal and were not involved with the hypo-echoic lesion. Using a 22 gauge EchoTip/procore Cook needle, a fine needle aspiration (FNA) biopsy of the lesion was performed. This confirmed the presence of heterotopic pancreatic parenchyma, with pancreatic ducts and acinar cells with pink zymogen granules (figure 4).

As this lesion was an incidental finding, and its contribution to the patient’s symptom of functional dyspepsia was rather untenable, no further action was advised.

Ectopic pancreas is defined as pancreatic tissue with no anatomical or vascular connections with the normal body of the pancreas [3]. It is reportedly more common in males, usually aged 30 to 50 years. Variable incidence of 0.5-13.7% has been reported in autopsies[3].
Heterotopic pancreatic tissue is morphologically and physiologically identical to pancreatic tissue


Gaspar-Fuentes classified heterotopia of the pancreas into four types. Type I heterotopia consists of normal pancreatic parenchyma, sucha as acini, ducts, and islet cells. Type II heterotopia (canalicular type) only includes pancreatic ducts. Type III heterotopia is comprised of only exocrine acinar tissue. Type IV heterotopia includes only endocrine islet cells

The pancreas develops from many evaginations inside the wall of the primordial duodenum; some of these evaginations fail to migrate to their normal place and give rise to ectopic pancreatic tissue[5]. Pancreatic metaplasia of the endodermis in the gastric submucosa during embryogenesis is proposed in a separate theory

25-38% of cases have ectopic pancreatic tissue in the stomach, 17-36% in the duodenum and 15-21.7% in the jejunum. It is rarely observed in the esophagus, common bile duct, gallbladder, mesentery, spleen, mediastinum and fallopian tubes. The antrum is the most common location in the stomach, observed in 85-95%, of cases with heterotopic tissue in the stomach, especially along the greater curvature[5]. The gastric submucosal layer is the most commonly involved, followed by the muscularis and subserosal layers. In the presented cases, the pancreatic tissue involved the submucosa in case 1 and the muscularis propria in case 2.



This condition is usually asymptotic, but complications such as acute or chronic pancreatitis, abscess and pseudocyst formation can occur.
Pain may occur due to inflammation of the pancreatic tissue


Mucosal erosion, ulceration and perforation can lead to a GI bleed, especially in the small intestine.

Formation of a pre-pyloric mass can cause gastric outlet obstruction. Other unusual presentations include obstructive jaundice due to bile duct obstruction[8]. Usually lesions bigger than 1.5 cm in size are more likely to cause clinical symptoms

Carcinoma can rarely develop[10]. Heterotropic pancreatic cancer must be located inside or close to the ectopic pancreas, with a transition zone between the pancreatic tissue and the cancerous neoplasm. The acini and ducts should make normal pancreatic tissue[7]. Ectopic pancreas adenocarcinomas have a favorable prognosis compared to pancreas cancers

Upper GI endoscopy typically reveals an umbilicated subepithelial lesion. Diagnosis may be confirmed by biopsy[10]. Computed tomography lacks specificity in diagnosing ectopic pancreatic tissue as it cannot differentiate ectopic pancreas and other submucosal neoplasms

Endoscopic ultrasonography can detect submucosal rests of 0.5-2 cm in size and allows fine-needle aspiration for cytologic evaluation with 80%-100% sensitivity

In this report, both cases were diagnosed histologically. An endoscopic biopsy was positive for case 1, and subsequently confirmed by surgical excision. Case 2 was diagnosed with EUS guided biopsy. An intra-operative frozen section can help in differentiating pancreatic
heterotopia from gastrointestinal autonomic nerve tumour, gastrointestinal stromal tumour (GIST), lymphoma, carcinoid tumour or even gastric cancer. Surgical resection is curative in most cases.


Pancreatic heterotopia/ectopic pancreas is one of the differential diagnoses of extramucosal gastrointestinal lesions. Clinical presentation may vary from an asymptomatic incidentally detected lesion to catastrophic GI haemorrhage leading to anaemia and even cancer.
It can be challenging to diagnose, especially when located entirely submucosally. Endoscopic ultrasound (EUS)-guided biopsy can help to make a confident diagnosis in most cases. Surgery is the definitive treatment, but may only be required in a minority of cases.

Elfving G, Hästbacka J. Pancreatic heterotopia and its clinical importance. Acta ChirScand [Internet]. 1965;130:593-602. Available from: http://www.ncbi.nlm.nih.gov/pubmed/5865465

Mulholland KC, Wallace WD, Epanomeritakis E, Hall SR. Pseudocyst formation in gastric ectopic pancreas. JOP [Internet]. 2004;5:498-501. Available from: http://www.ncbi.nlm.nih.gov/pubmed/ 15536290

Zhang L, Sanderson SO, Lloyd RV, Smyrk TC. Pancreatic intraepithelial neoplasia in heterotopic pancreas: evidence for the progression model of pancreatic ductal adenocarcinoma. Am J Surg Pathol [Internet]. 2007;31:1191-1195. Available from: https://dx.doi.org/10.1097/PAS.0b013e31806841e1

Chandan VS, Wang W. Pancreatic heterotopia in the gastric antrum. Arch Pathol Lab Med [Internet]. 2004;128:111-112. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14692822

Gaspar Fuentes A, Campos Tarrech JM, Fernández Burgui JL, Castells Tejón E, Ruíz Rossello J, Gómez Pérez J, Armengol Miró J. Pancreatic ectopias. Rev EspEnferm Apar Dig [Internet]. 1973;39:255-268. Available from: http://www.ncbi.nlm.nih.gov/pubmed/4699117

Emerson L, Layfield LJ, Rohr LR, Dayton MT. Adenocarcinoma arising in association with gastric heterotopic pancreas: A case report and review of the literature. J Surg Oncol [Internet]. 2004;87:53-57. Available from: https://dx.doi.org/ 10.1002/jso.20087

 Armstrong CP, King PM, Dixon JM, Macleod IB. The clinical significance of heterotopic pancreas in the gastrointestinal tract. Br J Surg [Internet]. 1981;68:384-387. Available from: https://dx.doi.org/10.1002/bjs. 1800680606

Ormarsson OT, Gudmundsdottir I, Mårvik R. Diagnosis and treatment of gastric heterotopic pancreas. World J Surg [Internet]. 2006;30:1682-1689. Available from: https://dx.doi.org/10.1007/s00268-005- 0669-6

Osanai M, Miyokawa N, Tamaki T, Yonekawa M, Kawamura A, Sawada N. Adenocarcinoma arising in gastric heterotopic pancreas: clinicopathological and immunohistochemical study with genetic analysis of a case. Pathol Int [Internet]. 2001;51:549-554. Available from: https://dx.doi.org/10.1046/j.1440-1827.2001.01240.x

Rodriguez FJ, Abraham SC, Allen MS, Sebo TJ. Fine-needle aspiration cytology findings from a case of pancreatic heterotopia at the gastroesophageal junction. Diagn Cytopathol [Internet]. 2004;31:175-179. Available from: https://dx.doi.org/ 10.1002/dc.20066

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A Mountain and a Molehill: Report of Two Cases of Ectopic Pancreas

Department of General Medicine, Aster MIMS Hospital, Kozhikode, Kerala, India

Jabir M P

Nikitha K 

Department of Nephrology, Aster MIMS Hospital, Kozhikode, Kerala, India

Ismail N A 

COVID-19, Thrombotic thrombocytopenic purpura, plasma exchange, ADAMTS13

A 22-year-old female with no previous morbidities presented with acute onset neurological symptoms in the form of hemi-sensory phenomena.  On evaluation, she had fever. Routine COVID-19 RT-PCR testing proved to be positive. During the course of hospital stay, the patient developed classical features of acquired TTP. Her ADAMTS13 level was 36% of normal activity, which is suggestive of direct, viral-mediated thrombotic microangiopathy.  High VWF levels and low ADAMTS13 activity have both previously been reported with SARS-Cov-2 infection. In rare cases like ours, this can mimic classical TTP.

TTP – Thrombotic thrombocytopenic purpura; COVID-19 – Coronavirus disease 2019; ADAMTS13 – A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13; VWF – von Willebrand factor; HUS – Haemolytic uremic syndrome; RT-PCR – Real time reverse transcriptase polymerase chain reaction; MAHA – Macroangiopathic haemolytic anaemia; LDH – Lactate dehydrogenase; ANA – Antinuclear antibody; ELISA – Enzyme-linked immunosorbent assay; PLEX – Plasma exchange; TMA – Thrombotic microangiopathy; SARS-CoV2 – Severe acute respiratory distress Coronavirus 2. 

Thrombotic thrombocytopenic purpura (TTP) is a rare haematological disorder which can be hereditary or acquired.  Hereditary TTP is a rare autosomal recessive disorder, caused by mutations in gene ADAMTS13, which result in the absence or severe deficiency of the plasma metalloprotease ADAMTS13. Immune-mediated ADAMTS13 deficiency (iTTP) is most frequently acquired via ADAMTS13 auto-antibodies.  Half of all iTTP cases present secondary to clinical conditions such as bacterial infections, systemic lupus erythematosus (SLE), Anti-phospholipid syndrome, pregnancy, drugs, pancreatitis, HIV infection, cancers and organ transplantation. Co-presentation of COVID-19 related thrombotic microangiopathy with TTP and haemolytic uremic syndrome (HUS) has been described in the literature (1-6). We report a case of TTP in a young female in the setting of SARS-Cov-2 infection.

A 22-year-old, previously healthy, obese female presented with sudden weakness and numbness of the right side of her body. She also had slurring of her speech and facial deviation which resolved within a few hours. The patient did not report fever, anosmia, and cardio respiratory or gastrointestinal symptoms. There was no recent exposure to drugs. The family history was negative and there was no history of any illness during childhood.  On evaluation in the emergency room, the patient’s readings were as follows- temp 38’C, HR 100/min, BP 120/80 mmHg, RR 12/min. Pallor was noted. No lymph nodes or purpura were seen.  A neurological examination showed power of 5/5 for all of the limbs.  There were no sensory, cranial nerve or cerebellar deficits. The rest of the systems were normal on examination. 

In view of the pandemic setting, a nasopharyngeal swab was taken which tested positive for COVID-19 by RT-PCR. Laboratory investigations revealed anaemia, thrombocytopenia, unconjugated hyperbilirubinemia, and elevated reticulocyte count (18%) (Table 1). A peripheral smear showed normocytic anaemia, thrombocytopenia and schistocytes (12%), consistent with microangiopathic haemolytic anaemia (MAHA). Coagulation parameters including fibrinogen, PT-INR and APTT were normal. LDH and D-Dimer were both markedly elevated. Direct and indirect Coombs’ tests were negative. Serum C3 and C4 were normal.  Troponin was also normal. ANA by ELISA and antiphospholipid antibody IgM results were negative. The automated blood cultures were sterile. Serology test results for HIV, Hep B, Hep C and Dengue viruses were also negative. A rapid malarial antigen test was negative. 

Urinalysis revealed trace albuminuria and microhaematuria. The renal function was normal. Liver function showed mild elevation of SGOT.  A bone marrow examination was consistent with peripheral platelet destruction. Radiological investigations revealed a normal chest X ray. MRI and MRV-Brain results were also normal. ADAMTS13 testing revealed 36% of normal activity. An inhibitor assay was not available.  

A diagnosis of TTP was made and the patient was started on IV methyl prednisone and plasma exchange. She received daily plasma exchanges of 2-2.5 litres, with replacement using fresh frozen plasma. She had only minimal symptoms of COVID-19.  After 3 sessions of PLEX, the patient’s haematological parameters started improving. Her neurological symptoms also improved.  Rituximab was not given in view of COVID-19. She showed a good response and achieved remission. The patient was discharged on oral prednisone.  A COVID-19 antigen test was negative on day 10 post-admission. She has not shown any signs of relapse after discharge.

TTP can be hereditary or acquired, characterised by deficiency of ADAMTS13, a polymer which degrades multimers of von-Willebrand factor. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 auto antibodies, but rarely inherited via mutations of the ADAMTS13 gene.  Hereditary TTP usually presents in childhood and has a relapsing tendency. The first episode of TTP most commonly occurs during adulthood (90% of all TTP cases). In 50% of the cases, another clinical condition triggers the onset of TTP. Well-described triggers include bacterial infections, SLE, pregnancy, drugs, HIV infection and organ transplantation. In 50% cases the trigger remains `idiopathic`. 

SARS-Cov-2 infection & COVID-19 vaccination have been reported to cause thrombocytopenia & macro-thrombosis (1). Thrombotic microangiopathy involving the lungs and kidneys are also described. SARS-CoV-2 causes endothelial injury by binding to ACE-2 receptors expressed in the vascular endothelial cells.  Generation of auto-antibodies to ADAMTS13 leads to TTP (2). Other suggested potential mechanisms include elevated VWF factor and low ADAMTS13 activity. Both have been reported to predict development of TMA in COVID-19 (3).

As of April 2021, varying presentations ranging from ‘Classical TTP’ to ‘TTP-like illness of COVID-19’ numbering fewer than 20 cases have been reported in the literature. Two case reports with clinical features consistent with TTP in the setting of COVID-19 infection have been reported (4).  ADAMTS13 levels are not provided for either of those cases.  However, very low ADAMTS13 activity and positive inhibitor leading to iTTP have been reported by Albiol-et-al (2). Law-et-al report that COVID-19 infection can trigger autoimmune haemolytic anaemia & iTTP (5). A case series from Iran reported 4 patients with classical clinical and haematological parameters consistent with classical TTP during COVID-19 infection (6).  COVID-19 infection has also been reported to trigger anti-phospholipid antibodies leading to thrombosis and thrombocytopenia.  COVID-19 infection has been reported to cause high von Willebrand Factor (vWF) levels with low ADAMTS 13 activity which may lead to the development of thrombotic microangiopathy (3). 

In our case, female gender, obesity and COVID-19 were the only risk factors for TTP. Both the clinical and haematological parameter features were classical of TTP. ADAMTS13 activity being 36% of normal raises the question of whether this is mechanistically more like ‘TTP-like illness of COVID-19’ rather than acquired iTTP, in which ADAMTS13 activity falls to <10%. An increased incidence of young stroke in COVID-19 has been reported. Possible mechanisms include a hypercoagulable state resulting from systemic inflammation, cytokine storm and direct viral-induced endothelial damage leading to cerebral arterial and venous thrombosis (3).  TTP should be considered in young individuals with COVID-19 and neurological symptoms.

SARS-Cov-2 infection is emerging as a strong risk factor for the development of thrombotic microangiopathy. ‘COVID-19 induced TTP’ is likely a spectrum ranging from classical iTTP (<10% ADAMTS13 activity and anti-ADAMTS13 antibodies in plasma) to COVID-19 induced TTP (direct endothelial damage leading to a high VWF/ADAMTS13 ratio).  Plasma exchanges and steroids have shown anecdotal benefit in all reported case series. The role of Rituximab remains unclear. Neurological and haematological parameters have shown sustained improvement with a lower reported relapse rate than classical immune TTP, suggesting a strong causative role for COVID-19.

Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, Goldblatt D, Kotoucek P, Thomas W, Lester W. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. N Engl J Med. 2021 Apr 16. doi: 10.1056/NEJMoa2105385. Epub ahead of print. 

Mancini I, Baronciani L, Artoni A, Colpani P, Biganzoli M, Cozzi G, Novembrino C, Boscolo Anzoletti M, De Zan V, Pagliari MT, Gualtierotti R, Aliberti S, Panigada M, Grasselli G, Blasi F, Peyvandi F. The ADAMTS13-von Willebrand factor axis in COVID-19 patients. J Thromb Haemost. 2021 Feb;19(2):513-521. doi: 10.1111/jth.15191. Epub 2020 Dec 18. 

Altowyan E, Alnujeidi O, Alhujilan A, Alkathlan M. COVID-19 presenting as thrombotic thrombocytopenic purpura (TTP). BMJ Case Rep. 2020 Dec 17;13(12):e238026. doi: 10.1136/bcr-2020-238026. 

Aminimoghaddam S, Afrooz N, Nasiri S, Motaghi Nejad O, Mahmoudzadeh F. A COVID-19 pregnant patient with thrombotic thrombocytopenic purpura: a case report. J Med Case Rep. 2021 Mar 1;15(1):104. doi: 10.1186/s13256-020-02577-5. 

Law L, Ho G, Cen D, Stenger J. Atypical manifestations of coronavirus disease 2019 (COVID-19)-associated autoimmune thrombotic thrombocytopenic purpura. Clin Case Rep. 2021 Jan 14;9(3):1402-1404. doi: 10.1002/ccr3.3787. 

Tehrani HA, Darnahal M, Vaezi M, Haghighi S. COVID-19 associated thrombotic thrombocytopenic purpura (TTP) ; A case series and mini-review. Int Immunopharmacol. 2021 Apr;93:107397. doi: 10.1016/j.intimp.2021.107397. Epub 2021 Jan 22. 

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Thrombotic Thrombocytopenic Purpura (TTP) – a Rare Presentation with COVID-19

Department of Paediatric Cardiology, Aster Ramesh Hospitals, Vijayawada, India

Murtaza Kamal

UHL’s anomaly; congestive cardiac failure; right ventricle; myocardium; right ventricular dysfunction.

The authors acknowledge Mr P Satheesh Kumar, Pediatric Echo Labora- tory in charge for his technical assistance.

Uhl’s anomaly is a rare congenital anomaly of the heart in which there is a congenital absence of the right ventricular myocardium. Only a few cases have been reported in the literature. It normally presents in infancy with features of congestive cardiac failure; however, cases have been reported in adults with right heart failure. Although the prognosis is not good, palliative surgical modalities are being performed in the Indian population. We report below two cases of children with Uhl’s anomaly who presented to us with this rare condition and are under medical management.

Uhl’s anomaly is a rare form of congenital right ventricular cardiomyopathy which is characterized by the partial or complete absence of the right ventricular myocardium. The epicardium and endocardium of the right ventricle are opposed, but the septum and papillary muscles of the right ventricle are normally muscularized. The condition is mainly sporadic, though some familial occurrences are present in the literature. About a century ago, Ostler1 described a “parchment heart”, but the first case was officially reported in 1952 by Henry Stephen Mc Graw Uhl.2 It is such a rare condition that until 1993 only 84 cases were reported, as summarized in a systemic review by Gerlis.3 A close differential diagnosis of this condition is arrhythmogenic right ventricular dysplasia (ARVD). We present the cases of two children who presented to us with this rare anomaly and are under medical management.

An 8-month old, apparently asymptomatic male child was referred from an outside hospital as a case of pulmonary atresia, having presented there with excessive crying and breathing difficulty with mild cyanosis. On examination, the child had a heart rate of 106/ min, regular, BP: 98/58mm Hg, RR: 28/min with no retractions, Spo2: 90% room air. The cardiac apex was in the 4th intercostal space, 0.5 cm lateral to the midclavicular line. The first sound was normal in intensity and duration, and the second heart sound had normal split and intensity. A soft pan systolic murmur of 2/6 intensity was heard at the lower left sternal border. Soft, non-tender hepatomegaly of 1 cm was present, with no splenomegaly. CXR revealed massive cardiomegaly. ECG showed sinus rhythm with right atrial enlargement. An echocardiogram revealed a dilated right atrium, and ventricles with a thin right ventricular lateral wall. The leaflets of the tricuspid valve were non-coapting and thence, there was severe low-pressure tricuspid regurgitation. Severe RV dysfunction was observed. The left ventricle had normal function.

 Due to suspicion of Uhl’s anomaly, cardiac magnetic resonance (CMR) imaging was performed, which confirmed Echo findings of dilated RA, RV (RVEDV-123ml/m2) with severe tricuspid regurgitation. There was poor right ventricular function (RV EF-15%), with a thin free wall with flattened inter-ventricular septum during diastole. There was no evidence of fibro-fatty RV wall infiltration, thus ruling out ARVD. 

On delayed enhancement imaging, we observed enhancement along the RV free wall, apical RV, and RV portion of the distal IVS (Fig: 1). Minimal pericardial effusion was present. The CMR findings confirmed Uhl’s anomaly, and the parents were counselled about the management options. They did not prefer surgical palliation. The child was discharged on diuretics and ACE inhibitors and is in follow up without any symptoms presently.

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A 2-year-old, apparently asymptomatic boy was referred to us with an incidental murmur. On examination, his vitals were normal with HR: 98/mins regular, RR-20/min, BP: 102/64 mm Hg, saturation in room air: 94%. The apex was in the 5th intercostal space, 1 cm lateral to the midclavicular line. The first heart sound was normal in intensity and duration and the second heart sound was normal in intensity with normal splitting. A soft systolic murmur was present at the left lower sternal border. CXR showed mild cardiomegaly. Echocardiography showed dilated RA and RV, with severe tricuspid regurgitation and right ventricular dysfunction. A diagnosis of organic TR was made, diuretics were started and the child was placed under follow up. The child developed features of congestive heart failure. CMR imaging showed dilated RA and RV, with a thinned out RV wall without any fatty infiltration of the RV wall, suggesting Uhl’s anomaly (Fig: 2). The parents were informed about the condition and prognosis and they too preferred medical management over the palliative surgical procedure.

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Uhl’s anomaly is the congenital complete or partial absence of the right ventricular myocardium. There is no evidence of deposition of adipose tissue, inflammation or necrosis. Since the first description of Uhl’s anomaly about 70 years ago, different theories have been proposed for this anomaly, although the exact cause still is not known. Initially, it was thought to occur due to embryologic failure of the right cardiogenic fold, which in turn leads to a congenital absence of the right ventricular myocardium. Apoptotic destruction of the myocardium after the heart has fully developed is a recent explanation which has been forwarded by some studies, including by Uhl himself in 1996.4 A potential genetic predisposition is also a possibility, as the anomaly has been described in twins and family members.

In most cases, the anomaly presents in the early years of age with congestive cardiac failure.3 Cyanosis is also not uncommon as a symptom. Cases have been reported in which Uhl’s anomaly has presented with massive peripheral oedema or pleural effusion leading to cardiac tamponade.7,8 It may rarely mimic other congenital cardiac anomalies like Ebstein’s anomaly or even functional pulmonary atresia. 9,10 The baby in our first case was referred to us with a diagnosis of pulmonary atresia. The association of other congenital anomalies with Uhl’s anomaly is relatively rare. The first diagnosis of Uhl’s anomaly was made by Uhl on autopsy, but presently, with the advent of echocardiography and cardiac magnetic resonance (CMR) imaging, early diagnosis is possible.

Arrhythmogenic right ventricular dysplasia (ARVD) is an entity closely related to this condition.12 The characteristic feature of ARVD is fibrofatty tissue replacement of RV myocardium, whereas Uhl’s anomaly has a complete absence of muscle in the parietal wall of RV (composed only of the opposing layers of endocardium and epicardium). The features of these two conditions overlap each other, so in 1993 Gerlis and co-workers enumerated certain features to differentiate between the 2 conditions.3 The diagnosis of Uhl’s anomaly is favoured due to the younger age of presentation, predominant features of cardiac failure, and lack of family history and other associated congenital heart diseases. Even in Uhl’s anomaly, RV is known to be arrhythmogenic.

The prognosis of Uhl’s anomaly is not good, therefore only palliative surgical procedures can be performed. The aim of surgical management of Uhl’s anomaly is the alleviation of right heart failure by the complete exclusion of RV with bidirectional Glenn or Fontan connection, or a reduction plasty of RV combined with bidirectional Glenn (one and a half ventricle). Each of these palliative procedures is described as having good results nowadays.

Uhl’s anomaly is a rare cause of congestive heart failure in infancy, which can be diagnosed adequately by echocardiography and CMR. Early diagnosis will prevent the morbidity associated with this disease. Palliative surgical procedures are increasingly being performed around the globe, yet still the prognosis is poor.

WM. The Principles and Practice of Medicine. 6th ed. New York: D. Appleton; 1905. p. 280.

Uhl HS. A previously undescribed congenital malformation of the heart: almost total absence of the myocardium of the right ventricle. Bull Johns Hopkins Hosp. 1952;91(3):197-209. 

Gerlis LM, Schmidt-Ott SC, Ho SY, Anderson RH. Dysplastic conditions of the right ventricular myocardium: Uhl's anomaly vs arrhythmogenic right ventricular dyspla- sia. Br Heart J. 1993;69(2):142-150.

Uhl HS. Uhl’s anomaly revisited. Circulation. 1996; 93:1483–1484.

Hoback J, Adcoff A, From AHL, et al. A report of Uhl’s disease in identical twins: evaluation of right ventricular dysfunction with echocardiography and nuclear angiog- raphy. Chest. 1981; 79:306–310.

Digglemann U, Baur HR. Familial Uhl’s anomaly in the adult. Am J Cardiol. 1984; 53:1402–1403.

Kilinc M, Akademir M, Sivasli E. A case of Uhl’s anomaly presenting with severe right heart failure. Acta Cardiol. 2000;55:367-69.

Kisacik HL, Ozdemir K, Altunkeser B, Oguzham A, Goksel S. Uhl’s anomaly. Jpn Heart J. 1999;40:503-07.

Benson CB, Brown DL, Robert’s DJ. Uhl’s anomaly of the heart mimicking Ebstein’s anomaly in utero. J Ultrasound Med. 1995;14:781-783.

	Tumbarello R, Adatiya I, Yatman A, Boutin C, Izukawa T, Freedom RM. From func- tional pulmonary atresia to right ventricular restriction. Long term follow up of Uhl’s anomaly. Int J Cardiol. 1998;67:161-64.

	Ikari NM, Azeka E, Aiello VD, Atik E, Barbero-Marcial M and Ebaid M. Uhl’s anomaly. Differential diagnosis and indication for cardiac transplantation in an infant. Arq Bras Cardiol 2001; 77: 69–76.

	Fontaine G, Guiraudon G, Frank R. Mechanism of ventricular tachycardia with and without associated chronic myocardial ischemia: surgical management based on epi-cardial mapping. In: Narula OS, ed. Cardiac Arrhythmias. Baltimore and London, UK: Williams and Wilkins; 1979:516-523.

Kalita JP, Dutta N, Awasthy N, Chowdhuri KR, Girotra S, Radhakrishnan S et al. Sur- gical Options for Uhl’s Anomaly. World Journal for Pediatric and Congenital Heart Surgery. 2017; 8(4), 470–474.

UHL’s Anomaly: A Rare Form of Congestive Cardiac Failure in Early Childhood

Specialist in Internal Medicine, Aster Hospital, Ibri, Oman

Dr. Jamal Thottungal

Specialist Pathologist, Aster Hospital, Ibri, Oman

Dr. Shayfa Palliyalil

Infective endocarditis, 
Native valve endocarditis, 
Aortic stenosis, 
Streptococcus viridans

Infective endocarditis is a life-threatening medical condition that is not frequently encountered in routine clinical practice. The overall incidence of infective endocarditis is 3-10 per 100000 people, with a mortality rate of up to 30% at 30 days post-admission. Presentation can be unusual and diverse and can vary from person to person. A high index of clinical suspicion is required. A delay in diagnosis can be fatal. 

Here we present a case of infective endocarditis. The patient was initially evaluated for anaemia in another hospital. No cause was found, and the case was treated as anaemia of unknown chronic disease. The patient came to our centre a few weeks later, and we were able to diagnose them with infective endocarditis. She was promptly referred and operated upon, but died in the post-operative period.  

This case highlights the importance of early diagnosis and treatment before full-blown valve damage and cardiac failure ensues.  A thorough history and clinical examination, in conjunction with careful selection of investigative modalities, is the only way to make an accurate diagnosis.

Infective endocarditis (IE), first described by William Osler in 1885, is defined as an infection of the endocardial surfaces of the heart— primarily of the heart valves, the mural endocardium, or a septal defect. The intracardiac effects of IE include severe valvular insufficiency, intractable congestive heart failure and myocardial abscesses. If left untreated, IE is inevitably fatal.1-3 IE occurs most frequently in patients with a damaged heart valve, a prosthetic valve, or a pacemaker lead. Any structural heart disease can predispose a person to develop IE. The overall incidence of infective endocarditis is 3-10 per 100000 people, with a mortality rate of up to 30% at 30 days post-admission.2-3 In the past, rheumatic heart disease was the main precursor to IE and it is still prevalent in developing countries.

The endocardium, which covers the heart valves, is the primary area affected by IE. If the infection remains untreated, it will damage the valves completely, resulting in congestive heart failure.  Early diagnosis is key to improving clinical outcomes and survival. Antibiotics are the mainstay of treatment, but surgery may be required for some patients.  

Staphylococcus aureus, Streptococcus viridans, Coagulase negative staphylococci, Enterococci and Streptococcus bovis are the most common organisms causing IE. S. aureus can produce acute infective endocarditis. Native valve endocarditis caused by S. aureus has a more aggressive course. Despite technological advances in diagnostic and therapeutic modalities, the overall mortality has not improved. Aortic valve infective endocarditis is still a life-threatening disease, which is associated with high mortality and morbidity.2-3

A 75-Year-old Omani woman, with ongoing treated diabetes, hypertension and hypothyroidism, presented with a history of fever with duration of more than 3 weeks, along with chills, rigor, generalized body pain, arthralgia and severe fatigue. She had been investigated extensively in another hospital for severe anaemia, but no specific diagnosis had been established. The patient was treated with iron and erythropoietin injection, and a provisional diagnosis of anaemia of chronic disease was made. 

There was no history of cough or breathlessness, but the patient had nausea and occasional episodes of loose stools. She had a history of significant weight loss. There was no history of any joint pains, rash or tremor, and no history of dental procedures. There was a history of documented high body temperature of more than 39°C on several occasions. 

On examination, the patient looked ill and was pale. Her temperature was 39°C. She had a pulse rate of 90/minute and a blood pressure of 130/80mm Hg. A systemic examination revealed a Grade 3 ejection systolic murmur in the aortic area, and mild hepatomegaly. All other systems were within normal limits. 

The clinical differentials considered at this point were a urinary tract infection (common in diabetics), enteric fever (prolonged fever with occasional loose stools), malignancy (consistent with an elderly lady with anaemia and body pain), Brucellosis (consumption of unpasteurized milk is common in the GCC), and infective endocarditis (in view of the pallor and cardiac murmur).

Laboratory investigations revealed a haemoglobin level of 6.9 g/dl and WBC of 7140/mm3, with differentials of 77% (neutrophils), 13% (lymphocytes) 8.8% (monocytes), 1.2% (eosinophils). Platelet count was 192 × 103/µl, and ESR 75 mm/hour. Urine microscopy showed pus cells 10-15/ Hpf. A Widal test was positive with titer of 1/320 for S. typhi O. A routine stool examination was normal, the patient’s HIV status was negative and an IgM brucella test was also negative.

Though the Widal test was positive with significant titers and there were minimal pus cells in the urine, the clinical picture was not consistent with UTI or enteric fever. The fever was mild and enteric fever could not explain the chronic anaemia. 

In view of the chronic anaemia, elevated ESR and cardiac murmur, the possibility of infective endocarditis was considered. A blood culture was performed, showing growth of a viridans Streptococcus species (S. mitis) on Vitek 2 Compact (Biomerieux), making infective endocarditis a distinct possibility.  The isolated organism was sensitive to ampicillin, moxifloxacin, levofloxacin, tetracycline, doxycycline, vancomycin and linezolid, but resistant to clindamycin.

The patient was referred to another center for an echocardiogram (ECHO), which demonstrated severe aortic stenosis and mild aortic regurgitation with multiple vegetations on the aortic valve, extending up to the root of the aorta. The patient underwent surgery, but unfortunately succumbed post-operatively. 

Infective endocarditis (IE) is an infection of the heart valves characterized by an aggregation of bacteria in a fibrin plaque known as ‘vegetation’. The most common causative agents are the streptococci that are commensals of the oropharyngeal cavity. IE is treated based on blood culture report findings if positive, and empirically if negative.(1) The viridans streptococci, a heterogeneous group of alpha-haemolytic streptococci, is part of the normal flora of the mouth, and is responsible for dental caries and pericoronitis as well as subacute infective endocarditis.(5-6)   The most relevant species clinically are Streptococcus oralis (mitis) and Streptococcus sanguis, which are responsible for 40- 60% of endocarditis cases occurring on normal valves.(7)  Speciating Streptococci has become much easier with the development of automated systems such as VITEK.

Although rarely associated with renal failure and septic shock, endocarditis caused by viridans Streptococci is commonly associated with peri-annular lesions (abscesses, pseudoaneurysms, or fistulas) or heart failure.(8) The risk of death is around 15%. Although the viridans Streptococci are non-aggressive microorganisms, the associated valvular destruction is similar to that caused by other pathogens in that it causes left-sided endocarditis.(8)

The clinical presentation of IE has been traditionally classified as sub-acute and acute. Sub-acute IE presents as a prolonged low-grade fever for weeks, or even months, with other symptoms such as fatigue, chills, myalgia, and weight loss. (9-11) Fever may be minimal or even absent in patients with underlying debilitating illnesses such as chronic liver disease.(19) Acute IE, on the other hand, presents with high fever and rapidly deteriorates if not recognized early.(9,10) According to the modified Duke’s criteria,(18) the diagnosis of infective endocarditis was supported by two major criteria that were met, namely positive blood cultures of viridans Streptococci and the identification of the vegetation, both echographically and intra-operatively. Laboratory abnormalities that can frequently be seen in IE include elevated acute phase reactants (erythrocyte sedimentation rate and C-reactive protein), anaemia, thrombocytopaenia, haematuria, and positive rheumatoid factor.(9,10)  Cardiac echocardiography is essential for the diagnosis and for monitoring vegetation size and cardiac function. However, it is important to note that the absence of vegetation on echocardiography does not necessary rule out IE.

Three sets of blood cultures taken before starting antibiotics are likely to detect bacteremia in 98% of cases. Duke’s criteria have an overall sensitivity of 80%, but this is significantly lower in prosthetic valve endocarditis and infections around implantable electronic devices. The sensitivity of Transthoracic Echocardiography (TTE) is around 70% for detecting vegetations on native valves, but this is reduced to 50% in prosthetic valve endocarditis and is lower in the case of implanted electronic devices. Transoesophageal echocardiography (TOE) has both sensitivity and specificity exceeding 90% for vegetations,(2) but initial studies may yield false negative results in 6-18% of cases(12). Three-dimensional TOE may occasionally augment the findings of standard TOE. In addition, 18-fluorodeoxyglucose positron emission tomography may identify perivalvular or perigraft infections not seen with TOE(12). 

The viridans streptococci, Staphylococcus aureus and enterococcus spp. together account for 80-90% of all cases of IE(2). A study conducted in 16,867 patients with infective endocarditis in Spain over the period 2003-2014, documents an increasing trend of infections with coagulase negative Staphylococcus and Enterococcus species(13).  S. aureus and the enterococci are associated with poorer outcomes(14). Infections with unusual organisms including gram negative bacilli and fungi are often seen in intravenous drug users(15).  Duration of illness is found to be shorter in Staphylococcus infections and longer in the case of Streptococcus infections, and higher mortality is observed in infections with a shorter duration of illness.

Even though antibiotic therapy is the mainstay of treatment, surgery may be needed in one third of patients during active illness, and in another third after the initial healing process.(17) A prognosis of infective endocarditis depends on several factors including age, comorbid conditions such as diabetes, delayed diagnosis, involvement of prosthetic valves or the aortic valve, antibiotic resistance etc.(12) In developed countries, the overall survival rate is 80-85%, however rates vary considerably among sub-populations of IE patients.(12) Overall survival rates after 1 year of successful treatment range from 80-90%.(12) Antibiotic prophylaxis before dental and surgical procedures to prevent IE was once very wide spread in clinical practice. However, due to lack of evidence, the American Heart Association and European Society of Cardiology now recommend prophylactic antibiotics only for those patients who are at a high risk of morbidity and mortality due to IE.

As the frequency of IE in day-to-day practice is very low, and the presentation varies from person to person, if not suspected clinically, diagnosis may be missed or delayed. Clinical diagnosis depends upon proper history taking and examination. Infective endocarditis should always be suspected in a febrile patient, irrespective of cardiac status. The presence of anaemia with valvular heart disease significantly increases the probability of infective endocarditis. Timely and prompt diagnosis is very crucial. A late diagnosis may not help the patient, as in this case. Apart from the delay in diagnosis, she had other predictors of mortality, including diabetes, old age and aortic valve involvement. A history of fever is extremely important in the anaemia work-up, as this redirects the evaluation process. Fever in infective endocarditis may be low grade, and is often overlooked. If anaemia is associated with fever, a thorough clinical examination must be performed to make sure that a cardiac murmur is not missed. 

Raja K, Antony M, Harikrishnan S. Infective endocarditis due to Streptococci and Enterococci: A 3-year retrospective study. Indian journal of pathology & microbiology,  2018;61(4):545–548. 

Rajani R, Klein JL. Infective endocarditis: A contemporary update. Clinical medicine, 2020;20(1):31–35.

Mostaghim AS, Lo H, Khardori N. A retrospective epidemiologic study to define risk factors, microbiology, and clinical outcomes of infective endocarditis in a large tertiary-care teaching hospital. SAGE open medicine, 2017;5:2050312117741772.4.

Awada A, van der Auwera P, Meunier F, et al. Streptococcal and enterococcal bacteremia in patients with cancer. Clinical Infectious Diseases, 1992;15(1):33–48.5. 

Elting LS, Bodey GP, Keefe BH. Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clinical Infectious Diseases, 1992;14(6):1201–1207.6. 

Johnson CC, Tunkel AR, Mandell GL, et al. Viridans Streptococci and groups C and G streptococci. Principles and Practice of Infectious Diseases. New York: Churchill Livingstone; 1995, 1845–61.

Mylonakis E, Calderwood, SB. Infective endocarditis in adults. The New England journal of medicine, 2001;345(18):1318–1330.  

López J1, San Román JA, Revilla A, et al. Clinical, echocardiographic and prognostic profile of Streptococcus viridans left-sided endocarditis.  Rev Esp Cardiol, 2005;58:153–8

Baltimore RS, Gewitz M, Baddour LM, et al. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation, 2015; 132:1487-515.

Bragg L, Alvarez A. Endocarditis. Pediatr Rev, 2014;35:162-8.

Martin JM, Neches WH, Wald ER. Infective endocarditis: 35 years of experience at a Children’s Hospital. Clin Infect Dis, 1997;24:669-75.

. 	Loscalzo J, Fauci A, Kasper D, et al. Harrison’s principles of internal medicine,21st edition; pages:925, 926, 932.

Olmos C, Vilacosta I, Fernández-Pérez C, et al. The Evolving Nature of Infective Endocarditis in Spain: A Population-Based Study (2003 to 2014). J Am College Cardiology, 2017;70(22):2795–2804.

Shah ASV, McAllister DA, Gallacher P, et al. Incidence, microbiology and outcomes in patients hospitalized with infective endocarditis. Circulation, 2020;141(25):2067-2077.

Tan C, Shojaei E, Wiener J, et al. Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis. JAMA Netw Open. 2020;3(8):e2012974.

Issa VS, Fabri Jr J, Pomerantzeff PMA, et al, Duration of symptoms in patients with infective endocarditis. Int J Cardiology, 2003;89(1):63-70.

Al-Attar N. Infective endocarditis. European Society of Cardiology, 2008;7:15-31.

Li JS, Sexton DJ, Mick N, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clinical Infectious Diseases, 2000;30(4):633–638.

Crawford MH. Current Diagnosis and treatment, Cardiology. 5th edition. New York: McGraw Hill Educational, 2017.

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Missed Opportunity to Suspect and Diagnose Infective Endocarditis at an Early Stage

Jyoti Upadhyay

Rahul Tugnait

Moni Suseelan

Acute cholecystitis, pancreatitis,
CBD calculus, laparoscopic
cholecystectomy, Rendezvous ERCP,
traditional ERCP.


Retrospective, non-randomized, observational, using historical control subjects.



Twenty-five consecutive patients with gallbladder and CBD calculi, for whom both ERCP and LC were considered clinically indicated, were recommended to receive joint LC and IOR-ERCP. Detailed informed consent was taken forboth procedures. Their outcomes were compared with an equivalent number of patients who underwent conventional management.

This case series compares thetraditional approach of endoscopicretrograde cholangiopancreatography
(ERCP) with separate laparoscopiccholecystectomy (LC), versuscombined LC and intra-operativerendezvous ERCP (IOR-ERCP). Weconsider the costs and benefits ofeach approach in terms of applicability,efficacy, safety, cost effectivenessand duration of hospital stay.25 patients with cholelithiasis andcholedocholithiasis were selected
for laparoscopiccholecystectomy (LC) and IOR-ERCP.Informed consent was obtained.

A laparoscopic surgeon performedcholecystectomy and a gastroenterologistperformed ERCP during the
same anaesthesia.Rendezvous ERCP was successfullycompleted in 22 of 25 patients.
The Rendezvous procedure couldnot be accomplished in 3 patientsdue to difficulty passing the guidewire from the cystic duct to the duodenum.One patient had a tortuouscystic duct, another had abnormalconnection of the cystic duct to theright hepatic duct and the thirdhad malignancy of the gallbladderoccluding the connection with thecommon hepatic duct (CHD). Allthree underwent successful retrograde-canulation of the commonbile duct (CBD) during the sameanaesthesia.


The 22 successful rendezvousERCP procedures were comparedwith 22 control patients withcholelithiasis and choledocholithiasis,who underwent ERCP and LCseparately. The mean (cumulative)operating theatre (OT) time for RendezvousERCP was 2.34 hrs. vs 3.15hrs. for separate procedures. Themean cumulative procedure-related
hospital stay for IOR-ERCP was 2.77days vs 7.50 days for traditional LCand ERCP. There was no case of postERCP pancreatitis (PEP) or othercomplications in the study group.In the control group 4.5 % patientshad pancreatitis (mild), 4.5% had aminor GI bleed and 4.5% had basalatelectasis with transient respiratoryfailure.


Rendezvous ERCP appearseffective and safe; it helps decreaseOT time, hospital stay, and it maydecrease the cost of treatment. Challengesassociated with this approachare that the procedure requiresexpertise; a surgeon and gastroenterologistshould be available atthe same time; crowding in the OT;multiple instruments in the field of
fluoroscopy causes deteriorationin quality of imaging; air insufflation during ERCP causes small bowel distension whichinconveniences the surgeon, and that ERCP must beperformed in a supine position.


Approximately 15% of patients who have laparoscopiccholecystectomy also have CBD calculi [1,2], and accordingto Collins et al. (2004), two thirds of these patientsneed some intervention to remove them.[3] Currentpractice is to perform ERCP followed by laparoscopiccholecystectomy or vice versa, depending on localexpertise and protocols.[4] With this approach, patientsmust undergo anaesthesia/sedation on two occasions.

There is a 40-70% chance of false negative pre-operativeERCP [5], as a CBD stone will pass spontaneously in 50%cases before the procedure.[8] In 12.9 % of cases, newCBD stones may be discovered after laparoscopic cholecystectomy.[6] If ERCP is performed post-laparoscopiccholecystectomy, there is a 5% risk of failed cannulation,leading to a second surgery.

The above pitfalls can be avoided using the IntraoperativeRendezvous ERCP technique. This procedurealso reduces the risk of inadvertent cannulation of thepancreatic duct and risk of post ERCP pancreatitis.[8] Incase ERCP fails, the option of CBD exploration is availableduring the same surgical session.

In our case series, 25 patients (13 female and 12 males)with CBD and GB stones, with or without cholecystitis,pancreatitis or cholangitis, were selected for intraoperativeERCP. The rendezvous technique was followedas previously described [9]. Laparoscopic surgery wasperformed by one of three laparoscopic surgeons- AK,RT or MS. ERCP was performed by APU in all cases. Alaparoscopic surgeon performed the intra-operativecholangiogram after isolating and opening the cysticduct. Once CBD calculi were confirmed, the surgeonpassed a guidewire via the cystic duct into the CBD andduodenum. The Endoscopist then retrieved this wirethrough the instrument channel of the side-viewingduodenoscope using a snare, and used this guidewire toperform further instrumentation. Wire-guided biliarysphincterotomy was performed with or without balloonampuloplasty. CBD stones were removed using stone
retrieval balloons. CBD stenting was performed if stoneextraction was considered incomplete, or if requested bythe operating surgeon on a case-by-case basis. An occlusioncholangiogram was performed in all cases, to makesure of adequate clearance of the biliary tree. In caseswhere the guide wire could not be passed into the duodenumthrough the cystic duct (3 cases), we proceeded toperform ERCP in a supine posture in the same surgicalsession using standard cannulation techniques. This wassuccessful in all 3 cases.


These outcomes were compared with 22 similar historicalcontrols who underwent LC and ERCP separately.

Procedure-related hospital stay- the number of dayspatients had to stay in hospital specifically to undergothe procedure(s).

◆ Procedure-related cumulative OT time- the total timespent by the patient under anaesthesia for LC andERCP separately versus IOR-ERCP. Time under anaesthesiawas retrieved from the OT procedure log.

Procedure-related complications such as pancreatitis,bleeding, infection, perforation etc.

Of a total of 25 patients, 12 were male and 13 werefemale. Ten cases had CBD calculus with acute calculuscholecystitis; 5 had biliary acute pancreatitis andevidence of retained CBD calculus after recovery, alongwith cholelithiasis; 9 patients had CBD calculus withcholelithiasis without cholecystitis; 1 case had gallbladderand CBD sludge, with microliths causing recurrentbiliary colic (Table 1).
Rendezvous ERCP was successful in 22 patients (88%),11 male and 11 females. The guide wire did not pass intothe distal CBD in 3 (1 male and 2 female) patients (12%),who then had retrograde cannulation of the CBD duringthe same surgery, followed by completion of lap cholecystectomy.Of these three, one patient had a corkscrewcystic duct and guidewire coiled up in the duct/neckof the GB repeatedly. One patient had an anatomicalvariation wherein the cystic duct was inserted into theright hepatic duct (figure 2); the guide wire could not benegotiated into the CBD. One patient was found to have aCarcinoma gall bladder that was not diagnosed on priorimaging, this patient also had carcinoma of the stomach(figure 1). The cystic duct was completely blocked, and theguide wire could not be negotiated.


The outcomes of the study population are shown inTable 1. Post-operative outcomes of successful rendezvous
ERCP were compared with similar numbers ofhistorical controls. Hospital records of the last consecutive22 patients (11 female; 11 male) having CBD stonesand cholelithiasis who underwent ERCP followed bylaparoscopic cholecystectomy were retrieved. Comparativeoutcomes of the study group and the control groupare shown in Table 2.The average (procedure-related) hospital stay in thestudy group was 2.77 days, ranging from 2-5 days, compared
to 7.5 days with a range of 5-12 days in the controlgroup. The average (procedure-related, cumulative) OTtime for the rendezvous procedure was - 2.34 hrs (range2.0-3.2hrs). The cumulative OT time for traditionallymanaged patients was 3.15 hrs with a range of 1.55-5.15hrs.There were no cases of post ERCP pancreatitis or othercomplications in the study group. Three patients hadminor complications in the control group. One (4.5%) hadmild pancreatitis; One (4.5%) had minor post ERCP GIbleed, and one (4.5%) had basal atelectasis with transientrespiratory failure. There was no mortality in either group.


There are several potential advantages to performingrendezvous ERCP during lap-cholecystectomy, suchas: single anaesthesia, decreased cumulative OT time,decreased hospital stay and potentially a reduced riskof pest-ERCP pancreatitis. All of these may translate toreduced costs for the patient.The average hospital stay in our series was 2.77 days.Most procedures were performed for patients who presentedwith acute cholecystitis or biliary acute pancreatitis.Procedure-related hospital stay was calculated byspecifically considering the number of days patients hadto stay in hospital for undergoing ERCP or surgery, afterdiscounting the time spent in recovery from pancreatitis
or acute cholecystitis.The duration of hospital stay for the control group was7.5 days. This appears to be unusually long. The reasonsfor this may be administrative in nature; Administrativeissues such as insurance approvals, scheduling by theOT/surgeon etc. consume time and need to be factored in.


Since joint procedures require a single approval from thepayer, time is saved. This emerges as a distinct advantage
of the combined approach wherein, time spent in hospitaldue to administrative issues is also shortened.The most alluring potential advantage of the joint approachis, however, a decrease in post-ERCP pancreatitis(PEP), since accidental cannulation of the pancreaticduct can be avoided. Pancreatitis may still occur byvirtue of passage of the guidewire through the ampulla,involuntary pushing stones through the papilla, refluxof the biliary contrast into the pancreatic duct etc.Nevertheless, most studies have shown a trend towardreduction in rates of PEP. We did not have any cases ofpancreatitis in our series.We observed one patient who was pregnant with GBand CBD stones. IOR-ERCP was performed without fluoroscopy.This was only possible because of the certaintyof biliary access that is offered by the joint approach.


This came across as an advantage in our brief experience.Theoretically, it may be redundant to have an MRCPbefore LC + IOR-ERCP, since an intra-operative cholangiogramwill be performed in all cases. We, however, stillprefer to perform MRCP prior to surgery as it can givevaluable information about biliary anatomy. One of ourpatients had a cystic duct inserted in the RHD and theguide wire could not be negotiated distally. The rendezvousprocedure can be avoided in such cases.
There are several challenges associated with a jointapproach. Firstly, the operating surgeon and endoscopistmust be available at the same time. This can prove challengingin busy hospitals.There is also some crowding of equipment in the OT.It takes several sessions to streamline the positioningof surgical equipment and endoscopy tower before each
team can position themselves comfortably. Multipleinstruments interfere with the field of procedure andimaging (Figure 3); this causes deterioration in thequality of fluoroscopy due to interference from laparoscopicports. ERCP must be performed in a supineposture (not all endoscopists are comfortable with this).


Gas insufflation in the small bowel during ERCP can alsocause technical difficulty for the operating surgeon. Inour experience, various operating teams adapted readilyto these challenges and the learning curve was very brief.Since all ERCPs in our hospital are performed under GAand in a supine posture, this issue was not an obstacle inour experience. However, practice of ERCP varies acrossthe world.
Since our endoscopy suite does not have lead-linedwalls, we perform all our ERCPs in the OT under GA. Thishas not changed in this study. We do not have data tocompare time spent on the actual performance of ERCPas this is not routinely recorded. We assume that timespent in attempting selective bile duct canulation wouldbe significantly shortened using the combined approach.
As previously mentioned, we faced failure of antegradeCBD access by guide wire in three cases due to various
technical reasons- one due to a “corkscrew” cystic duct,one due to variant anatomy of the CBD’s abnormalconnection with the right hepatic duct and one due topreviously undiagnosed gallbladder malignancy. Careful
analysis of MRCP images in retrospect suggested thatwe could have avoided the Rendezvous procedure in twoof these patients from the outset. This also highlightsthe fact that the Endoscopy team must be prepared toperform ERCP using retrograde canulation of the CBD ina supine posture, should the need arise.


Rendezvous ERCP during laparoscopic cholecystectomyis a promising technique that is technically feasiblein most setups. It is an efficient and safe treatment forpatients with choledocholithiasis and cholelithiasis. Ithelps to reduce overall length of hospital stay as well astime spent under anaesthesia [10]. There may be additionaladvantages such as reduction in rates of post-ERCPpancreatitis that need to be confirmed in larger studies.

ERCP endoscopic retrograde cholangiopancreatography

MRCP magnetic resonance cholangiopancreatography

. Williams EJ, Green J, Beckingham I, Parks R, Martin D, Lombard M.Guidelines on the management of common bile duct stones (CBDS). Gut.2008; 57:1004-1021. DOI: 10.1136/gut.2007.121657

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Collins C, Maguire D, Ireland A, Fitzgerald E, O’Sullivan GC. A prospectivestudy of common bile duct calculi in patients undergoing laparoscopiccholecystectomy: Natural history of choledocholithiasis revisited. Annalsof Surgery. 2004; 239:28-33

Lu J, Xiong XZ, Cheng Y, Lin YX, Zhou RX, You Z, et al. One-stage versustwo-stage management for concomitant gallbladder stones and commonbile duct stones in patients with obstructive jaundice. The AmericanSurgeon. 2013; 79:1142-1148

Erickson RA, Carlson B. The role of endoscopic retrograde cholangiopancreatographyin patients with laparoscopic cholecystectomies.Gastroenterology. 1995; 109:252-263. DOI: 10.1016/0016-5085(95)90292-9

Pierce RA, Jonnalagadda S, Spitler JA, Tessier DJ, Liaw JM, Lall SC, et al.Incidence of residual choledocholithiasis detected by intraoperativecholangiography at the time of laparoscopic cholecystectomy in patientshaving undergone preoperative ERCP. Surgical Endoscopy. 2008; 22:2365-2372. DOI: 10.1007/s00464-008-9785-3

Rhodes M, Sussman L, Cohen L, Lewis MP. Randomised trial of laparoscopicexploration of common bile duct versus postoperative endoscopicretrograde cholangiography for common bile duct stones. Lancet. 1998;351:159-161. DOI: 10.1016/S0140-6736(97)09175-7

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