Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial.

OBJECTIVE: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction. METHODS: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3-5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival. RESULTS: Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3-5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85-100%; n=29) and for cediranib 88% (IQR 76-93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4-11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1-20.4 months; n=17). Median follow-up was 12.4 months (8.9-not reached; n=17). CONCLUSIONS: The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated. TRIAL REGISTRATION NUMBER: EudraCT 2016-004618-93.

18F-FDG PET/CT in Bilateral Breasts Metastasis From Ovarian Carcinoma.

ABSTRACT: Ovarian carcinomas generally metastasize within the peritoneal cavity due to exfoliation of malignant cells from primary tumor. Metastasis to the breasts is an unusual event and may mimic primary neoplastic disease. Usually, breast metastasis presents as a single isolated, well-circumscribed soft tissue lesion, and serous papillary carcinoma is the most common type of ovarian tumor that can metastasize to the breast. Concurrent bilateral breast metastasis is rare event. We present a follow-up case of metastatic carcinoma ovary, demonstrating FDG-avid soft tissue density masses in the bilateral breast parenchyma along with bilateral axillary lymphadenopathy, biopsy of which revealed metastatic deposits from carcinoma ovary.

Acute promyelocytic leukemia presenting as pulmonary thromboembolism: Not all APLs bleed.

We present a rare case of acute promyelocytic leukemia (APL) presenting as pulmonary thromboembolism being misdiagnosed as community-acquired pneumonia. Thrombotic phenomenon in APL are poorly understood and grossly underreported. In our case, following no response to standard antibiotic treatment, the patient was further investigated and detected to have an acute pulmonary thromboembolism following right lower limb deep vein thrombosis (DVT). Though, complete blood picture revealed only mild hyperleukocytosis, bone marrow biopsy and aspiration revealed 60% blasts and a positive t (15,17)(q22,12) and PML retinoic acid receptor alpha (RARA) fusion protein on molecular cytogenetics. He was diagnosed as APL and received treatment with all-transretinoic acid (ATRA) and arsenic trioxide (ATO) and therapeutic anticoagulation.

Mediastinal germ cell tumour causing superior vena cava tumour thrombosis.

We report a rare case of a 35-year-old man who presented with a 1-week history of retrosternal chest pain of moderate intensity. A positron emission tomography CT (PET-CT) showed a large fluorodeoxy-glucose (FDG)-avid heterogeneously enhancing necrotic mass in the anterosuperior mediastinum with a focal FDG-avid thrombosis of the superior vena cava (SVC) suggestive of tumour thrombus and vascular invasion. α-Fetoprotein levels were raised (5690 IU/L). Image guided biopsy of the mediastinal mass was suggestive of non-seminomatous germ cell tumour (NSGCT). The patient received four cycles of BEP (bleomycin, etoposide and cisplatin) along with therapeutic anticoagulation with low-molecular-weight heparin. Follow-up whole body PET-CT revealed complete resolution of mediastinal mass and SVC tumour thrombosis. The documentation of FDG-PET-avid tumour thrombus resolving with chemotherapy supports the concept of circulating tumour cells being important not only in common solid tumours such as breast and colon cancer but also in relatively less common tumours such as NSGCT. The detection of circulating tumour cells could help deploy aggressive regimens upfront.

Langerhans cell histiocytosis presenting as hypothyroid goitre: a unique presentation.

Langerhans cell histiocytosis (LCH) is a disease involving the antigen presenting cells, which can range from a single system involvement with an indolent course to a multisystem disease with increased morbidity. We present a rare case of LCH presenting as hypothyroid goitre that was successfully treated as per the LCH III trial protocol with a combination of vinblastine and oral prednisolone. We highlight the need for awareness of this rare presentation of LCH as a painless goitre which is often misdiagnosed as poorly differentiated thyroid carcinoma or overlooked as a benign disease.

Fatal measles presenting as acute respiratory distress syndrome in an immunocompetent adult.

Fatal measles is known to occur among immunocompromised adults. We report a rare case of an immunocompetent non-pregnant young lady who suffered from fatal acute respiratory distress syndrome due to measles. Physicians must be vigilant to this deadly presentation of measles even in immunocompetent individuals. We emphasise the inadequacies of vaccination programmes in India reflected not only by the existing high measles-related childhood mortalities, but also an emerging rise in deaths among adults.

Acute hepatitis E complicated by acute pancreatitis and multiorgan dysfunction.

We report this rare case of a 27-year-old man who presented with acute hepatitis E and went on to develop acute epigastric pain. He was diagnosed to have acute severe pancreatitis with shock and acute renal failure due to hepatitis E. Such a phenomenon has rarely been reported in the literature, with patients following a benign course and complete recovery after conservative management and analgesia. Awareness of this potentially life-threatening complication, especially in young men from endemic areas with acute hepatitis E presenting with abdomen pain has been highlighted.

Intracerebral bleed, right haemiparesis and seizures: an atypical presentation of vivax malaria.

Falciparum malaria is notoriously known to produce life-threatening complications. Despite growing reports of chloroquine resistance and severe disease, vivax malaria continues to be viewed as a benign disease. We report a rare case of a 47-year-old healthy man from a malaria-endemic region, presenting with intracerebral bleed, right haemiparesis, aphasia and seizures following vivax malaria. This was successfully managed conservatively, without any neurosurgical intervention, with combination therapy of intravenous artesunate, oral hydroxychloquine and primaquine. In a country where Plasmodium vivax is responsible for majority of cases of malaria, it is high time the national malaria control programmes focus on the elimination of P. vivax in addition to its more dangerous counterpart, P. falciparum.

Utility of total lymphocyte count as a surrogate for absolute CD4 count in the adult Indian HIV population: A prospective study.

BACKGROUND: Standard methods of CD4 counts and plasma viral load estimation require specialized equipment, highly trained personnel and are extremely expensive. This remains a major challenge for the initiation of anti-retroviral therapy for patients in resource-limited settings. OBJECTIVE: To assess the clinical utility of the total lymphocyte count (TLC) to serve as a surrogate marker for predicting a CD4 counts <350 cell/mm(3) in patients with HIV. MATERIALS AND METHODS: A prospective study of 200 consecutive newly detected highly active anti-retroviral therapy (HAART) naïve HIV patients admitted over a one year period was conducted. Linear regression, Pearson correlation and receiver operating characteristic (ROC) curves were used to calculate the relationship between TLC and CD4 counts. RESULTS: A significant correlation between TLC and CD4 count was observed (r = 0.682, P < 0.001). TLC cut off of 1200 cell/mm(3) as a predictor of CD4 count <350 cell/mm(3) had 73.1% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 51.4% negative predictive value (NPV). Raising the cutoff to 1500 cells/mm(3) improved the sensitivity to 82.1% with 88.2% specificity, 96.5% PPV, 44.4% NPV. The ROC curve demonstrated highest area under curve (AUC = 0.8) for TLC of 1500 cell/mm(3). CONCLUSION: The study showed that TLC cutoff value of 1500 cells/mm(3) was a cost effective surrogate marker for CD4 counts <350 cells/mm(3) in resource-limited settings.

Melanonychia and mucocutaneous hyperpigmentation from hydroxyurea use for the treatment of essential thrombocytosis.

Hydroxyurea is an antineoplastic agent commonly used to treat essential thrombocytosis. We report the case of a 50-year-old woman who was incidentally detected to have essential thrombocytosis after suffering an episode of cerebrovascular accident with faciobrachial monoparesis. She was subsequently initiated on hydroxyurea. Within seven weeks of therapy, the patient noticed irregular hyperpigmented patches over her feet, hands and perioral region, with bluish-grey longitudinal bands on all 20 nails. Hydroxyurea-induced hyperpigmentation and melanonychia are not commonly reported. To the best of our knowledge, this is only the third published report of hydroxyurea-induced hyperpigmentation and melanonychia involving all 20 nails. Physicians need to be aware of such mucocutaneous side effects to avoid misdiagnosis and unwarranted fear in patients. The decision to discontinue the intake of the drug depends heavily on the future risk of thrombotic events.

Infratentorial subdural empyemas mimicking pyogenic meningitis.

Infratentorial subdural empyema is an extremely rare condition which unfortunately mimics pyogenic meningitis in 75% of cases. While an ill-planned lumbar puncture in these cases may be fatal, an inadvertent delay in treatment may be detrimental to the outcome for the patient. We present a case of a young boy with long standing history of chronic suppurative otitis media (CSOM) presenting with an infratentorial empyema with features suggestive of pyogenic meningitis. We also review the available literature to further define the condition in terms of clinical features, treatment options, and outcome. A misdiagnosis of this condition with failure to institute appropriate surgical intervention and antibiotic therapy is potentially life threatening. We highlight this rare condition which requires a high degree of suspicion especially in the presence of associated risk factors.

Pure cerebellitis due to scrub typhus: a unique case report.

We report the case of a 24-year old Indian man who presented with: high fever; drowsiness; an eschar and gross cerebellar dysfunction with horizontal gaze nystagmus; ataxic speech; and truncal ataxia. Scrub typhus was diagnosed by serological tests. This is the first case of a pure cerebellar involvement as the only manifestation of scrub typhus in the published literature.

Community acquired bilateral upper lobe pneumonia with acute adrenal insufficiency: A new face of Achromobacter Xylosoxidans.

Achromobacter xylosoxidans is an uncommon pathogen of low virulence known to cause serious nosocomial infection in the immunocompromised. Its inherent multi-drug resistance makes treatment difficult. Community-acquired infections are rare despite its ubiquitous existence. We present a 50-year-old immunocompetent woman who presented with one-month history of coughing with expectoration who was subsequently diagnosed with bilateral upper lobe pneumonia and acute adrenal insufficiency. Achromobacter xylosoxidans was isolated from sputum and bronchoalveolar lavage culture. The acute adrenal insufficiency recovered after appropriate antibiotic therapy. Amongst the myriad of presentations, we highlight the rarity of acute adrenal insufficiency triggered by the infection.

Refractory hypocalcemia precipitated by dual infection with typhoid fever and hepatitis A in a patient with congenital hypoparathyroidism.

We present this rare occurrence of a 17 yr old boy, a known case of congenital hypoparathyroidism, who presented with fever and jaundice for 8 days and 2 episodes of generalised tonic-clonic seizures. Premorbidly patient was on regular oral calcium supplementations with normal serum calcium levels. Investigations revealed severe hypocalcaemia (3.2 mg/dL), low 25 hydroxyvitamin D levels and hypomagnesaemia. The marked elevation of serum bilirubin was accompanied by derangement of liver enzymes. Microbiological investigations were confirmatory for both hepatitis A and typhoid fever. In spite of the aggressive management with intravenous calcium gluconate infusion, refractory hypocalcaemia persisted with recovery only after gradual decline in the bilirubin levels. We inferred that the cholestatic process produced by both acute viral hepatitis A and typhoid fever precipitated this state of refractory hypocalcaemia in the previously well preserved patient.

Polymyositis-like syndrome with rhabdomyolysis in association with brucellosis.

Diffuse myositis with progression to rhabdomyolysis has been reported in association with wide range of viral infections. We report a case of polymyositis-like syndrome complicated by rhabdomyolysis secondary to brucellosis. This case report thus contributes yet another atypical presentation to a disease already infamous for its protean manifestations.

Unilateral massive hemothorax in Dengue hemorrhagic fever: a unique presentation.

Dengue hemorrhagic fever is a more serious form of disease characterised by plasma leakage syndrome, thrombocytopenia and disseminated intravascular coagulation. We present a 51 year old male who presented with fever, petechiae and acute onset of breathlessness. Emergency chest rhoentogram showed a massive right sided pleural effusion. On insertion of intercostal drain, there was a sudden gush of blood tinged fluid suggestive of hemothorax. There was no history of trauma or bleeding tendencies. Laboratory investigations revealed a raised hematocrit and severe thrombocytopenia. Dengue IgM was surprisingly positive. After aggressive supportive management the patient gradually improved and was discharged. While bilateral pleural effusion is a known occurrence in dengue hemorrhagic fever, massive hemothorax is unheard of. We report the first case in literature of dengue hemorrhagic fever presenting as unilateral massive hemothorax. A suspicion of dengue must also be borne in mind in cases of non-traumatic hemothorax especially in endemic areas.

Dual infection with hepatitis A and E virus presenting with aseptic meningitis: a case report.

We report the case of a young male who presented with features of aseptic meningitis and elevated serum liver enzymes, but no symptoms or signs suggestive of an acute hepatitis. Subsequently, he was diagnosed with dual infection with hepatitis A and E viruses, and recovered completely with symptomatic therapy. Isolated aseptic meningitis, unaccompanied by hepatitic features is an unusual presentation of a hepatotrophic viral infection, and is yet to be reported with hepatitis A and E virus co-infection.

A rare case of community acquired Burkholderia cepacia infection presenting as pyopneumothorax in an immunocompetent individual.

Burkholderia cepacia (B. cepacia) infection is rarely reported in an immunocompetent host. It is a well known occurence in patients with cystic fibrosis and chronic granulomatous disease where it increases both morbidity and mortality. It has also been included in the list of organisms causing nosocomial infections in an immunocompetent host, most of them transmitted from the immunocompromised patient in which this organism harbors. We report a rare case of isolation of B. cepacia from the bronchoalveolar lavage fluid of an immunocompetent agriculturist who presented with productive cough and fever associated with a pyopneumothorax. This is the first case of community acquired infection reported in an immunocompetent person in India.

Pencil in the brain: a case of temporal lobe abscess following an intracranial penetrating pencil injury.

The case of a 7-year-old girl with an intracranial penetrating injury due to a pencil is presented. The difficulties in diagnosis and the need for a high degree of suspicion and for prompt adequate surgical treatment are highlighted.