Metastatic pancreatic carcinoma and experience with FOLFIRINOX - a cross sectional analysis from a developing country

Background: Pancreatic cancer is the fourth leading cause of cancer related death with median survival ranging from 3 to 6 months for metastatic disease. Palliative chemotherapy has been the backbone of treatment in advanced stage and has evolved over time. Data pertaining to the disease are scarce from our part of the world where treatment poses a significant challenge due to lack of resources.MATERIALS AND Methods: A retrospective chart review was performed for all patients presenting with stage IV pancreatic carcinoma at a tertiary care hospital in Karachi, Pakistan between January 2008 and December 2012. Data were collected using a pre-designed, coded questionnaire looking at patient characteristics, treatment given and outcome.Results: 101 patients were found to be eligible. Mean age was 56.7 ± 12.8 years, the male to female ratio was 2:1 and most patients had a good performance status. More than half of the tumors were located in the head (57%, n=58) and almost all were adenocarcinomas (95%, n=96). Some 58% (n=59) received first line chemotherapy of which 49% (n=29) received gemcitabine-based regimens and 39% (n=23) received FOLFIRINOX. The median progression free survival for gemcitabine based treatment was 2.9 months (IQR=1.6-5.6) as opposed to 7.3 months (IQR=4.5-9.2) for FOLFIRINOX (P=0.02). Median overall survival was 4.9 months (IQR=2.3-9.5) for first line gemcitabine based treatment and 10.5 months (IQR=7.0-13.2) for first line FOLFIRINOX therapy (P=0.002). Patients on FOLFIRINOX had better survival across all subgroups. Inpatient admissions and dose reductions were more frequent with FOLFIRINOX but the difference between the two regimens was not statistically significant. FOLFIRINOX could be successfully administered as outpatient therapy to a number of patients.CONCLUSIONS: FOLFIRINOX remains a suitable first line option in patients with metastatic pancreatic cancer with good performance status even in a resource-poor country where diagnostic and supportive care facilities may be less than optimal and cost is a limitation

Pleomorphic lobular carcinoma of the male breast with axillary lymph node involvement: A case report and review of literature

Background: Carcinoma of the male breast is responsible for less than 1% of all malignancies in men but the incidence is rising. Invasive ductal carcinoma is the most common histological subtype while invasive lobular carcinoma is responsible for only 1.5% of the total cases of which pleomorpic lobular carcinoma is an extremely rare variant. We report the case of a gentleman with node positive, pleomorphic lobular carcinoma of the breast.Case Presentation: An elderly gentleman with a past history of type 2 diabetes and long term ethanol use presented to us with a self-discovered palpable lump in the left breast. Physical examination revealed bilateral gynaecomastia along with a well circumscribed subareolar mass and palpable lymphadenopathy in the ipsilateral axilla. The breast nodule revealed atypical cells on fine needle aspiration biopsy and the patient underwent a modified radical mastectomy after systemic surveillance was negative for metastatic disease. The lesion was reported as grade III pleomorphic lobular carcinoma with a lack of E-cadherin expression on immunohistochemistry and the neoplastic cells exhibited strong positivity for estrogen receptor in the absence of Her2 gene amplification. Six out of the eleven dissected regional lymph nodes showed evidence of disease. The patient completed 4cycles of adjuvant chemotherapy without evidence of recurrent disease and was subsequently lost to follow up.Conclusion: Although invasive lobular carcinomas comprise 12% of all female breast cancers, they are very rare in males due to lack of acini and lobules in the normal male breast. Pleomorphic lobular carcinoma, an aggressive variant of ILC is even rarer in males. Chronic consumption of ethanol by our patient may have resulted in some degree of hepatic impairment with resultant hyperestrogenism. This in theory may have been the cause of his gynaecomastia, resultant breast cancer and is a plausible explanation for development of the invasive lobular subtype in a male. The prognosis and clinicopatholocial features of pleomorphic lobular carcinoma in men are less clearly defined due to its rarity. Additional studies are hence necessary to improve our understanding of this disease in males

Capecitabine-associated loss of fingerprints: A case report of a 62-year-old man with colorectal cancer suffering from capecitabine-induced adermatoglyphia

Background: Capecitabine is a prodrug of 5-fluorouracil (5-FU) and is converted to 5-FU in tumor tissue. Its primary mechanism of action is the suppression of DNA synthesis via inhibition of thymidylate synthetase. It is mostly used for neoadjuvant chemoradiation, adjuvant chemotherapy for colorectal cancer, metastatic breast, and localized and metastatic gastric cancer, among others. Adverse effects of capecitabine include diarrhea, hand-foot syndrome (HFS), pancytopenia, stomatitis, increased bilirubin, nausea, vomiting, and very rarely adermatoglyphia. Dermatoglyphics refers to fingerprints. Adermatoglyphia refers to the loss of fingerprints.Case review summary: We report the case of a 62-year-old male patient known case of locally advanced colorectal cancer. He presented in the clinic with residual disease after initially being treated with local surgery and chemoradiation with 5-FU. Positron emission tomography (PET) scan done at the time of presentation showed locally advanced disease. He was managed with surgery followed by chemotherapy with oxaliplatin 130 mg/m2 and capecitabine (Xeloda) 1500 mg twice a day for two weeks via three weekly cycles. Post cycle five, the patient complained of grade I HFS symptoms and inability to open a bank account due to loss of fingerprints. The patient was oblivious about this condition before that. After completing his adjuvant treatment that is six cycles of oxaliplatin and Xeloda, his symptoms of the HFS and loss of fingerprints, improved.Conclusion: As this case describes, adermatoglypia is a rare but noticeably side effect of capecitabine with a high chance of reversibility. Similar case reports have been reported with some normalization of fingerprints, after stopping treatment. Fingerprints have been used for centuries as means of identification in banks, aviation, immigration, computers, and mobile phones, amongst others. Awareness regarding the loss of fingerprints due to capecitabine is important for the patient and clinician, and alternative means of identification or other adaptive methods of recognition should be used for these patients

Incidence of venous thromboembolism in cancer patients treated with cisplatin based chemotherapy - a cohort study

Background: Cancer related thrombosis not only increases morbidity and mortality but also poses a significant financial burden on health care system. Risk of venous thromboembolism (VTE) in these patients substantially increases with the addition of chemotherapy. Lately, cisplatin has been implicated as an independent factor. There is little data estimating the risk of venous thromboembolism in patients receiving cisplatin based chemotherapy when compared to other chemotherapeutic agents.Methods: Patients who had received chemotherapy between November 2010 and October 2012 were retrospectively identified from a single institute cancer registry. 200 patients who had received cisplatin based chemotherapy were identified as the exposed group while 200 patients who had received non-Cisplatin based regimens were identified as the non-exposed group. Patients were followed for development of VTE throughout the entire duration of therapy and one month thereafter. Cox proportional hazard model was used to compute relative risks with 95% confidence intervals.Results: The baseline characteristics were similar in the two groups. Mean age for the entire cohort was 55.4±10.7years and male to female ratio was almost 1:1. On univariate analysis, cisplatin based chemotherapy, presence of central venous catheter, female gender, poor performance status, high risk stratification according to the Khorana model and use of granulocyte colony stimulating factor were all significantly associated with the development of VTE. The crude relative risk for the incidence of VTE in cisplatin group was 2.8 (95% CI, 1.4 - 4.2) times compared to the non-Cisplatin group. When the relative risk was adjusted for the above variables in multivariable analysis, it increased to 3.3 (95% CI, 1.6 - 6.8) compared to the control group.CONCLUSION: A high incidence of VTE in patients receiving cisplatin based chemotherapy was demonstrated in this study. Prospective studies are warranted to establish this observation with certainty and to explore the possible use of thromboprophylaxis in patients receiving cisplatin based chemotherapeutic regimens

Ewing\u27s sarcoma arising from the adrenal gland in a young male: a case report

Background: Ewing\u27s sarcoma uncommonly arises from extraosseous soft tissue or parenchymal organs. Primary adrenal Ewing\u27s Sarcoma, although very rare, is extremely aggressive and commonly fatal. CASE PRESENTATION: A 17 year old Pakistani male was referred to the outpatient oncology clinic at our center with a three month history of concomitant pain, swelling and dragging sensation in the right hypochondrium. Abdominal examination revealed a large, firm mass in the right hypochondrium extending into the right lumbar region and epigastrium. His genital exam was unremarkable and there were no stigmata of hepatic or adrenal disease.Computed tomography scans revealed a large peripherally enhancing mass in the hepatorenal area, biopsy of which showed a neoplastic lesion composed of small round blue cells which exhibited abundance of glycogen and stained diffusely positive for CD99 (MIC2 antigen). Fluorescence in situ hybridization demonstrated gene rearrangement at chromosome 22q12 which confirmed the diagnosis of Ewing\u27s sarcoma. Staging scans revealed pulmonary metastasis and hence he was commenced on systemic chemotherapy. CONCLUSION: This case report highlights the importance of keeping Ewing\u27s sarcoma in mind when a young patient presents with a large non-functional adrenal mass

Clinical features and outcome of sporadic colorectal carcinoma in young patients: A cross-sectional analysis from a developing country

Background: Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival.Methods: Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals.Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of rectal carcinoma patients received appropriate therapy as opposed to 65% of colon cancers. On multivariable analysis, appropriate reception of therapy (PR 4.99; 95% CI, 1.21-20.6) and signet ring morphology (PR 2.40; 95% CI, 1.33-4.32) were significantly associated with rectal cancers as opposed to colon cancer. Kaplan-Meier analysis revealed a trend towards inferior survival for rectal carcinoma 2 years after diagnosis.Conclusion: A high prevalence of early onset CRC was noted in the study. A trend towards inferior survival was seen in patients with rectal cancer. This finding raises the possibility of rectal carcinoma being an aggressive subset of young CRC

Difficulty breathing or just a case of the nerves? Incidental finding of primary pleural schwannoma in a COVID-19 survivor

Schwannoma is a rare tumor that arises from the Schwann cells, which are specialized, myelin-producing cells of the peripheral nerve sheaths. As anatomic logic would dictate, these masses commonly occur in the skull base, cerebellopontine angle, and posterior spinal roots. Of this already rare entity, rarer still are the pleural schwannomas, representing approximately 1-2% of thoracic tumors. These tumors commonly affect adults with a propensity for the third and sixth decades of life and a comparative male predilection. Schwannomas are benign, indolent, and follow an asymptomatic course. As such, they often come to light incidentally.Here we report a case of primary pleural schwannomas in a 68-year-old female, found incidentally on a CT scan of the chest. To the best of our knowledge and literature review, no other similar case has been reported in our country, Pakistan. Around three weeks before her presentation, she was diagnosed with COVID-19. Her infection had run a mild course with quick recovery without the need for any hospitalization. Therefore, the manifestation of shortness of breath after resolution of all other symptoms prompted a further workup. Radiographic chest x-ray revealed an incidental finding of a large right upper lobe lung mass, slightly impinging on the trachea. This was followed by a chest CT scan at our radiological imaging facility, which showed a large, well-encapsulated, right upper lobe lung mass in the paraspinal apical location. She then underwent an image-guided biopsy of the aforementioned mass, pathological analysis of which was suggestive of a benign peripheral nerve sheath tumor (PNST) arising from the pleura (pleural schwannoma). She underwent right posterolateral thoracotomy with uneventful complete surgical removal of the pleural-based lung mass. Postoperative investigations included a chest x-ray that showed interval complete resection of the mass. Currently, she is asymptomatic and her clinical condition has improved with the successful resumption of her daily routine.Physicians thus need to keep pleural schwannomas in mind as a probable diagnosis of intrathoracic tumors. Indolent and asymptomatic, they are very amenable to surgical resection with little to no chances of recurrence in the long term. However, these patients should be closely followed with repeat imaging studies when symptomatic

Cisplatin-induced posterior reversible encephalopathy syndrome and successful re-treatment in a patient with non-seminomatous germ cell tumor: a case report

UNLABELLED: Introduction: Cisplatin is a platinum compound that has revolutionized the treatment of various solid organ tumors. Cisplatin is associated with a variety of side effects and has recently been indicted in the development of posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome is a potentially reversible condition, with the mainstay of therapy being correction of the underlying cause and withdrawal of the offending drug. However, there are no clear guidelines regarding the possibility of subsequent re-treatment with the causative agent.CASE PRESENTATION: A 23-year-old Asian man presented to our Emergency Department with a four-month history of concomitant abdominal pain and backache and a two-week history of left-sided leg swelling. Diagnostic investigations revealed bilateral pulmonary embolism, extensive deep venous thrombosis and widespread lung and liver metastatic deposits with abdomino-pelvic lymphadenopathy. His biopsy and tumor markers were consistent with non-seminomatous germ cell tumor and he was subsequently started on an initial cycle of cisplatin and etoposide chemotherapy. On the second day of treatment he developed posterior reversible encephalopathy syndrome clinically and radiologically. Cisplatin was stopped for the next two days while etoposide was continued, resulting in complete resolution of his symptoms. He was re-challenged with cisplatin on day five of chemotherapy because a platin-based chemotherapy regimen was his only hope of potential cure. He tolerated it well, with no recurrence of his neurological symptoms and the remainder of his in-patient stay remained uneventful. He was discharged on day eight. He has since then completed treatment and is currently in remission.CONCLUSIONS: The occurrence of posterior reversible encephalopathy syndrome after cisplatin use has been well reported in the literature. We strongly believe that our patient also developed posterior reversible encephalopathy syndrome secondary to cisplatin. The uniqueness of our patient\u27s case lies in the successful re-treatment of our patient with the offending drug. To the best of our knowledge, this is the first instance where a patient was successfully re-treated with cisplatin after having developed posterior reversible encephalopathy syndrome as a result of cisplatin use. The excellent response to re-treatment without recurrence of neurological symptoms in our patient\u27s case provides insight into re-treatment as an option in scenarios where treatment options are limited

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Fungal flora and aflatoxin contamination in Pakistani wheat kernels (Triticum aestivum L.) and their attribution in seed germination

This study aimed to isolate fungal pathogens and to subsequently quantify aflatoxin (AF; B1 + B2 + G1 + G2) contamination in wheat crops grown in Pakistan. Accordingly, a total of 185 wheat samples were collected from different areas of Pakistan and numerous potent fungal pathogens were isolated. AF contamination attributed to the presence of intoxicating fungal pathogens and resulting metabolic activities were quantified using a high performance liquid chromatography-fluorescence detector coupled with postcolumn derivatization. Additionally, the effect of fungal pathogens on seed germination was also examined. The results obtained showed that 50% of tested wheat samples were found to be contaminated with a diverse range of fungal species. The rate of recurrence of fungal pathogens were Aspergillus 31%, Penicillium 9%, Fusarium 8%, Rhizopus 3%, and Alternaria 2%. The presence of Tilletia indica and Claviceps purpurea species was found to be inevident in all tested wheat samples. AFB1 contamination was detected in 48 (26.0%) samples and AFB2 in 13 (7.0%) samples. AFG1 and AFG2 were not found in any of the tested samples. The contamination range of AFB1 and AFB2 was 0.05–4.78 μg/kg and 0.02–0.48 μg/kg, respectively. The total amount of AFs (B1 + B2) found in 48 (26.0%) samples had a mean level of 0.53 ± 0.40 μg/kg and a contamination range of 0.02–5.26 μg/kg. The overall results showed that in 137 (74.0%) samples, AFs were not found within detectable limits. Furthermore, in 180 (97.2%) samples, AF levels were found to be below the maximum tolerated levels (MTL) recommended by the European Union (4 μg/kg). In five (2.7%) samples, AF contamination was higher than the MTL of the European Union. However, these samples were fit for human consumption with reference to the MTL (20 μg/kg) assigned by the USA (Food and Drug Administration and Food and Agriculture Organization) and Pakistan (Pakistan Standards and Quality Control Authority). Germination rates in healthy and contaminated wheat kernels were 84.6% and 45.2%, respectively. Based on the obtained results, it was concluded that the levels of fungal pathogen and AF contamination in Pakistani-grown wheat are not a potential threat to consumer health. However, control procedures along with a strict monitoring policy are mandatory to further minimize the prevalence of fungal carriers and the potency of AFs in crops cultivated in Pakistan