Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients. METHODS: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls. RESULTS: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers. CONCLUSIONS: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.

Cancer incidence in Khyber Pakhtunkhwa, Pakistan, 2020.

BACKGROUND: To present the population-based cancer statistics for Khyber Pakhtunkhwa (KP), Pakistan, an incidence study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan, in 2023. METHODS: Records from various centres on new cancers diagnosed among residents of KP between January and December 2020 were gathered. Both active and passive methods of data collection were applied, and the information was saved in a central repository at SKMCH&RC. The incidence rates were computed by age group and sex and presented per 100,000 population. RESULTS: Among children (0-14 years), the Age-Standardised Incidence Rate (ASIR) was 4.0 in girls and 6.1 in boys, and haematologic malignancies were more prevalent; in adolescents (15-19 years), the ASIR was 7.7 in females, 9.4 in males, and bone tumours, haematologic malignancies, and neurological cancers were prominent; in adult females (> / = 20 years), the ASIR was 84.9, and cancers of the breast, digestive system, and reproductive organs were predominant; and adult males, the ASIR was 73.0, and cancers of the gastrointestinal tract, lip/oral cavity/pharynx, prostate, and Non-Hodgkin Lymphoma (NHL) were common. CONCLUSIONS: It is crucial to investigate the aetiology of these diseases at the community level because dietary elements, infectious diseases, and tobacco use all appear to be significant contributors. Prospective studies could play a key role in highlighting the factors linked to these diseases. Therefore, cancer registration must continue in conjunction with the exploration of risk factors.

Relapse of Non-Gastrointestinal Langerhans Cell Histiocytosis in the Rectum in a Child: A Case Report.

Langerhans cell histiocytosis (LCH) is a rare disorder most commonly involving skin, bone and lung. The gastrointestinal tract (GIT) is an uncommon site of disease and only a handful of case reports exist. We present a case of a 15-year old boy with treated LCH involving the skin, bones, central nervous system (CNS) and pituitary gland. He presented with rectal bleeding and on investigation was found to have a single rectal polyp which was confirmed histologically and immunologically to be LCH. Further investigation revealed no other foci of disease.

Cancer care in times of conflict: Treatment of patients from Afghanistan, in Pakistan.

Introduction: Afghanistan has been in a near-continuous armed conflict, which has degraded the country's health infrastructure. Due to this, Afghans have opted to seek cancer treatment in Pakistan. This manuscript aims to understand the complex cancer journey of patients from Afghanistan seeking care in the largest tertiary care cancer institutions in Pakistan. Methods: This retrospective study explores the demographics, epidemiology and outcomes of Afghan cancer patients treated at the Shaukat Khanum Memorial Cancer Hospital and Research Centres (SKMCH&RC) in Lahore and Peshawar, Pakistan, over the period from 1995 to June 2022. Results: A total of 6,370 patients from Afghanistan have undergone cancer care since 1995. The mean age at presentation was 40.7 years, 57% were male, and 87% were adults >19 years. Close to 30% of these patients came from Kabul and Nangarhar districts. 56% of all patients presented with stage III or IV disease. 34% of adult patients achieved a complete response to treatment, but more than half of all patients have since been lost to follow-up. Children generally had better outcomes, with 43% showing a complete response to treatment. Discussion: The cancer journey for these patients remains long and difficult and the inability to ensure follow-up in so many remains frustrating for both patients and providers. The lack of a cancer infrastructure in Afghanistan after decades of conflict, means that policymakers need to develop and support alternative systems and structures to provide post-conflict domestic and cross-border cancer care.

Assessing the utility of universal preprocedure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing at a cancer center.

We implemented preprocedure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing for cancer patients. The overall positivity rate was 0.3%. Preprocedure testing may be limited to operative procedures as community rates of SARS-CoV-2 exceed 7%. Nonoperative aerosol-generating procedures may be performed without preprocedure testing, wearing the appropriate personal protective equipment.

Glucagonoma Syndrome: A Rare Paraneoplastic Disorder due to Neuroendocrine Tumor of the Pancreas.

Glucagonoma syndrome is an extremely rare paraneoplastic disorder. The key presenting feature is a rash (necrolytic migratory erythema) which can easily be misdiagnosed as a primary skin disorder. Moreover, 50 to 80 % of patients already have metastatic disease at diagnosis. We report a case of a 38-year female presenting with epigastric pain and a skin rash all over the body. Workup revealed a neuroendocrine tumor (NET) of the pancreas, for which she underwent resection, resulting in a complete cure. A follow-up MRI after 8 months showed a hyperintense and arterially enhancing nodular liver lesion which did not show any uptake on the octreotide scan. However, a subsequent biopsy revealed a recurrence of the tumor. This was a unique finding in our case where a highly sensitive octreotide scan failed to identify metastasis, emphasising the importance of biopsy in such cases. Key Words: Glucagonoma, Necrolytic migratory erythema, Alpha-cell adenom.

Control of Oesophageal Tumour-related Bleeding with a Fully Covered Self-expandable Metallic Stent (SEMS) Insertion.

The role of metallic stents in the management of refractory variceal bleeding is now well established however, they have been rarely used in the treatment of malignant gastrointestinal (GI) tract bleeding. To our knowledge, there are only three case reports in this regard, where fully covered self-expandable metallic stents (SEMS) were placed for the treatment of bleeding duodenal tumours. We have shared an experience of a novel and successful treatment of the oesophageal tumour-related bleeding with a fully covered SEMS. The 49-year male with oesophageal cancer presented with haematemesis and had received neo-adjuvant chemotherapy 3 weeks back. Upper GI endoscopy revealed an obstructing distal oesophageal tumour with the diffuse oozing of blood. While injection of adrenaline over a large ulcerated surface area was not possible, an attempt to treat it with hemospray was also unsuccessful. Thus, a temporary fully covered SEMS was inserted across the tumour to create a tamponade effect which resulted in the immediate cessation of the bleeding. This was endoscopically removed after a week and there was no further bleeding in one-month follow-up. Key Words: Upper gastrointestinal bleeding, Metallic stent, Oesophageal cancer.

Body Mass Index and Other Risk Factors Effects on Colon Cancer Prognosis in Pakistan.

Introduction: Asian developing countries share the burden of colorectal cancer (CRC) with rising mortality rates. This prospective study aims to apprehend the clinical relevance of age, gender, lifestyle choices (dietary habits and addiction) and body mass index (BMI) to the occurrence and progression of colon cancer (CC). Methods: A cohort of non-cancer (NC) and CC patients of South-Central Asian origin registered for screening colonoscopy or surgery at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC), Lahore, Pakistan, from 2015 to 2020 was identified. BMI (Kg/m2) was classified according to the World Health Organization criteria as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2) and overweight (≥25 Kg/m2). Results: Among 236 participants, 99 (41.9%) belonged to the NC group, and 137 (58.1 %) participants had CC Overall, participants included 74 women and 162 men aged 20-85 years (mean ± SD; 49.9 ± 14.9). Notably, 46.0% of cancer patients had a family history of cancer. There was a direct relationship between CC with abnormal BMI (underweight and overweight), positive smoking history and positive family history of cancer. Conclusion: Being underweight or overweight is a potential risk factor for CC patients. The overall survival in patients with CC is clinically associated with lifestyle choices before CC diagnosis. A balanced diet, walking and other forms of exercise should be strongly recommended to the community and those undergoing screening colonoscopy.

A Case of Esophageal Squamous Papilloma: An Unusual Cause of Dysphagia and Hematemesis in a Patient with Concurrent Malignancies.

Introduction: The esophageal squamous papilloma (ESP) is a rare cause of dysphagia and hematemesis. The malignant potential of this lesion is uncertain; however, the malignant transformation and concurrent malignancies have been reported in the literature. Case Description: We report a case of esophageal squamous papilloma in a 43 years old female who had a background diagnosis of metastatic breast cancer and liposarcoma of the left knee. She presented with dysphagia. Upper gastrointestinal (GI) endoscopy showed a polypoid growth, and its biopsy confirmed the diagnosis. Meanwhile, she presented again with hematemesis. A repeat endoscopy showed that the previously seen lesion had likely broken off, leaving behind a residual stalk. This was snared and removed. The patient remained asymptomatic, and a follow-up upper GI endoscopy at six months did not show any recurrence. Practical Implications: To the best of our knowledge, this is the first case of ESP in a patient with two concurrent malignancies. Moreover, the diagnosis of ESP should also be considered when presenting with dysphagia or hematemesis.

Presentation of Acute Lymphoblastic Lymphoma and Colorectal Carcinoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome: A Case Report with Literature Review.

Introduction: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive disease carrying an increased risk of cancers (paediatric tumours of central nervous system, haematolymphoid malignancies along with gastrointestinal (GI) cancer(s), which are usually seen in the second and third decades), leading to syndromic presentation. Causal mutations are detected in DNA mismatch repair (MMR) genes, including MLH1, PMS2, MSH2 and MSH6 that are also known for their established role in Lynch syndrome. We describe a case of CMMRD with an earlier (first decade of life) presentation of mediastinal acute lymphoblastic lymphoma and colorectal malignancy. Case Presentation: A 5-year-old boy presented with respiratory complaints, bilateral cervical lymphadenopathy, multiple café-au-lait macules (CALMs) on the lower back and history of parental consanguinity with the death of three sisters due to brain tumour within 6 months of diagnosis. Computerised tomographic scan chest revealed a huge mediastinal mass. The patient underwent a trucut biopsy of the mass. The results were significant for a pre-T-cell acute lymphoblastic lymphoma. Suspicion of CMMRD was raised based on a combination of factors described above. A panel of MMR proteins was applied on the biopsy tissue that revealed loss of nuclear expression of MLH1 and PMS2 immunostaining in tumour cells with positive external controls. While on maintenance therapy for lymphoma, about a year later, the patient developed subacute intestinal obstruction due to a stenosing polypoidal circumferential tumour in the mid-sigmoid colon found on flexible sigmoidoscopy that was followed by endoscopic biopsies and insertion of a fully covered self-expanding metallic adult biliary stent with a diameter of 10 mm and length of 6 cm leading to immediate relief of obstruction. Biopsies revealed adenocarcinoma with neuroendocrine differentiation. Metastatic tumour deposits were seen in the omentum, anterior abdominal wall and the left peritoneal wall. Practical Implications: Earlier (first decade) presentation of GI malignancy warrants that an earlier screening through radiological scans for any possible tumours and MMR protein expression analysis (loss in tumour plus normal non-tumour cells) are essential in patients having CALMs and family history of paediatric tumours.

Pyloric stent insertion in malignant gastric outlet obstruction: moving beyond palliation.

BACKGROUND: Self-expandable metallic stents have not only largely replaced surgical gastrojejunostomy for unresectable gastric cancers, but their role as bridging therapy for resectable obstructing tumours is also evolving. OBJECTIVE: To evaluate the efficacy and safety of pyloric stents in gastric outlet obstruction in patients with gastric cancer and assess survival in patients with resectable obstructing gastric tumours in whom stents were inserted as a bridge to surgery. METHODS: We retrospectively reviewed the electronic medical records of patients who underwent self-expandable metallic stent insertion for gastric outlet obstruction due to gastric cancer from January 2014 to March 2019. RESULTS: Out of 161 patients, clinical improvement was observed in 159 (99%) and 156 (97%) at 1 and 12 weeks of stent placement, respectively. None of these patients experienced serious complications, such as perforation or aspiration pneumonia. Of these 161 patients, enteral stents were placed as bridging therapy prior to surgery in 40 (24.8%). Among these, 35 (87.5%) of 40 underwent neo-adjuvant chemotherapy followed by curative surgery. Of the 35 patients, 3 failed to follow-up. One-year survival following curative surgery was 87.5%. Stent helped to reduce vomiting and improve nutrition, measured by the body mass index (p = 0.36) and serum albumin (p = 0.05), over a 4-week period following stent insertion. CONCLUSION: Pyloric stents are useful in relieving malignant gastric outlet obstruction, maintaining nutrition during neo-adjuvant treatment and improving survival without additional risk of postoperative complications. They have traditionally been used for palliation, but should also be considered as bridging therapy for obstructing resectable gastric tumours during neo-adjuvant treatment.

Cancer Hospital Stockpiles: Strategizing for an Efficient and Sufficient Inventory List of Essential Items.

PURPOSE: The COVID-19 pandemic has affected health care systems worldwide, resulting in critical shortages of essential items and materials. The available guidelines are of little use for cancer hospitals in low-income and low-middle-income countries. They have been designed for community hospitals serving in a centralized health care network. This study aimed to draft and field test a framework to establish a list of essential supplies that should be stockpiled for subsequent waves of the COVID-19 virus by a tertiary care cancer hospital in a low-middle-income country. MATERIALS AND METHODS: A model was formulated using the consumption trends during the peak month of the first wave of COVID-19 infection to compile a list of essential materials and supplies. Furthermore, costing analyses were conducted to determine the financial benefits of stockpiling. RESULTS: A proposed list of items to stockpile, including personal protective equipment, radiology supplies, laboratory reagents, medication, and oxygen, was shared with the hospital administration. However, the hospital administration only accepted the proposals for stockpiling personal protective equipment and oxygen. CONCLUSION: This paper provides a framework and strategies that cancer hospitals and health care systems can modify and use as per individual, institutional requirements and specifications for stockpiling essential items during the COVID-19 or other similar pandemics.

Salvage therapy of bleeding esophageal tumor by fully covered self-expandable metallic stent: A case report.

The role of self-expandable metallic stents is gradually evolving for a diverse group of benign and malignant gastrointestinal tract problems, with luminal obstruction being by far the most common. Although its role in refractory variceal bleeding is well established, it has rarely been tried for tumor-related bleeding, with only a few case reports in this regard. We share our experience of successfully controlling esophageal tumor-related bleeding with the use of a fully covered self-expandable metallic stent. A 58-year-old woman with irresectable distal esophageal cancer, presented with hematemesis. Esophago-gastro-duodenoscopy revealed an obstructing esophageal tumor with diffuse oozing of blood. This was unamenable to local injection of adrenaline and hemospray; therefore, a temporary self-expandable metallic stent was parked to create a tamponade effect. This successfully stopped bleeding and the patient remained asymptomatic till discharge. However, she was lost to follow-up, and therefore, the stent was removed after a period of 5 months instead of 2 weeks.

EUS-FNA, ancillary studies and their clinical utility in patients with mediastinal, pancreatic, and other abdominal lesions.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is an important modality to obtain tissue diagnosis from mediastinal, pancreatic, and intra-abdominal lesions in close proximity to the pulmonary and gastrointestinal tract. It is considered to be a relatively safe, rapid, and minimally invasive technique with low complication rates. AIMS: To determine the diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and outcome of EUS-FNA, with histological correlation where applicable. METHODS: Data of all 1059 consecutive patients who underwent EUS-FNA from 1 January 2005 to 31 December 2017 at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore was reviewed in this retrospective study. The major sites that were targeted for EUS-FNA were pancreatic (423), mediastinal (376), and other abdominal lesions (260). RESULTS: The average number of passes per patient was 2.22. Rapid on-site evaluation (ROSE) was adequate in 969 patients (91.4%). Concordance between ROSE and final cytology was 99.5%. Follow-up was available in 810 patients (76.4%). The overall diagnostic yield was 94.3%. Ancillary studies, including immunohistochemical stains and flow cytometry, helped to increase the diagnostic yield from 78.1% to 94.3%. The overall sensitivity, specificity, PPV, NPV, and diagnostic accuracy for EUS-FNA were 94.8%, 98.6%, 99.9%, 65.5%, and 95.1%, respectively. Seven of 1059 patients (0.6%) developed complications. CONCLUSION: EUS-FNA is a very sensitive and specific diagnostic tool with a minimal complication rate. Ancillary studies helped to increase the sensitivity, as well as the diagnostic yield.

Cancer care in times of conflict: cross border care in Pakistan of patients from Afghanistan.

Armed conflict in Afghanistan has continued for close to 40 years and has devastated its health infrastructure. The lack of a cancer care infrastructure has meant that many Afghans seek cancer care in neighbouring countries, like Pakistan. There remains a significant lack of empirical data on the new therapeutic geographies of cancer in contemporary conflicts. This retrospective single centre study explores the therapeutic and clinical geographies of Afghan cancer patients who were treated at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan over a 22-year-period (1995 to 2017) covering major periods of conflict and relative peace. Data was available for 3,489 Afghan patients who received treatment at SKMCH&RC. The mean age at presentation was 42.7 years, and 60% were men. 30.2% came from Kabul and Nangarhar districts of Afghanistan, which have relatively short travel times to Pakistan, but patients from all parts of Afghanistan migrated to SKMCH&RC for treatment. Overall, 34.1% were diagnosed with upper gastrointestinal malignancies and 55.7% presented with late stage III/IV cancer. A wide range of treatments were provided, with 25.4% of patients receiving a combination of chemotherapy and radiation treatment. 52.7% of all patients were lost to follow-up. Outcomes were more favourable for children with cancer, 42% of whom had a complete response to therapy. Complex migration patterns, mixed political economies (refugees, forced and unforced migrants) and models of care that must be adapted to the realities of the patients rather than notional international standards all reflect the new therapeutic geographies that long-term conflict creates. This requires significant new domestic and international (e.g., United Nations High Commissioner for Refugees) policy and practises for providing cancer care in today's contemporary conflict ecosystems that frequently cross national borders.

Prevalence and spectrum of MLH1, MSH2, and MSH6 pathogenic germline variants in Pakistani colorectal cancer patients.

BACKGROUND: Pathogenic germline variants in MLH1, MSH2 and MSH6 genes account for the majority of Lynch syndrome (LS). In this first report from Pakistan, we investigated the prevalence of pathogenic MLH1/MSH2/MSH6 variants in colorectal cancer (CRC) patients. METHODS: Consecutive cases (n = 212) were recruited at the Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), between November 2007 to March 2011. Patients with a family history of > 3 or 2 HNPCC-associated cancers were classified as HNPCC (n = 9) or suspected-HNPCC (n = 20), respectively (group 1; n = 29). Cases with no family history were designated as non-HNPCC (group 2; n = 183). MLH1/MSH2/MSH6 genes were comprehensively screened in group 1. Pathogenic/likely pathogenic variants identified in group 1 were subsequently evaluated in group 2. RESULTS: Eight distinct pathogenic/likely pathogenic MLH1/MSH2 variants were found in group 1 (10/29; 34.5%), belonging to HNPCC (5/9; 55.6%) and suspected-HNPCC (5/20; 25%) families and in group 2 (2/183; 1.1%) belonging to non-HNPCC. Overall, three recurrent variants (MSH2 c.943-1G > C, MLH1 c.1358dup and c.2041G > A) accounted for 58.3% (7/12) of all families harboring pathogenic/likely pathogenic MLH1/MSH2 variants. Pathogenic MSH6 variants were not detected. CONCLUSION: Pathogenic/likely pathogenic MLH1/MSH2 variants account for a substantial proportion of CRC patients with HNPCC/suspected-HNPCC in Pakistan. Our findings suggest that HNPCC/suspected-HNPCC families should be tested for these recurrent variants prior to comprehensive gene screening in this population.

Proteomics analysis of colon cancer progression.

BACKGROUND: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). METHODS: A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). RESULTS: Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. CONCLUSION: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.