Exploring treatment outcomes in Stage II-III rectal cancer patients undergoing neoadjuvant therapy at a tertiary care center in Pakistan: a comprehensive analysis of pathological outcomes.

BACKGROUND: Rectal cancer treatment has transformed in recent years, with neoadjuvant treatment (NT) and total neoadjuvant treatment (TNT) aiming to enhance pathological responses. This pioneering study in our country delves into rectal cancer management, offering crucial insights by examining pathological outcomes in patients treated with the NT and TNT approach, shaping the evolving landscape. METHODS: In this retrospective-cohort study spanning January 2017 to December 2022 at a tertiary care hospital in Pakistan, ethical approval was obtained to examine outcomes of two treatments. Patients were divided into TNT (chemoradiation and pre-surgery 5 FU-based chemotherapy) and NT (chemoradiation, surgery, and subsequent 5 FU-based chemotherapy). The primary end-point was response rates-no response, pathological complete response (pCR), near complete response (near CR), and partial response (PR). The Chi-Square Test for Independence assessed the association between treatment response and type (TNT or NT). Data analysis used STATA MP 64; significance was set at p < 0.05 for all two-tailed tests. RESULTS: We analyzed 77 patients, 60 underwent standard neoadjuvant chemoradiation, and 17 followed the total neoadjuvant approach. Predominantly male, most were > 65 with ECOG 0-1. The TNT group showed higher response rates (76% vs 62%, p = 0.039), with 40.38% achieving pCR. In the overall population, pCR and near-CR were similar (27.2% vs 26%), while PR were 14%. Treatment characteristics correlated significantly with chemotherapy type, concurrent chemoradiation, LVI, PNI, and T, N, M staging (p < 0.05). Median overall survival was not reached, and mean survival was 89.1 months (CI: 95.0 to 83.3). Side effects varied, with notable differences in neuropathy, diarrhea, oral mucositis, and thrombocytopenia between NT and TNT groups. CONCLUSION: Our study adds to evidence favoring neoadjuvant approaches in managing rectal cancer in pakistan. Demonstrating a favorable pcr rate, ongoing research with extended follow-up is essential, given the dynamic landscape of rectal cancer treatment for improved patient outcomes.

Outcomes of patients with anal cancer treated with definitive chemoradiation: A single centre experience.

Background: Anal cancers are uncommon neoplasms that make up to <1% of all tumours globally. Concurrent chemoradiation remains the standard of care treatment for patients who present with non-metastatic anal squamous cell carcinomas (ASCCs). Methods: We aimed to evaluate the response rate and 2-year survival outcome of the definitive chemoradiation approach in patients with non-metastatic ASCCs of our population. We conducted a cross-sectional review of these patient populations who were treated and then followed after completion of treatment at our institute during the last 10 years. Results: A total of 17 patients were enrolled after fulfillment of the eligibility criteria. The responses were documented in 16 patients through magnetic resonance imaging or computed tomography of the pelvis, done at 3 months of treatment completion. More than 80% of the patients had complete radiological responses. Among the surviving participants, the 2-year disease-free survival rate was found to be more than two-thirds. Approximately 20% of the study participants had disease recurrence during the subsequent clinic visits following treatment completion. Conclusion: This review emphasises the impact of definitive chemo-radiation in achieving radiological and clinical responses in patients with non-metastatic ASCCs. Moreover, to our knowledge, this is the first review to highlight anal cancer's incidence and characteristics in Pakistan.

A case report and literature review on primary intracranial malignant melanoma: Challenges and insights.

INTRODUCTION AND IMPORTANCE: Primary central nervous system (CNS) melanoma is a rare entity. Primary CNS malignant melanomas account for 1 % of melanomas and 0.07 % of intracranial tumours. These are highly aggressive and are associated with poor prognosis. Herein, we have discussed one such rare case of PIMM. CASE PRESENTATION: 62-year-old man with primary CNS melanoma underwent craniotomy and resection of left temporal lesion. Postoperative MRI showed no evidence of residual disease. He received 28 fractions of radiation. Follow-up MRI showed no evidence of disease. However, he later developed worsening symptoms and repeat imaging revealed disease progression with hydrocephalus and drop metastasis to spine. He underwent VP shunting and was started on Temozolomide. He progressively declined functionally and eventually died from his disease. CLINICAL DISCUSSION: Primary CNS melanoma is characterized by its rarity, challenging diagnosis, and aggressive behaviour. Current literature suggests limited treatment options, which depend on complete resection of the primary tumour. Molecular analysis may play a key role in deciding future treatment options, including immune checkpoint inhibitors and targeted therapies targeting the BRAFV600E mutation. CONCLUSION: Primary intracranial malignant melanoma (PIMM) is an extremely rare tumour of CNS, and its treatment paradigm is very limited based on available literature. Currently any long-term survival depends on the complete resection of tumour. Our case is unique as it talks about the limited therapeutic options in case of rapidly declining performance status in a resource constraint setting.

Unmasking the enigma: A case of Fumarate Hydratase-deficient renal cell carcinoma.

INTRODUCTION: Fumarate Hydratase-deficient-renal cell carcinoma (FH-dRCC) is an uncommon and extremely aggressive variant of renal cell carcinoma (RCC) resulting from inactivating mutations in the tumor suppressor gene, fumarate hydratase (FH). CASE PRESENTATION: We report a case of a young male who presented with the complaint of painless hematuria. Upon workup, he was found to have a renal mass with bony metastases. The histopathology was consistent with renal cell carcinoma with features of FH-deficient variant. Germline testing showed a pathogenic mutation in the FH gene. He was started on a treatment combination of Pembrolizumab and Axitinib along with Zoledronate for bone metastasis. His response to the combination therapy was short with early progression of disease. He was switched to a second-line treatment Bevacizumab and Erlotinib, which achieved significant disease response. DISCUSSION: Systemic therapy is the mainstay of treatment for metastatic disease. Although the novel agents approved for other subsets of RCC have been used, the responses are grim. There is no consensus on the sequence of further lines of treatment for FH-dRCC and is based on the physician's choice, availability of the drugs, cost, toxicity, and tolerance of the patient. CONCLUSION: This case report emphasizes the occurrence, presentation, management and prognosis of FH-dRCC, which is an aggressive entity, presenting at a young age with early distant metastases, not diagnosed appropriately due to its poorly characterized cytologic features. Being an infrequent neoplasm, it is an area that warrants oncological exploration to improve outcomes in these individuals. The combination of Erlotinib and Bevacizumab provides promising outcomes in terms of progression-free survival.

Chaotic transformation of parotid acinic cell carcinoma to metastatic dedifferentiated high-grade pathology - A rare case with clinical and emotional challenge.

INTRODUCTION AND IMPORTANCE: Acinic cell carcinoma (AciCC) is a rare entity in which high-grade transformation (HGT), formerly dedifferentiation, is uncommon. This case report presents a rare case of AciCC, with rapid transformation to metastatic high-grade dedifferentiated pathology after initial curative treatment. CASE PRESENTATION: A 58-year-old woman presented in the medical oncology clinic with a progressive swelling on the right side of her face. Magnetic resonance imaging revealed a 5 × 5 cm lobulated parotid gland lesion, and fine needle aspiration biopsy was consistent with carcinoma. After informed consent, a Modified-Blair incision was given as a standard approach to the right preauricular area under general anaesthesia, and a right superficial parotidectomy with the removal of the tumor and selective lymph node dissection was performed. Histopathology of the resected mass was reported as parotid AciCC. She was given adjuvant radiation therapy. A repeat PET CT scan ten weeks after the completion of her adjuvant radiation treatment showed local disease recurrence as well as multiple pulmonary deposits. A repeat biopsy was reported as DOG-1 positive dedifferentiated (high-grade) acinic cell carcinoma, and she was offered platinum-based palliative systemic chemotherapy. CLINICAL DISCUSSION: Parotid acinic cell carcinomas with high-grade transformation are rare. This case highlights its critical diagnostic markers, curative and palliative management and long-term follow-up. CONCLUSION: The transformation of parotid AciCC to high-grade, dedifferentiated pathology is unusual and belligerent. Hence, these tumors need intense treatment with a multimodality approach. Close follow-ups with history and physical examination, along with periodic imaging, should be considered for these patients.

Primary endo-bronchial muco-epidermoid carcinoma in a 22-year-old female: A case report.

INTRODUCTION: Muco-epidermoid carcinomas are primarily the subtypes of salivary gland tumors that can rarely originate within the respiratory tract. Our case highlights the occurrence of an unusual, localized, endo-bronchial muco-epidermoid cancer. We aim to strengthen the evidence of occurrence of this distinct variety of lung cancer in our country as little is known about this rare subclass of lung cancer. CASE PRESENTATION: We report a case of a 22-year-old female patient, belonging to Karachi, Pakistan, who presented with respiratory symptoms and upon work-up, was diagnosed with a low-grade, localized muco-epidermoid carcinoma of the lung. She underwent surgical resection successfully and was advised to get evaluated for adjuvant radiotherapy. CLINICAL DISCUSSION: Localized low-grade MEC respond well to surgical resection in contrast to high-grade MEC which is associated with poor prognosis thus requiring adjuvant radiotherapy to improve survival outcomes. CONCLUSION: Lung cancers can be unusually of muco-epidermoid origin. It has been uncommonly found in the world including Pakistan. Special attention with validated data is therefore needed, for developing guidelines for the optimal management of such neoplasms.

Mean level of pretreatment neutrophil to lymphocyte ratio in patients with squamous cell carcinoma of the head and neck-Cross-sectional study.

Background: Squamous cell carcinoma of the head and neck have been characterized using various prognostic parameters. These include advanced age, lifestyle habits such as smoking, higher tumor stage at presentation & presence of metastasis. Many patients are diagnosed with head and neck cancers annually in Pakistan, but limited data is available for the prognosis of these patients. This study aims to investigate a new biomarker by estimating the mean level of pretreatment neutrophil to lymphocyte ratio (NLR) in patients with Squamous cell carcinoma of the head & neck. Methods: We conducted a cross-sectional study using non-probability consecutive sampling techniques for 222 biopsy-proven cases of head & neck squamous cell carcinoma. Clinical & pathological variables were analyzed, including the patient's profile and tumor characteristics. The NLR of each patient before treatment was calculated using the absolute neutrophil count divided by the absolute lymphocyte count in preoperative blood samples. An independent sample t-test was used to assess the mean difference. A p-value less than or equal to 0.05 was taken as statistically significant. Results: Of 222 patients, a male predominance was seen in the entire cohort. A median pretreatment NLR of 3.19 (2.47-4.97) was identified, and patients were classified into high and low NLRs based on this value. Data analysis revealed a statistically significant increase in NLR among patients with nodal metastasis. In addition, patients with NLR above the median cutoff value of 3.19 demonstrated that there was a significant increase in NLR values with high tumor (T) and nodal (N) classifications with a p-value of 0.001 and 0.003, respectively. Conclusion: Pretreatment neutrophil to lymphocyte ratio may be associated with increased nodal involvement. It may serve as a useful prognostic predictor for patients with squamous cell carcinomas of the head and neck. Identifying high-risk patients in the pretreatment phase with the help of such biomarkers will also facilitate early inclusion in clinical trials.

Role of circulating-tumor DNA in the early-stage non-small cell lung carcinoma as a predictive biomarker.

Lung cancer is one of the most common solid malignancies. Tissue biopsy is the standard method for accurately diagnosing lung and many other malignancies over decades. However, molecular profiling of tumors leads to establishing a new horizon in the field of precision medicine, which has now entered the mainstream in clinical practice. In this context, a minimally invasive complementary method has been proposed as a liquid biopsy (LB) which is a blood-based test that is gaining popularity as it provides the opportunity to test genotypes in a unique, less invasive manner. Circulating tumor cells (CTC) captivating the Circulating-tumor DNA (Ct-DNA) are often present in the blood of lung cancer patients and are the fundamental concept behind LB. There are multiple clinical uses of Ct-DNA, including its role in prognostic and therapeutic purposes. The treatment of lung cancer has drastically evolved over time. Therefore, this review article mainly focuses on the current literature on circulating tumor DNA and its clinical implications and future goals in non-small cell lung cancer.

Cardiac sarcoma: A rare case of primary cardiac sarcoma.

INTRODUCTION AND IMPORTANCE: Primary cardiac sarcoma is a rare malignancy with a poor prognosis because of diagnostic delay, therapeutic difficulties, and high metastatic potential. The therapeutic approach includes surgery, chemotherapy, and radiation therapy, alone or in combination. However, there is a lack of evidence to guide the treatment. CASE PRESENTATION: We present a case of primary cardiac sarcoma. Our patient was presented in the department of emergency medicine (ED) in our institute with shortness of breath on exertion associated with orthopnea. Based on the history and cardiovascular examination, he underwent an echocardiogram, which revealed a sizeable echogenic density in the right ventricular outflow tract. He underwent surgical resection of the cardiac mass via median sternotomy and total cardiopulmonary bypass approach. The patient was eventually diagnosed with primary cardiac sarcoma, confirmed by tissue biopsy after surgical intervention. CLINICAL DISCUSSION: Through this report, we highlight the rarity of primary cardiac sarcomas, the importance of multidisciplinary tumor board (MDT) discussion and provide evidence of surgical excision being the treatment of choice, followed by systemic chemotherapy in selected cases. CONCLUSION: Cardiac sarcoma is a rare but highly malignant tumor with a poor prognosis. However, early diagnosis and surgical resection of a primary cardiac sarcoma can significantly increase the patient's survival and quality of life. Therefore, physicians should keep a high suspicion of a patient with clinical features suggestive of cardiac sarcoma, and echocardiography should be the diagnostic modality of choice in such patients.

Abdominal myoepithelial carcinoma: A rare abdominal wall entity of an uncommon tumor.

INTRODUCTION AND IMPORTANCE: Myoepithelial carcinomas are a diverse group of tumors exhibiting myoepithelial differentiation. There have been increasing reports of extra-salivary sites of origin for myoepithelial carcinomas such as soft tissues, bone and visceral areas. Due to this entity's rarity, definite diagnostic and treatment parameters are somewhat limited. We present the case of a myoepithelial carcinoma arising from the abdominal wall, a rare site of origin of an uncommon tumor. CASE PRESENTATION: A 37-year-old gentleman presented to our institution in Oct 2018 with a recurrent abdominal mass for which he underwent wide local excision after completing the workup, which included systemic scans and relevant blood investigations. The histopathology report was consistent with malignant abdominal myoepithelial carcinoma. However, subsequent follow-up scans in May 2019 showed disease progression with the appearance of multiple lung metastases. After a detailed discussion, he was started on Pazopanib 800 mg orally once a day, on which he remained stable till May 2022. It was then when he experienced clinical disease progression confirmed on systemic scans, so he was offered palliative systemic chemotherapy. CLINICAL DISCUSSION: Abdominal malignant myoepithelial carcinomas are an infrequent entity. However, this case highlights its critical diagnostic markers and primary and recurrent abdominal myoepithelial carcinoma management. CONCLUSION: Abdominal myoepithelial carcinomas, although rare, are also under-recognized. Thus, keeping an index of high suspicion for these tumors and being armed with knowledge regarding the heterogeneity of its features would lead to better diagnostic awareness and documentation, paving the way for better evidence-based treatments.

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.

Knowledge, attitude and perceptions of Muslim cancer patients regarding cancer treatment during Ramadan: Results from a tertiary care hospital Karachi.

OBJECTIVE: To assess the knowledge and attitude of Muslim cancer patients regarding cancer treatment during Ramadan. METHODS: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from July to August 2015, and comprised cancer patients. .Adult Muslim cancer patients receiving active oncological treatment or on surveillance were included. Patients on only supportive treatment were excluded. SPSS 19 was used for data analysis. RESULTS: Of the 265 patients, 87(32.8%) were males and 178(67.2%) were females. The overall mean age was 49±13.87 years. Besides, 184(70.9%) patients belonged to the middle class. Breast cancer was the most common cancer 106(40.6%). Overall, 153(57.9%) patients had stage II disease. Further, 201(80%) patients had 0-1 performance status. Moreover, 180(72%) patients were receiving different forms of chemotherapeutic agents. It was found that 113(54.3%) patients sought advice regarding fasting. Most of the patients who observed fast, i.e. 214(81%), had an early stage disease and 19(7.1%) were on hormonal therapy. Patients who did not fast mostly attributed this to fatigue 69(26.3%). Conclusion: Only half of the patients sought advice on fasting and those having early disease more. CONCLUSIONS: Only half of the patients sought advice on fasting and those having early disease more frequently observed fast.

Psychosocial impact of cancer on adult patients.

OBJECTIVES: To explore the effects of cancer on psychosocial aspects of Pakistani patients and their families, assessing the need for interventions to improve their quality of life. METHODS: A prospective, Cross-sectional study was performed on 200 patients visiting the oncology outpatient facility of AKUH from December 2010 to May 2011 through an interview. Responses were recorded on pre-designed questionnaires including FACT-G QOL (Functional Assessment of Cancer Therapy-General Quality Of Life) component. RESULTS: Out of the 200 patients 52 (26%) were males and 148 (74%) were females. Mean age was 51.8 +/- 14.2 years. Breast cancer accounted for the commonest cancer in females 116 (58%) and lung in males 30 (15%), 100 (50%) patients were currently undergoing chemotherapy. In all 148 (74%) patients were well aware of their diagnosis and were able to cope better and 142 (71%) were well supported by families (majority being financially stable). Major financial impact was found in 42 (21%) cases. Religious/spiritual help was sought by 138 (69%) patients predominantly females- 113 (76%) and 22 (11%) patients consulted a psychiatrist; 20 (94%) subjects of this group felt this intervention was helpful. Responses regarding effect on the patient's sexual life were poor and 126 (63%) denied answering the question. CONCLUSION: In our study one third of cancer patients were found to be depressed mainly affecting those who were receiving multimodality treatment or facing financial issues. Religious help was the main coping strategy for them.