Grading pancreatic adenocarcinomas on fine needle aspiration cytology. The outstanding issues.

OBJECTIVE: The three-tier grading scheme described in "The Papanicolaou Society of Cytopathology (PSC) System for reporting Pancreaticobiliary Cytopathology" (TPSCRPBC) which remained unchanged following the WHO Reporting System for Pancreaticobiliary Cytopathology (WRPBC) was evaluated on pancreatic adenocarcinomas (PACs) reported on endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNAC). METHODS: The Papanicolaou and May Grunwald Giemsa-stained smears from 116 cases of PACs were graded using the three-tier grading scheme laid down by TPSCRPBC/WRPBC. Cases exhibiting multiple grades were assigned primary, secondary and tertiary grades. Each case was assigned a grade score, either by adding the primary and secondary grades, by adding the primary and tertiary grades when the tertiary grade was 3 or by doubling the grade when only one grade existed. Necrosis was estimated semi-quantitatively. The inter-observer reproducibility in grading was evaluated using Kappa and Kendall's tau-c. Correlations between the various grades, the stage of the tumour and the amount of necrosis were assessed using Spearman rho and Kendall's tau-b. RESULTS: 31.89% of cases showed one grade, and 68.11% showed at least two grades. 16.38% showed three grades. The two commonest grade scores were 3 and 5. The inter-observer reproducibility for grading and grade scoring was satisfactory. A positive correlation was noted between the grades and the amount of necrosis. No significant correlation was found between the grades, grade scores and the stage of the tumours. CONCLUSIONS: The TPSCRPBC/WRPBC grading scheme can be suitably applied to PACs with good inter-observer reproducibility. Cases often show multiple grades in the same tumour.

Safety and tolerability of regorafenib: a real-life experience.

BACKGROUND: Regorafenib has been approved among the treatment options for patients with advanced stage colorectal cancer (CRC), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumors (GIST). In this study, we aim to report the real-life experience of the safety and tolerability regorafenib in our institution. METHODS: We conducted a retrospective chart review of 43 patients who received regorafenib in Kuwait Cancer Control Center (KCCC) from 2016 to the end of 2019. Data collected include diagnosis, patient demographics, performance status, number of previous lines of treatment, number of treatment cycles, side effects, best-tolerated dose, and treatment discontinuation due to intolerability. Univariate analysis with Pearson chi-square test were conducted to study co-relation between discontinuation rates and several factors. RESULTS: We had available data for 43 patients (23 males and 20 females). Of the patients, 83.7% had an ECOG performance status of 0 or 1. Seventy-three percent were diagnosed with metastatic CRC, 21% were diagnosed with HCC and 6% were diagnosed with GIST tumors. Half of the patients received 3 lines or more of treatment prior to regorafenib. The median number of cycles received was 3.7 with 11.6% of patients still on active treatment at the time of analysis. The most reported grade 3 and above side effects included rash (41.9%), fatigue (39.6 %), hypertension (25.6%), mucositis (21.9%), hand-foot syndrome (2.3%), and hyperbilirubinemia (4.6%). The best-tolerated dose was 80 mg and that was achieved in 44.2% of patients. The recommended dose of 160 mg could only be achieved in 20.9% of patients. The treatment was discontinued because of intolerability in 25.6% of patients. The discontinuation rates in those with ages 60 years and above versus below 60 years were 91% and 68%, respectively. CONCLUSION: In our cohort, the best-tolerated dose of regorafenib was 80 mg. Toxicity and intolerability of regorafenib lead to treatment discontinuation in nearly a quarter of patients. Patient age may influence tolerance and adherence to regorafenib.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology of Pancreatic Adenocarcinomas Revisited. A Detailed Cytological Analysis.

BACKGROUND: Early detection of pancreatic adenocarcinomas is essential for improving survival. In this regard, endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) has established itself as the method of choice for its ability to target lesions smaller than those which could be targeted by the traditional imaging methods like transabdominal ultrasound. Identifying these tumors correctly on FNA may be challenging because pancreatic adenocarcinomas may show a wide range of morphological features and the presence of contaminants from the gastrointestinal tract may show up as potential pitfalls. This study presents detailed cytomorphological analyses of 59 cases reported as pancreatic adenocarcinomas on smears and cell blocks. The clinical and histopathology follow-up data wherever available have also been presented. MATERIALS AND METHODS: EUS-FNAC smears and cell blocks from cases reported as pancreatic adenocarcinomas were retrospectively evaluated with individual assessments of a range of features related to cellularity, cellular arrangement, cytoplasmic qualities, and nuclear features. Aspirates from peripancreatic lymph nodes, histopathology sections, and clinical records were reviewed wherever available. RESULTS: Nonneoplastic cells like pancreatic ductal cells and acinar cells, duodenal, and gastric epithelia were detected along with neoplastic cells showing a wide range of variations in different cytomorphological characters. Often, a mixture of features was noted in the same case. Cell block preparations served as useful adjuncts since they made it possible to render unequivocal diagnoses of malignancies in cases where smears were hypocellular. CONCLUSION: The study creates a useful knowledge base of cytomorphological features of pancreatic adenocarcinomas.

An Overview of Medullary Thyroid Cancer Cases Treated at Kuwait Cancer Control Center.

INTRODUCTION: Medullary thyroid cancers (MTC) constitute about 5% of all thyroid cancers. The 10-year overall survival (OS) rate of patients with localized disease in thyroid for this pathology is 80% to 90% which is comparable with differentiated thyroid cancers, figures drop to 75% for cases with nodal metastases. Only 20% of patients with distant metastases at diagnosis survive for 10 years. In metastatic disease there are variations with smoldering less active disease to progressive active disease. Surgery is cornerstone of the management with total thyroidectomy and nodal dissection as main treatment. Adjuvant treatment with radiotherapy is case selective, varies from case to case. The management of residual, recurrent disease is possible re-surgery with external beam radiation therapy. The development of targeted therapy has brought in a major advantage in management of metastatic disease. Two drugs -vandetanib and cabozantinib- have been approved for use in metastatic MTC. The optimum management in this group of patients is a challenge and long-term use of TKI needs to be balanced with monitoring side effects of TKI and dose adjustments of TKI. MATERIALS AND METHODS: A retrospective review of cases with diagnosis of medullary thyroid cancers treated or registered at Kuwait Cancer Control Center was conducted. The data of patients registered between 1987 till 2017 was analyzed. The data was collected and analyzed using SPSS (version 20) software program. For analysis we considered date of surgery as the date of diagnosis. Final state of disease along with emphasis on prognostic factors was correlated with Kaplan Meyer survival curves. RESULTS: There were total 31 cases out of which 15(48.4%) were male and 16(51.6%) females. The median age at presentation was 51.6 years (range-28years-77years). MEN syndrome was diagnosed in 6(19.4%) patients. Staging revealed Stage I - 7/31 (22.58%), Stage II-3/31(9.67%), Stage III-7/31(22.58%), Stage IVA (nonmetastatic) -12/31 (38.70%), Stage IVC (metastatic) - 2/31 (6.45%). Total thyroidectomy and central compartment neck dissection was optimum surgery (29%). Total thyroidectomy with central compartment neck dissection and unilateral neck dissection was done in 38.7% patients, comprehensive neck dissection and total thyroidectomy was done in 32.2% patients. External beam radiotherapy (EBRT) with conformal or IMRT technique was used in 13 out of 31 patients. One patient was treated for bony metastasis with palliative intent. Four patients were treated by TKI for metastatic disease or at progression. Median follow up was 79 months. Median overall survival was 93 months. Median progression free survival irrespective of stage was 62 months. At the end of 5 years 61% patients were alive irrespective of stage of disease. Due to the small sample size and natural history of advanced MTC the observed p-value for several pathological variables in relation with survival was not significant. CONCLUSION: Stage I and stage II cases of our study did well and were all alive and disease free till our last follow up. EBRT in our cohort of patient did not revealed any added benefits in survival. The use of TKI in metastatic disease was associated with many issues including availability of drug. Elevated serum calcitonin and CEA levels in absence of measurable disease should be dealt cautiously.

Brain Metastasis from Colorectal Adenocarcinoma: A Case Report.

Colorectal cancer (CRC) is the third leading cause of cancer death in the Western world, accounting for approximately 140,000 new cases and more than 51,000 deaths in 2010 in the United States. In Kuwait, CRC is the first most-diagnosed neoplasm among males and overall, the second leading cause of death from cancer. The 5-year survival rate in 2002-2004 was 61% for men and 62% for women. Even after complete resection of the colorectal tumor, distant metastases have been noted to develop in 10%-15% of patients. Of all metastases, those to the liver were found in 20%-30% of cases, and to the lung, in 10%-20%; brain metastases are quite rare. The percentage of CRC patients developing brain metastases during the course of their disease is reported to range from 2% to 12%, but the effect of such metastases on the patient's prognosis is significant. With the advent of new targeted therapies and the resulting improvements in outcome for CRC patients, the management policy for brain metastases has changed. Regardless of the therapy used to address brain metastases, reported median survival ranges from 2.8 months to 6 months. We report a case of brain metastasis in a patient of primary colorectal adenocarcinoma. He was evaluated for convulsion, CT findings showed brain metastasis.

Skull metastasis from carcinoma of the cervix: a rare case and review of the literature.

Skeletal metastasis from carcinoma of the cervix occurs in 0.8-23% of cases. The majority of bone metastases occur either in the long bones or in the vertebrae. Metastasis to distal bones like the skull is rare. Metastasis to bone is commonly associated with advanced stage and poor control of primary disease. We present a rare case of scalp metastasis in a patient with stage IIIB carcinoma of the cervix. The patient had completed radiation therapy treatment resulting in controlled primary disease until she was diagnosed with skull bone metastasis. We present this case because of its rarity and for documentation and discussion.

Acute myelogenous leukemia following treatment of invasive cervix carcinoma: a case report and a review of the literature.

Second malignancy is one of the late complications of long-term cancer survivors, treated with radiation or chemotherapy. Here is a case report on acute myelogenous leukemia, which developed after 63 months following the completion of treatment with surgery and platinum-based chemoradiation in a patient of carcinoma cervix IB. The above-mentioned second malignancy is one of the late sequelae of platinum-based chemoradiation. This case is reported here for documentation because of its rarity.