Patient education and mind diversion in supportive care.

Cancer is a growing health problem worldwide. Common treatments include surgery, chemotherapy and radiation therapy. Systemic anti-cancer medications often result in an array of physical and psychological side effects. Supportive care assists patients with cancer in managing multidimensional symptoms that result from treatment or the illness itself. This review discusses supportive care and examines patient counselling and mind-diversion activities, which are safe and cost-effective strategies. Improving cancer patients' health and wellbeing should be encouraged in oncology nursing practice and by teaching students the knowledge and skills needed to provide supportive care.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

Sulfonamides as a new scaffold for hypoxia inducible factor pathway inhibitors.

Solid tumors generally grow under hypoxic conditions, a pathophysiological change, which activates the expression of genes responsible for malignant, aggressive, and treatment-refractory properties. Hypoxia inducible factor (HIF) is the chief transcription factor regulating hypoxia-driven gene expression. Therefore, the HIF pathway has become a critical target for cancer therapeutics development. We screened a privileged library of about 10,000 natural-product-like compounds using a cell-based assay for HIF-dependent transcriptional activity and identified several arylsulfonamide HIF pathway inhibitors. Among these compounds, the most potent ones showed an IC(50) of ∼0.5 µM in the hypoxia-responsive element (HRE)-luciferase reporter system. Further studies are needed to fully elucidate the mechanism of action of this class of compounds and their structure-activity relationship.

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.

Molecular and radiological characterization of glioblastoma multiforme using magnetic resonance imaging.

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant, aggressive and common form of primary brain cancer. Currently, GBM is considered to be a homogenous mass as all its margins are treated equally at the time of resection. However, it is not known whether radiologically distinct regions of GBM are also distinct at molecular level. We conducted this study to see if radiologically distinct regions were also different at the molecular level. METHODS: In 20 patients, MRI derived variance known as Apparent Diffusion Coefficient (ADC) was plotted against Contrast Enhancement (CE). Four radiologically distinct regions were identified: 1) high ADC and low CE; 2) low ADC and low CE; 3) high ADC and high CE; and 4) low ADC and high CE. Biopsy samples were collected from these four regions of interest in each patient and immunohistochemistry was conducted to characterize cellular features and identify oncogene and stem cell marker expressing cells. RESULTS: Markedly increased nuclear pleomorphism, cellularity and necrosis were seen in region 2. Oncogene IDH was expressed in all regions, however, it was highest in region 4. Stem cell marker, CD44 expression was highest in region 1 and lowest in region 2 and 3. The expression of CD133 was highest in region 3. CONCLUSIONS: This study shows that ADC/CE plot can divide GBM into four regions, whose heterogeneity is evidenced by differential expression of nuclear pleomorphism, necrosis, cellularity and mitotic rate as well as the expression of oncogene and stem cell markers.

Karachi Cancer Registry (KCR): Age-Standardized Incidence Rate by Age-Group and Gender in a Mega City of Pakistan.

OBJECTIVES: To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19. SETTINGS: The population of Karachi division is 16.1 million according to national census 2017. 'Karachi Cancer Registry' which is a part of 'National Cancer Registry' is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0-14, 15-19 and ≥20 years), in both genders and all cancer site/type. METHODS: The population denominators were based on the population of Karachi division estimated at 16.1 million in the population census, 2017. Counts and age-standardized incidence rates (ASIR) were calculated for each of the three age categories. RESULTS: From Jan 2017 till Dec 2019 a total of 33,309 malignant cases were recorded in KCR database comprising 17,490 (52.5%) females and 15,819 (47.5%) males. ASIRs in age groups 0-14, 15-19 and ≥ 20 years, among female were 11.5, 2.4 and 223.6 and in males were 17.6, 3.2 and 216.7 respectively. The commonest diagnosis in children, adolescent and adults were (1) among females: children; bone (3.12),  leukemia (2.09) brain/CNS (1.26); in adolescents: bone (0.78), brain/CNS (0.27), connective and soft tissue (0.11), in adults: breast cancer (76.07), oral cancer (16.68) and ovary (10.89) respectively, and (2) among males: children; bone (4.56),  leukemia (2.79) and brain/CNS (1.88); in adolescent; bone (1.19), brain/CNS (0.31) and leukemia (0.21) and in adults: oral cancer (42.83), liver (16.10) and bone (13.37) respectively. CONCLUSION: Oral Cancer, a largely preventable cancer is the leading cancer in Karachi adult males while in female adults Breast Cancer is the leading cancer followed by Oral Cancer. In children and adolescents Bone, Leukemia and Brain/CNS malignancies are most common.
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Survival and treatment outcomes of metaplastic breast carcinoma: Single tertiary care center experience in Pakistan.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare disease with incidence of less than 1%. MBC present with a larger tumor size, less number of nodes involved, mostly undifferentiated triple negative tumors. We aimed to determine progression-free and overall survival and reported hospital-based incidence of MBC. MATERIAL AND METHODS: A retrospective closed Cohort study elicited data of 42 patients with MBC from January 2008 to December 2013; followed till August 2016. Kaplan-Meier method was applied to compute overall and progression-free survival analysis. Cox Proportional hazard ratios were computed to assess associations between survival and independent variables. RESULTS: Hospital-based incidence of MBC was 1.92% (42/2187), 95% CI [1.41-2.56]. The median age at tumor diagnosis was 54 years (range, 25-81 years). Thirty-nine (92.9%) patients had Grade III tumor. The most common histopathology was squamous (69%). The median tumor size was 4.5 cm (range, 0.8-17 cm). Nineteen (45.2%) patients had nodal involvement at diagnosis. Four patients (9.5%) had metastatic disease at presentation. Hormone receptors were positive in 19 (45.2%) patients. Her-2 neu receptor was positive in 9 (19%) patients. Sixteen (38.1%) patients had triple negative disease. Neoadjuvant and adjuvant chemotherapy was received by 10 (31.25%) and 19 (45.2%) patients respectively. Both median progression-free and overall survival was 38 months. CONCLUSION: Five-year progression-free and overall survival was 79.5% and 76.3%, respectively. We report better survival outcomes when compared to series described earlier despite our patient population presenting mostly with high grade, large tumors, and half of them exhibiting nodal and hormonal involvement.

Solitary Brain Metastasis: A Rare Initial Presentation of Prostate Carcinoma.

Cerebral metastasis as an initial clinical presentation of prostate carcinoma is extremely rare. Usually, patients have widespread metastasis in the body before presenting with brain metastasis. In the absence of extensive metastasis, especially without bony metastasis, only brain metastasis is an unusual presentation of the disease. We report a case of a 59-years-old patient who presented with a lack of concentration and decreased vision. Magnetic resonance imaging (MRI) of the brain revealed a large right parietal-occipital space-occupying lesion. He underwent surgery and the pathological diagnosis of the tumor turned out to be metastatic prostate carcinoma. Further evaluation by a whole-body computed tomography (CT) scan revealed an enlarged prostate with no other metastatic deposit and a mildly raised level of prostate-specific antigen (PSA). It was possible for us to provide this patient with multi-modality treatment with the help of multidisciplinary tumor board meetings. Further studies addressing the biological as well as clinical characteristics of prostate carcinoma with this rare metastatic presentation will help us to define prognostic factors and therapeutic intervention and will help us to understand the basis of this unique presentation without bone metastasis.

Influence of supportive care on chemotherapy patients' self-care behaviour and satisfaction: A pilot study conducted in Karachi, Pakistan.

BACKGROUND AND AIM: Cancer is a daunting illness affecting a vast number of people globally. During the illness trajectory, cancer patients suffer from physical and/or psychosocial issues. These physical and psychosocial issues demand conscious actions by patients to maintain their well-being. Hence, the objective of the pilot study was to evaluate the level of self-care behaviors and satisfaction in women suffering from cancer after exposure to supportive care (education and mind diversion activities) delivered via a patient help group program. METHODS: The study was conducted at the chemotherapy day care unit of one of the tertiary care hospitals located in Karachi, Pakistan. In this study, supportive care interventions were offered via the patient help group program over a 5-week period, and in the 6th week, data were collected. The total sample size of this pilot study was n = 17. Female cancer patients receiving weekly chemotherapy regimen and diagnosed with breast or gynecological cancers were a part of the study. Outcome variables, self-care behavior and satisfaction, were assessed via a self-developed questionnaire. Content validity index of the questionnaire was calculated on the basis of expert review and was found to be 96% for relevancy and 94% for clarity. Frequencies were calculated to evaluate outcome variables. Outcome variable satisfaction was also assessed via few open-ended questions. RESULTS: Participants reported moderate-to-high self-care behaviors and satisfaction after exposure to supportive care interventions delivered via the patient help group program. CONCLUSION: Counseling and mind diversion activities are effective in producing a positive change in chemotherapy patients' self-care behaviors and satisfaction. Therefore, oncology nurses must utilize them in chemotherapy patient care. Future studies should evaluate the effectiveness of these interventions with larger sample size and comparative analysis.

Quality of Life and Its Determinants in Adult Cancer Patients Undergoing Chemotherapy Treatment in Pakistan.

OBJECTIVE: Cancer is a leading cause of death worldwide. Likewise, in Pakistan, it is a major health problem, with an approximate increase each year. Cancer treatment, particularly chemotherapy, produces a detrimental effect on individuals' well-being. Since the past few years, quality of life (QOL) is considered as the primary goal of cancer treatment in patients' survival. This study aimed to assess the QOL and its determinants in adult cancer patients undergoing chemotherapy treatment. METHODS: An analytical cross-sectional design was employed to achieve the study objectives, utilizing consecutive sampling technique. A total of 150 adult (>19 years) cancer patients were recruited from a Tertiary Care Hospital in Karachi, Pakistan. The data were collected using the Functional Assessment of Cancer Therapy-General, a QOL questionnaire. Multiple linear regression was run to determine the effect of predictor variables, with a mean QOL score. RESULTS: The overall mean score of QOL as 57.37. The domains of physical and emotional well-being were mainly affected by the chemotherapy treatment. Variables such as no previous hospitalization and no significant changes in life events were positively associated with the QOL. On the other hand, being female, unemployed, chemotherapy side effects (>1 week), impaired socialization, and discrimination by family/relatives were negatively associated with the QOL. CONCLUSIONS: The study findings suggested an overall low QOL among adult cancer patients undergoing chemotherapy treatment. It is recognized as a stressful treatment, which adversely affects the QOL of cancer patients. Interventions should focus on both the physical and psychological issues and need to be addressed to improve the QOL of adult cancer patients.

Gangliosides regulate tumor cell adhesion to collagen.

The ability of tumor cells to adhere to extracellular matrix proteins is critical for migration and invasion. The factors that regulate tumor cell adhesion are poorly characterized. Gangliosides promote platelet adhesion and may also play a role in the adhesion of other cell types. We hypothesized that pharmacological depletion of membrane gangliosides from adherent cells would abrogate adhesion to collagen and promote migration and invasion. To test these hypotheses, LA-N1 neuroblastoma cells, which avidly adhere to collagen and are rich with membrane gangliosides (43.69 nmol/10(8) cells), were cultured in the presence of D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl. Endogenous gangliosides were reduced by 98% (0.76 nmol/10(8) cells) and adhesion to collagen decreased by 67%. There were no changes in cell morphology, viability, proliferation rate or apoptosis. Pre-incubation of ganglioside-depleted cells in conditioned medium from control cells restored adhesion to collagen (0.45 +/- 0.002), comparable to that of control cells (0.49 +/- 0.035). Similarly, pre-incubation of ganglioside-depleted cells with purified GD2 completely restored adhesion in a concentration-dependent manner. When LA-N1 cells were cultured with retinoic acid, a biological response modifier known to increase endogenous gangliosides, adhesion to collagen increased. Next, we questioned whether changes in adhesion would be reflected as changes in migration and invasion. Cells depleted of endogenous cellular gangliosides migrated more than control cells. Finally, control cells replete with their endogenous gangliosides demonstrated less invasive potential than control cells. The data demonstrate that endogenous tumor gangliosides increase neuroblastoma cell adhesion to collagen and reduce migration and invasion in vitro.

Arylsulfonamide KCN1 inhibits in vivo glioma growth and interferes with HIF signaling by disrupting HIF-1α interaction with cofactors p300/CBP.

PURPOSE: The hypoxia-inducible factor-1 (HIF-1) plays a critical role in tumor adaptation to hypoxia, and its elevated expression correlates with poor prognosis and treatment failure in patients with cancer. In this study, we determined whether 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, KCN1, the lead inhibitor in a novel class of arylsulfonamide inhibitors of the HIF-1 pathway, had antitumorigenic properties in vivo and further defined its mechanism of action. EXPERIMENTAL DESIGN: We studied the inhibitory effect of systemic KCN1 delivery on the growth of human brain tumors in mice. To define mechanisms of KCN1 anti-HIF activities, we examined its influence on the assembly of a functional HIF-1α/HIF-1ß/p300 transcription complex. RESULTS: KCN1 specifically inhibited HIF reporter gene activity in several glioma cell lines at the nanomolar level. KCN1 also downregulated transcription of endogenous HIF-1 target genes, such as VEGF, Glut-1, and carbonic anhydrase 9, in a hypoxia-responsive element (HRE)-dependent manner. KCN1 potently inhibited the growth of subcutaneous malignant glioma tumor xenografts with minimal adverse effects on the host. It also induced a temporary survival benefit in an intracranial model of glioma but had no effect in a model of melanoma metastasis to the brain. Mechanistically, KCN1 did not downregulate the levels of HIF-1α or other components of the HIF transcriptional complex; rather, it antagonized hypoxia-inducible transcription by disrupting the interaction of HIF-1α with transcriptional coactivators p300/CBP. CONCLUSIONS: Our results suggest that the new HIF pathway inhibitor KCN1 has antitumor activity in mouse models, supporting its further translation for the treatment of human tumors displaying hypoxia or HIF overexpression.

Design and synthesis of novel small-molecule inhibitors of the hypoxia inducible factor pathway.

Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility, and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels but interfere with the ability of HIF-1α/HIF-1ß to interact with cofactors p300/CBP to form an active transcriptional complex.

Gangliosides promote platelet adhesion and facilitate neuroblastoma cell adhesion under dynamic conditions simulating blood flow.

BACKGROUND: Aberrant gangliosides are produced and shed by some tumors into the extracellular milieu. Their concentration is related to disease progression in children with neuroblastoma and in experimental models. The mechanism for this tumor promoting effect is not known. PURPOSE: Here, we investigated the effect of gangliosides on platelet and tumor cell adhesion under shear forces simulating venous and arterial flow. RESULTS: High shear force increased platelet adhesion 2.5-fold compared to low force. Pre-incubation of platelets with gangliosides increased adhesion at low shear to a level comparable to high shear alone. The addition of gangliosides to platelets perfused at high shear did not further increase adhesion. LAN1 neuroblastoma cells are adherent to collagen in static assays. No effect of either shear or gangliosides was observed on cell adhesion under dynamic conditions. However, when perfused in the presence of platelets, an increase in binding of tumor cells was observed at both shear forces compared to cells alone. CONCLUSIONS: These results demonstrate that shear and gangliosides increase dynamic platelet adhesion to collagen. In addition, platelets facilitate tumor cell binding. Therefore, by acting as a mediator of platelet activation, gangliosides may promote blood borne metastasis by increasing platelet binding to the vessel wall and in turn facilitate tumor cell arrest in circulation.

Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene.

Hemophilia is a genetic disease caused by a deficiency of blood coagulation factor VIII or IX. Bleeding into joints is the most frequent manifestation of hemophilia. Hemarthrosis results in an inflammatory and proliferative disorder termed hemophilic synovitis (HS). In time, a debilitating, crippling arthritis, hemophilic arthropathy, develops. Although the clinical sequence of events from joint bleeding to synovitis to arthropathy is well documented, the component or components in blood and the molecular changes responsible for hemophilic synovitis are not known. Iron has long been suspected to be the culprit but direct evidence has been lacking. Previously, we showed that iron increased human synovial cell proliferation and induced c-myc expression. Here we show that bleeding into a joint in vivo and iron in vitro result in increased expression of the p53-binding protein, mdm2. Iron induced the expression of mdm2 by normal human synovial cells approximately 8-fold. In a murine model of human hemophilia A, hemarthrosis resulted in pathologic changes observed in human hemophilic synovitis and a marked increase in synovial cell proliferation. Iron, in vitro, induced the expression of mdm2. The molecular changes induced by iron in the blood may be the basis of the increase in cell proliferation and the development of hemophilic synovitis.

c-myc proto-oncogene expression in hemophilic synovitis: in vitro studies of the effects of iron and ceramide.

Hemophilia is a rare congenital bleeding disorder that is due to the deficiency of blood coagulation factor VIII or IX. Recurrent musculoskeletal bleeding is common and bleeding into joints results in a chronic inflammatory condition termed hemophilic synovitis. This destructive process is characterized by hemosiderin deposition in the superficial and deeper layers of the synovial membrane as well as a proliferation of synovial fibroblasts and vascular cells. The hyperplastic synovium and neovascular changes are reminiscent of the histopathologic appearance observed in malignant tissues. Indeed, the benign hyperplastic synovium in patients with hemophilia displays similar invasive and destructive behaviors suggesting the possibility of analogous disturbances in growth control and locally invasive mechanisms. Iron plays a role in malignant cell growth, local invasion, and tumor progression, possibly due to changes in the expression of the proto-oncogene, c-myc. We hypothesized that iron plays a similar role in hemophilic synovitis. To explore this hypothesis, we investigated the in vitro effects of iron on the proliferation of a primary, human synovial fibroblast cell (HSFC) line and the involvement of c-myc in this process. We also examined the role of ceramide, a sphingolipid capable of inducing apoptosis in this model system. HSFC proliferation was increased in a dose-dependent fashion and c-myc expression was enhanced by ferric citrate compared to sodium citrate control. Ceramide prevented both the iron-induced increases in HSFC proliferation and c-myc expression. These results indicate that iron probably plays a role in the proliferative changes observed in hemophilic joint disease and that aberrant expression of c-myc may underlie the iron effects. Furthermore, these results suggest that there may be a therapeutic role for ceramide in reversing these changes.