Kangri Cancer Research Articles

Development of bioflavonoid containing chemotherapeutic delivery systems for UV-damaged skin and kangri cancer

Abstract Background The lower abdomen and inner thighs are most likely to become affected by kangri cancer because those areas are exposed to continuous exposure to kangri. Objective In this article, formulation and characterization of a water-in-oil microemulsion of 5-fluorouracil with rutin (R-5FU) for better skin penetration and inhibition of kangri cancer (skin cancer surfactant) is discussed. Method To produce R-5-FU microemulsions, surfactant-cosurfactant was mixed with oil. Distilled water was added dropwise with the help of a burette by gentle stirring at a constant temperature. The surfactant and co-surfactant were mixed into three particular ratios 1:1, 2:1, and 3:1. Further characterizations were performed, such as visual inspection and thermodynamic stability including a stress test and centrifugation. In visual inspection included assessment of the colour, homogeneity, and odour of the formulation of FU microemulsion. Result All three microemulsions, labeled RME1, RME2, and RME3, are highly stable. An oval shape of surface morphology of 5-FU was noticed by using a TEM image. The viscosity of RME3 was found to be 17.25±0.22 pa-s. The average globule size was 100–300 nm for all three RME. The results of human cadaver skin permeability are almost of the same pattern, butRME3 indicates the best skin permeability with negligible side effects on the skin. Conclusion The quantity of 5-FU released from all formulations at 3-hr ranged from 95.57% to 83.67%. None of the three formulations resulted in skin irritation, with irritancy score of zero (IS=0). Observation revealed no lysis, hemorrhage, or coagulation after application.

Epileptic burn injuries in Kashmir valley: Is “Kangri” a boon or bane?

Background: During seizure attacks, patients may suffer severe trauma such as deep burns, limb fractures, and head-and-neck injuries. Most burns in epileptic patients occur during major seizures. Such burns are always full-thickness. Because of extreme cold conditions people in Kashmir valley, especially in rural areas use Kangri to keep themselves warm. This Kangri which is already notorious for causing Kangri cancer has an additional disadvantage in causing deep burns mainly to the hands in epileptic patients. Objective: (1) To analyze the epidemiological data of burnt hospitalized epileptic patients. (2) To determine the frequency, causes, and consequences of burns in patients with epilepsy stressing on Kangri burns in epileptics. (3) To determine the various preventive measures to reduce the incidence of such injuries. Materials and Methods: This was a retrospective study conducted in the Department of Burns, Plastic, and Reconstructive Surgery at Sher-e-Kashmir Institute of Medical Sciences, Srinagar, India, from January 2005 to December 2018. All epileptic patients with burns admitted in the hospital were included in the study. Results: Of 157 patients, 67 (43%) were in the age group of 16–30 years. The mean age was 32.7 years. Majority of the patients 99 (63%) were female. One hundred and two (84%) patients belonged to rural areas. Kangri was the most common etiological agent of epileptic burns in 99 (63%) patients. Eighty-four (53%) had sustained full-thickness burns and total body surface area involved was up to 5% only. The most common site of burns was hands 88 (56%). Amputation of the gangrenous digits/hands was the most common surgery performed in 39 (25%) patients. Complication in burnt epileptic patients was loss of a body part 47 (44%) followed by contracture (32.4%), wound infection (22%), and loss of vision in 1 (0.6%) patients. There was no mortality in our series. Conclusion: Epileptic patients should avoid high-risk situations like working alone in kitchen. Kangri should be replaced by alternative simple and safe warming devices.

Burns in Epileptics with Special Reference to Kangri Burns

Background: During seizure attacks patients may suffer severe trauma such as deep burns, limb fractures, head and neck injuries. Most burns in epileptic patients occur during major seizures. Such burns were always full-thickness. Because of extreme cold conditions people in Kashmir valley especially in rural areas use Kangri to keep themselves warm. This Kangri which is already notorious for causing Kangri cancer has an additional disadvantage in causing deep burns mainly to the hands in epileptic patients. Objective: (1) To analyse the epidemiological data of burnt hospitalised epileptic patients. (2) To determine the frequency, causes and consequences of burns in patients with epilepsy stressing on Kangri burns in epileptics. Study design and Method: It was both a retrospective and prospective study. All patients of epileptic burns admitted in the hospital from Jan 2005 to Nov 2012 were included. In the retrospective group, the case records of epileptic burnt patients were carefully analysed. All new patients were evaluated in detail. Results: Out of 73 patients 32(43%) were in the age group of 16–30 years. Mean age was 26 ± 17 years. Majority of the patients 46(63%) were females. 61(84%) patients belonged to rural areas. Kangri was the most common etiological agent of epileptic burns in 46(63%) patients.37 (52%) had sustained full thickness burns and Total Body Surface Area (TBSA) involved was up to 5% only. Commonest site of burns was hands/upper limbs 40 (56%). Amputation of the gangrenous digits/hands was the commonest surgery performed in 22(25%) patients. Complication in burnt epileptic patients was the loss of a body part 22(41%) followed by contracture 16(36%), wound infection 11(21%) and loss of vision in 1(2%) patients. Conclusion: Epileptic patients should avoid high risk situations like working alone in the kitchen. Kangri should be replaced by alternative simple and safe warming devices.

Histopathological analysis of the cutaneous changes due to Kangri use in Kashmiri population: A hospital based study

Background:Kangri cancer is peculiar to the valley of Kashmir as people of all age groups are accustomed to warm their bodies by the use of Kangri baskets. The clinical spectrum of skin cancer in the Kashmir valley is entirely different from the rest of the country, which could be attributed to the use of Kangri in this geographical region.[12]Aims:Histopathological analysis of the cutaneous changes due to kangri use in Kashmiri population.Materials and Methods:This is a prospective hospital based study. All the patients attending the outpatient department of Dermatology, STD and Leprosy at SMHS Hospital, an associated hospital of govt. medical college in Srinagar and presented with suspicious lesions (i.e., erythema ab igne, papular or nodular skin growths) due to Kangri use were taken up for the study. A detailed history including the use of Kangri and a physical examination was done in each patient followed by a histopathological examination in case of suspicious lesions.Results:The cutaneous changes which were observed during the study period of 8 months were erythema ab igne, bowen's disease and squamous cell carcinoma.Conclusion:Although this is a preliminary study we will be studying more of such changes caused due to Kangri use in the future.

Kangri Cancer Invading the Brain in a Kashmiri Lady (Marjolins Ulcer)

Kangri Cancer Invading the Brain in a Kashmiri Lady (Marjolins Ulcer)

Impact of codon 72 Arg > Pro single nucleotide polymorphism in TP53 gene in the risk of kangri cancer: a case control study in Kashmir

Kangri cancer found only in Kashmir (north India) is a unique thermally induced squamous cell carcinoma of the skin that develops because of chronic and persistent irritation due to the use of a kangri (a brazier) by the Kashmiri people to combat the chilling cold temperature during winter. Being unique to this region, the molecular etiology of the invasive kangri cancer is not known fully. The TP53 gene, codon 72 polymorphism (Arg72Pro), has been found to be associated with cancer susceptibility but has not been investigated in kangri cancer risk. A case control study was conducted to find the genotype distribution of TP53 Arg72Pro SNP and to elucidate the possible role of this SNP as risk factor in kangri cancer development. Using the polymerase chain reaction-restriction fragment length polymorphism approach, we tested the genotype distribution of 106 kangri cancer patients in comparison with 200 cancer-free controls from the same geographical region. A significant difference was observed between the control and kangri cancer patients with odds ratio = 2.02 and 95% confidence interval = 1.2-3.3 (p = 0.01). Interestingly, the proline form was abundantly observed in advanced-grade tumors (p < 0.05). We also found a significant association of the variant allele (GC + CC) with male subjects and patients >45 years of age (p < 0.05). Thus, it is evident from our study that Arg72Pro SNP is implicated in kangri cancer and that the rare, proline-related allele is connected with higher susceptibility to kangri cancer.

Kangri cancer

Kangri cancer is a heat-induced skin carcinoma associated with the use of the Kangri. This Kangri, which is a traditional fire pot, is an ingenious mode of providing warmth. The Kangri is an earthenware container with an outer encasement of wickerwork that is filled with ignited coal inside for providing a source of heat in winter months. Its prolonged use may result in formation of erythema ab igne, a reticulate hypermelanosis with erythema, which may transform into cutaneous cancer. Currently, this skin cancer rarely is found in the Kashmir valley. Between 2003 and 2008, all those having Kangri cancer were studied. A 5-year study was conducted during which 17 patients who were documented with a Kangri cancer were treated. Sixteen patients had cancer on a thigh and 1 had cancer on the abdominal wall. All had an excision of the neoplasm. Histopathology documented squamous cell carcinoma in all patients. Kangri cancer still occurs in patients who live in remote areas of Kashmir where there is a chilling cold in winter months and have no modern and alternative cheap means of warming other than the Kangri.

Mutational spectrum of conserved regions of TP53 and PTEN genes in Kangri cancer (of the skin) in the Kashmiri population

Kangri cancer is a unique, thermally induced squamous cell carcinoma (SCC) of the skin that develops due to persistent use of a Kangri (a brazier) by the Kashmiri people to combat the cold temperature during winter. Unlike classical UV-induced SCC of the skin, Kangri cancer appears on the legs and abdomen. Its common features are erythematous patches, recurrence and metastasis. In the absence of any molecular etiology, we made a preliminary attempt to estimate the nature and frequency of mutations in the TP53 and PTEN genes in Kangri cancer patients from Kashmir. PCR-SSCP analysis followed by direct sequencing revealed that TP53 mutations account for 40% (12/30) of sporadic Kangri cancer patients and that PTEN mutations account for only 6.6% (2/30). There were 16 mutations in TP53 exons 5 and 7, found in 12 patients. They consisted of 11 substitutions (7 transitions, 3 transversions and 1 double-base) and 5 insertions. The 11 substitutions represent 8 distinct missense mutations, 3 of which were silent mutations. The mutations detected in the PTEN gene consisted of one insertion and one C > T transition. This high percentage of TP53 mutations (especially A > G) showed a statistically significant association with age and positive lymph node status. Our results indicate that TP53 is a predominant target of chronic hyperthermia in the development of Kangri cancer in the moderate risk Kashmiri population. The differences in the TP53 mutation spectrum of UV-induced SCC of the skin and Kangri cancer are probably due to the nature of the respective environmental carcinogens. The study also suggests that TP53 may function as a potential molecular marker and prognostic tool, at least in a subset of sporadic Kangri tumors.

Polymorphic analysis of MHClinked Heat Shock Protein 70 genes: Their susceptibility and prognostic implication in Kangri cancer cases of Kashmiri population

Kangri cancer is a unique thermally-induced squamous cell carcinoma (SCC) of skin that develops due to persistent use of Kangri (a brazier), used by Kashmiri people, to combat the chilling cold during winter months. We designed a large scale case-control study to characterize the frequency of two polymorphisms within the MHC class III-linked HSP70genes, Hsp70-2 and Hsp70-hom, in order to find any association of these genotypic variants for predisposition to and clinical outcome of Kangri cancer patients from Kashmir valley in North India. Polymerase Chain Reaction and restriction enzymes were utilized to characterize the frequency of two polymorphisms with in Hsp70-2 and Hsp70-hom genes in 118 Kangri carcinoma cases and 95 healthy controls from the same population of Kashmir. Association of high frequency allelic variants of Hsp70genes with various clinicopathological features of prognostic significance was assessed by Chi-square test using SPSS software. In this study, allelic frequency of Hsp70-2 A/G heterozygote (0.87) (P = 0.012) was found to be significantly high in Kangri cancer cases compared to control (0.736) with a Relative Risk of 2.45 fold. Conversely, the allelic frequency of Hsp70-2 A/A allele in homozygous condition was significantly low in Kangri cancer cases and worked out to be 0.084 (Vs 0.252 in control) with P is equal to 0.001, implicating it as a protective allele against Kangri cancer in subjects with this genotype. Similarly, significantly high frequency of 0.50 (Vs 0.29 in control) of Hsp70-homC/C allele was found in homozygous condition in Kangri cancer cases suggestive of a positive relative risk associated with this genotype (RR is equal to 2.47) (P is equal to 0.002). The overall allele frequency data analysis of Hsp70-2 and Hsp70-hom genes was significant (χ2 is equal to 12.38, P is equal to 0.002; and χ2 is equal to 12.21, P is equal to 0.002). The study also reveals considerable association of high frequency alleles of HSP70 genes, especially of Hsp70-2 A/G or G/G in Kangri tumors with clinico-pathological features of poor prognosis. These results indicate that the relative risk of Kangri cancer associated with Hsp70-2 and Hsp70- hom gene polymorphisms is confined to Hsp70-2 A/G or G/G and Hsp70homC/C haplotype in our population. The study, therefore, suggests Hsp70-2 A/G or G/G and Hsp70homC/C genotypes as potential susceptibility markers and independent prognostic indicators in Kangri carcinoma patients in Kashmiri population.

Recurrence pattern in squamous cell carcinoma of skin of lower extremities and abdominal wall (Kangri cancer) in Kashmir valley of Indian subcontinent: Impact of various treatment modalities

Background:The spectrum of skin cancer in Kashmir valley is drastically different from the rest of the country. Maxwell was the first to report skin cancer of lower extremities in Kashmiri population, developing on/over erythema ab igne, and attributed it to the use/or exposure of Kangri. These tumors have an aggressive biological behavior with a substantial risk of loco-regional metastasis in 30-50% cases. Because of unique geographical distribution of Kangri cancer, there is dearth of literature regarding the natural history, loco-regional and distant metastatic pattern and treatment recommendations in these tumors.Aims:To study the metastatic pattern of these skin tumors and to assess the impact of various treatment modalities and use of prophylactic nodal treatment in this clinical entity.Methods:The retrospective study (study period 1993-2005) included 266 patients of squamous cell carcinoma of skin of lower extremities and abdominal wall. Two hundred and forty-four cases with a follow-up of 2-7 years were included for final analysis with stress on loco-regional relapse pattern and methods of treatment evolved and used at our institute from time to time. Statistical analysis was done using yates corrected Chi-square test and odds ratio analysis.Results:Our results favor the use of post operative radiotherapy to primary and prophylactic treatment of regional nodes on the lines of head and neck tumors in these cases.Conclusion:Post operative radiotherapy significantly decreases the loco-regional recurrences and a trial of prophylactic nodal irradiation is justified in a selected group of such patients.

Recurrent Kangri cancer treated with external beam radiotherapy on a cobalt unit

Recurrent Kangri cancer treated with external beam radiotherapy on a cobalt unit

Clinicopathological behavior of Kangri cancer

Clinicopathological behavior of Kangri cancer