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There's almost an equal split between the sexes on Tumblr - 51% male, 49% female.

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Editorial

Cancer is a group of disease characterized by the uncontrolled growth and spread of abnormal cells which may lead to death. According to a report by GLOBOCAN the number of new cancer cases would increase to 19.3 million by 2025 worldwide. Thus globally cancer has become a big threat to human beings, among various diseases. Carcinogen induced deregulation in cellular signaling pathway, may leads to the cancer development. Chemotherapy is an important mode of cancer treatment that used to cure and improve the patient’s quality of life [1]. At the same time chemotherapy is known to induce drug resistance and toxicity that hurdles the improvement of overall response and survival of cancer patients. Many cancers contain a sub-population of self-renewing and expanding stem cells known as cancer stem cells (CSCs). These are associated with chemotherapeutic resistant leading to tumor recurrence and poor patient prognosis. Acquired drug resistance renders subsequent anticancer therapy effectiveness leading to tumor recurrence and progression. Hence it is urgency of time to identify effective and safer anticancer agents, which can be found in natural agents. The use of natural products is promising because they target multiple signaling pathways and have minimal toxicity compared to conventional chemotherapeutics. Malignancy transformation and progression are multistage progress involved gene alterations and multi signaling pathways. In this regard herbal products may do a lot. Several natural compounds viz., vinblastine, etoposide, paclitaxel, camptothecin, bleomycin, and doxorubicin are known to prevent the occurrence and/or spread of various cancers by targeting numerous key elements in intracellular signaling network involved in carcinogenesis and is being investigated in clinical trials.

Abbreviations: CSCs: Cancer Stem Cells; NICD: Notch Intracellular Domain; TACE: Tumor Necrosis Factor-α-Converting Enzyme; CADD: Computer Aided Drug Designing; ADME\T: Absorption, Distribution, Metabolism, Excretion and Toxicity

Introduction

Different signaling pathways play critical role in maintaining the homeostasis of cell proliferation, differentiation and apoptosis. Wnt and Notch signaling pathways have been reported to play role in various kind of cancer. Wnt signaling is involved in cell proliferation, cell migration and developmental processes. On the other hand Notch pathway beside developmental process has been well documented for its role in cancer stem cells survival (self renewal ability) and drug resistance. The binding of the Wnt proteins to the Frizzled receptor allows β-catenin, the key mediator of Wnt signaling, to accumulate in the cytoplasm and then translocate into the nucleus. In the nucleus, it regulates target gene expressions which are involved in homeostasis of cell growth and other cellular functions as well. Notch signaling has been reported to maintain the cancer stem-cell (CSCs) pool by the process of self-renewal, epithelial-mesenchymal transition (metastasis) induction and chemo-resistance [2]. CSCs are associated with chemotherapeutic resistant and tumor recurrence leading to poor prognosis. Binding of Notch ligand and its receptor, between two neighboring cells activates Notch signaling. Upon activation the cleaved Notch releases Notch intracellular domain (NICD) through a cascade of metalloprotease mediated proteolytic cleavage, tumor necrosis factor-α-converting enzyme (TACE) and γ-secretase. NICD translocate to nucleus and transcriptionally activates Notch target genes. Inhibition of γ-secretase function may prevent the cleavage of the Notch receptor and blocks Notch signal transduction. Currently, several classes of Notch inhibitors have been developed but γ-secretase inhibitors are the most common studied tool for Notch signaling inhibition. Several tumor types often contain over activated Wnt/β-catenin and/or Notch signaling cascade. Some proteins of this pathway that are tumor suppressors can mutate and act as oncogenes. Therefore, inhibition of these signaling pathways by natural agents may be a strategy to target cancer cell progression inhibition, chemotherapeutic resistance to cancer cells as well as inhibition of self renewal property of cancer stem cells. While there are some reported inhibitors of Wnt and Notch pathways, there exists a significant unmet medical need to identify new, more efficient inhibitors.

The majorities of cancer drugs are small molecules designed to bind, interact and modulate the biological activity of the receptors. Computer aided drug designing (CADD) is being exploited to identify hits, pick leads and optimize drug leads by studying their physicochemical, pharmaceutical and ADME\T (absorption, distribution, metabolism, excretion and toxicity) properties. The objective of CADD is to augment the set of molecules with prudent active, drug-like properties and abolish compounds with undesirable properties such as inactive, reactive, toxic, poor ADME/T. The ADEM/T property of compound gives some important in silico prediction of the lead compound that includes bio availability, blood brain barrier crossing and inhibition of K ion channels etc. It is broadly accepted that drug discovery and development are risky, costly,time and resource-consuming processes [3]. In silico screening approach is the leading technique for preliminary identification of natural products as inhibitors of targets protein and predicting their biological binding mode. In other words in silico modeling is used considerably to minimize time and resource requirements of chemical synthesis and biological in vitro and in vivo testing. While there are some reported inhibitors of Wnt and Notch pathways, there exists a significant unmet medical need to identify new, more efficient inhibitors of natural origin. These novel inhibitors may inhibit the cancer cell growth as well as drug resistance and self renewal ability of cancer stem-like cells. Furthermore, the Identified novel inhibitors may use as further anticancer leads for in vivo and clinical trial studies.

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Abstract

This article aims to standardize terms used in Surgical Oncology that are the basis for the treatment of cancer patients. Terms like: Patient out of cancer treatment, Patient in stage IV, In block tumor resection, Ganglionic relay, Local and regional control, Systemic Control, Unknown Primary Origin, Unresectability, Inoperability, Multiple Organ Resection, Preoperative Nutritional Status, Minimum Oncologic Procedure, Resection margins, Prognostic Factors, Peritoneal Washing Cytology, Adjuvant, Neoadjuvant and Peri-adjuvant Therapy.

Keywords: Basic terms in Surgical Oncology; Cancer Surgery

Abbreviations: OCT: Patient Out of Cancer Treatment; UPO: Unknown Primary Origin; BMI: Body Mass Index.

Introduction

There are basic oncological principles universally accepted and those principles were born from the experience accumulated in Cancer Treatment Centers after years of observing the results obtained in large series of patients undergoing various treatment protocols both medical and surgical. We will define these concepts or basic criteria that should be on the minds of all physicians who manage patients with cancer. To address the issue we will split the patients into two groups: OCT patients and patients admitted for treatment.

Patient out of cancer treatment (OCT)

A patient is OCT when IS NOT A CANDIDATE for treatment except palliation. This is accomplished with the following criteria:Patient in stage IV not requiring palliative surgery:Patients that should be excluded from this category are:Unknown Primary Origin:Since in this case the patient may have a neoplasm that may be treatable (such as lymphoma).Lymphoma, myeloma or leukemia:These patients can be offered node biopsy or bone marrow studies and treatment with chemotherapy or radiotherapy.Choriocarcinoma and Gestational Trophoblastic Disease:These tumors are very sensitive to Methotrexate.Ovarian Cancers:These patients are candidates to Cytoreductive Surgery and Chemotherapy.Seminoma and testicular tumors:Patients that are also candidates to cytoreductive surgery and radiotherapy.Breast cancer:Advanced stage may be treated with chemotherapy and radiotherapy.Prostate cancer:These are radiosensitive tumors.Palliation should only be done when the patient himself requests it.

Gallbladder and bile duct Cancers CAN NOT BE TREATED WITH SURGERY. Those are best palliated with computerized brachytherapy.

Multiple studies have shown that a temporary palliation can be achieved with ultrasound-guided percutaneous drainage. But currently the best palliative treatment for these cancers is computerized brachytherapy. Gallbladder cancer in an early stage is curable with cholecystectomy alone. Advanced stages do not improve their prognosis with surgical resection (segmentectomy of IV segment, lobectomy). Surgery has proven to be counterproductive (it shortens survival and impairs the patient’s quality of life). Patients with gallbladder and bile duct cancer (intra or extrahepatic) are not admitted for surgical treatment as they are inoperable, they cannot receive Chemotherapy (tumor is not chemosensitive), neither radiotherapy (liver tissue is too sensitive to radiation and it will damage the liver before it hits the tumor). The only suitable treatment is computerized brachytherapy.

A Patient is in Stage IV When

  1. There is ganglionic invasion beyond a certain node relay.
  2. There are lung metastases (circular images in X-rays).
  3. There are liver metastases (demonstrated by ultrasonography or elevated transaminases).
  4. There are bone metastases (in X-ray series and bone alkaline phosphatase elevation).
  5. There are brain metastases (CT Scan).

It is important to first do all these determinations to decide whether or not a patient is in stage IV.

Patient Admitted for Cancer Treatment

Before deciding on the type of surgery and the purpose of it (palliative, diagnostic or curative) is necessary to consider each of the following concepts.

In Block Tumor Resection

It is when a tumor is removed in continuity with its ganglionar nodes in a single block. This is the ideal in Oncology because if the tumor is removed and the ganglionar tissue is removed apart, the lymph paths between the nodes and the tumor will be open and we will be spreading the tumor. It may not always be possible to do so, but if the tumor is in continuity with the corresponding relay node, an In block resection must be planned.

First Lymph Node Relay

In cancers with lymphatic spread a group of nodes is established for each tumor that are the gateway for producing metastasis. A better local and regional control of the disease is achieved if this group of nodes is removed. Ganglionic relays for some tumors are (Table 1):

Local and regional control.

No radical surgery can achieve a Cancer Systemic Control. It has been established that there is no surgical procedure in any type of tumor (except carcinoma in situ in some cases) which can guarantee that no tumor cells have been left in the patient. The surgeon can only remove the tumor and the first lymph node levels. In gastric cancer Japanese have proposed extensive resections but no significant advantages have been found. In breast cancer the three nodal levels can be removed and in neck cancers a radical dissection can be performed but even in these cases the surgeon is only cleaning the first node levels. The only way to achieve a Cancer Systemic Control is with chemotherapy, radiation and/or hormone therapy. So in general a patient should be referred to the Medical Oncologist.In some cancers, radiation therapy has replaced surgery as it has been shown to achieve the local and regional control equally or even better than surgery, because surgery sometimes is mutilating. In Oral Cavity and Pharynx Cancers Radiotherapy is better than surgery for stages I-II. Also Radiotherapy is better than Surgery for Cervical Uterine Cancer stage IIB. When operating a patient with Uterine Cervical Cancer one should keep in mind that if we find parametrial induration the Surgery should be suspended, and the patient should be referred for Radiation Therapy. We would only increase the morbidity of these patients if we perform a hysterectomy.

Unknown primary origin (UPO)

In this term there is a discrepancy in the literature but I consider it is more practical to define it as a stage IV cancer in which it was not possible to identify the primary origin. These patients are examined because a treatable tumor can be found, especially when the biopsy reports an undifferentiated tumor (that usually is really a lymphoma). In these patients a laparoscopic retroperitoneal lymph node biopsy is performed if needed for diagnosis. In such cases the purpose of surgery is to make diagnosis or palliation, not a curative surgery.

Unresectability

It is considered that a tumor is unresectable if it is in an advanced stage and the tumor cannot be removed, even if a radical surgery is performed. This occurs in stage IV tumors or in cases of Carcinomatosis. Unresectability does not contraindicate surgery and can be done with palliative or diagnostic purposes.

Inoperability

It is when the patient’s physical condition has a prohibitive surgical risk, such as in elderly patients with heart, renal, respiratory or liver failure, etc. Inoperability in some patients can be treated and the patient becomes suitable for surgery.

Multiorgan resection

It is defined when a radical resection may affect three or more organs. This is an Inoperability criterion. This is a treatable condition because in some tumors preoperative chemotherapy or radiotherapy can reduce tumor volume and thus make it operable.

Nutritional status

Allows evaluating the patient’s condition to tolerate the post-surgical metabolism. It is very important to determine the nutritional status in every patient that will be subjected to any type of surgery, especially in cancer patients because tumors producing catabolism is something very common. This ideally should be determined by the nutritionist. But when you do not have an expert in this field the surgeon can make a fairly accurate estimate with the following parameters:BMI or Body Mass Index:It is determined by dividing weight in kilograms by the square of height in meters. An index that is less than 20 is an inoperability criteria.Serum Albumin:A serum albumin value lower than 2 g/dl is an inoperability criteria.Total lymphocyte count:This value is obtained by multiplying the percentage of lymphocytes by the total leukocytes (white blood cell count). A value less than 1000 total lymphocytes is an inoperability criteria.

There are more parameters to determine the nutritional status but with only these three that are accessible in almost all hospitals the surgeon can justify the patient’s condition for surgery. When the nutritional status of a patient indicates inoperability criteria, the patient must be submitted to a supplementary diet until the total number of lymphocytes and serum albumin levels are correct, which usually requires a dietary supplement (like Ensure 1 can 3 times a day) and a high calorie and a high protein diet for a period of at least 15 days.

Minimum Oncological procedure

The minimum surgical procedures are already defined in the literature. These are to be performed for certain types of tumors and are the minimal tumor resection for an oncologically valid surgery (Table 2).

Resection margins

Is the distance in centimeters left between the edge of the tumor and the cut made to remove it. To avoid the risk of leaving tumor cells the surgeon should always remove a certain amount of healthy tissue around the tumor. This amount of healthy tissue is measured in centimeters and in the literature is already determined how many centimeters away from the edge of the tumor are necessary. This should be measured in the surgical specimen during the operation by the pathologist to see if it is necessary to expand the resection. In general most tumors need a resection margin of at least 2 cm for a proper oncological resection but some tumors need a wider resection margin.

Adverse prognostic factors.

These serve to establish the prognosis of a cancer patient and therefore the need for surgery. These are not the “Risk factors”. A Risk factor is a history of factors that increases the chances of having a cancer, such as: smoking for lung cancer, contraceptives for breast cancer, etc. Adverse prognostic factors are those that determine the probability of death at 1 and 5 years in a patient who has been diagnosed with cancer. These vary according to the type of tumor and usually these are determined by the pathological study of a biopsy or a surgical specimen.

The stage of the tumor.The TNM classification is universal. As a rule all tumors having ganglionic invasion beyond the first relay node or tumors that invade the muscle layer or the serous membrane have a poor prognosis. There is data available to determine the probability of death at 1 and 5 years for each tumor. It has been established that a surgical procedure is justified when the probability of survival at 1 year is greater or equal to 15% (or mortality at one year is less than 85%).The degree of differentiation.Grade II or III (moderately differentiated and poorly differentiated tumors) is a factor of poor prognosis.The pattern of spread.Well defined tumor edges have a better prognosis than infiltrating edges. “Fingerlike” or “raindrops” pattern of spread have a poor prognosis.Tumor volume.This can be measured in the CT Scan (ask the radiologist). Except in epithelial ovarian cancer and choriocarcinoma it has been observed that a tumor volume close to 1 kg is incompatible with life.

Peritoneal Lavage Cytology

This is a mandatory procedure in surgery of any tumor that is within the abdominal cavity. It consists of instilling 100 cc of Sterile Saline Solution in the abdominal cavity and then 50 cc should be recovered. During the operation this sample is sent to be studied by the pathologist. If the pathologist reports neoplastic cells in the peritoneal lavage this is a criterion of unresectability and the surgical procedure should be interrupted if it is not for palliation purposes. In this case it is not convenient to realize an extensive surgery because all tissue cleavage sites release growth factors and trophic factors that accelerate the implantation of tumor cells and thus the spread of the tumor, and the patient survival will be shortened. Other protocols use in addition multiple biopsies including: biopsy of para-aortic nodes, biopsy of parietal peritoneum, spleen and liver biopsy to determine if there is tumor spread before performing the surgical procedure.

Adjuvant, neoadjuvant and peri-adjuvant

In several types of cancers is necessary to apply Chemoradiotherapy before surgery or after. Before surgery (neoadjuvant therapy) reduces the tumor stage and increases the likelihood that the resection margins will be negative to tumor cells. Also we must remember that no radical surgery can achieve Systemic cancer control. For example, in rectal cancer it is already accepted worldwide that preoperative Chemoradiotherapy increases the likelihood of a curative resective surgery. In some tumors where the neoadjuvant Chemoradiotherapy is not used a subsequent systemic treatment (adjuvant therapy) within 6 to 8 weeks after the surgery it is recommended. Peri-adjuvant is when you apply Chemoradiotherapy before and after surgery [1-5].

Conclusion

It is important to standardize the basics of Surgical Oncology.

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For more articles in Open Access Journal of Cancer Therapy & Oncology please click on: https://juniperpublishers.com/ctoij/index.php

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Cancer Therapy and Oncology — Juniper Publishers

Abstract

Poorly differentiated neuroendocrine tumors are uncommon neoplasms of the lung and the gastrointestinal tract. However, 3–5% of these tumors are diagnosed as metastatic disease with unknown primary. Here, we describe a case of neuroendocrine small cell carcinoma of unknown primary diagnosed by inguinal node biopsy. A 53-year-old male patient with a history of heavy smoking presented with cough, back pain and altered mental status. Whole body imaging studies (CT — MRI — FDG PET) favored a diagnosis of hematological disease (lymphoma) or diffuse metastatic melanoma. However, inguinal node biopsy revealed morphological and immunohistochemical features of a neuroendocrine carcinoma, probably originating from the lung. The patient received palliative whole brain irradiation and etoposide/platinum-based chemotherapy.

Abbreviations: CUP: Cancer of Unknown Primary; IHC: Immunohistochemistry; CT: Computed Tomography; MRI: Magnetic Resonance Imaging; PET: Positron Emission Tomography

Introduction

Metastatic cancer of unknown primary (CUP) accounts for 3–5% of all malignant neoplasms. International registries from seven countries have reported incidences ranging from 2.3% to 7.8% [1]. More than 50% of CUP patients present with multiple sites of involvement, while the rest have a single site. The progression of such cancer with unknown origin is rapid in most cases and shows atypical metastatic patterns. Most frequent locations of dominant metastatic sites are mediastinum, retroperitoneum and peripheral lymph nodes [2]. CUP is also more common in lymph nodes of the neck and axillary regions, while inguinal involvement accounts for <5% of cases [3]. Since CUP in the inguinal region is rare, there is a paucity of literature on the management of such patients.

Neuroendocrine carcinomas with widely varying clinical and histologic features account for approximately 3% of all CUP [4]. Neuroendocrine cells are distributed widely throughout the body and neoplasms of these dispersed cells can occur at many sites. Of major importance is the classification of this group into tumors with low-grade histology (classic carcinoid) and indolent clinical course vs those with high-grade histology (small or large cell with neuroendocrine features) and an aggressive clinical course [5]. The origin of these high-grade neuroendocrine carcinomas remains unclear. Panels of immunohistochemical (IHC) stains or molecular gene expression tumor profiling are used for the determination of the tissue of origin in CUP patients [6]. CUP of the neuroendocrine type may have arisen from an occult extra-pulmonary site, but are correctly described as neuroendocrine car¬cinoma of an unknown primary site. Patients with small cell carcinoma at a metastatic site are considered for systemic therapy at the time of diagnosis. Although the optimum regimen is undefined, a platinum/etoposide-based regimen is currently used [7]. In this case report, we describe an uncommon case of inguinal lymph node small cell metastasis of unknown origin, accompanied by multiple sites of involvement.

Case Presentation

A 53-year-old male, with a history of heavy smoking, presented with polyuria, polydipsia and episodes of transient memory loss. He suffered from back pain, night cough, cyanosis and an altered mental status. There was no history of fever or night sweats. On clinical examination, there were multiple palpable subcutaneous nodules on the trunk and tenderly swollen inguinal lymph nodes. The remainder of clinical examination and initial laboratory investigations had normal findings. The results of laboratory examinations, including urinalysis, liver and renal function tests, revealed no abnormalities. Upper and lower gastrointestinal endoscopy was normal. Serum carcinoembryonic antigen, carbohydrate antigen 19–9 and prostate specific antigen were within normal range. Cytology examination of the sputum was negative. The contrast-enhanced computed tomography (CT) scan of the chest revealed emphysematous blebs/bullae, enlarged mediastinal lymph nodes and a suspicious (6mm) nodule in the upper lobe of the right lung. The CT scan of the upper and lower abdomen revealed adrenal glands swelling, nodules near the left kidney, multiple subcutaneous nodules anteriorly and posteriorly around the thorax and the abdomen as well as enlarged inguinal lymph nodes (Figure 1).

Magnetic resonance imaging (MRI) of the brain revealed multiple and diffuse pathological supra- and infratentorial lesions (1.5cm max. diameter) of the brain parenchyma (Figure 2). With no primary site of cancer identified, the patient underwent an excisional biopsy of a left inguinal lymph node. Histopathology was suggestive of small cell carcinoma probably originating from the lung. The IHC stains for TTF1, CK7 and synaptophysin were positive and also revealed high expression of Ki-67 (>80%). In order to find the primary lesion diagnosed by biopsy of the inguinal lymph node, a positron emission tomography (PET) scan was performed. This showed increased tracer uptake in multiple node groups over and under the diaphragm (SUVmax 10 in mediastinum), in bones, bone marrow, pleura, mesentery, adrenal glands (SUV max 13) as well as the subcutaneous tissue of the whole body (Figure 3).

Lungs, liver, spleen and pancreas revealed no tracer uptake. The primary site could not be visualized generating a differential diagnosis between hematological disease (lymphoma) and diffuse metastatic melanoma. Finally, the histopathological diagnosis was reviewed and confirmed by the pathologists of our Hospital. An appropriate battery of immunostains revealed the following immunophenotype: AE1/AE3+, CK8/18+, TTF1+, CD56+, NSE+, synaptophysin++/-, chromogranin — /+, CK7 — /+, CK20-, CD45-, S100-, NF-. Cell proliferation index Ki67/MIB1 was high (>80%). The lymph node metastasis showed morphological and immunohistochemical features of neuroendocrine small cell carcinoma (Figure 4) indicating a possible primary site in the lung. Palliative whole brain radiotherapy was performed in our department delivering 30 Gy in 10 fractions. Significant clinical improvement in terms of memory loss was immediately observed. Chemotherapy was administered as a platinum/ etoposide-based combination schedule with remarkable clinical response immediately. After chemotherapy, the CT imaging study confirmed substantial regression of all metastatic lesions (Figure 5).

Discussion

Our patient suffered from cough, worsening back pain and altered mental status. He clinically presented multiple palpable subcutaneous nodules on the trunk and swelling of the groin lymph nodes. At FDG PET, the lungs, the liver, the spleen and the pancreas revealed no tracer uptake raising the suspicion of hematological disease (lymphoma) or diffuse metastatic melanoma. However, the diagnosis of neuroendocrine small cell carcinoma was established by the characteristic morphology on histology and an IHC neuroendocrine marker pattern (CD56, chromogranin, synaptophysin, TTF1). Patients with small or large cell histology and a history of cigarette smoking should be suspected of having an occult lung primary. Our patient presented widespread metastatic disease, for which no primary site could be detected after clinical examination and extensive investigations.

CT scan revealed no mass lesions, except a small indeterminate nodule in the lung. It is rather unlikely for this to have been the primary site as the nodule was very small and negative on PET-CT. CUP is a diagnosis of exclusion, since many studies did not include other types of tumors such as lymphoma, melanoma and sarcoma, as well as tumors of unusual primary sites. However, since those types of carcinomas often enter the clinical and pathological differential diagnosis, they should be considered [5,8]. The diagnostic procedure begins, if necessary, by determining the cell lineage (epithelial, melanocytic, lymphoid, mesenchymal or germinal) with the aid of appropriate IHC markers. The choice of the IHC panel deeply influences subsequent diagnosis. In some cases IHC algorithms can allow the identification of a primary site with adequate accuracy [9].

Metastases of unknown primary origin are divided in two groups: 1) those in which the primary site might be defined at least by their IHC profile; 2) those which really remain ‘orphan’ even after an appropriate IHC screening [10]. The primary site may either have a slow growth or may possibly become involute and therefore unlikely to manifest itself. In some instances, although the metastatic pattern is often unpredictable, the site of primary origin can be found during lifetime or autopsy. Generally it is a small nodule often localized in the lungs or in the bilio-pancreatic tract [11]. Since the unknown primary mass can be located anywhere in the body, a cross-sectional whole-body imaging modality is the proper method to search for it. Small lesions or pathological changes in normal-sized tissues can be missed by CT and MRI [12]. From this perspective, PET using the radiotracer 18 F-fluoro-2-deoxyglucose is the leading approach, since it provides functional and metabolic information.

Notably, PET/CT imaging is known to have good sensitivity and specificity, mainly in head/neck and lung cancers [13]. Patients with high-grade neuroendocrine tumors are initially responsive to combination chemotherapy and should be considered for a trial of treatment. However, the treatment is approached similarly to extensive stage small cell lung cancer, as these cancers have similar histology. Treatment includes standard chemotherapy used to treat lung cancers, including platinum-based or platinum-taxane combination chemotherapy. This group of patients presented response rates up to 55% with 20% complete responders and overall survival of 15 months as well as almost 10–15% long-term survivors [14].

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Authored by  Vishal Rao

In Indian early one in two men and one in five women use tobacco causing eight to nine lakh adult deaths a year [1,2]. Government of India enacted the ‘Cigarettes and Other Tobacco Products (Prohibition of Advertisement and Regulation of Trade and Commerce, Production, Supply and Distribution) Act, in 2003 (hereafter referred to as COTPA). The major provisions of COTPA include;   

  1. Prohibition of smoking in public places;
  2.        
  3. Prohibition of direct and indirect advertisement of tobacco products;
  4.        
  5. Prohibition on sale of tobacco products to and by minors, and within 100 yards of educational institutions; and
  6.        
  7. Display of pictorial health warnings on tobacco products [3].
  8.        

However, after a decade of enactment the compliance remains sub-optimal [4]. There is dearth of literature on how COTPA is being implemented and how it could be improved [5]. This paper analyzes COTPA implementation in Karnataka, India and hypothesizes it’s effectiveness as a Nicotine displacement therapy an effective alternative or supplement to nicotine replacement therapy (NRT).

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Authored by  H Kennecke MD

Carcinoma of the anal canal is relatively uncommon, yet incidence is on the rise. The accepted current standard regimen for patients with stage I-III squamous cell carcinoma (SCC) of the anal canal is radiotherapy (50.4 Gy) with concurrent infusional 5-fluorouracil (5-FU) (825 mg/m2 per oral bi-daily) administered on radiation days during weeks one and five and mytomycin C (MMC) (12 mg/m2) administered on week one. This study describes the efficacy and safety of substituting oral capecitabine (Cap) for the infusional 5-FU and compares the planned versus delivered therapy, and describes treatment-related patient toxicities and early outcomes in a population-based setting. A retrospective chart review was conducted on a sequential cohort of SCC patients treated at one of the five BC Cancer Agency treatment centers since February 2010. Of 66 patients were treated, 99% of patients received the planned radiation dose, 13 patients (20%) required Cap dose reductions and three patients (5%) required MMC dose reductions. Most patients experienced minor treatment-related toxicities.

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Historically locally advanced cancer of the cervix has been treated with radiotherapy and brachytherapy and it was not until 1999 that the use of concurrent chemotherapy was formalized due to excellent results in terms of rate of overall and disease-free survival. Box technique in radiotherapy is the most widely known providing excellent results, with some variations as oblique fields, but greatly increasing irradiation potentially healthy tissue, leading to the higher proportion of own side effects of each treatment. Therefore present a radiant treatment planning mode Dynamic Conformal Arc for cervical carcinoma.

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Malignant neoplasms are the second cause of death in Argentina, according to official data from the Argentine Ministry of Health, 25% of annual deaths are due to cancer, although it has detected a reduction of approximately 10% mortality rate cancer over the last 15 years. This condition causes between 55 and 60,000 deaths annually in Argentina. Values between 1% and 2.5% of the adult population, with a strong increase as the population ages. The new systemic cancer therapies are the result of decades of investment in research and clinical.

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Authored by  Awatef Msolly

Mutations in the BRCA1/BRCA2 genes account for varying proportions of breast cancer families studied, and demonstrate considerable variation in mutational spectra coincident with ethnic and geographical diversity. This work aimed to identify mutations in BRCA1 and BRCA2 genes to explore the existence of population-specific recurrent or founder mutations, in Tunisian breast cancer families. We have screened for germline mutations in seventeen Tunisian high-risk breast cancer patients using direct sequencing. Index patients, diagnosed before age 45, possessing a positive family history or bilateral breast cancer were asked for detailed information on family history of breast or any other cancer type in their families. One family out of 17 (6%) carried BRCA 1 mutations and no BRCA2 mutations was found. One recurrent mutation in BRCA 1 was identified, c.798-799delTT, which appear to represent founder mutation in this population. Thirty-one variants were considered of unknown clinical significance according to BIC and UMD-BRCA1/BRCA2 databases.

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