An ecological resilience perspective on cancer: Insights from a toy model

In this paper we propose an ecological resilience point of view on cancer. This view is based on the analysis of a simple ODE model for the interactions between cancer and normal cells. The model presents two regimes for tumor growth. In the first, cancer arises due to three reasons: a partial corruption of the functions that avoid the growth of mutated cells, an aggressive phenotype of tumor cells and exposure to external carcinogenic factors. In this case, treatments may be effective if they drive the system to the basin of attraction of the cancer cure state. In the second regime, cancer arises because the repair system is intrinsically corrupted. In this case, the complete cure is not possible since the cancer cure state is no more stable, but tumor recurrence may be delayed if treatment is prolongued. We review three indicators of the resilience of a stable equilibrium, related with size and shape of its basin of attraction: latitude, precariousness and resistance. A novel method to calculate these indicators is proposed. This method is simpler and more efficient than those currently used, and may be easily applied to other population dynamics models. We apply this method to the model and investigate how these indicators behave with parameters changes. Finally, we present some simulations to illustrate how the resilience analysis can be applied to validated models in order to obtain indicators for personalized cancer treatments.     

Hepatic metastasis of gastroenterological cancer: its tumor biology and oncological surgery.

Tumor angiogenesis and ability of basement membrane invasion for invasion of cancer cells into the tumor vessels and for circulating in the blood stream for hepatic metastasis are required. The molecular detection of cancer cells in the circulatory system strongly indicates the possibility of hepatic metastasis of a gastroenterological cancer. As an effect of the general anesthesia or the surgical procedure, a large amount of cancer cells in the tumor vessels may easily enter into the circulatory system at once from the primary tumor beds. Oncological surgeons should understand that the operation is not only the best treatment for gastroenterological cancer but also the crucial event of hepatic metastasis for cancer cells. Although further investigations are required to determine the relationship between circulating cancer cells and hepatic metastasis, at present, the most important issue to be addressed is the development of new strategies for the prevention of hepatic metastasis following the tumor resection in gastroenterological cancer.     

膀胱副神经节瘤的诊治分析(附1 例病例报告并文献复习)

目的:总结膀胱副神经节瘤的诊治方法及体会,提高膀胱副神经节瘤的诊断和治疗水平。方法:报告1例膀胱嗜铬细胞瘤的临床资料并结合文献复习分析总结膀胱副神经节瘤的诊断治疗方法。结果:患者行腹腔镜下膀胱部分切除术,手术成功,术后顺利出院,随访至今无转移。结论:膀胱副神经节瘤的诊断主要依靠临床表现和实验室检查,血尿、高血压和排尿时典型发作三联征为膀胱副神经节瘤的主要症状,对于瘤体较小的患者要警惕CT检查漏诊的可能性,可行活组织检查进行确诊。腹腔镜下切除是目前治疗膀胱副神经节瘤最有效、创伤最小的方法,但术后要严格随访。     

Tumores hipofisarios no funcionantes: actualización 2012

Non-functioning pituitary adenomas are the most common pituitary macroadenomas in adults, accounting for approximately 14%-28% of all clinically relevant pituitary tumors. They are a heterogeneous group of tumors that cause symptoms by compression and/or hormone deficiencies. The possibility of tumor growth is increased in macroadenomas and solid tumors as compared to microadenomas and cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance imaging), but there are studies reporting promising potential biomarkers. Transsphenoidal surgery remains the first therapeutic option for large tumors with compressive symptoms. There is no evidence that endoscopic procedures improve outcomes, but they decrease morbidity. There is no unanimity in finding prognostic predictors of recurrence. Radiosurgery achieves tumor control and, sometimes, adenoma size reduction. Its adverse effects increase with higher doses and tumor sizes > 4 cm³. Drug treatment is of little value. In aggressive non-functioning tumors, temozolomide (TMZ) may be used with caution because no controlled studies are available. TMZ achieves tumor control in 38%-40% of aggressive non-functioning tumors. The optimal treatment regimen and duration have not been defined yet. Lack of response to TMZ after 3 cycles predicts for treatment resistance, but initial response does not ensure optimal mid or long–term results. O6-methylguanine-DNA methyltransferase expression has a limited predictive value of response to treatment with TMZ in aggressive non-functioning tumors. It should therefore not be a determinant factor in selection of patients to be treated with TMZ.     

Pleomorphic vulvar leiomyoma with local invasive behavior

A case of pleomorphic leiomyoma in Bartholin gland's area in a 26-year-old woman is reported. After diagnostic treatment, primary excision was done. A large, solid tumor 10 x 7.5 cm was extirpated. The tumor showed locally invasive behavior, which suggested a malignant tumor of Bartholin gland, because of it's localization and outlook. Pathohistological examination and immunohistochemical reactions proved that it was a mesenchymal tumor of smooth muscle origin with marked polymorphism, without mitosis, with a myxoid stroma and with biological aggressivity, and the possibility of local recurrence. Thus, a second more radical surgical procedure, was performed. In the excised tissue, no residual tumor was found and all lymph nodes were negative.     

The simultaneous occurrence of chronic lymphatic leukemia with malignant tumors and the lymphatic reaction caused by malignant growths

In 352 patients affected with chronic lymphatic leukemia (CLL) the authors simultaneously detected a solid second tumour 22 times (= 6.22%) (6 cancers of the prostrate, 5 cancers of the skin, 4 cancers of the uterus, 2 cancers of the stomach, 2 cancers of the lung, one case of rectal and mamma cancer each and one case of eye sarcoma). In one third of the cases the two malignomas were simultaneously detected, thus it was excluded that the second tumour was induced by the antimitotic treatment of the primary disease. In seven cases the solid tumour was identified after diagnosing CLL, without any cytostatic therapy having been made here before. In addition, a report is given on a patient showing symptoms of gastric cancer not radically removed and a lymphocytic reaction. Initially, the case was explained as gastric adenocancer with simultaneous CLL because even 5 years after surgical treatment there were 16-20 X 10(6)/l of leukocytes with 64% of lymphocytes in the peripheral blood and 85% of lympho-reticular cells in the bone marrow. Two years later, however, the blood picture was normal and remained to be unchanged further on. Thus, it seems that the healing of the gastric cancer has caused the lymphocytic reaction to have ceased. In addition, it should be noted that in 1974 the patient suffered from an epithelium after a scratch-mark on the nose tip, which was irradiated, however, without eliciting any lymphocytic reaction. The patient is still alive (June 1985).     

On the epistemology of mental illness.

The most important epistemological problem in psychiatry is the detection of malingering. This is a consequence of the fact that there is no objective way to confirm any psychiatric diagnosis. Psychiatric diagnosis is based on subjective complaints. The discovery of objective markers for psychiatric diagnosis is problematic because it presupposes we can tell valid from faked subjective symptoms. But this is the difficulty. If we use pervasive irrationality as a sign of mental illness, we encounter the problem of identifying pervasive irrationality. To understand someone's behaviour, we have to assume it is largely rational. This precludes us from using behaviour to separate genuine from faked mental illness. There are a number of strategies used to solve any epistemological problem, and the most successful is the hypothetico-deductive method. If we use this, we can solve our epistemological problem. Genuine mental illness can be identified when it is the best explanation of the person's overall behaviour. Consilience of inductions is critical in supporting the validity of such explanations. This implies that it is merely a hypothesis that mental illness exists, and that we might discover that many mental illnesses, perhaps all, do not exist. We must embrace this possibility--only if we take a risk will we gain any knowledge.     

Apport du 68Ga-PSMA-TEP dans la prise en charge initiale par radiothérapie des cancers de la prostate

Radiotherapy is one of major modality for prostate cancer treatment. Technical improvements allow to deliver higher doses to the tumor, and improve protection of healthy tissues. Those improvements are enlarging indications and change treatment modalities for prostate cancer patients, on primary staging or at time of relapse (local or metastatic). Accounting to recent publications, 68Ga-PSMA PET should have an impact on radiotherapy treatment planning for those patients, especially in case of intermediate to high risk tumor. In case of metastatic disease, early detection of metastasis allows selection of patients with oligo-metastatic cancer for whom local treatments are in development. For localized prostate cancer, diagnosis of nodal extension permit volumes and doses modifications for radiotherapy. An accurate detection of the dominant intra-prostatic lesion gives the possibility of a focalized dose escalation to this significant cancer (“index lesions”). This new treatment strategies coming from technical progress are currently evaluated to assess their clinical benefit.     

Gamma probes and their use in tumor detection in colorectal cancer

The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful.     

Menopausal symptoms emerging during hormonal therapy of breast cancer, and their treatment

Hormonal compounds play an important role in the treatment of breast cancer. Their side effects may lead to suspension of therapy and consequently to the failure of the expected effect. Common and the same way most prevalent side effects of hormonal compounds are the menopausal complaints which can alter quality of life significantly. The early recognition and treatment of menopausal complaints and symptoms help to reach therapeutic success. In general, of menopausal related complaints the role of hot flash, atrophic vaginitis and sexual dysfunction is emphasized. Within the topic, it is possible to mention some musculo-skeletal complaints according to their similar etiology, the failure of estrogen effect. In the treatment of hot flash non-pharmacologic and pharmacologic methods can be distinguished. Based on meta-analyses anti-depressants, some anti-convulsants and clonidine proved to be effective. Musculo-skeletal complaints explained by the lack of estrogen effect do not cause permanent impairment but may indicate greater efficacy of endocrine treatment. In the context of osteoporosis it is important to emphasize prevention. The main goal of endocrine therapies is to ameliorate remission rate or survival, but we should not forget to treat side effects which can influence quality of life.     

Corticosteroids and liver amoebiasis.

Patients with amoebiasis who receive steroid treatment may suffer adverse affects including acute amoebic dysentery and exacerbation of the amoebiasis. In some cases the presenting symptoms are initially misdiagnosed and steroids prescribed, which provokes fulminating progression of hepatic amoebiasis. Repeated stool examinations often yield negative results. Any patient being considered for treatment with corticosteroids who has lived in the tropics should be investigated for amoebiasis serologically and by repeated stool examination. Even after negative results the possibility of amoebiasis should be reconsidered if diarrhoea or fever develops during or after steroid treatment.     

Breast cancer local recurrence under the form of inflammatory carcinoma,treated with concurrent radiation and chemotherapy,a case report

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor.There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.     

Multiphoton tomography in differentiation of morphological and molecular subtypes of breast cancer: A quantitative analysis

In this study multiphoton tomography, based on second harmonic generation (SHG), and two-photon-excited fluorescence (TPEF) was used to visualize both the extracellular matrix and tumor cells in different morphological and molecular subtypes of human breast cancer. It was shown, that quantified assessment of the SHG based imaging data has great potential to reveal differences of collagen quantity, organization and uniformity in both low- and highly- aggressive invasive breast cancers. The values of quantity and uniformity of the collagen fibers distribution were significantly higher in low-aggressive breast cancer compared to the highly-aggressive subtypes, while the value representing collagen organization was lower in the former type. Additionally, it was shown, that TPEF detection of elastin fibers and amyloid protein may be used as a biomarker of detection the low-aggressive breast cancer subtype. Thus, TPEF/SHG imaging offers the possibility of becoming a useful tool for the rapid diagnosis of various subtypes of breast cancer during biopsy as well as for the intraoperative determinination of tumor-positive resection margins.     

Systemic dissemination of chronic necrotizing pulmonary aspergillosis in an elderly woman without comorbidity: a case report

ABSTRACT: INTRODUCTION: Chronic necrotizing pulmonary aspergillosis usually occurs in mildly immune-compromised hosts or those with underlying pulmonary disease. The radiographic pattern of chronic necrotizing pulmonary aspergillosis is typically a progressive upper lobe cavitary infiltrate with pleural thickening. We report here an atypical case of chronic necrotizing pulmonary aspergillosis mimicking lung cancer, which developed into a disseminated fatal disease in an older woman with no comorbidity. CASE PRESENTATION: An 80-year-old Japanese woman was referred to our hospital for a chest roentgenogram abnormality. Repeated fiber-optic bronchoscopy could not confirm any definite diagnosis, and she refused further examinations. Considering the roentgenogram findings and her age, she was followed-up as a suspected case of lung cancer without any treatment. Then, 10 months later, she complained of visual disturbance and was admitted to our department of ophthalmology. She was diagnosed as having endophthalmitis. After treatment with corticosteroids for 20 days, she developed acute encephalitis and died four weeks later. Autopsy revealed dissemination of Aspergillus hyphae throughout her body, including her brain. CONCLUSIONS: In older patients, even if they do not have any comorbidity, chronic necrotizing pulmonary aspergillosis should be added to the differential diagnosis of solitary pulmonary lesions in a chest roentgenogram.     

Hormone therapy after endometrial cancer

Endometrial carcinoma is listed among the absolute contra-indications to hormone therapy. After all the existing opinions so far, hormone therapy after FIGO stage I or II endometrial cancer is still thought of as a possibility, and up to now the continuous combined oestrogen/progestogen replacement therapy would be recommended. However, until today, only observational studies have been put forward. Although no study has established an increased rate of recurrences or mortality, alternatives such as phytopreparations, tibolone, or, in, particular, psychotherapeutic drugs such as venlafaxine should be considered for the relief of climacteric complaints. Progestogen-only therapy also comes particularly into question. Indeed, the wider discussion about the gestagen effects regarding the risks of breast cancer is to be considered. Generally, after hysterectomy, at least for patients with cardiovascular risk factors, the preference today is to use low-dose oestrogen therapy (patches, gels) instead of continuous combined oestrogen/progestogen replacement therapy, and this also is now recommended for patients after endometrial cancer. This is to be noted because of the risk factors for endometrial carcinomas, such as hypertension, obesity, polycystic ovary syndrome, diabetes mellitus, etc. However, each form of hormone therapy should only be exceptionally recommended, and the patients must be informed about the risks that exist and the use of alternatives.     

Intracranial tumors simulating vascular lesions of the brain; a preliminary report

Occasionally in the presence of atypical symptoms it is difficult to distinguish between cerebrovascular disorders and intracranial tumors. Intracranial tumor should be suspected in cases of atypical symptoms of vascular lesion or even in typical cases in which the patient does not show expected improvement. In a group of eight cases the problem of differential diagnosis was not confined to those in which the patients were elderly. Furthermore, papilledema and elevated spinal fluid pressure were absent in all these cases. The absence of these signs, therefore, does not eliminate the possibility of an intracranial tumor.The electroencephalogram is an important adjunct in differential diagnosis. In this series, electroencephalograms lateralized the lesion correctly in every case and localized it in one. The importance of repeated electroencephalographic examination if wave patterns are normal in the first tracing was clearly illustrated in three instances.Ventriculography, which in six cases finally established the diagnosis, and the site of the lesion, should not be postponed unnecessarily.     

可脱球囊栓塞治疗创伤性颈内动脉海绵窦瘘的研究

目的：研究微导管可脱球囊技术治疗创伤性颈内动脉-海绵窦痿（TCCF）的临床意义。方法：4例TCCF患者采用微导管可脱球囊技术进行栓塞治疗,所有患者均随访6月以上。结果：3例TCCF患者一次性成功栓塞瘘口井保持颈内动脉通畅,1例瘘口复杂患者因球囊过早泄漏复发而行2次栓塞治疗闭塞颈内动脉。本组病例来发生严重并发症。结论：微导管可脱球囊技术对TCCF是一种微创、安全、有效的治疗方法。     

Anti-Ri-associated paraneoplastic cerebellar degeneration. Report of a case and revision of the literature

Paraneoplastic cerebellar degeneration associated with anti-Ri antibodies mainly presents with opsoclonus-myoclonus-ataxia. We report here the case of a patient with anti-Ri-antibody paraneoplastic syndrome, who presented four years after treatment for small-cell lung cancer (SCLC) with oscillopsia and gait disorder. On neurological examination vertical nystagmus, ataxic gait and postural tremor of all four limbs was detected. He died one year after the onset of the symptoms because of a acute exacerbation of his severe chronic obstructive pulmonary disease. No SCLC relapse or new cancer has been detected during the one-year follow-up period.To our knowledge, our patient is the first case of anti-Ri associated disorder with oscillopsia and vertical nystagmus as the initially prominent clinical features. The findings of this case study support the variability of anti-Ri-antibody-associated paraneoplastic syndrome. Further studies must be directed to better characterize the mechanisms underlying this syndrome. Finally, paraneoplastic neurological syndromes should be kept in mind also when a neoplastic disease is not demonstrated.     

Relationships between stem cells and cancer stem cells

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.