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Malignant tumors in an advanced phase of diffusion have a very poor prognosis. However, there are conditions in the body which may impede, even if only partially, further spread of the disease. In addition to currently available treatments, other favorable conditions can help to improve the prognosis, even if only relatively, such as the presence of inhibitors of metalloproteinases, antiangiogenic factors, the absence of particular proteins that favor tumor development, and the possibility of positively activating the immune system. The authors believe that in cases where such conditions are concurrent, the addition of a new favorable condition could be very useful. On the other hand, cases of total spontaneous regression of malignancies, even if in metastatic diffusion, are well known. It was recently emphasized that the spread of metastasis of renal cell carcinoma, arising in patients on hemodialysis for a long time, is considerably reduced at the post-mortem examination compared to patients with renal cell carcinoma and not on hemodialysis. This may suggest a positive effect exerted by the dialytic membrane on metastatic spread. The authors hypothesize that extracorporeal circulation of the blood, used mainly for cardiovascular interventions and hemodialysis, could be used by applying filters suitable for cancer treatments, similar to those used in hemodialysis, even if without accomplishing the hemodialytic function, provided there are no objections to their biocompatibility. In this case, the block of metastatic cells could lead to a relative increase in the cellular elements of the immune system (NK cells and T lymphocytes) compared to cancer cells, or rather to the relative reduction in the number of cancer cells compared to NK cells and T lymphocytes. Such a block would prevent any feedback reactions, so frequent and damaging to the prognosis when using overall medical stimulation for the immune system., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

It has been established that malignant tumors as well as metastases, of almost all histological types, can regress spontaneously although certain histological types regress more frequently than others. Various causes thereof include apoptosis, the immune system and particular conditions of the tumor microenvironment. The action of the genome in the regression of tumors is not clear, but some data, apart from those of apoptosis, support its involvement. The hypothesis that the immune system exhibits variations in efficacy, even to a marked extent, in determining partial or total regression of tumors appears to be plausible. Such variable efficacy may be supported by blockage of growth and the proliferation of cancer cells at the level of the tumor microenvironment, the intervention of various factors such as inhibitors of metalloproteinases and angiogenesis, and the absence or scarcity of particular proteins. The consequence of such a blockage would be a relative increase in the number of natural killer cells and other elements involved in the immune system in relation to the number of circulating cancer cells in the blood. A relative increase in the number of elements of the immune system is more effective than an absolute increase, since an absolute increase is able to stimulate, as frequently occurs for feedback in biological equilibria, inhibitor receptors that reduce the efficacy of the same elements (mainly natural killer and CD8(+) T cells). Such an increase in the efficacy of the immune system can lead, at least in certain cases, to the so-called spontaneous regression of malignant tumors. Clinical practice has demonstrated that metastases are less frequent in patients with renal carcinoma undergoing hemodialysis compared with patients with renal carcinoma not on hemodialysis. This finding can be interpreted, in correlation with the blockage of cancer cells in tissues, as a consequence of a partial blockage of metastatic cancer cells at the level of the dialytic membrane, with a subsequent increase in the relative efficacy of the immune system.

Since results in the literature show that series of patients with kidney cancer on hemodialysis present at the postmortem examination an incidence of metastases significantly lower than such patients not on hemodialysis, the author asks what part of this favorable prognostic result is due to the dialysis membrane and what part is due to the immune system. The part due to the dialysis membrane is with every probability a blockade of metastatic cancer cells. This block, very likely consequent to phenomena of adhesion of cells to the dialysis membrane, allows a selection in that it blocks those cells that have the greatest possibility of adhesion also to the endothelium of capillaries in sites of potential colonization. The immune system would thus have, in the presence of the dialysis membrane, a greater possibility to concentrate its action on residual metastatic cells, even though uremia can have a negative influence on the clinical result. The possibility is discussed that among the various therapies of neoplasms, that for melanoma in particular may benefit from the presence of the dialysis membrane. Melanoma has demonstrated a certain sensitivity to the action of cytokines, in part also due to the presence of receptors for the latter in melanoma cells. However, the early and intense metastatic diffusion worsens the prognosis in the course of the neoplasm, and an eventual blockade, although partial, of metastatic cells could thus lead to a positive clinical result. An increase in cytokines, verified in patients on hemodialysis, does not appear to have any particular affect on the course of the disease. No signs of particular activity of the cytokines most active in an antineoplastic sense or in the sense of immune tolerance have been observed.

From a critical review of series of patients on hemodialysis for chronic renal failure and operated for renal neoplasms, it appears there is a low incidence of metastases compared to series of patients operated for malignant renal neoplasms and who have not undergone hemodialysis. In patients on hemodialysis, there are various elements that can influence the diffusion of metastatic cells, such as cytokines, tumor necrosis factor-alpha, anticoagulants and bisphosphonates. However, particular reference must be made to the possibility of the dialysis membrane in the blocking or inactivation of tumor cells.

The inspiratory pump (inspiratory muscles and the rib cage) translates inspiratory commands in alveolar ventilation by applying expanding forces to the lungs. Its functioning is of paramount importance to the physiology of breathing and of many pathological situations. Major difficulties in studying its function in relationship with its structure arise from the extremely complex geometrical disposition of its active and passive elements. We herein describe a two-compartment model of the inspiratory pump, with model parameters identification derived from actual measurements obtained by magnetic resonance imaging in normal humans. The equations governing the model are presented. Numerical simulations validate the model by showing a behaviour similar to physiological observations. This opens the possibility of predicting the behaviour of the respiratory system during diseases involving changes in its mechanical or geometrical characteristics.

Aims and Background: Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck., Methods: A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives., Results: Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences., Conclusions: 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.

The relatively frequent finding of long-term relapses from breast cancer, eight years or more after the mastectomy, could indicate that breast cancer is a particular neoplasm and even suggests that it could be a systemic disease. The study of receptors in cases of long-term relapses instead indicate that breast cancer, with the exception of the presence of hormonal receptors which influence the clinical behavior, is similar to neoplasms that arise in other parts of the body. It is possible that the presence of receptors indirectly conditions the formation of antimitotic factors more effective than those known today, up to determining in some cases the phenomenon of long-term relapses. Such factors are presumably active also for neoplasms arising in other parts of the body., (Copyright 2000 Harcourt Publishers Ltd.)

Purpose: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer., Methods: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR)., Results: A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases., Conclusions: This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.

The characteristics of a prototype computer-assisted dynamic multileaf collimator (DMLC), specifically designed for small-field conformal radiotherapy, were evaluated at the Istituto Nazionale Tumori of Milan. The collimating device consists of two opposing banks of 16 pairs of 8 cm thick, 3.6 mm wide tungsten leaves and allows shaping of a radiation field up to a size of 10 x 10 cm2 at the isocentre. The screening thickness of each leaf is 6.25 mm at the accelerator gantry isocentre. The leaves have a trapezoidal cross section and move along an arched path, thus providing a 'double focused' collimation system. The DMLC was installed on the head of a Varian Clinac 2100C linear accelerator. Mechanical and dosimetric evaluations were performed to test the stability of the mechanical isocentre and to determine leaf leakage, penumbra width, accuracy of leaf positions and uniformity of leaf speed. Displacement of the mechanical isocentre was less than 1 mm at all gantry angles. Standard radiographic films exposed to 6 MV x-ray radiation were used for dosimetric evaluations. Leakage between leaves was less than 2.5%, and leakage through abutted leaves was less than 5.5%. The penumbra width between 20% and 80% isodose at different positions of leaf banks was 2.7 mm in the direction of the leaf motion and 3.1 mm along the side of the leaf with a standard deviation of 0.2 mm in both directions. Accuracy in the positioning of the leaf was 0.3 mm, whereas the maximum repositioning error was less than 0.2 mm. Finally, during movement of the leaves at the maximum speed of 0.5 mm s(-1), the standard deviation of the leaf positioning error was 0.2 mm, proving an accurate uniformity of leaf speed.

Whether a terminally ill cancer patient should be actively fed or simply hydrated through subcutaneous or intravenous infusion of isotonic fluids is a matter of ongoing controversy among clinicians involved in the care of these patients. Under the auspices of the European Association for Palliative Care, a committee of experts developed guidelines to help clinicians make a reasonable decision on what type of nutritional support should be provided on a case-by-case basis. It was acknowledged that part of the controversy related to the definition of the terminal cancer patient, since this is a heterogeneous group of patients with different needs, expectations, and potential for a medical intervention. A major difficulty is the prediction of life expectancy and the patient's likely response to vigorous nutritional support. In an attempt to reach a decision on the type of treatment support (artificial nutrition vs. hydration) which would best meet the needs and expectations of the patient, we propose a three-step process: Step 1: define the eight key elements necessary to reach a decision; Step II: make the decision; and Step III: reevaluate the patient and the proposed treatment at specified intervals. Step I involves assessing the patient concerning the following: 1) oncological/clinical condition; 2) symptoms; 3) expected length of survival; 4) hydration and nutritional status; 5) spontaneous or voluntary nutrient intake; 6) psychological profile; 7) gut function and potential route of administration; and 8) need for special services based on type of nutritional support prescribed. Step II involves the overall assessment of pros and cons, based on information determined in Step I, in order to reach an appropriate decision based on a well-defined end point (i.e., improvement of quality of life; maintaining patient survival; attaining rehydration). Step III involves the periodic reevaluation of the decision made in Step II based on the proposed goal and the attained result.

One hundred and fifty-five consecutive previously untreated adult patients with supradiaphragmatic pathologic stage IA (71) and IIA (84) Hodgkin's disease treated only with radiotherapy (RT) at the Istituto Nazionale Tumori of Milano from 1970 to 1978 were reviewed. Staging procedures included lymphangiography and laparotomy in all cases. Most patients were irradiated with a conventional cobalt machine. Mantle fields were adopted for 36.8% of cases, mainly at stage I, whereas 63.2% received mantle plus paraaortal irradiation. Doses were above 40 Gy for involved sites and 35-40 Gy for prophylactically irradiated nodes. Minimum and median follow-up were 30 months and 6 years, respectively. All patients achieved complete remission at the end of RT. As of June 1981, 89 of 155 patients (57.5%) were alive and free from progression, 60.6% at stage I, and 54.8% at stage II. Relapses occurred in 54 of 155 cases (35%) after a median free interval of 21 months. Marginal recurrences accounted for 5.8%, true recurrences for 9%, nodal extensions for 8.4%, and extranodal extensions for 11.6%. Males older than 40 years and mediastinal involvement were correlated with higher relapse rates. Salvage treatment consisted of RT alone in 8 patients and chemotherapy plus or minus RT in 44, whereas 2 patients died before a new treatment could start. As of June 1981, 38 of 54 relapsed patients (70.4%) were alive and disease free, whereas 2 were alive with evidence of disease. Actuarial overall survival at 6 years was 90.3% for all cases, 97.1% for stage I, and 84.8% for stage II. Treatment toxicity was analyzed, and problems concerning surgical staging procedures, optimal RT and role of chemotherapy as primary or salvage treatment were discussed.

Studies in humans and animals have suggested that the distribution of histologic types of radio-induced thyroid cancers is different from that of naturally occurring tumors. In an attempt to verify that finding, histologic results of 31 patients with thyroid cancer, who had received irradiation to the head, neck or upper chest for other causes, were compared with those of 389 non irradiated patients. The two groups were homogeneous for age and sex. There was a significantly higher prevalence of the papillary type in the irradiated group, with an higher incidence of metastatic lymph nodes. Other histopathologic findings, coexisting with the papillary carcinoma (i.e., ground glass subtype, size less than 1.5 cm, multicentricity) did not differ significantly in the two groups. Some theoretical considerations concerning radio-induced thyroid carcinoma are proposed.

The natural history of 292 consecutive cases of reticulum cell sarcoma and lymphosarcoma of Waldeyer's ring and the survival rate after radiotherapy are reported. In our institute since 1928 from 30 to 35% of pharyngeal neoplasms have been lymphomas, and of these 55% have been reticulum cell sarcomas, 21% lymphosarcomas, and 1% Hodgkin's disease. This high incidence may probably be ascribed to the fact that in all malignant lymphomas, irrespective of the clinical presentation, a systematic biopsy of the whole Waldeyer's ring was carried out. Pharyngeal lymphomas were confined to Waldeyer's ring in 19.6% of cases, with initial spread to contiguous cervical nodes in 43.8%, to distant nodes in 24.2%, and to extranodal tissues in 12.4%. Lymphography showed abnormal retroperitoneal lymph nodes in 38.3% of cases. There was gastrointestinal involvement either initially or later in 17.6% of cases. High-energy radiation therapy to both sides of the neck was the treatment of choice for local and regional disease. It achieved a five-year survival rate of 41.9% in the group of 97 patients treated during the past decade. The incidence of relapse (recurrence and new manifestations) was highest in the first year after treatment.