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Program Director, Cleveland Clinic Lerner College of Medicine

N1 M0 M1 Clinical presentation A patient with soft tissue sarcoma may present with the primary, secondaries or as distant non-metastatic disease; most lumps are benign. Features suggestive of malignancy are tumour size greater than 5 cm, an increase in size, a lump deep to the deep fascia, and pain. Guidance has been issued to general practitioners to refer lumps meeting any of these criteria. Haematogenous metastases are common: 40% of sarcomas present with these metastases, usually to the lung. Paraneoplastic syndromes are uncommon, but unexplained pyrexia or cachexia is occasionally seen. Examination should note size, site and mobility, loss of function, and any stigmata of an underlying condition. It is recommended that both tests be requested as soon as a diagnosis of soft tissue sarcoma is strongly suspected. Investigation and staging A core biopsy is required for diagnosis and should be performed in all cases in which malignancy is considered in an extremity. This procedure is followed because excision margins of 1 cm are desirable for a sarcoma but would be excessive for benign conditions. The needle track should be excised at a definitive operation, and a poorly placed biopsy increases the extent and morbidity of surgery. Frozen tissue biopsy at the time of definitive surgery may also be acceptable, particularly when the diagnosis of soft tissue sarcoma is fairly certain and when excising the track of a wide-bore needle en bloc might be difficult. A fine needle aspirate is adequate for a confirmation of relapse, but it probably provides inadequate material for making the initial diagnosis. Treatment overview Patients should be managed by a specialist multidisciplinary team. The aim of treatment is to maximise the chance of a cure while safely minimising treatment-related morbidity. Appropriate limb-sparing operations have the same local control and cure rates as amputation: surgery should be undertaken by specialists. Fairly high-dose doxorubicin and ifosfamide are the most active agents against advanced disease, but they are toxic and have response rates of only 20%, and so palliative care alone may be appropriate. Local disease: surgical treatments the primary tumour should be excised with a 1 cm margin, although the extent of the margin has not been investigated in a clinical trial. The wider margins that have been historically recommended are no longer felt necessary and excision beyond fascial boundaries is not needed. The functional loss from arm amputation is considerably more than that from leg amputation, and limb salvage should always be considered. Below the knee, the functional outcome from amputation and limb-sparing surgery are the same, but patient well-being and satisfaction, although high for both, is greater with limb salvage. Radiotherapy Postoperative radiotherapy Poor, possibly inadvertent, surgery results in a high local relapse rate, and, where feasible, re-excision should be undertaken. Sometimes limb salvage means accepting close or involved margins, for example, where a tumour abuts the sciatic nerve. Another trial has shown the same for brachytherapy for high- but not low-grade tumours (Pisters et al. A survey of international practice has shown that 60% of oncologists apply a 5 cm margin to both the surgical scar and the tumour bed when planning preoperative treatment (M. However, the radial margin of 2 cm and longitudinal margin of 4 cm in the brachytherapy trial were acceptable. It is common practice to use a shrinking field, with a 5 cm margin to 50 Gy and a 2 cm margin to 60 to 66 Gy, but because the majority of local relapses occur in the high-dose volume, the shrinking field may not be necessary. Local relapse appears unacceptably high with a dose of 50 Gy and the functional outcome is worse after 66 Gy than after 60 Gy. This study was ended prematurely at a planned interim analysis, when a statistically significant increase in wound healing problems was found after 50 Gy preoperatively. Where possible, a strip of skin should always be spared to minimise the late complication of lymphoedema.

Objective: to establish a Ki67 cut-off point for carcinoid tumors and to determine its prognostic implications in overall survival and disease-free survival in both histological subtypes. Once this point was identified, the regression analysis was repeated using Ki-67 as a dichotomous variable (equal or greater than the cut-off point versus lower). The analysis was carried out with the program R: A Language and Environment for Statistical Computing version 3. Using this value as a predictive variable, there was no significant association between% Ki-67 and mortality (p = 0. The regions of secondary recurrence after lung resection were as follows: lung: 28 (cases), liver: 7, brain: 3, mediastinal lymph nodes: 5, other: 5. Cases who underwent lung metastasectomy had a significantly higher survival rate (p=0. The regions of secondary recurrence after liver resection were as follows: lung: 47 (cases), liver: 66,brain: 2, abdominal lymph nodes: 9, dissemination: 6, other: 7. While there were 5 cases of subsequent brain metastasis after lung resection, no subsequent brain metastasis was found after liver resection. All but one of the 8 cases of brain metastasis after lung resection were treated with surgery or CyberKnife. In addition, all cases were experiencing associated symptoms when brain metastasis was detected, and only one patient was undergoing regular examinations to detect brain metastasis. Conclusion: While appropriate surgical intervention is recommended in cases of lung metastasis and metachronous liver metastasis,it is debatable in cases of synchronous liver metastasis. Cases of lung metastasis should give attention to brain metastasis and recieve early detection and intervention. Harita Okayama Saiseikai General Hospital, Okayama/Japan Background: the resectability is often debated in cases of lung and liver metastases. Further, we had reported previously that the incidence of brain metastasis is significantly higher in colorectal cancer with lung metastasis than cases with liver metastasis (lung: 7. We compared and investigated the therapeutic outcomes of cases of lung, liver and brain metastasis. Method: Between 2002 and 2013, we retrospectively studied the prognosis of 90 cases of colorectal cancer cases that underwent lung metastasectomy, and 148 cases that underwent liver metastasectomy. The course of treatment in 8 cases of subsequent brain metastasis was also evaluated. Result: the 5-year survival Background: Recurrent cervical and mediastinal lymph node metastasis after the surgery of thyroid carcinoma is frequently reported. Generally, surgery is the best treatment but there is still no established standard surgical procedure. Method: Surgical procedure for recurrent cervical and mediastinal lymph node metastasis after thyroid carcinoma varies throughout each institute. We report 2 resected cases of cervical and mediastinal lymph node metastasis after thyroid cancer which underwent dissection through median sternotomy. Result: A 68-year-old Japanese man underwent left thyroid lobectomy for poorly differentiated thyroid cancer in September 2009. Therefore, the patient underwent mediastinal lymph node dissection through median sternotomy. The second patient was a 58-yearold Japanese man who had been treated by subtotal thyroidectomy in May 2008. The patient noticed a gradual increase of a mass near his right lower jaw from 2011. As a result of further examination, mediastinal lymph node metastasis was suspected. The patient underwent mediastinal lymph node dissection through median sternotomy and neck collar incision. In our hospital, the possibility of micrometastases is also considered in cases of post-operative lymph node recurrence. Therefore, we completely resect the mediastinal lymph nodes by median sternotomy approach. Calvinho Santa Marta Hospital, Lisboa/Portugal Background: Thymoma is the most common thymic neoplasm. In the majority of cases, patients are asymptomatic and the diagnosis is incidental. Method: A review of 50 cases of thymomas submitted to surgical excision at our Thoracic Surgery Department was made by accessing their clinical records, in a six-year period, from January 2012 to December 2018.

A pathologic description of this process has been provided by our colleagues and by others (see Asnis et al). Perivascular cuffing by lymphocytes and other mononuclear leukocytes and plasma cells as well as a patchy infiltration of the meninges with similar cells are the usual histopathologic hallmarks of viral encephalitis. Of the arbovirus infections in the United States, eastern equine encephalitis is among the most serious, since a large proportion of those infected develop encephalitis; about one-third die and a similar number, more often children, are left with disabling abnormalities- mental retardation, emotional disorders, recurrent seizures, blindness, deafness, hemiplegia, extrapyramidal motor abnormalities, and speech disorders. While only a small proportion of those exposed become infected, the poliomyelitis and parkinsonian syndromes of the flaviviruses may be permanent residua as mentioned earlier (see Solomon). The mortality rate in other arbovirus infections varies from 2 to 12 percent in different outbreaks, and the incidence of serious sequelae is about the same. Clinical Features the symptoms, which evolve over several days, are in most cases like those of any other acute encephalitis- namely, fever, headache, seizures, confusion, stupor, and coma. In some patients these manifestations are preceded by symptoms and findings that betray the predilection of this disease for the inferomedial portions of the frontal and temporal lobes. They include olfactory or gustatory hallucinations, anosmia, temporal lobe seizures, personality change, bizarre or psychotic behavior or delirium, aphasia, and hemiparesis. Although several seizures at the onset of illness are not an uncommon presentation, status epilepticus is rare. An affection of memory can often be recognized, but usually this becomes evident only later, in the convalescent stage, as the patient awakens from stupor or coma. Swelling and herniation of one or both temporal lobes through the tentorium may occur, leading to deep coma and respiratory arrest during the first few days of the illness. The cells are mostly lymphocytes, but there may be a significant number of neutrophils early on. In a few cases, 3 to 5 percent in some large series, the spinal fluid has been normal in the first days of the illness, only to become abnormal when re-examined. Also, in only a minority of cases, red cells, sometimes numbering in the thousands, and xanthochromia are found, reflecting the hemorrhagic nature of the brain lesions; but it should be emphasized that more often red cells are few in number or absent. Pathology the lesions take the form of an intense hemorrhagic necrosis of the inferior and medial temporal lobes and the medioorbital parts of the frontal lobes. The region of necrosis may extend upward along the cingulate gyri and sometimes to the insula or the lateral parts of the temporal lobes or caudally into the midbrain but always contiguous with areas of mediotemporal lobe necrosis. This distribution of lesions is so characteristic that the diagnosis can be made by gross inspection or by their location and appearance on imaging studies. In the acute stages of the disease, intranuclear eosinophilic inclusions are found in neurons and glial cells, in addition to the usual microscopic abnormalities of acute encephalitis and hemorrhagic necrosis. The virus is thought to be latent in the trigeminal ganglia and, with reactivation, to infect the nose and then the olfactory tract. Alternatively, with reactivation in the trigeminal ganglia, the infection may spread along nerve fibers that innervate the leptomeninges of the anterior and middle fossae. The lack of lesions in the olfactory bulbs in as many as 40 percent of fatal cases (Esiri) is a point in favor of the second pathway. Diagnosis Acute herpes simplex encephalitis must be distinguished from other types of viral encephalitis, from acute hemorrhagic leukoencephalitis of Weston Hurst (page 792), and from subdural empyema, cerebral abscess, cerebral venous thrombosis, and septic embolism (Chap. When aphasia is the initial man- Herpes Simplex Encephalitis this is the commonest and gravest form of acute encephalitis. About 2000 cases occur yearly in the United States, accounting for about 10 percent of all cases of encephalitis in this country. Between 30 and 70 percent are fatal, and the majority of patients who survive are left with serious neurologic abnormalities. The type 2 virus may also cause acute generalized encephalitis, usually in the neonate and in relation to genital herpetic infection in the mother. Type 2 infection in the adult may cause an aseptic meningitis and sometimes a polyradiculitis or myelitis, again in association with a recent genital herpes infection. Exceptionally, the localized adult type of encephalitis is caused by the type 2 virus and the diffuse neonatal encephalitis by type 1. Spinal fluid that contains a large number of red cells may be attributed to a ruptured saccular aneurysm. T1-weighted images demonstrate areas of low signal intensity with surrounding edema and sometimes with scattered areas of hemorrhage occupying the inferior parts of the frontal and temporal lobes. Almost always the lesions enhance with contrast infusion or with gadolinium, indicating cortical and pial abnormalities of the blood-brain barrier. It should be noted that these destructive lesions are almost unique among the viral encephalitides, being seen only occasionally in other viral infections of the brain, among them La Crosse encephalitis in children (McJunkin et al).

However, the former pattern (so-called alpha coma) is not limited to the posterior cerebral regions, is not monorhythmic like normal alpha activity, and displays no reactivity to sensory stimuli. This alpha-like activity pattern may be associated with pontine or diffuse cortical lesions and has a poor prognosis (Iragui and McCutchen; page 29). In these conditions the slow waves become higher in amplitude as coma deepens, ultimately assuming a high-voltage rhythmic delta pattern and a triphasic configuration. There is also a general correspondence between the intensity of stimuli required to elicit motor activity and the degree of slowing of the background rhythm. In cases of intoxication with sedatives, exemplified by barbiturates, fast activity initially replaces normal rhythms. The Anatomy and Neurophysiology of Alertness and Coma Our current understanding of the anatomy and physiology of alertness comes largely from the elegant experiments of Bremer and of Magoun and Moruzzi in the 1930s and 1940s. He interpreted this to mean, in large part correctly, that a constant stream of sensory stimuli, provided by trigeminal and other cranial sources, was required to maintain the awake state. Several years later, Morrison and Dempsey demonstrated a system of "nonspecific" projections from the thalamus to all cortical regions, independent of any specific sensory nucleus. The sites at which stimulation led to arousal consisted of a series of points extending from the nonspecific medial thalamic nuclei down through the caudal midbrain. These points were situated along the loosely organized core of neurons that anatomists had referred to as the reticular system or formation. The anatomic studies of the Scheibels have described widespread innervation of the reticular formation by multiple bifurcating and collateral axons of the ascending sensory systems, implying that this area was maintained in a tonically active state by ascending sensory stimulation. In this way, despite a number of experimental inconsistencies (see Steriade) the paramedian upper brainstem tegmentum and lower diencephalon came to be conceived as the locus of the alerting system of the brain. The anatomic boundaries of the upper brainstem reticular activating system are somewhat indistinct. This system is interspersed throughout the paramedian regions of the upper (rostral) pontine and midbrain tegmentum; at the thalamic level, it includes the functionally related posterior paramedian, parafascicular, and medial portions of the centromedian and adjacent intralaminar nuclei. In the brainstem, nuclei of the reticular formation receive collaterals from the spinothalamic and trigeminal-thalamic pathways and project not just to the sensory cortex of the parietal lobe, as do the thalamic relay nuclei for somatic sensation, but to the whole of the cerebral cortex. Thus, it would seem that sensory stimulation has a double effect- it conveys information to the brain from somatic structures and the environment and also activates those parts of the nervous system on which the maintenance of consciousness depends. The cerebral cortex not only receives impulses from the ascending reticular activating system but also modulates this incoming information via corticofugal projections to the reticular formation. Although the physiology of the reticular activating system is far more complicated than this simple formulation would suggest, it nevertheless, as a working idea, retains a great deal of clinical credibility and makes comprehensible some of the neuropathologic observations noted further on, under "Pathologic Anatomy of Coma. This activity, coordinated by the thalamus, has been theorized to synchronize widespread cortical activity and to account perhaps for the unification of modular aspects of experience (color, shape, motion) that are processed in different cortical regions. In this way the rhythm has been theorized to "bind" various aspects of a sensory experience or a memory. Using such electrophysiologic methods, Meador and colleagues have shown that the rhythm can be detected over the primary somatosensory cortex after an electrical stimulus on the contralateral hand is perceived, but not if the patient fails to perceive it. The clinical meaning of the rhythm is controversial, but it has elicited great interest because it may give insight into several intriguing questions about the states of consciousness. Metabolic Mechanisms that Disturb Consciousness In a number of disease processes that disturb consciousness, there is direct interference with the metabolic activities of the nerve cells in the cerebral cortex and the central nuclei of the brain. Hypoxia, global ischemia, hypoglycemia, hyper- and hypo-osmolar states, acidosis, alkalosis, hypokalemia, hyperammonemia, hypercalcemia, hypercarbia, drug intoxication, and severe vitamin deficiencies are well-known examples (see Chap. In general, the loss of consciousness in these conditions parallels the reduction in cerebral metabolism or blood flow. Lower levels are tolerated if arrived at more slowly, but neurons cannot survive when flow is reduced below 8 to 10 mL/min/100 g. In other types of metabolic encephalopathy or with widespread anatomic damage to the hemispheres, blood flow stays near normal levels while metabolism is greatly reduced. Oxygen consumption of 2 mg/min/100 g (approximately half of normal) is incompatible with an alert state.