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F. Cruz, M.S., Ph.D.

Program Director, University of California, Riverside School of Medicine

Following massive trauma, shock may be hypovolaemic (blood loss), obstructive (tamponade or tension pneumothorax), cardiogenic (cardiac contusion), neurogenic (spinal cord injury) or anaphylactic (drug reaction). Careful examination should clarify the aetiology in most cases, and will aid in determining severity by identifying end-organ effects. Tests should include a full blood count and estimation of electrolytes as well as assessment of renal function, liver function, clotting and blood group/ cross-match, serum glucose, blood cultures and inflammatory markers. This is calculated from the area under a curve of distal temperature (recorded by a thermistor at the catheter tip) plotted against time. It is calibrated by a transpulmonary thermodilution technique, following injection of cold saline into a central line. Arterial blood gas analysis provides rapid results, and the newer analyzers often measure a serum lactate level. Careful and regularly repeated recording of vital signs (heart rate, respiratory rate, blood pressure, oxygen saturation) and indicators of end-organ perfusion (consciousness level, urine output) are crucial. The initial severity of illness at assessment, and subsequent response to initial resuscitative and treatment measures will dictate the need for more advanced and invasive monitoring tools. Continuous invasive blood pressure and central venous pressure monitoring are generally required, and are essential if vasoactive drugs are required, both to enable safe drug delivery and to allow titration of dosing. As with pulse contour analysis, peripheral resistance and data indicating likely fluid responsiveness are calculated beat-to-beat. It does also have, unlike many other devices, positive outcome data in high-risk patients. Definitive treatment of the underlying cause of shock should be commenced alongside resuscitative measures. The aim should be to support the circulation to allow adequate tissue oxygen delivery, whilst mitigating or reversing the effects of the initial insult. This may be rapidly successful, for example in decompression of a tension pneumothorax; in other cases it may prove impossible to correct the underlying pathology. Fluid therapy Often large volumes are needed, guided by clinical response and monitored indicators of filling. These variations in stroke volume may be more useful indicators of likely fluid responsiveness than other methods. The choice of fluid is dictated by the underlying cause of the shock and local policies. There is an optimum amount of fluid to target resuscitation and it should be recognized that overenthusiastic transfusion, as with fluid restriction, is also associated with increased complications. Combinations may be required, guided by haemodynamic data from monitoring equipment and clinical response. Cardiac output monitoring is much better than making decisions based on the arterial blood pressure. Endocrine support Inotropes/vasopressors this treatment should be instituted if the patient remains hypotensive despite adequate fluid resuscitation. There is considered to be some benefit from the use of steroids with septic shock with an improvement in haemodynamic response but this is still the subject of considerable debate and there is a lack of cogent outcome data. The use of vasopressin has traditionally been reserved for patients with catecholamine-resistant septic shock but new evidence suggests that there may be some benefit for those requiring lower doses of noradrenaline. Tight control of blood glucose levels has also been shown to lead to improved outcomes in the sickest patients in intensive care. It represents the net result of altered host defence and deregulation of the inflammatory response and the immune system. The condition has emerged with medical advances as a result of increasing availability of intensive care facilities. Recognized as a syndrome in the early 1970s, progress in the management of critically ill patients has unmasked this frequently lethal cocktail of sequential pulmonary, hepatic and renal failure. This pattern of progressive organ impairment and failure complicates illnesses with diverse aetiologies and, despite progress in understanding the underlying mechanisms involved, it carries a mortality rate that remains depressingly high. The outcome data is remarkably consistent between the studies, with mortality linked to the number of organs failed. The first pattern usually follows a direct pulmonary insult, such as trauma or aspiration.

Chronic sesamoid pain and tenderness should signal the possibility of sesamoid displacement, local infection (particularly in a diabetic patient) or avascular necrosis. Sesamoid chondromalacia is a term coined by Apley (1966) to explain changes such as fragmentation and cartilage fibrillation of the medial sesamoid. X-rays in these cases may show a bipartite or multipartite medial sesamoid, which is often mistaken for a fracture. Treatment, in the usual case, consists of reduced weightbearing and a pressure pad in the shoe. In resistant cases, a local injection of methylprednisolone and local anaesthetic often helps; otherwise the sesamoid should be shaved down or removed, taking great care not to completely interrupt the flexor hallucis brevis tendon. It usually affects the second metatarsal head (rarely the third) in young adults, mostly women. X-rays show the head Sesamoiditis Pain and tenderness directly under the first metatarsal head, typically aggravated by walking or passive dorsi- (a) (b) (c) (d) 620 21. If discomfort is marked, a walking plaster or moulded sandal will help to reduce pressure on the metatarsal head. If pain and stiffness persist, operative synovectomy, debridement and trimming of the metatarsal head should be considered. Surgical intervention is often successful; the nerve should be released by dividing the tight transverse intermetatarsal ligament; this can be done through either a dorsal longitudinal or a plantar incision; most surgeons will also excise the thickened portion of the nerve. This is successful in about 90 per cent of patients; the remaining 10 per cent will continue to experience varying degrees of discomfort. The dorsum of the foot may be slightly oedematous and the affected shaft feels thick and tender. The x-ray appearance is at first normal, but later shows fusiform callus around a fine transverse fracture. The pain is often worse at night and the patient may seek relief by walking around or stamping the foot. Paraesthesia and numbness may follow the characteristic sensory distribution, but these symptoms are not as well defined as in other entrapment syndromes. The patient typically complains of pain on walking, with the sensation of walking on a pebble in the shoe, or of the sock being rucked-up under the ball of the foot. The pain is worse in tight footwear and often has to be relieved by removing the footwear and massaging the foot. Activities that load the forefoot (running, jumping, dancing) exacerbate the condition, which often consists of severe forefoot pain and then a reluctance to weightbear. The lesion, and an associated bursa, occupy a restricted space between the distal metatarsals, and are pinched, especially if footwear also laterally compresses the available space. Treatment A step-wise treatment programme is advis- To decompress the nerve it is exposed behind the medial malleolus and followed into the sole; sometimes it is trapped by the belly of adductor hallucis arising more proximally than usual. Corns and calluses these are hyperkeratotic lesions that develop as a reaction to localized pressure or friction. Treatment consists of paring the hyperkeratotic skin, applying felt pads that will prevent shoe or toe pressure, correcting any significant deformity (if necessary by operation) and attending to footwear. Simple offloading of the metatarsal heads by using a metatarsal dome insole and wider fitting shoes may help. If symptoms do not improve with these measures then a steroid injection into the interspace will bring about lasting relief in about 50 per cent of cases. Treatment is much the same as for corns; it is important to redistribute foot pressure by altering the shoes, fitting pressure-relieving orthoses and ensuring that the shoes can accommodate the malshaped feet. Ingrown toe-nails Plantar warts Plantar warts resemble calluses but they tend to be more painful and tender, especially if squeezed. These are viral lesions but it is usually local pressure that renders them painful. Salicylic acid plasters are applied at regular intervals, and smaller lesions may respond to cryosurgery. Surgical excision is avoided as this usually leaves a painful scar at the pressure site.

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Only 8% of the respondents were diagnosed with Lynch syndrome although about 28% reported some family history. The late stage diagnosis subjected young patients to aggressive therapies and a substantial decrease in quality of life including neuropathy, anxiety, clinical depression, and sexual dysfunctions. Most respondents (63%) waited 312 months before visiting a doctor, with higher proportion of females waited more than 12 months compared with males (22% vs. Moreover, even when visited their doctors, most patients indicated that they were initially misdiagnosed. The majority of the respondents (67%) saw at least 2 physicians, and some more than 4 physicians, prior to their diagnosis. Patients that saw 3 or more physicians prior to diagnosis were more likely to be diagnosed with advanced disease. Interestingly, half of the patients that were seen by one physician also claimed they were initially misdiagnosed. In total, 197 histopathologically distinct areas of liver metastases and 72 peripheral blood samples at multiple time points from 15 patients with colorectal cancer were analysis in this study. Results: In responding patients, mutation load from plasma were reduced from baseline (P, 0. Transcriptomic analysis and immunohistochemistry revealed that increased infiltration of neutrophils and monocytes were associated with worse outcomes and insensitive response to chemotherapy (Neutrophils: P = 0. Combination of bevacizumab with chemotherapy facilitated T cell infiltrating to the tumor microenvironment which might consequently benefit from checkpoint immunotherapy (P = 0. Conclusions: Our integrative and comparative genomic analysis provides a new paradigm for understanding the evolution and treatment resistance of colorectal cancer liver metastases, with implications for identifying ways to advance treatment regimen and monitoring treatment response of colorectal cancer liver metastases. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. Overall survival, recurrence-free and colostomy-free survival at one year were 94. Six (13%) patients had a colostomy with abdomino-perineal amputation due to a tumour recurrence. Methods: Inclusion criteria was non-metastatic anal squamous cell carcinoma treated with a definitive course of chemotherapy and radiation between 2005 and 2018 at a single institution. Results: During the study period, 111 patient initiated definitive treatment for anal cancer. The most significant predictors of local recurrence were advanced T-stage, increased time from diagnosis to treatment initiation, and prolonged treatment time. Outcomes of salvage surgery for anal squamous cell carcinoma: A systematic review and meta-analysis. Because only small cohorts have been reported, we synthesized the evidence for salvage surgery to gain a comprehensive understanding of outcomes. Quality assessment was performed using the Institute of Health Economics Quality Appraisal Checklist. We used meta-regression, subgroup and sensitivity meta-analyses to explore sources of heterogeneity. Major complications and perineal wound complications are common, but postoperative mortality is rare. Comparative effectiveness studies comparing surgery to other treatments are warranted. Quality improvement initiatives to optimize treatment continuity and completion are needed. This valuable strategy outperforms immunoscore and clinical outcome prediction models. Main metastatic sites were the liver (73%), lungs (33%), lymph nodes (39%) and peritoneum (26%). D594 (34%), G469 (15%), K601 (11%), N581 (7%) and L597 (7%) were the most frequent mutations. Younger patients tend to present with more advanced disease, thought to be in part related to lack of routine screening colonoscopies.

Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Updated and detail clinical and exploratory biomarker outcome will be presented at the annual meeting. The sensitivity and specificity for lung cancer diagnosis using the best individual gene was 64-85% and 55-79% respectively. A three-gene combination of the best individual genes has sensitivity and specificity of 92% and 78%. Cross validation combining gene methylation with clinical information correctly predicted lung cancer in 86% of subjects using plasma detection. These epigenetic biomarkers could potentially be used to identify patients with high risk of lung cancer development. During consolidation (11 evaluable patients with V; 10 with P), G3 anemia (1 vs 0), G3 anorexia (1 vs 0), G3 weight loss (0 vs 1), G3 dehydration (1 vs 0), G3 dysphagia (2 vs 0), G3 fatigue (1 vs 0), G3 hypomagnesemia (0 vs 1), G3 nausea (1 vs 0), G4 hyperglycemia (0 vs 1), G3-4 neutropenia (3 vs 0), G3 thrombocytopenia (1 vs 0), G3-4 lymphopenia (2 vs 1); a G5 pneumonitis occurred in the P arm. Here we report extended clinical follow-up and long-term molecular response data from this trial. Blood for correlative studies was taken prior to each dose of nivolumab, prior to surgery, 2-4 weeks post-surgery, and during long-term follow up. Results: At median follow up of 30 months (m), 15 of 20 pts are disease-free and alive. In one patient with ongoing disease free status, expansion of tumor-associated T-cells has persisted in peripheral blood beyond 15m from surgery. First Author: Atsushi Kamigaichi, Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan Background: Despite increasing evidence of favorable outcomes after segmentectomy for indolent lung cancer, such as ground glass opacity-dominant tumors, the adaptation of segmentectomy for radiologically aggressive lung cancer remains controversial. We attempted to elucidate oncologic outcomes after segmentectomy for radiologically aggressive lung cancer. Results: Multivariable analysis showed that consolidation to maximum tumor (C/T) ratio on preoperative highresolution computed tomography (P= 0. The criteria for radiologically aggressive lung cancer were determined as C/T ratio $ 0. Conclusions: For radiologically aggressive smallsized lung cancer, oncologic outcomes of segmentectomy were equivalent to those of lobectomy. Safety was similar and durvalumab had no detrimental effect on patient-reported outcomes. Results: In total, 713 patients were randomized of whom 709 received treatment (durvalumab, n = 473; placebo, n = 236). The last patient had completed the protocol-defined 12 months of study treatment in May 2017. Results: From November 2010 to June 2017, 86 patients were enrolled from 11 institutions. This concurrent phase was followed by a consolidation phase consisting of two 3-week cycles of nab-paclitaxel plus carboplatin. Results: Between October 2014 and November 2016, 58 patients were enrolled at 14 institutions in Japan, with 56 of these individuals being evaluable for treatment efficacy and safety. Common toxicities of grade 3 or 4 in the concurrent phase included leukopenia (60. First Author: Xin Zhang, Zhongshan Hospital Fudan University, Shanghai, China Background: Bronchial washing is the most common technique for sampling the components of the alveolar space. Preliminary analysis of safety profile and efficacy was planned after at least 20 patients had received operation. Interestingly, diversity in the blood at baseline and in the tumor post-therapy were positively correlated ([n = 7], r = 0. Importantly, higher baseline T cell clonality in the blood was associated with a lower % of viable tumor at time of surgery in both treatment arms ([n = 7], r = -0. Patient data included demographics, histologic subtypes, stage, and treatment type.