Analysis of Tumor Microenvironment Changes after Neoadjuvant Chemotherapy with or without Bevacizumab in Advanced Ovarian Cancer (GEICO-89T/MINOVA Study).

PURPOSE: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. EXPERIMENTAL DESIGN: IHC and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 patients with ovarian cancer enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. RESULTS: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells, and an upregulation in effector/regulatory cell ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophage-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significantly associated with progression-free survival (PFS). CONCLUSIONS: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at the cellular level, changes in CD4+, CD8+ lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. On the basis of our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T-effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first-line treatment of advanced epithelial ovarian cancer. See related commentary by Soberanis Pina and Oza, p. 12.

Intraoperative ultrasound margin evaluation as a tool to reduce positive superficial margins in nipple and skin sparing mastectomy in breast cancer patients.

BACKGROUND: Intraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. METHODS: This prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. RESULTS: Fifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ≥5 mm and 36 patients (61.02%) had margins of ≤5 mm. Of the 36 patients with superficial margins ≤5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ≤2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. CONCLUSION: The results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.

What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage. / O que todo intensivista deve saber a respeito da síndrome do desconforto respiratório agudo e dano alveolar difuso?

Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and

A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

O que todo intensivista deve saber a respeito da síndrome do desconforto respiratório agudo e dano alveolar difuso? / What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage

RESUMO A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

ABSTRACT Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and (c) how enrichment in diffuse alveolar damage may improve the results of pharmacological clinical trials tried out on patients with acute respiratory distress syndrome.

Criptococosis cutánea primaria asociada a oncotaxia en un paciente inmunodeprimido / Primary cutaneous cryptococcosis associated with oncotaxis in an immunosuppressed patient

La criptococosis es una infección oportunista causada por Cryptococcus neoformans que afecta principalmente a pacientes inmunodeprimidos. Se presenta un varón de 72 años diagnosticado de leucemia linfática crónica tipo B asociada a hipogammaglobulinemia, tratado con ciclofosfamida, vincristina y prednisona. Consultó por la presencia de una lesión tuberosa asintomática en el muslo, la cual evolucionó hacia la ulceración. No refería traumatismo previo ni contacto con palomas. La biopsia cutánea demostró una reacción granulomatosa con numerosos hongos asociada a un fenómeno de oncotaxia. En el cultivo de la lesión se aisló C. neoformans. No se objetivó afectación sistémica. Con el diagnóstico de criptococosis cutánea primaria se realizó tratamiento con fluconazol que condujo a la curación. Destaca su asociación a una leucemia linfática crónica de tipo B y la coexistencia con un fenómeno de oncotaxia (AU)

Relapsing upper bleeding in non-Hodgkin's oesophageal lymphoma associated with achalasia.

Achalasia is a disease of unknown origin in which there is a denervation of the myenteric plexus on the smooth muscle of the lower oesophageal sphincter, causing a cardial stenosis and a loss of efficacy of oesophageal peristalsis. The predominant symptoms are dysphagia for solids and liquids and regurgitation of the retained food. Occasionally, there may be oesophageal haemorrhage as a consequence of oesophagitis and stasis ulcers. An important but uncommon complication is the development of oesophageal cancer, which is typically squamous cell carcinoma. We report an exceptional case of a 77-year-old woman with a long-term achalasia and mega-oesophagus who presented four episodes of upper gastrointestinal bleeding in a 2 month period. The patient underwent surgical resection of the 10 cm of distal oesophagus, performing a partial fundoplication, and the pathological study revealed an oesophageal infiltration by a low-grade non-Hodgkin's lymphoma. After an insidious outcome, she died on the 47th day after admission.