Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy.

PURPOSE: Axillary Lymph Node Dissection (ALND) is recommended for breast cancer patients who present with clinically node positive disease (cN1) especially if they have residual nodal disease (ypN+) following neoadjuvant therapy (NAT). It is unknown whether axillary dissection improves outcome for these patients. METHODS: A prospectively maintained database was used to identify all patients who were diagnosed with cTis-T4N1M0 breast cancer treated with NAT. RESULTS: In our study, of 292 cN1 breast cancer patients who received NAT, we compared ALND with targeted axillary surgery (TAS) in ypN+ patients. ALND was performed in 75% of the ypN+ subgroup, while 25% underwent TAS. Axillary recurrence occurred in four ALND patients, but no recurrence was observed in the TAS group (p = 0.21). Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND (p = 0.21). Overall survival at five years was 97% for TAS and 85% for ALND (p = 0.39). Disease-free survival rates at five years were 51% for TAS and 61% for ALND (p = 0.9). Clinicopathological variables were similar between the groups, although some differences were noted. ALND patients had smaller clinical tumor size, larger pathological tumor size, more lymph nodes retrieved, larger tumor deposits, higher rates of extranodal extension, and greater prevalence of macrometastatic nodal disease. Tumor subtype and size of lymph node tumor deposit independently predicted survival. CONCLUSION: Axillary recurrence is infrequent in cN1 patients treated with NAT. Our study found that ALND did not reduce the occurrence of axillary recurrence or enhance overall survival. It is currently uncertain which patients benefit from axillary dissection.

Organ-specific heterogeneity in tumor-infiltrating immune cells and cancer antigen expression in primary and autologous metastatic lung adenocarcinoma.

BACKGROUND: Tumor immune microenvironment (TIME) and cancer antigen expression, key factors for the development of immunotherapies, are usually based on the data from primary tumors due to availability of tissue for analysis; data from metastatic sites and their concordance with primary tumor are lacking. Although of the same origin from primary tumor, organ-specific differences in the TIME in metastases may contribute to discordant responses to immune checkpoint inhibitor agents. In immunologically 'cold' tumors, cancer antigen-targeted chimeric antigen receptor (CAR) T-cell therapy can promote tumor-infiltrating lymphocytes; however, data on distribution and intensity of cancer antigen expression in primary tumor and matched metastases are unavailable. METHODS: We performed a retrospective review of a prospectively maintained database of patients who had undergone curative resection of pathological stage I-III primary lung adenocarcinoma from January 1995 to December 2012 followed by metastatic recurrence and resection of metastatic tumor (n=87). We investigated the relationship between the primary tumor and metastasis TIME (ie, tumor-infiltrating lymphocytes, tumor-associated macrophages, and programmed death-ligand 1 (PD-L1)) and cancer antigen expression (ie, mesothelin, CA125, and CEACAM6) using multiplex immunofluorescence. RESULTS: Brain metastases (n=36) were observed to have fewer tumor-infiltrating lymphocytes and greater PD-L1-negative tumor-associated macrophages compared with the primary tumor (p<0.0001); this relatively inhibitory TIME was not observed in other metastatic sites. In one in three patients, expression of PD-L1 is discordant between primary and metastases. Effector-to-suppressor (E:S) cell ratio, median effector cells (CD20+ and CD3+) to suppressor cells (CD68/CD163+) ratio, in metastases was not significantly different between patients with varying E:S ratios in primary tumors. Cancer antigen distribution was comparable between primary and metastases; among patients with mesothelin, cancer antigen 125, or carcinoembryonic antigen adhesion molecule 6 expression in the primary tumor, the majority (51%-75%) had antigen expression in the metastases; however, antigen-expression intensity was heterogenous. CONCLUSIONS: In patients with lung adenocarcinoma, brain metastases, but not other sites of metastases, exhibited a relatively immune-suppressive TIME; this should be considered in the context of differential response to immunotherapy in brain metastases. Among patients with cancer antigen expression in the primary tumor, the majority had antigen expression in metastases; these data can inform the selection of antigen-targeted CARs to treat patients with metastatic lung adenocarcinoma.

Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma.

INTRODUCTION: Patients with stage II to III lung adenocarcinomas are treated with adjuvant chemotherapy (ACT) to target the premetastatic niche that persists after curative-intent resection. We hypothesized that the premetastatic niche is a scion of resected lung tumor microenvironment and that analysis of tumor microenvironment can stratify survival benefit from ACT. METHODS: Using tumor and tumoral stroma from 475 treatment-naive patients with stage II to III lung adenocarcinomas, we constructed a tissue microarray and performed multiplex immunofluorescent staining for immune markers (programmed death-ligand 1 [PD-L1], tumor-associated macrophages [TAMs], and myeloid-derived suppressor cells) and derived myeloid-lymphoid ratio. The association between immune markers and survival was evaluated using Cox models adjusted for pathologic stage. RESULTS: Patients with high PD-L1 expression on TAMs or tumor cells in resected tumors had improved survival with ACT (TAMs: hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.12-2.85; tumor cells: HR = 3.02, 95% CI: 1.69-5.40). Among patients with high PD-L1 expression on TAMs alone or TAMs and tumor cells, ACT survival benefit is pronounced with high myeloid-lymphoid ratio (TAMs: HR = 3.87, 95% CI: 1.79-8.37; TAMs and tumor cells: HR = 2.19, 95% CI: 1.02-4.71) or with high stromal myeloid-derived suppressor cell ratio (TAMs: HR = 2.53, 95% CI: 1.29-4.96; TAMs and tumor cells: HR = 3.21, 95% CI: 1.23-8.35). Patients with low or no PD-L1 expression on TAMs or tumor cells had no survival benefit from ACT. CONCLUSIONS: Our observation that PD-L1 expression on TAMs or tumor cells is associated with improved survival with ACT provides rationale for prospective investigation and developing chemoimmunotherapy strategies for patients with lung adenocarcinoma.

Spread Through Air Spaces (STAS) in Non-Small Cell Lung Carcinoma: Evidence Supportive of an In Vivo Phenomenon.

Tumor spread through air spaces (STAS) is associated with locoregional recurrence in patients undergoing limited resection (LR) for non-small cell lung carcinoma (NSCLC). We hypothesized that the observation of STAS in both the initial LR specimen and the additional resection specimen from the same patient, processed using different knives, would provide evidence that STAS is an in vivo phenomenon contributing to locoregional recurrence. We retrospectively identified patients with NSCLC (9 adenocarcinoma, 1 squamous cell carcinoma) who underwent LR, had STAS in the LR specimen, and underwent additional resection (lobectomy or LR). The LR and additional resection specimens from each patient were processed at different times using different tissue-processing knives. All specimens were analyzed for STAS. All 10 patients underwent LR with negative margins (R0). All additional resection specimens had STAS: 8 patients had STAS clusters in their completion lobectomy specimens, and 2 had STAS in their additional LR specimens. In 2 patients, STAS was found in the completion lobectomy specimen only after extensive sampling (>10 sections) from the staple line adjacent to the initial LR. The presence of STAS in both the LR and the additional resection specimen processed using different knives supports the concept that STAS is an in vivo phenomenon, rather than an artifact from tissue processing. This observation indicates that occult STAS tumor cells can be present in the lung tissue of the remaining unresected lobe after LR and supports the concept that STAS is a contributing factor for locoregional recurrence following LR.

Restoring Intestinal Continuity in a Hostile Abdomen: The Deloyers Procedure.

BACKGROUND: Deloyers procedure enables anastomosis of the ascending colon to the rectum following extended resections that prevent usual fashion anastomosis. During the procedure, the right colon is completely mobilized and counterclockwise rotated to allow tension free and well-vascularized anastomosis while preserving the ileocecal valve. The purpose of this manuscript is to report our experience with laparoscopic Deloyers procedure in a hostile abdomen due to adhesions from previous surgeries. METHODS: We report the outcomes and our technique of laparoscopic Deloyers procedure in three patients. All patients had a surgical complication necessitating the creation of end colostomy with a short colonic remnant. The bowel status prevented restoration of continuity by the common colorectal anastomosis and laparoscopic Deloyers was elected. RESULTS: The procedure was successful in all patients, with no intra-operative complication and average surgery duration of three hours. Patients had uneventful postoperative recovery with only one case of minor complication and an adequate functional outcome. CONCLUSION: Laparoscopic Deloyers is safe and allows the restoration of bowel continuity with preservation of ileocecal valve and good functional outcome even in hostile abdomen.

Conversion for failed adjustable gastric banding warrants hiatal scrutiny for hiatal hernia.

BACKGROUND: Failure or complications following laparoscopic adjustable gastric banding (LAGB) may necessitate band removal and conversional surgery. Band position and band-induced chronic vomiting create ideal conditions for de novo hiatal hernia (HH) formation. HH presence impedes and complicates conversional surgery by obscuring crucial anatomical landmarks and hindering precise gastric sleeve or pouch formation. The aim of this study was to evaluate the incidence of a HH in patients with an LAGB undergoing conversion compared to patients undergoing primary bariatric surgery (BS). METHODS: Retrospective review of consecutive BS performed between 2010 and 2015. Data collected included demographics, anthropometrics, comorbidities, previous BS, preoperative and intra-operative HH detection, operation time, perioperative complications and length of hospital stay. RESULTS: During the study period, 2843 patients (36% males) underwent BS. Of these, 2615 patients (92%) were "primary" (no previous BS-control group), 197 (7%) had a previous LAGB (study group), and 31 (1%) had a different previous BS and were excluded. Reasons for conversion included weight regain, band intolerance and band-related complications. Mean age and body mass index were similar between the study and the control groups. HH was preoperatively diagnosed by upper gastrointestinal (UGI) fluoroscopy in 9.1% and 9.0% of the LAGB and control groups (p = NS), respectively. However, HH was detected intra-operatively in 20.3% and 7.3%, respectively (p < 0.0001). CONCLUSIONS: Preoperative diagnosis of a HH by UGI fluoroscopy for patients who have undergone LAGB is unreliable. Intra-operative hiatal exploration is highly recommended in all cases of conversional BS after LAGB.

Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: We investigated the risk factors, incidence, and role of thromboprophylaxis in the development of thrombosis following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: We reviewed data of patients with CRS/HIPEC in three hospitals. RESULTS: Overall, 192 patients underwent CRS/HIPEC during 2007-2016. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h before surgery until discharge) was provided for all patients; and 116 (60.4%) also received an extended course of enoxaparin for 2-4 weeks after discharge. Twenty-six patients experienced thrombotic complications (13.5%) including portal-splenic-mesenteric venous thrombosis (n = 11, 5.7%), pulmonary embolism (n = 10, 5.2%), and deep vein thrombosis (n = 5, 2.6%); most (n = 21, 80.8%) occurred after hospital discharge. Univariate analysis identified Peritoneal Cancer Index, intraoperative transfusion requirement, operative blood loss, operative time, lengths of hospital, and intensive care unit stay, and lack of administration of anticoagulation at discharge as significantly associated with thrombosis. With multivariate analysis, only the lack of anticoagulation therapy at discharge remained significantly associated with thrombosis (P = 0.0001). CONCLUSIONS: Thromboembolic complications are common following CRS/HIPEC. As significantly lower rates of thrombosis were found in patients who received an extended course of anticoagulation, we support its use for at least 2 weeks after discharge.

The Impact of Bariatric Surgery on Thyroid Function and Medication Use in Patients with Hypothyroidism.

BACKGROUND: Bariatric surgery (BS) is effective in treating obesity and its associated comorbidities. However, there is a paucity of data on the effect of BS on thyroid function in hypothyroid patients, specifically in those treated with thyroid hormone replacement therapy (THR). The aim of this study was to assess the effect of BS on thyroid function and on THR dosage in patients with hypothyroidism. METHODS: A retrospective analysis of prospectively collected data of all hypothyroid patients who underwent BS between 2010 and 2014 was performed. Data collected included demographic and anthropometric measurements, as well as changes in thyroid hormone levels and THR dosage up to a year from surgery. RESULTS: During the study period, 93 hypothyroid patients (85 females, 91%), 83 of which treated with replacement thyroid hormone, underwent BS. Laparoscopic sleeve gastrectomy was performed in 77 (82.8%) and Roux-en-Y gastric bypass in 16 patients. Average age and body mass index (BMI) were 46.6 ± 11.2 years and 43.7 ± 6.4 kg/m2, respectively. Mean BMI and thyroid-stimulating hormone (TSH) significantly deceased after 6 and 12 months following surgery whereas mean free T4 levels remained stable. TSH decrease was directly correlated to baseline TSH but not to BMI reduction. One year after surgery, 11 patients (13.2%) did not require THR, while the rest required a significantly lower average dose (P < 0.02). CONCLUSIONS: There is a favorable effect of BS on the hypothyroid bariatric population. This includes improvement of thyroid function and reduction of thyroid medication dosages. Further studies are required to evaluate an influence of THR absorption and compare different types of bariatric surgeries.

Stenting in malignant colonic obstruction--is it a real therapeutic option?

BACKGROUND: Malignant colonic obstruction is commonly treated surgically. Colonic stents are a therapeutic option for palliation or used as a bridge to surgery or chemotherapy. OBJECTIVE: The aim of the study was to evaluate the clinical success rate of stenting as a bridge to one-step surgery, chemotherapy, or as a palliative measure. DESIGN: This was a retrospective observational study. SETTINGS: The study was conducted at a university-affiliated tertiary referral center. PATIENTS AND INTERVENTIONS: From 2007 to 2014, 45 patients with malignant colonic obstruction were referred for stent insertion. MAIN OUTCOME MEASURES: Patients were grouped according to three pre-defined treatment goals: group 1: restorative one-step procedure without an ostomy, group 2: completion of scheduled chemotherapy before surgery, and group 3: palliation without surgical intervention. RESULTS: Group 1 included 11 patients. Three patients (27.3 %) met the treatment goal of one-step surgery. Eight patients (72.7 %) did not reach the primary goal due to stent insertion failure (four patients), stent-related complications (two patients), and failure to perform a one-step surgery after successful stent insertion (two patients). Group 2 included 12 patients. Chemotherapy was successfully completed prior to surgery in six patients (50 %). Six patients (50 %) did not achieve treatment goal due to stent insertion failure (two patients), stent migration (two patients), stent-related perforation (one patient), and mortality (one patient). Group 3 included 20 patients. Long-term palliation without surgical intervention was achieved in eight patients (40 %). Stent insertion failed in seven patients (35 %). Five patients (25 %) needed urgent surgery due to stent complications (three migrations and two perforations). LIMITATIONS: The study was limited by its retrospective nature and small sample size. CONCLUSIONS: This study demonstrates only a modest success rate of colonic stents in the treatment of malignant colonic obstruction. Although colonic stenting seems to be an effective method of relieving colonic obstruction, high failure rates limits its applicability.