Serologic reactivity of unidentified specificity in antenatal testing and hemolytic disease of the fetus and newborn: The BEST collaborative study.

BACKGROUND: The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN). STUDY DESIGN AND METHODS: Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined. RESULTS: SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibody reactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibody reactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188). CONCLUSION: The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

Multicenter Study of Presentation, Management, and Postoperative and Long-Term Outcomes of Septegenerians and Octogenerians Undergoing Gastrectomy for Gastric Cancer.

BACKGROUND: The optimal treatment strategy for elderly patients with gastric cancer is still controversial. This study aimed to assess the impact of age on short- and long-term outcomes after treatment for primary gastric cancer. METHODS: From January 2004 to December 2014, a total of 507 patients underwent gastrectomy for gastric adenocarcinoma at two high-volume upper gastrointestinal (GI) centers. The patients were classified into three groups as follows: group A (patients ≤ 69 years old, n = 266), group B (patients 70-79 years old, n = 166), and group C (patients ≥ 80 years old, n = 75). Clinicopathologic characteristics as well as, short- and long-term outcomes were compared between the groups. RESULTS: The patients in groups B and C had more comorbidities, whereas the younger subjects (group A) had more advanced tumor stages. Less extensive surgery was performed in the groups B and C. Older patients (age ≥ 70 years) had more postoperative medical complications. Moreover, group C had a higher postoperative mortality rate (8.1%) than group A (1.8%) or group B (1.9%). In the multivariable analysis, age older than 80 years (group C) was a negative independent factor for overall survival (OS) (hazard ratio [HR], 2.36) compared with group A, whereas group B seemed to have a comparable risk (HR, 1.37). Notably, the three groups did not show significant differences in disease-related survival (DRS). CONCLUSION: The data suggest that patients 70-79 years of age show a risk of postoperative death comparable with that of younger subjects. However, patients older than 80 years should be carefully selected for surgical treatment due to the increased risk of postoperative mortality.

Long-term Health-related Quality of Life Following Esophagectomy: A Nonrandomized Comparison of Thoracoscopically Assisted and Open Surgery.

OBJECTIVE: The aim of this study was to assess long-term health-related quality of life (HRQL) in patients after thoracoscopic and open esophagectomy. SUMMARY OF BACKGROUND DATA: Trials comparing minimally invasive with open transthoracic esophagectomy have shown improved short-term outcomes; however, long-term HRQL data are lacking. This prospective nonrandomized study compared HRQL and survival after thoracoscopically assisted McKeown esophagectomy (TAMK) and open transthoracic Ivor Lewis esophagectomy (TTIL) for esophageal or gastroesophageal junction (GEJ) cancer. METHODS: Patients with esophageal or GEJ cancer selected for TAMK or TTIL completed baseline and follow-up HRQL assessments for up to 24 months using the EORTC generic and disease-specific measures, QLQ-C30 and QLQ-OES18. Baseline clinical variables were examined between the treatment groups and changes in mean HRQL scores over time estimated and tested using generalised estimating equations with propensity score (generated by boosted regression) adjustment. RESULTS: Of the 487 patients, 377 underwent TAMK and 110 underwent TTIL. Most clinical variables were similar in the 2 groups; however, there were significantly more patients with AJCC stage 3 disease who underwent TTIL than TAMK (54% vs 32%, P < 0.01) and this was reflected in the survival data.Mean symptom scores for pain were significantly higher in the TTIL group than in TAMK for 2 years postoperatively (P = 0.036). In addition, mean constipation scores were significantly higher for the TTIL group, with a 15-point difference in mean score at 3 months postoperatively (P = 0.037). CONCLUSIONS: This large comprehensive nonrandomized analysis of longitudinal HRQL shows that TTIL is associated with more pain and constipation than TAMK.

New-onset atrial fibrillation post-surgery for esophageal and junctional cancer: incidence, management, and impact on short- and long-term outcomes.

OBJECTIVE: To study new-onset postoperative atrial fibrillation in patients with esophageal and junctional cancer. DESIGN: Retrospective cohort study from a prospective data base. BACKGROUND: Atrial fibrillation (AF) is common after thoracic and esophageal surgical procedures. The full spectrum of risk factors, associations, and implications are unclear. METHODS: All patients undergoing multimodal therapy or surgery with curative intent from 2006 to mid-2013 were studied. New-onset AF was recorded prospectively. Risk factors, management and resolution, association with other complications, and impact on in-hospital mortality and longer-term oncologic outcomes were analyzed in retrospective cohort analysis. RESULTS: A total of 473 patients (mean age: 63 years; 73% male) underwent resection, 51% 2-stage, 18% 3-stage, 12% transhiatal, and 19% extended total gastrectomy. Ninety-six (20%) patients developed new-onset AF, in 18%, 27%, 29%, and 14% of 2-, 3-, transhiatal, and extended total gastrectomy cohorts, respectively (P=0.05). Age, diabetes, neoadjuvant therapy, and cardiac history predisposed (P<0.05) to AF, and AF was significantly (P<0.0001) associated with pneumonia, pleural effusions requiring drainage, and maximum postoperative C-reactive protein (CRP) (P<0.05) but not with anastomotic leak/conduit necrosis or mortality. Amiodarone was the primary treatment in 63% of cases, 1% underwent cardioversion, and 92% were in sinus rhythm on discharge. At a median follow-up of 40 months (7-109 months), the median survival was 40 months versus 53 months in the AF and non-AF cohorts, respectively (P=0.353) CONCLUSIONS: New-onset AF is common, linked to age, diabetes, cardiac disease, and neoadjuvant therapy. It is strongly associated with complications, principally respiratory sepsis, and systemic inflammation. For most, it resolves, with no impact on oncologic outcomes.

Incarcerated thoracic gastric herniation after nephrectomy: a report of two cases.

Iatrogenic diaphragmatic hernias can occur after abdominal or thoracic surgery. Acute presentation of a diaphragmatic hernia varies depending on the extent and nature of the organ which has herniated. The initial diagnosis can be challenging due to the nonspecific nature of the presenting symptoms. Delay in diagnosis poses a significant risk to the patient, and a rapid deterioration can occur in the context of strangulation. We outline two cases of acute gastric herniation through a defect in the diaphragm after an open and a laparoscopic nephrectomy. Both had characteristic findings on imaging, required emergency, surgery and had a successful outcome. Both cases highlight the potential for late presentation with non-specific symptoms and the necessity for urgent surgical management where gastric perfusion is compromised.

Management of squamous cell cancer of the oesophagus in a patient with a polyglandular endocrinopathy (APECED) and achalasia.

INTRODUCTION: We report a case of a 37-year-old man, with a background of a rare polyglandular autoimmune syndrome and achalasia, who developed an oesophageal tumour. Both autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or type I polyglandular syndrome and achalasia confer increased risk of development of oesophageal squamous cell carcinoma. METHODS: Despite having had multiple endoscopic examinations and dilatations in the recent past, this patient presented with dysphagia, and on endoscopy, he was found to have a mid-oesophageal tumour. A multidisciplinary team approach was vital in his management as careful monitoring of underlying disorders including Addison's disease and hypoparathyroidism were challenging during neoadjuvant chemoradiotherapy and in the perioperative period. RESULTS: He made an uneventful recovery after a three-stage oesophagectomy, and histologically, he had a complete pathological response. CONCLUSION: To our knowledge, this is the first successful outcome of a patient with APECED and oesophageal carcinoma in the literature.

Perianal dermatofibrosarcoma protuberans: a case report.

A 67-year-old man presented with a perianal lump that had increased in size. On examination he had a 3-cm irregular, mobile, elevated, red, polypoid lump at the edge of the anus at the 8-o'clock position. Biopsy results unexpectedly revealed a spindle cell lesion extending deep into the subcutaneous tissue with occasional mitoses. The lesion was positive for CD34 and negative for epithelial markers, consistent with dermatofibrosarcoma protuberans (DFSP). Magnetic resonance imaging of the pelvis showed the mass extending deep into the ischiorectal space with no involvement of the external or internal anal sphincter. He underwent excision of the lesion with circumferential margins of 1 cm and formation of a skin rotation flap to achieve primary closure. Histology confirmed DFSP. Both the deep and lateral resection margins were involved. He proceeded to have a wider excision of margins, which was free of any remaining tumor. Dermatofibrosarcoma protuberans is a rare lesion. It most commonly occurs on the trunk; the perianal presentation in this case is unique. Surgical excision and preservation of functionality with cosmesis was an issue in this case, as DFSP is a locally aggressive tumor with a high recurrence rate.

Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: progesterone receptor B hypermethylation in breast cancer.

INTRODUCTION: Oestrogen receptor alpha (ER alpha) is traditionally measured on all breast tumour specimens to identify those patients more likely to respond to anti-oestrogens. Progesterone receptor (PR) status has contributed useful information in defining more responsive subgroups. PR negativity may be a marker for increased signalling through growth factor receptor tyrosine kinase pathways. Progesterone acts through two PRs, PRA and PRB. PRB, the functionally active PR, can be silenced by promoter hypermethylation. METHODS: Following DNA and RNA extraction from 94 breast carcinomas, the methylation status of the PRB promoter was assessed by sodium bisulphite modification and methylation sensitive PCR (MSP). A quantitative realtime PCR analysis (QRTPCR) was used to determine the levels of PRB mRNA expression. Protein expression was evaluated immunohistochemically with a commercially available PRB antibody. RESULTS: 76% of the primary breast carcinoma samples demonstrated a methylated band for PRB. PRB methylation significantly compromised total PR immunohistochemistry (IHC) expression (P = 0.03). PRB mRNA correlated positively with total PR IHC (r = 0.58, P = 0.04), ER alpha IHC (P = 0.02), and tumour grade (P = 0.01). PRB protein expression was significantly associated with a number of favourable prognostic variables including smaller (P = 0.004) lower grade (P = 0.007), ER alpha IHC positive tumours (P < 0.001), and tumours with a low Nottingham Prognostic Index (NPI) (P = 0.0008). PRB mRNA levels were significantly associated with better overall survival (P = 0.04) in a univariate analysis. CONCLUSION: The majority of tumours were methylated for PRB. This did not directly compromise PRB expression suggesting that other factors may down regulate the PR gene. When PRB was expressed, it correlated with good prognostic markers and better overall survival.

Role of the progesterone receptor (PR) and the PR isoforms in breast cancer.

Known risk factors for breast cancer include overexposure to exogenous or endogenous hormones, namely, estrogen and progesterone. The effects of progesterone acts via two isoforms of the progesterone receptor (PR) termed A (PRA) and B (PRB). There is a single human PR gene with two distinct promoter regions in exon 1 encoding the two isoforms. Studies have shown that in poor prognostic tumors, the ratio between PRA and PRB is altered, with a predominance of PRA and loss of PRB. PRA and PRB regulate different subsets of genes involved in particular functional pathways. Breast tumors that express PR are associated with slow growth, better differentiation, and better overall prognosis in the short term. Both estrogen receptor alpha (ERalpha) and total progesterone receptor (PR) are immunohistochemically measured on breast cancer specimens to help determine those patients who would benefit from hormonal treatment. Depending on the hormone receptor status and the menopausal status of the patient, different treatments are available. Although the value of ERalpha in predicting response to hormone therapy in early breast cancer patients is undisputed, the value of PR is currently under debate. Historically, PR was thought to be a surrogate marker for ER expression; however, it is now known that lack of PR expression can indicate underlying epidermal growth factor receptor signaling or promoter methylation. This has implications for and can dictate hormone therapy responsiveness. Further studies investigating the specific isoforms and their pathways will help to reveal the underlying mechanisms of PR-induced breast tumori-genesis and help in assigning the most appropriate patient-tailored treatment.