Bile Spillage as a Prognostic Factor for Gall Bladder Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Biliary spillage (BS) is a common complication following initial cholecystectomy for gall bladder cancer (GBC). Few studies have explored the importance of BS as a long-term prognostic factor. We perform a meta-analysis of the association between BS and survival in GBC. METHODS: A systematic literature search was performed in February 2023. Studies evaluating the incidence of BS and its association with long-term outcomes in patients undergoing initial laparoscopic or open cholecystectomy for either incidental or resectable GBC were included. Overall survival (OS), disease-free survival (DFS), and rate of peritoneal carcinomatosis (RPC) were the primary end points. Forest plot analyses were used to calculate the pooled hazard ratios (HRs) of OS, DFS, and RPC. Metaregression was used to evaluate study-level association between BS and perioperative risk factors. RESULTS: Of 181 published articles, 11 met inclusion criteria with a sample size of 1116 patients. The rate of BS ranged between 9% and 67%. On pooled analysis, BS was associated with worse OS (HR = 1.68, 95% confidence interval [CI] = 1.32-2.14), DFS (pooled HR= 2.19, 95% CI = 1.30-3.68), and higher RPC (odds ratio = 9.37, 95% CI = 3.49-25.2). The rate of BS was not associated with higher T stage, lymph node metastasis, higher grade, positive margin status, reresection, or conversion rates. CONCLUSIONS: Our meta-analysis shows that BS is a predictor of higher peritoneal recurrence and poor survival in GBC. BS was not associated with tumor characteristics or conversion rates. Further research is needed to identify other potential risk factors for BS and investigate the ideal treatment schedule to improve survival.

Preoperative Breast MRI for Newly Diagnosed Ductal Carcinoma in Situ: Imaging Features and Performance in a Multicenter Setting (ECOG-ACRIN E4112 Trial).

Background There are limited data from clinical trials describing preoperative MRI features and performance in the evaluation of mammographically detected ductal carcinoma in situ (DCIS). Purpose To report qualitative MRI features of DCIS, MRI performance in the identification of additional disease, and associations of imaging features with pathologic, genomic, and surgical outcomes from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E4112 trial. Materials and Methods Secondary analyses of a multicenter prospective clinical trial from the ECOG-ACRIN Cancer Research Group included women with DCIS diagnosed with conventional imaging techniques (mammography and US), confirmed via core-needle biopsy (CNB), and enrolled between March 2015 and April 2016 who were candidates for wide local excision (WLE) based on conventional imaging and clinical examination results. DCIS MRI features and pathologic features from CNB and excision were recorded. Each woman without invasive upgrade of the index DCIS at WLE received a 12-gene DCIS score. MRI performance metrics were calculated. Associations of imaging features with invasive upgrade, dichotomized DCIS score (<39 vs ≥39), and single WLE success were estimated in uni- and multivariable analyses. Results Among 339 women (median age, 60 years; interquartile range, 51-66 years), most DCIS cases showed nonmass enhancement (NME) (195 of 339 [58%]) on MRI scans with larger median size than on mammograms (19 mm vs 12 mm; P < .001). Positive predictive value of MRI-prompted CNBs was 32% (21 of 66) (95% CI: 22, 44), yielding an additional cancer detection rate of 6.2% (21 of 339) (95% CI: 4.1, 9.3). MRI false-positive rate was 14.2% (45 of 318) (95% CI: 10.7, 18.4). No imaging features were associated with invasive upgrade or DCIS score (P = .05 to P = .95). Smaller size and focal NME distribution at MRI were linked to single WLE success (P < .001). Conclusion Preoperative MRI depicted ductal carcinoma in situ (DCIS) diagnosed with conventional imaging most commonly as nonmass enhancement, with larger median span than mammography, and additional cancer detection rate of 6.2%. MRI features of this subset of DCIS did not enable prediction of pathologic or genomic outcomes. Clinical trial registration no. NCT02352883 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kuhl in this issue. An earlier incorrect version of this article appeared online. This article was corrected on August 4, 2021.

Hashimoto's Thyroiditis Minimizes Lymph Node Metastasis in BRAF Mutant Papillary Thyroid Carcinomas.

Hashimoto's thyroiditis (HT) (autoimmune thyroiditis) is a clinicopathological entity associated with chronic lymphocytic infiltration resulting in hypothyroidism. HT is a double-edged sword that increases the risk of papillary thyroid cancer (PTC), yet it serves as a protective factor for PTC progression. BRAF mutation in PTCs is associated with rapid cell growth, aggressive tumor characteristics, and higher mortality rates. Here, we aimed to analyze the influence of HT in patients with PTCs and its effect on lymph node metastasis (LNM) in BRAF mutant tumors. Adults diagnosed with PTC between 2008 and January 2021 were retrospectively included. A total of 427 patients, 128 of whom had underlying HT, were included. The HT group had significantly higher rates of microcarcinoma (49.2% vs. 37.5%, p = 0.025) and less lateral LNM (8.6% vs. 17.1%, p = 0.024). Interestingly, BRAF-mutated PTCs were found to have significantly less overall LNM (20.9% vs. 51%, p = 0.001), central LNM (25.6% vs. 45.1%, p = 0.040) and lateral LNM (9.3% vs. 29.4%, p = 0.010) in patients with HT when compared to those without underlying HT. HT was found to be an independent protective predictor of overall and lateral LNM. Altogether, HT was able to neutralize the effect of BRAF mutation and was determined to be an independent protective factor against LNM. Specifically, our work may influence treatment-aggressiveness decision making for endocrinologists, oncologists and surgeons alike.

Association Between Surgery Preference and Receipt in Ductal Carcinoma In Situ After Breast Magnetic Resonance Imaging: An Ancillary Study of the ECOG-ACRIN Cancer Research Group (E4112).

Importance: Guiding treatment decisions for women with ductal carcinoma in situ (DCIS) requires understanding patient preferences and the influence of preoperative magnetic resonance imaging (MRI) and surgeon recommendation. Objective: To identify factors associated with surgery preference and surgery receipt among a prospective cohort of women with newly diagnosed DCIS. Design, Setting, and Participants: A prospective cohort study was conducted at 75 participating institutions, including community practices and academic centers, across the US between March 25, 2015, and April 27, 2016. Data were analyzed from August 2 to September 24, 2021. This was an ancillary study of the ECOG-ACRIN Cancer Research Group (E4112). Women with recently diagnosed unilateral DCIS who were eligible for wide local excision and had a diagnostic mammogram within 3 months of study registration were included. Participants who had documented surgery and completed the baseline patient-reported outcome questionnaires were included in this substudy. Exposures: Women received preoperative MRI and surgeon consultation and then underwent wide local excision or mastectomy. Participants will be followed up for recurrence and overall survival for 10 years from the date of surgery. Main Outcomes and Measures: Patient-reported outcome questionnaires assessed treatment goals and concerns and surgery preference before MRI and after MRI and surgeon consultation. Results: Of the 368 participants enrolled 316 (86%) were included in this substudy (median [range] age, 59.5 [34-87] years; 45 women [14%] were Black; 245 [78%] were White; and 26 [8%] were of other race). Pre-MRI, age (odds ratio [OR] per 5-year increment, 0.45; 95% CI, 0.26-0.80; P = .007) and the importance of keeping one's breast (OR, 0.48; 95% CI, 0.31-0.72; P < .001) vs removal of the breast for peace of mind (OR, 1.35; 95% CI, 1.04-1.76; P = .03) were associated with surgery preference for mastectomy. After MRI and surgeon consultation, MRI upstaging (48 of 316 [15%]) was associated with patient preference for mastectomy (OR, 8.09; 95% CI, 2.51-26.06; P < .001). The 2 variables with the highest ORs for initial receipt of mastectomy were MRI upstaging (OR, 12.08; 95% CI, 4.34-33.61; P < .001) and surgeon recommendation (OR, 4.85; 95% CI, 1.99-11.83; P < .001). Conclusions and Relevance: In this cohort study, change in patient preference for DCIS surgery and surgery received were responsive to MRI results and surgeon recommendation. These data highlight the importance of ensuring adequate information and ongoing communication about the clinical significance of MRI findings and the benefits and risks of available treatment options.

Factors That Predict Biological Aggressiveness in Estrogen Receptor-Positive / Human Epidermal Growth Factor Receptor 2-Negative / Lymph Node-Negative Breast Cancer.

Background: Traditionally, breast cancer is staged using TNM criteria: tumor size (T), nodal status (N), and metastasis (M). The Oncotype DX assay provides a recurrence score (RS) based on genomics that predicts the likelihood of distant recurrence in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-)/lymph node-negative (LN-) tumors. Methods: We retrospectively reviewed the medical records of patients with ER+/HER2-/LN- breast cancer tumors who were evaluated between 2007 and 2017 with Oncotype DX RS. We compared the RS to tumor size, patient age, progesterone receptor (PR) status, and LN immunohistochemistry to assess for factors that may independently predict recurrence risk. We also compared tumor size to tumor grade. Results: The data set included 296 tumors: 248 ER+/PR-positive (PR+)/HER2- and 48 ER+/PR-negative (PR-)/HER2-. RS ranged from 0 to 66, patient age ranged from 33 to 77 years, and tumor size ranged from 1 to 65 mm. No significant correlation was found between age and RS (r=-0.073, P=0.208). PR- tumors had a significantly higher RS regardless of size (PR- mean RS 30.8 ± 12.7; PR+ mean RS 16.3 ± 7.3; t(53)=7.6, P<0.0001). No significant correlation was seen between tumor size and RS for all tumors (r=-0.028, P=0.635), and this finding remained true for the PR+ tumor subgroup (r=0.114, P=0.072). However, a significant negative correlation was seen between tumor size and RS in the PR- subgroup (r=-0.343, P=0.017). Further analysis to ensure that differences in tumor grade did not account for this correlation showed equal distribution of well differentiated, moderately differentiated, and poorly differentiated tumors with no significant correlation between tumor size and grade. Conclusion: Increasing tumor size may not be associated with increasing biological aggressiveness. Traditionally, smaller tumors are thought to be lower risk and larger tumors higher risk, with a tendency to use chemotherapy with large tumors. However, our data showed a negative correlation between tumor size and RS in the PR- subgroup. A tumor with PR negativity that reaches a large size without metastasizing may suggest a favorable tumor biology. These tumors may not receive as much benefit from chemotherapy as previously thought. Also, the higher RS seen in smaller PR- tumors may demonstrate PR- status as a predictor for higher risk of distant recurrence. We propose that all tumors meeting the ER+/PR-/LN- criteria, regardless of size, should be considered for genotyping, with the RS used to guide chemotherapy benefit.

Peritoneal Encapsulation With Incarcerated Meckel Diverticulum Contributing to Small Bowel Obstruction.

Background: Meckel diverticulum is the most common congenital gastrointestinal malformation, but it is rarely symptomatic. Peritoneal encapsulation is a rare abnormality of embryonic development and may present with obstruction, although it too is usually asymptomatic. Case Report: We report the case of an 82-year-old male who presented with symptoms and imaging findings consistent with small bowel obstruction. During laparotomy, a peritoneal encapsulation was observed containing the majority of the small bowel. A Meckel diverticulum was discovered tethered to the small bowel mesentery by a mesodiverticular band, preventing egress from the accessory peritoneal membrane and appearing to be the cause of the obstruction. Conclusion: This patient had 3 rare findings-peritoneal encapsulation, Meckel diverticulum, and a mesodiverticular band-contributing to cause an acute small bowel obstruction. The presence of all of these features in one patient is extremely rare, and we believe this is the first description of such a phenomenon.

Association of Magnetic Resonance Imaging and a 12-Gene Expression Assay With Breast Ductal Carcinoma In Situ Treatment.

IMPORTANCE: Advanced diagnostics, such as magnetic resonance imaging (MRI) and gene expression profiles, are potentially useful to guide targeted treatment in patients with ductal carcinoma in situ (DCIS). OBJECTIVES: To examine the proportion of patients who converted to mastectomy after MRI and the reasons for those conversions and to measure patient adherence to radiotherapy guided by the 12-gene DCIS score. DESIGN, SETTING, AND PARTICIPANTS: Analysis of a prospective, cohort, nonrandomized clinical trial that enrolled women with DCIS on core biopsy who were candidates for wide local excision (WLE) from 75 institutions from March 25, 2015, to April 27, 2016, through the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial E4112. INTERVENTIONS: Participants underwent breast MRI before surgery, and subsequent management incorporated MRI findings for choice of surgery. The DCIS score was used to guide radiotherapy recommendations among women with DCIS who had WLE as the final procedure and had tumor-free excision margins of 2 mm or greater. MAIN OUTCOMES AND MEASURES: The primary end point was to estimate the conversion rate to mastectomy and the reason for conversion. RESULTS: Of 339 evaluable women (mean [SD] age, 59.1 [10.1] years; 262 [77.3%] of European descent) eligible for WLE before MRI, 65 (19.2%; 95% CI, 15.3%-23.7%) converted to mastectomy. Of these 65 patients, conversion was based on MRI findings in 25 (38.5%), patient preference in 25 (38.5%), positive margins after attempted WLE in 10 (15.4%), positive genetic test results in 3 (4.6%), and contraindication to radiotherapy in 2 (3.1%). Among the 285 who had WLE performed after MRI as the first surgical procedure, 274 (96.1%) achieved successful breast conservation. Of 171 women eligible for radiotherapy guided by DCIS score (clear margins, absence of invasive disease, and score obtained), the score was low (<39) in 82 (48.0%; 95% CI, 40.6%-55.4%) and intermediate-high (≥39) in 89 (52.0%; 95% CI, 44.6%-59.4%). Of these 171 patients, 159 (93.0%) were adherent with recommendations. CONCLUSIONS AND RELEVANCE: Among women with DCIS who were WLE candidates based on conventional imaging, multiple factors were associated with conversion to mastectomy. This study may provide useful preliminary information required for designing a planned randomized clinical trial to determine the effect of MRI and DCIS score on surgical management, radiotherapy, overall resource use, and clinical outcomes, with the ultimate goal of achieving greater therapeutic precision. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02352883.

Rosai-Dorfman disease of the breast and parotid gland.

Rosai-Dorfman disease or sinus histiocytosis with massive lymphadenopathy (SHML) is a histiocytic proliferative disorder that typically involves the cervical lymph nodes with or without extranodal involvement of the skin, soft tissues, respiratory tract, or virtually any other site of the body. We present a case report of SHML involving the cervical lymph nodes, parotid gland and breast. There is only one other Rosai-Dorfman registered case that involves both breast and parotid disease and no previously published case reports. The patient presented atypically with breast masses found on screening mammogram rather than massive cervical lymphadenopathy. We describe the subsequent radiographic and surgical pathologic evidence that led to the diagnosis of this rare disease.

A Case of Malignant Pheochromocytoma Presenting 7 Years After the Initial Surgery.

BACKGROUND: Pheochromocytoma (PHEO) is a rare tumor of the adrenal medulla and sympathetic ganglion that produces the catecholamines norepinephrine and epinephrine. Traditionally, approximately 10% of PHEOs were thought to be malignant, but recent developments in PHEO research have noted that specific genetic mutations are associated with higher risk of metastatic spread. CASE REPORT: We report the case of a 71-year-old female who presented with abdominal pain in September 2009 when she was 64 years old. Evaluation at that time revealed cholelithiasis and bilateral adrenal masses. Workup showed elevated free normetanephrines, and positron emission tomography-computed tomography demonstrated bilateral adrenal hypermetabolic lesions concerning for malignancy. She underwent open bilateral adrenalectomies and cholecystectomy. The right adrenal mass was identified as a PHEO with nonaggressive features and negative margins, and the left adrenal mass was an adrenal cortical adenoma without dysplasia. In April 2016, the patient was referred by her endocrinologist for elevated blood pressure and 16-lb weight loss. The patient reported weakness, headaches, hot flashes, cold sweats, and fatigue. Laboratory workup revealed elevated plasma free normetanephrine, and imaging showed a recurrence of the PHEO in both the right adrenal bed and the head of the right humerus. CONCLUSION: Current predictors of PHEO recurrence failed to identify the original tumor as aggressive or likely to return as a metastatic lesion. Because of the rarity of these tumors, few consistent laboratory or radiologic predictors of malignancy based on initial presentation have been identified; predictors of malignancy in PHEO warrant further investigation.

Omental torsion mimicking acute appendicitis: a case report.

Primary omental torsion is an uncommon cause of an acute abdomen that can mimic acute appendicitis. Herein we report a case of suspected acute appendicitis that proved to be a distal segment of infarcted omentum secondary to primary torsion.

An Assessment of Margins after Lumpectomy in Breast Cancer Management.

We performed this study to evaluate our indications for margin re-excision (MRE) in the management of cancer patients opting for breast conservation therapy (BCT). We identified patients choosing breast conservation therapy from January 2012 to May 2014. Margins were considered negative if >2 mm, close if <2 mm, and positive if ink was detected abutting tumor. Patients with close and positive margins underwent MRE. We identified 247 patients of which 190 had negative margins and did not require MRE, 46 patients had a close margin, and 11 had a positive margin, leading to an MRE rate of 23 per cent (57 of 247). The following variables were evaluated: tumor size, stage, estrogen receptor, progesterone receptor, HER2/neu receptor, and node status. None predicted the presence of tumor in the MRE specimen (P > 0.05). Patients with close margins had a 6.5 per cent (3 of 46), and patients with positive margins had a 36.4 per cent (4 of 11) incidence of tumor in the MRE specimens; this difference was statistically significant (P = 0.02). The low rate of finding tumor in MRE specimens of patients with close margins after lumpectomy for breast carcinoma argues for limiting MRE to patients with positive margins (ink on tumor) only. We have adopted this approach in our institution.

Newly diagnosed breast cancer patients choose bilateral mastectomy over breast-conserving surgery when testing positive for a BRCA1/2 mutation.

In women diagnosed with breast cancer and testing positive for a BRCA1/2 mutation, decisions as to whether to undergo prophylactic risk-reduction surgery may differ from those women who test positive in a presymptomatic phase. Eighty-four women were identified who had undergone genetic testing at the time of breast cancer diagnosis. The study group consisted of 46 of these women who had initially undergone breast-conserving surgery. Eight patients (17.4%) tested positive for a mutation. Seven of the eight underwent bilateral prophylactic mastectomy prior to receiving radiation therapy. The only patient not undergoing bilateral mastectomy was awaiting liver transplant. Women who are candidates for breast-conserving surgery and who test positive for a breast cancer gene mutation choose mastectomy over surveillance.

Determining standards for laparoscopic proficiency using virtual reality.

Laparoscopic training using virtual reality has proven effective, but rates of skill acquisition vary widely. We hypothesize that training to predetermined expert levels may more efficiently establish proficiency. Our purpose was to determine expert levels for performance-based training. Four surgeons established as laparoscopic experts performed 11 repetitions of 12 tasks. One surgeon (EXP-1) had extensive Minimally Invasive Surgical Trainer-Virtual Reality (MIST VR) exposure and formal laparoscopic fellowship training. Trimmed mean scores for each were determined as expert levels. A composite score (EXP-C) was defined as the average of all four expert levels. Thirty-seven surgery residents without prior MIST VR exposure and two research residents with extensive MIST VR exposure completed three repetitions of each task to determine baseline performance. Scores for EXP-1 and EXP-C were plotted against the best score of each participant. On average, the EXP-C level was reached or exceeded by 7 of the 37 (19%) residents. In contrast, the EXP-1 level was reached or exceeded by 1 of 37 (3%) residents and both research residents on all tasks. These data suggest the EXP-C level may be too lenient, whereas the EXP-1 level is more challenging and should result in adequate skill acquisition. Such standards should be further developed and integrated into surgical education.

Pneumoperitoneum from gas gangrene of the pancreas: three unusual findings in a single case.

A 62-year-old man was first seen with acute pancreatitis with diffuse intrapancreatic gas and pneumoperitoneum. An immediate exploratory operation revealed diffuse pancreatic necrosis but no perforated viscus; postoperatively, the patient rapidly died. This case represents a constellation of extremely rare findings: Clostridium perfringens infection of the pancreas, pancreatic emphysema or "gas gangrene," and pneumoperitoneum without a perforated viscus.

Parathyroid hormone levels predict posttotal thyroidectomy hypoparathyroidism.

We hypothesized that parathyroid hormone (PTH) determination would be the most effective strategy to identify posttotal thyroidectomy hypoparathyroidism (PTTHP) compared with other clinical and laboratory parameters. We retrospectively reviewed our recent experience with total thyroidectomy. We recorded demographics, malignancy, thyroid weight, parathyroid autotransplantation, hospital stay, use of postoperative calcium and hormonally active vitamin D3 (calcitriol), and postoperative serum calcium and PTH levels. Patients were divided into two groups depending on whether supplemental calcitriol was required to maintain eucalcemia and therefore reflecting the diagnosis of PTTHP. From October 2010 to June 2013, a total of 202 total thyroidectomies were performed. Twenty-four patients (12%) developed PTTHP and required calcitriol replacement. Logistic regression analysis revealed that only postoperative calcium levels (P = 0.02) and PTH levels (P < 0.0001) statistically significantly predicted PTTHP. Twenty-two of 29 patients with PTH 13 pg/mL or less had PTTHP. Only two of 173 patients with a PTH level greater than 13 pg/mL were diagnosed with PTTHP. We recommend using PTH levels after total thyroidectomy to determine which patients will have hypoparathyroidism requiring calcitriol therapy. An early determination of PTTHP allows for prompt management that can shorten hospital stay and improve outcomes.