Purpose
Cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy is standard of care for diffuse malignant peritoneal mesothelioma (DMPM), but there is variability among ...institutions in the administration of adjuvant chemotherapy. Characterization of the largest series of DMPM patients treated at a single institution and identification of the demographic, disease, and treatment factors associated with overall survival were sought.
Patients and Methods
All DMPM patients who underwent initial cytoreductive surgery with the intention to undergo intraperitoneal chemotherapy and a second-look operation from 1995 to 2016 at our institution were retrospectively reviewed. The primary endpoint was overall survival.
Results
A total of 204 DMPM patients underwent initial cytoreduction. Median overall survival was 32 months from initial cytoreduction. Independent baseline prognostic factors of improved overall survival were female sex, age < 60 years, and epithelioid histology. Independent treatment factors associated with improved overall survival were attempted resection at initial operation, residual disease < 0.5 cm at the end of the initial operation, and dwell intraperitoneal chemotherapy.
Conclusions
Cytoreductive surgery with intraoperative and dwell intraperitoneal chemotherapy is a feasible approach for DMPM. Expanded access to these therapies may offer benefit to a larger population of patients. Demographic and operative parameters associated with overall survival in this large cohort are consistent with previous reports. In the context of this treatment protocol, dwell intraperitoneal chemotherapy is associated with longer overall survival.
The evaluation of the malignancy risk of thyroid nodules involves clinical factors, sonographic characteristics, cytopathology, and molecular profiling. Altogether, this algorithm can be costly and ...time consuming. We evaluated the stepwise contribution of each diagnostic step toward an accurate prediction of malignancy.
A retrospective study of dominant nodules of 137 patients who underwent surgical excision was performed. A baseline logistic regression model for predicting malignancy was regressed on clinical factors. In a stepwise fashion, the 2015 American Thyroid Association ultrasound risk stratification, Bethesda classification of fine-needle aspiration biopsies, and molecular profiling were added to the baseline model and the significance of each step analyzed using likelihood ratio test. Receiver operating characteristic curves were calculated for each model.
The addition of American Thyroid Association risk stratification and Bethesda classification to preceding models were statistically significant (P < .001). The addition of molecular profiling (as a strategy independent of a particular test) was not significant (P = .812). The areas under the curve of the baseline model and models sequentially including American Thyroid Association stratification, cytopathology, and molecular profiling were 0.76, 0.85, 0.91, and 0.91, respectively.
Clinical factors, sonographic characteristics, and cytopathology are sufficiently accurate in predicting malignancy risk of most thyroid nodules.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult-to-treat cancers. With an increasing incidence and inability to make major progress, it represents the very definition of unmet ...medical need. Progress has been made in understanding the basic biology-systematic genomic sequencing has led to the recognition that PDAC is not typically a heavily mutated tumor, although there are exceptions. The most consistently mutated genes are
, and
Study of familial PDAC has led to the recognition that a variety of defects in DNA repair genes can be associated with the emergence of pancreatic cancer. Recent studies suggest that epigenetics may play a larger role than previously recognized. A major new understanding is the recognition that PDAC should be considered a composite of tumor cells, as well as pancreatic stellate cells, immune cells, and extracellular matrix. The individual components contribute to metabolic aberration, immune dysfunction, and chemotherapy resistance, and therapeutic innovations may be needed to address them individually. It has also been recognized that metastatic seeding from PDAC occurs very early in the disease course-in an estimated 73% of cases, once the tumor reaches 2 cm. The implication of this is that therapies directed toward micrometastatic disease and increasing fractional cell kill are most needed. Neoadjuvant approaches have been taken to increase resectability and improve outcome. So much work remains, and most critical is the need to understand how this tumor originates and develops.
Pancreatic neuroendocrine tumors are a group of rare, heterogeneous neoplasms that have been increasing in incidence the past few decades largely because of the diagnosis of pancreatic incidentalomas ...on cross-sectional imaging. Although these tumors are classically associated with clinical syndromes that result from excess secretion of particular hormones, most pancreatic neuroendocrine tumors are nonfunctional tumors presenting with symptoms secondary to mass effect, metastatic disease, or as incidental findings. This article reviews the diagnostic algorithm, surgical management, and available systemic therapies for nonfunctional pancreatic neuroendocrine tumors.
Discussing the impact of pancreatic surgery on long-term health is poorly understood, but necessary for informed consent. Given the increased number of pancreatic operations being performed annually, ...further investigation is necessary.
Patients surviving longer than 5 years after pancreatic surgery were surveyed for postoperative hospitalizations, operations, pain, nutrition and diabetes. Variables were analyzed according to patient and peri-operative variables, and validated using medical records.
Eighty individuals completed the survey; median follow-up was 9.5 years (IQR:6.43,12.73). 47.5% underwent a pancreatoduodenectomy, and 25.0% a distal pancreatectomy; 40.0% had adenocarcinoma. 57.1% reported long-term weight loss, of which 65.9% was unintentional. While 1.3% took pancreatic enzymes before surgery, 38.8% utilized after. 12.5% had diabetes before, and 28.6% after surgery; 22 of 30 patients required insulin replacement therapy (73.3%). 41.3% reported hospitalizations, 17.5% required endoscopies and 28.8% additional operations after full recovery. Need for additional interventions were not related to pathology or post-operative complications, but were more common among patients undergoing a Whipple.
More than half of patients will have a long-term medical complication attributable to pancreatectomy. In comparison to the literature, it may be inferred that consequences occur within the first few years after surgery, and do not compound over time.
Aims
The prognostic significance of histological subtyping of epithelioid pleural mesotheliomas has been recently reported, but similar data are lacking for peritoneal mesotheliomas. The aim of this ...study was to investigate possible relationships between histological growth patterns of epithelioid peritoneal mesotheliomas, clinicopathological features, and patient outcome.
Methods and results
Eighty‐four cases of chemotherapy‐naive epithelioid peritoneal mesothelioma were classified into tubulopapillary, micropapillary, papillary, tubular, solid and trabecular growth patterns. Pathological features such as depth of invasion, lymphocytic host response, mitotic count, nuclear grade, lymphovascular invasion, lymph node metastasis and stromal desmoplasia were analysed. The most common histological patterns were solid (n = 37, 44%), tubulopapillary (n = 24, 29%), and micropapillary (n = 11, 13%). The overall median survival was 36 months. Patients with solid mesothelioma had shorter overall survival (median, 29 months) than patients with tubulopapillary and micropapillary growth patterns (median, 51 and 53 months, respectively; P = 0.053). A high mitotic index (>5 in 50 high‐power fields) was found to be associated with poor survival (P < 0.03). A moderate to severe lymphocytic host response was associated with longer median survival (P = 0.13).
Conclusions
Our study highlights the prognostic importance of the solid growth pattern among diffuse epithelioid peritoneal mesotheliomas, and reaffirms mitotic index as a predictor of overall survival.
Background
Recently, normocalcemic (NC) and normohormonal (NH) variants of primary hyperparathyroidism (pHPT) have been described, with distinct biochemical profiles from the typical high serum ...calcium and parathyroid hormone (PTH) levels. Here, we investigate whether biochemical profile affects cure rate, as well as the kinetics of intraoperative PTH (IOPTH).
Methods
This is a single-center, retrospective study of pHPT patients undergoing parathyroidectomy. Patients were grouped based on preoperative calcium and PTH levels into typical, NC (normal calcium, elevated PTH, no evidence of secondary hyperparathyroidism), and NH (elevated calcium, unsuppressed PTH) biochemical profiles. All patients had IOPTH monitoring and ≥6-month post-op serum studies to confirm surgical cure. Patient variables were analyzed with Kruskal–Wallis test and Chi-square analysis. IOPTH kinetic curves were analyzed using a linear mixed model.
Results
From June 2006 to October 2014, 646 patients met inclusion criteria. Biochemical profile was typical in 460 patients (71%), NC in 101 (16%), and NH in 85 (13%). IOPTH levels were higher at all time points in typical patients,
p
< 0.001. Surgical cure rates were significantly lower for NC patients (90.1%) than for typical (98.5%) or NH patients (97.7%),
p
< 0.001, although a stricter criteria for cure was used in this group (normal calcium AND normal PTH). In a multivariable linear mixed model, NC patients had a significantly slower rate of IOPTH decline (
p
< 0.001 at 10 min).
Conclusions
Here, we better characterize the atypical variants of pHPT. Using a stricter definition of cure in the NC variant, these patients have a lower surgical cure rate than typical or NH variants in pHPT. The IOPTH curve is affected by biochemical profile, with both NC and NH patients having lower absolute values and NC patients having a slower decline.
Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American ...Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines FG), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio OR = 2.08, 95% confidence interval CI = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.
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