Condyloma lata mimicking vulvar carcinoma in an immunocompromised patient: A case report.

Background: Syphilis is a sexually transmitted infection with increasing incidence in the United States. Presentations of syphilis vary widely and can be easily mistaken for other diagnoses, including cancer, especially in atypical cases. Case description: At her delivery after no prenatal care, a 35-year-old woman was found to have exophytic vulvar and perianal lesions, inguinal lymphadenopathy, and a new diagnosis of HIV, with a strong clinical concern for vulvar and/or anal carcinoma. She was subsequently diagnosed with presumed late latent syphilis and began weekly intramuscular penicillin G benzathine treatment. CT imaging demonstrated a perineal plaque-like area with bilateral inguinal, external iliac and retroperitoneal lymphadenopathy. She was seen in gynecologic oncology clinic one week after her initial presentation with notable improvement in the vulvar lesions, raising suspicion for condyloma lata rather than invasive or preinvasive disease on the vulva, however concern remained for dysplasia in the perianal lesion. Another week later, she underwent an exam under anesthesia with vulvar and perianal biopsies revealing chronic inflammation and granulomatous change without evidence of malignancy or dysplasia. At the four week post operative visit, there was almost complete resolution of the lesions. Conclusion: Syphilis should be considered in the differential diagnosis of atypical vulvar lesions.

Long-Term Survival and Curative-Intent Treatment in Hepatitis B or C Virus-Associated Hepatocellular Carcinoma Patients Diagnosed during Screening.

Background: We initiated a prospective screening trial in patients with hepatitis to diagnose HCC in the early stage and to evaluate the impact on long-term survival. Methods: From 1993−2006, 10,372 patients with chronic hepatitis B (14%), hepatitis C (81%), or both (5%) were enrolled in an HCC screening program. All patients underwent liver biopsy at enrollment. Transabdominal ultrasonography and serum alpha-fetoprotein were evaluated every 6 months. Abnormal screening results led to axial imaging and tumor biopsy. Results: Cirrhosis was confirmed on biopsy in 2074 patients (20%). HCC was diagnosed in 1016 patients (9.8%), all of whom had cirrhosis (49.0% HCC incidence in patients with cirrhosis). HCC was diagnosed at the initial screening in 165 patients (16.2%) and on follow-up in 851 patients (83.8%). The HCC diagnosis median time during follow-up screening was 6 years (range 4−10). Curative-intent treatment (resection, ablation, or transplant) was performed in 713 patients (70.2%). Overall survival at 5 and 10 years in those 713 patients was 30% and 4%, respectively, compared to no 5-year survivors in the 303 patients with advanced-stage disease (p < 0.001). Cause of death at 5 years in the 713 patients treated with curative intent was HCC in 371 patients (52%), progressive cirrhosis in 116 patients (16%), and other causes in 14 patients (2%). At 10 years, 456 patients (64%) had died from HCC, 171 (24%) from progressive cirrhosis, and 57 (8%) from other causes. Conclusions: Our screening program diagnosed early-stage HCC, permitting curative-intent treatment in 70%, but the 10-year survival rate is 4% due to HCC recurrence and progressive cirrhosis.

Implementation of a Hepatocellular Carcinoma Screening Program for At-risk Patients Safety-Net Hospital: A Model for National Dissemination.

OBJECTIVE: This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population. BACKGROUND: Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients. METHODS: In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance. RESULTS: From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32-282). Median overall survival for treated patients was 32 months. CONCLUSIONS: Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program's success. Next steps include expanding the program to additional at-risk populations.

Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection.

BACKGROUND: Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs. METHODS: We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0-1% viability; major (pMajR) = 2-49% viability; minor (pMinR) = 50-99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression. RESULTS: Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p < 0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p = 0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR). CONCLUSIONS: One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Effect of Co-mutation of RAS and TP53 on Postoperative ctDNA Detection and Early Recurrence after Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for patients undergoing hepatectomy for colorectal liver metastases (CLM). We hypothesized that post-hepatectomy ctDNA detection would identify patients at highest risk for early recurrence of CLM. STUDY DESIGN: Patients with CLM who underwent curative-intent hepatectomy with ctDNA analysis within 180 days postoperatively (1/2013 and 6/2020) were included. Tissue somatic mutations and ctDNA analyses were performed by next-generation sequencing panels. Survival analyses determined factors associated with clinical recurrence 1 year or earlier after hepatectomy. Patients with primary tumors in situ and without 1-year follow-up were excluded. Median follow-up was 28.3 months. RESULTS: Of 105 patients, 32 (30%) were ctDNA positive (ctDNA+) after curative-intent hepatectomy. Compared with ctDNA-negative patients, ctDNA+ patients had multiple CLM (84% vs 55%, p = 0.002) and co-mutated RAS/TP53 (47% vs 23%, p = 0.018). Multiple CLM (odds ration (OR), 5.43; p = 0.005) and co-mutated RAS/TP53 (OR, 3.30; p = 0.019) were independently associated with post-hepatectomy ctDNA. Although perioperative carcinoembryonic antigen levels were not prognostic, postoperative ctDNA+ (hazard ratio (HR), 2.04; p = 0.011) and extrahepatic disease (HR, 2.45, p = 0.004) were independently associated with worse recurrence-free survival. After adjusting for extrahepatic disease, preoperative chemotherapy, multiple CLM, tumor viability of 50% or greater, and co-mutated RAS/TP53, ctDNA+ within 180 days was the only independent risk factor for recurrence 1 year or earlier after hepatectomy (94% vs 49%; HR, 11.8; p = 0.003). CONCLUSION: Postoperative ctDNA detection is associated with early recurrence 1 year or earlier after curative-intent hepatectomy for CLM, and RAS/TP53 co-mutations result in a more than 3-fold increased risk for postoperative ctDNA positivity. This highlights the complementary effect of tumor tissue and circulating mutational profiling for patients with CLM.

Preliminary Analysis of Liquid Biopsy after Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Liquid biopsies are increasingly tested in patients with colorectal cancer to assess tumor burden, response to therapy, and prognosis. The significance of liquid biopsy results after resection of colorectal liver metastases (CLMs) is not well-defined. STUDY DESIGN: Sixty-three patients undergoing CLM resection between 2016 and 2018 had plasma drawn postoperatively for liquid biopsy evaluation. Next-generation sequencing analysis was performed to detect somatic mutations in 70 genes. RESULTS: Liquid biopsy after CLM resection was positive in 42 of 63 patients (67%). Eleven patients (18%) had 1 gene mutation, 14 patients (22%) had 2 to 3 mutations, and 17 patients (27%) had 4 or more mutations. The most common mutation was APC, detected in 32 patients (76%), followed by TP53 (74%) and KRAS (38%). Two-year overall survival rate from date of liver resection was significantly worse among patients with a positive liquid biopsy (70% vs 100%; p = 0.005), particularly for those with 4 or more gene mutations detected, whose 2-year overall survival rate was 41%. Sixteen of the 63 patients underwent serial liquid biopsies, resulting in 100 liquid biopsies with matched serum CEA and CT scan results. Metastases were identified in 74 CT scans, which correlated with positive liquid biopsy in 77% of samples (p < 0.001) and CEA > 3 ng/mL in 45% of samples (p < 0.22). CONCLUSIONS: Liquid biopsy results provide information about disease burden and prognosis that is complementary to serum CEA and CT imaging. A positive liquid biopsy after CLM resection is associated with worse overall survival, particularly when multiple gene mutations are detected.

Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience.

BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Variation in postacute care utilization after complex surgery.

BACKGROUND: Variation in use of postacute care (PAC), including skilled nursing facilities and inpatient rehabilitation, accounts for 73% of regional variation in Medicare spending. Studies of hospital variation in PAC use have typically focused on nonsurgical patients or have been limited to Medicare data. Consequently, there is no nationally representative data on how rates of postoperative discharge to PAC differ between hospitals. The purpose of this study was to explore hospital-level variation in PAC utilization after cardiovascular and abdominal surgery. MATERIALS AND METHODS: We evaluated 3,487,365 patients from the Nationwide Inpatient Sample and 60,666 from the Veterans Affairs health system, who had colorectal surgery, hepatectomy, pancreatectomy, coronary bypass, aortic aneurysm repair, and peripheral vascular bypass from 2008 to 2011. For each hospital, we calculated unadjusted and risk-adjusted observed-to-expected ratios for discharge to PAC facilities (skilled nursing or inpatient rehabilitation). RESULTS: A total of 631,199 (18%) non-veterans and 4744 (8%) veterans were discharged to PAC facilities. For veterans, 32% were ≥70 y old, and 98% were men. For non-veterans, 39% were ≥70, and 60% were men. Hospital rates of discharge to PAC facilities varied from 1% to 36% for veterans hospitals and from 1% to 59% for non-veteran hospitals. Risk-adjusted observed-to-expected ratios ranged from 0.10 to 4.15 for veterans and from 0.11 to 4.3 for non-veteran hospitals. CONCLUSIONS: There is substantial variation in PAC utilization and rates of home discharge after abdominal and cardiovascular surgery. To reduce variation, further research is needed to understand health systems factors that influence PAC utilization.

Hospital Minimally Invasive Surgery Utilization for Gastrointestinal Cancer.

OBJECTIVE: The aim of the study was to evaluate the impact of receiving care at high minimally invasive surgery (MIS)-utilizing hospitals BACKGROUND:: MIS techniques are used across surgical specialties. The extent of MIS utilization for gastrointestinal (GI) cancer resection and impact of receiving care at high utilizing hospitals is unclear. METHODS: This is a retrospective cohort study of 137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary, colon, and rectal cancer patients within the National Cancer Data Base (2010-2013). Disease-specific, hospital-level, reliability-adjusted MIS utilization rates were calculated to evaluate perioperative outcomes. Among patients for whom adjuvant chemotherapy (AC) was indicated, the association between days to AC and hospital MIS utilization was examined using generalized estimating equations. Association with risk of death was evaluated using multivariable Cox regression. RESULTS: Disease-specific MIS use increased significantly [42.0%-68.3% increase; trend test, P < 0.001 for all except hepatobiliary (P = 0.007)] over time. Most hospitals [range-30.3% (colon); 92.9% (pancreatic)] were low utilizers (≤30% of cases). Higher MIS utilization is associated with increased lymph nodes examined (P < 0.001, all) and shorter length of stay (P < 0.001, all). Each 10% increase in MIS utilization is associated with fewer days to AC [3.3 (95% confidence interval, 1.2-5.3) for MIS gastric; 3.3 ([0.7-5.8) for open gastric; 1.1 (0.3-2.0) days for open colon]. An association between MIS utilization and risk of death was observed for colon [Q2-hazard ratio (HR) 0.96 (0.89-1.02); Q3-HR 0.91 (0.86-0.98); Q4-HR 0.87 (0.82-0.93)] and rectal cancer [Q2-HR 0.89 (0.76-1.05); Q3-HR 0.84 (0.82-0.97); Q4-HR 0.86 (0.74-0.98)]. CONCLUSIONS: Most hospitals treating GI malignancies are low MIS utilizers. Our findings may reflect real-world MIS effectiveness for oncologic resection and could be useful for identifying hospitals with infrastructure and/or processes beneficial for multimodality cancer care.

Postacute Care and Recovery After Cancer Surgery: Still a Long Way to Go.

OBJECTIVE: To determine whether postacute care (PAC) facilities can compensate for increased mortality stemming from a complicated postoperative recovery (complications or deconditioning). BACKGROUND: An increasing number of patients having cancer surgery rely on PAC facilities including skilled nursing and rehabilitation centers to help them recover from postoperative complications and the physical demands of surgery. It is currently unclear whether PAC can successfully compensate for the adverse consequences of a complicated postoperative recovery. METHODS: We combined data from the Veterans Affairs Cancer Registry with the Surgical Quality Improvement Program to identify veterans having surgery for stage I-III colorectal cancer from 1999 to 2010. We used propensity matching to control for comorbidity, functional status, postoperative complications, and stage. RESULTS: We evaluated 10,583 veterans having colorectal cancer surgery, and 765 veterans (7%) were discharged to PAC facilities whereas 9818 veterans (93%) were discharged home. Five-year overall survival after discharge to PAC facilities was 36% compared with 51% after discharge home. Stage I patients discharged to PAC facilities had similar survival (45%) as stage III patients who were discharged home (44%). Patients discharged to PAC facilities had worse survival in the first year after surgery (hazard ratio 2.0, 95% confidence interval 1.7-2.4) and after the first year (hazard ratio 1.4, 95% confidence interval 1.2-1.5). CONCLUSIONS: Discharge to PAC facilities after cancer surgery is not sufficient to overcome the adverse survival effects of a complicated postoperative recovery. Improvement of perioperative care outside the acute hospital setting and development of better postoperative recovery programs for cancer patients are needed to enhance survival after surgery.

The seven attributes of the academic surgeon: Critical aspects of the archetype and contributions to the surgical community.

BACKGROUND: "Academic surgeon" describes a member of a medical school department of surgery, but this term does not fully define the important role of such physician-scientists in advancing surgical science through translational research and innovation. METHODS: The curriculum vitae and self-descriptive vignettes of the records of achievement of seven surgeons possessing documented records of academic leadership, innovation, and dissemination of knowledge were reviewed. RESULTS: Out analysis yielded seven attributes of the archetypal academic surgeon: 1) identifies complex clinical problems ignored or thought unsolvable by others, 2) becomes an expert, 3) innovates to advance treatment, 4) observes outcomes to further improve and innovate, 5) disseminates knowledge and expertise, 6) asks important questions to further improve care, and 7) trains the next generation of surgeons and scientists. CONCLUSION: Although alternative pathways to innovation and academic contribution also exist, the academic surgeon typically devotes years of careful observation, analysis, and iterative investigation to identify and solve challenging or unexplored clinical problems, ideally leverages resources available in academic medical centers to support these endeavors.

National Quality Forum Colon Cancer Quality Metric Performance: How Are Hospitals Measuring Up?

OBJECTIVE: To evaluate the impact of care at high-performing hospitals on the National Quality Forum (NQF) colon cancer metrics. BACKGROUND: The NQF endorses evaluating ≥12 lymph nodes (LNs), adjuvant chemotherapy (AC) for stage III patients, and AC within 4 months of diagnosis as colon cancer quality indicators. Data on hospital-level metric performance and the association with survival are unclear. METHODS: Retrospective cohort study of 218,186 patients with resected stage I to III colon cancer in the National Cancer Data Base (2004-2012). High-performing hospitals (>75% achievement) were identified by the proportion of patients achieving each measure. The association between hospital performance and survival was evaluated using Cox shared frailty modeling. RESULTS: Only hospital LN performance improved (15.8% in 2004 vs 80.7% in 2012; trend test, P < 0.001), with 45.9% of hospitals performing well on all 3 measures concurrently in the most recent study year. Overall, 5-year survival was 75.0%, 72.3%, 72.5%, and 69.5% for those treated at hospitals with high performance on 3, 2, 1, and 0 metrics, respectively (log-rank, P < 0.001). Care at hospitals with high metric performance was associated with lower risk of death in a dose-response fashion [0 metrics, reference; 1, hazard ratio (HR) 0.96 (0.89-1.03); 2, HR 0.92 (0.87-0.98); 3, HR 0.85 (0.80-0.90); 2 vs 1, HR 0.96 (0.91-1.01); 3 vs 1, HR 0.89 (0.84-0.93); 3 vs 2, HR 0.95 (0.89-0.95)]. Performance on metrics in combination was associated with lower risk of death [LN + AC, HR 0.86 (0.78-0.95); AC + timely AC, HR 0.92 (0.87-0.98); LN + AC + timely AC, HR 0.85 (0.80-0.90)], whereas individual measures were not [LN, HR 0.95 (0.88-1.04); AC, HR 0.95 (0.87-1.05)]. CONCLUSIONS: Less than half of hospitals perform well on these NQF colon cancer metrics concurrently, and high performance on individual measures is not associated with improved survival. Quality improvement efforts should shift focus from individual measures to defining composite measures encompassing the overall multimodal care pathway and capturing successful transitions from one care modality to another.

Preoperative cancer cachexia and short-term outcomes following surgery.

BACKGROUND: Cancer cachexia is an important measure of physiologic reserve associated with worse survival and represents an actionable factor for the cancer population. However, the incidence of cachexia in surgical cancer patients and its impact on postoperative outcomes are currently unknown. METHODS: A prospective cohort study enrolling patients having elective cancer surgery (2012-2014) at a Veterans Affairs tertiary referral center. Preoperative cancer cachexia (weight loss ≥5% over 6-mo period before surgery) was the predictor of interest. The primary outcome was 60-d postoperative complications (VA Surgical Quality Improvement Program). Patients were grouped by body mass index (BMI) category (<25, 25-29.9, ≥30), and interaction between cachexia and BMI was tested for the primary outcome. Multivariate logistic regression was used to examine the association between preoperative cachexia and postoperative complications. RESULTS: Of 253 patients, 16.6% had preoperative cachexia, and 51.8% developed ≥ 1 postoperative complications. Complications were more common in cachectic patients (64.3% versus 49.3%, P = 0.07). This association varied by BMI category, and interaction analysis was significant for those with normal or underweight BMI (BMI < 25, P = 0.03). After multivariate modeling, in patients with normal or underweight BMI, preoperative cachexia was associated with higher odds of postoperative complications (odds ratios, 5.08 [95% confidence intervals, 1.18-21.88]; P = 0.029). Additional predictors of complications included major surgery (3.19 [1.24-8.21], P = 0.01), ostomy (4.43 [1.68-11.72], P = 0.003), and poor baseline performance status (2.31 [1.05-5.08], P = 0.03). CONCLUSIONS: Cancer cachexia is common in surgical patients, and is an important predictor of postoperative complications, though its effect varies by BMI. As a modifiable predictor of worse outcomes, future studies should examine the role of cachexia treatment before cancer surgery.

Post-embolization syndrome as an early predictor of overall survival after transarterial chemoembolization for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common treatment for patients with unresectable hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is a common post-TACE complication. The goal of this study was to evaluate PES as an early predictor of the long-term outcome. METHODS: A retrospective cohort study of HCC patients treated with TACE at a tertiary referral centre was performed (2008-2014). Patients were categorized on the basis of PES, defined as fever with or without abdominal pain within 14 days of TACE. The primary outcome was overall survival (OS). Multivariate Cox regression was done to examine the association between PES and OS. RESULTS: Among 144 patients, 52 (36.1%) experienced PES. The median follow-up for the cohort was 11.4 months. The median and 3-year OS rates were 16 months and 18% in the PES group versus 25 months and 41% in the non-PES group (log rank, P = 0.027). After multivariate analysis, patients with PES had a significantly increased risk of death [hazard ratio 2.0 (95%CI 1.2-3.3), P = 0.011]. CONCLUSIONS: PES is a common complication after TACE and is associated with a two-fold increased risk of death. Future studies should incorporate PES as a relevant early predictor of OS and examine the biological basis of this association.