Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1) and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C) mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

Robotic-assisted transhiatal esophagectomy (RATE) is a minimally invasive approach to total esophagectomy with less morbidity but equivalent efficacy when compared with the traditional open approach. The robotic platform offers numerous technical advantages that assist with the esophageal dissection, which allows the procedure to be completed without entry into the thoracic cavity. The major criticism of the transhiatal approach is that it forfeits the ability of the surgeon to perform a formal lymphadenectomy, but this does not appear to affect long-term survival.

Background

Patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is critically important to optimizing outcomes. There is currently no literature regarding the safety of CRS/HIPEC in patients with cirrhosis. The aim of this case series is to report the outcomes of three patients with well-compensated cirrhosis who underwent CRS/HIPEC.

Methods

Patients were identified from a prospectively maintained peritoneal surface malignancy database. Patient, tumor, and operative-related details were recorded as short-term postoperative outcomes. Results were analyzed using descriptive statistics.

Results

All patients had well-compensated (Child-Pugh Class A) cirrhosis and Eastern Cooperative Oncology Group (ECOG) performance status of 0. One patient had preoperative evidence of portal hypertension. All safely underwent CRS/HIPEC with completeness of cytoreduction (CC) scores of 0. The postoperative morbidity profile was unique, but all complications were manageable and resulted in full recovery to preoperative baseline status.

Conclusions

Patient selection for CRS/HIPEC is critical for optimization of short- and long-term outcomes. This small series suggests that well-compensated cirrhosis should not be an absolute contraindication to CRS/HIPEC.

Background

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has an emerging role in the treatment of peritoneal malignancies. The CRS-HIPEC approach has known treatment-related toxicities. This study sought to determine the predictors of major postoperative complications after CRS-HIPEC in a high-volume center.

Methods

From a single-institution database, this study investigated complications experienced by patients undergoing CRS-HIPEC. Multiple preoperative and operative factors were analyzed for their ability to predict 60-day Clavien grade 3 and greater (major) complications by logistic regression. A predictive model was created from preoperative factors using multivariate logistic regression. The model was tested by Akaike's information criterion, the Hosmer and Lemeshow Goodness-of-Fit Test, the receiver operating characteristic, and the Youden Index.

Results

The study evaluated 247 patients undergoing CRS-HIPEC. The primary tumor site was the appendix in 166 cases (67.2 %), the colorectal area in 51 cases (20.6 %), the peritoneum (mesothelioma) in 22 cases (8.9 %), the ovary in 5 cases (2 %), and the small bowel in 3 cases (1.2 %). The median peritoneal cancer index was 14 (range 0-29), and 235 patients (95.1 %) had a complete (CC-0/1) cytoreduction. Major complications occurred for 41 patients (16.6 %), classified as grade 3 in 33 cases (13.4 %), grade 4 in 5 cases (2 %), and grade 5 (deaths) in 3 cases (1.2 %). The factors predictive of major complications in the multivariate analysis were a Charlson Comorbidity Index (CCI) score higher than 0 [odds ratio (OR), 2.505; p = 0.035], presence of preoperative symptoms (OR 1.951; p = 0.064), and prior resection status [no resection or prior CRS-HIPEC (OR 2.087) vs. prior resection without CRS-HIPEC (OR 3.209); p = 0.046]. These variables were used to create a tool predictive of postoperative complications.

Conclusion

Presence of symptoms, CCI, and prior resection status predict major complications and define a low-risk population after CRS-HIPEC.

Background

Circulating tumor DNA (ctDNA) is a promising technology for treatment selection, prognostication, and surveillance after definitive therapy. Its use in the perioperative setting for patients with metastatic disease has not been well studied. We characterize perioperative plasma ctDNA and its association with progression-free survival (PFS) in patients undergoing surgery for peritoneal metastases.

Patients and methods

We recruited 71 patients undergoing surgery for peritoneal metastases and evaluated their plasma with a targeted 73-gene ctDNA next-generation sequencing test before and after surgery. The association between perioperative ctDNA, as well as other patient factors, and PFS was evaluated by Cox regression.

Results

ctDNA was detectable in 28 patients (39.4%) preoperatively and in 37 patients (52.1%) postoperatively. Patients with high ctDNA [maximum somatic variant allele fraction (MSVAF) > 0.25%] had worse PFS than those with low MSVAF (< 0.25%) in both the pre- and postoperative settings (median 4.8 vs. 19.3 months, p < 0.001, and 9.2 vs.15.0 months, p = 0.049, respectively; log-rank test). On multivariate analysis, high-grade histology [hazard ratio (HR) 3.42, p = 0.001], incomplete resection (HR 2.35, p = 0.010), and high preoperative MSVAF (HR 3.04, p = 0.001) were associated with worse PFS. Patients with new postoperative alterations in the context of preoperative alteration(s) also had a significantly shorter PFS compared with other groups (HR 4.28, p < 0.001).

Conclusions

High levels of perioperative ctDNA and new postoperative ctDNA alterations in the context of preoperative alterations predict worse outcomes in patients undergoing resection for peritoneal metastases. This may highlight a role for longitudinal ctDNA surveillance in this population.

Background

Gastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival.

Methods

Two patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue.

Results

M5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800.

Conclusions

Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection.

Context

Low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria.

Objective

To determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP.

Design

The anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral.

Results

161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6%) contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50%) as adenocarcinoma and 23 cases (50%) as LAMN; however, the reference pathologist diagnosed 29 cases (63.0%) as LAMN, 13 cases (28.3%) as adenocarcinoma, and 4 cases (8.7%) as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23), LAMN (39.1%, 9 of 23), or simple mucocele (4.3%, 1 of 23). The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46) with an unweighted observed kappa value of 0.48 (95% CI, 0.27-0.69), consistent with moderate interobserver agreement. All of the observed discordance (28.3%) for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5%) had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic epithelium).

Conclusions

Appendiceal mucinous lesions remain a difficult area for appropriate pathological classification with substantial discordance due to over-interpretation in this study. The findings highlight the critical need for recognition and application of diagnostic criteria regarding these tumors. Recently published consensus guidelines and a checklist provided herein may help facilitate improvement of diagnostic concordance and thereby reduce over-interpretation and potential overtreatment. Further studies are needed to determine the extent of this phenomenon and its potential clinical impact.