Resection Of Metastases Research Articles

Incurring detriments of unplanned readmission to the intensive care unit following surgery for brain metastasis

ObjectPostoperative intensive care unit (ICU) monitoring is a common regime after neurosurgical resection of brain metastasis (BM). In comparison, unplanned secondary readmission to the ICU after initial postoperative treatment course occurs in response to adverse events and might significantly impact patient prognosis. In the present study, we analyzed the potential prognostic implications of unplanned readmission to the ICU and aimed at identifying preoperatively collectable risk factors for the development of such adverse events.MethodsBetween 2013 and 2018, 353 patients with BM had undergone BM resection at the authors’ institution. Secondary ICU admission was defined as any unplanned admission to the ICU during the initial hospital stay. A multivariable logistic regression analysis was performed to identify preoperatively identifiable risk factors for unplanned ICU readmission.ResultsA total of 19 patients (5%) were readmitted to the ICU. Median overall survival (mOS) of patients with unplanned ICU readmission was 2 months (mo) compared to 13 mo for patients without secondary ICU admission (p<0.0001). Multivariable analysis identified “multiple BM” (p=0.02) and “preoperative CRP levels > 10 mg/dl” (p=0.01) as significant and independent predictors of secondary ICU admission.ConclusionsUnplanned ICU readmission following surgical therapy for BM is significantly related to poor OS. Furthermore, the present study identifies routinely collectable risk factors indicating patients that are at a high risk for unplanned ICU readmission after BM surgery.

Prognostic significance of uncertain resection for metastasis in the highest mediastinal lymph node after surgery for clinical N0 non-small cell lung cancer.

The International Association for the Study of Lung Cancer defined types of surgical resection and considered the positivity of the highest mediastinal lymph node resected a parameter of "uncertain resection" (R-u). We investigated the metastases in the highest mediastinal lymph node, defined as the lowest numerically numbered station among those resected. We aimed to evaluate the prognostic value of R-u compared with R0. We selected 550 patients with non-small cell lung cancer at clinical Stage I, IIA, IIB (T3N0M0), or IIIA (T4N0M0) undergoing lobectomy and systematic lymphadenectomy between 2015 and 2020. The R-u group included patients with positive highest mediastinal resected lymph node. In the groups of patients with mediastinal lymph node metastasis, we defined 31 as R-u (45.6%, 31/68). The incidence of metastases in the highest lymph node was related to the pN2 subgroups (p < 0.001) and the type of lymphadenectomy performed (p < 0.001). The survival analysis compared R0 and R-u: 3-year disease-free survival was 69.0% and 20.0%, respectively, and 3-year overall survival was 78.0% and 40.0%, respectively. The recurrence rate was 29.7% in R0 and 71.0% in R-u (p-value < 0.001), and the mortality rate was 18.9% and 51.6%, respectively (p-value < 0.001). R-u variable showed a tendency to be a significant prognostic factor for disease-free survival and overall survival (hazard ratio: 4.6 and 4.5, respectively, p-value < 0.001). The presence of metastasis in the highest mediastinal lymph node removed seems to be an independent prognostic factor for mortality and recurrence. The finding of these metastases represents the margin of cancer dissemination at the time of surgery, so it could imply metastasis into the N3 node or distant metastasis.

Outcomes of surgical resection for pulmonary metastasis from pancreatic cancer.

As the number of long-term survivors of pancreatic cancer is expected to increase thanks to recent advances in multidisciplinary treatment and earlier diagnoses of pancreatic cancer, we are likely to encounter more cases of postoperative pulmonary nodules. We analyzed the clinical course and prognosis of resection of pulmonary metastases from pancreatic cancer to clarify the prognostic implication of pulmonary metastasectomy for pancreatic cancer. We retrospectively analyzed 35 patients who underwent resection of lung metastases after pancreatic cancer surgery. Short- and long-term outcomes and factors associated with the prognosis were analyzed. The observation period was 20 (range, 1-101)months, with 3- and 5-year survival rates of 88.3% and 64.5% from pancreatectomy and 44.1% and 28.3% from lung resection, respectively. A univariate analysis revealed that a period from pancreatic cancer resection to pulmonary nodule shadow detection of < 15months was associated with a significantly lower overall survival from pancreatic resection than a longer period. Conversely, histological type, stage, size of lung metastases, and resection technique were not associated with the overall survival. A long-term prognosis may be expected in some cases with a disease-free interval of ≥ 15months. Our findings suggest that the disease-free interval may influence the prognosis.

Adjuvant hepatic artery infusion pump chemotherapy for resected colorectal cancer liver metastases

First introduced in the late 1980s in the setting of unresectable liver metastasis, the use of the hepatic artery infusion pump was expanded to deliver chemotherapy in the adjuvant setting after hepatic resection about 1 decade later. Though the initial randomized clinical trial comparing the hepatic artery infusion pump to resection alone failed to show an improvement in overall survival, 2 large randomized clinical trials, namely the Memorial Sloan Kettering Cancer Center (1999) and European Cooperative Group (2002) trials, did report improved hepatic disease-free survival with the use of a hepatic artery infusion pump. There remained limited evidence of a replicable improvement in overall survival, and the expansion of hepatic artery infusion pump into the adjuvant space was cautioned by a Cochrane review in 2006, highlighting the need for further studies to establish a consistent benefit. Those data were forthcoming over the 2000s and 2010s in large-scale retrospective analyses for the most part, but the recommendations from international guidelines remain equivocal to this day.With widespread retrospective data and high-quality randomized clinical trial evidence that a hepatic artery infusion pump in the setting of resected hepatic metastasis from colorectal liver metastasis decreases hepatic recurrence and indications that it may improve overall survival, it is clear that there is a subset of patients that greatly benefit from this treatment modality. New randomized clinical trials, specifically in the adjuvant setting, are currently enrolling and should continue to elucidate the benefit that hepatic artery infusion pumps may confer. That being said, it remains a challenge to reliably identify these patients, and the procedure is limited by complexity and resources to high-volume academic centers, leaving accessibility as a further potential barrier for patients. It remains to be seen what volume of literature may shift the hepatic artery infusion pump into the standard of care, but adjuvant hepatic artery infusion pump in the setting of colorectal liver metastasis should certainly be explored further as a validated treatment for patients.

Adjuvant therapy for renal cell carcinoma in 2023: hopes and disappointments.

It is known that 30% of clear cell renal cell carcinomas (ccRCC) will develop progressive disease after surgical treatment. These patients with high-risk ccRCC require adjuvant therapy after nephrectomy or resection of metastases. The article presents an overview of the results of recent studies in adjuvant therapy. We analyzed the results of randomized trials of targeted therapy and checkpoint inhibitors in high-risk ccRCC patients. Targeted therapy did not significantly reduce this risk or/and did not affect overall survival. Three randomized studies investigating nivolumab, ipilimumab, and atezolizumab in the adjuvant setting also failed without improving disease-free survival. Pembrolizumab had a significant impact on the disease-free survival in the entire population, with the greatest effect in patients after metastasectomy, but mature overall survival data are not yet available. In conclusion, it must be noted that, at present, it has not been possible to achieve magnificent success in adjuvant therapy of RCC in patients at high risk of relapse after surgical treatment. There remains hope for adjuvant pembrolizumab, which has been used for high-risk population including patients with removed metastases who may benefit more from therapy.

Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.

Postoperative Management of Recurrence After Radiosurgery and Surgical Resection for Brain Metastases and Predicting Benefit From Adjuvant Radiation

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 patients with brain metastases treated with SRS from 2009 to 2017 followed by surgical resection were identified. Overall, 65% of cases had gross total resection (GTR) on postoperative imaging review. Twenty-one patients (9.3%) received adjuvant radiation therapy to the surgical cavity, and 204 (90.7%) were observed. Of these 204 patients, 118 had GTR with evidence of tumor within the pathology specimen. With a median follow-up of 13 months after resection, 47 patients (40%) developed LF after surgery. After salvage resection of a brain metastasis initially treated with SRS, the observed LF rate was 40% among those who had a GTR and evidence of tumor on pathologic examination. This LF rate is sufficiently high that adjuvant radiation to the surgical bed after salvage resection should be considered in these cases when there is tumor in the pathology, even after a GTR.

Fluorescein-guided resection of a left frontal pre-rolandic cerebral metastasis: how I do it.

Cerebral metastases (CM) are the most common intracranial tumors; several studies have underlined the fundamental role of neurosurgical lesion removal. We describe the surgical resection of a left frontal single metastasis. We attempted to achieve a radical resection under the intraoperative guidance of fluorescein, with the aid of intraoperative neurological monitoring. This technique can be applied to each contrast enhancing, intra-axial, infiltrative lesion. Fluorescein-guided surgery is a valuable tool in CM surgery to increase the rate of resection; further prospective evaluation of the role of fluorescein in this field is in planning, aiming to study the prognostic impact.

Circulating tumour DNA at baseline for individualised prognostication in patients with chemotherapy-naïve metastatic colorectal cancer. An AGEO prospective study

PurposeBaseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice. Patients and methodsChemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models. ResultsFrom July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31–0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001). ConclusionctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials.Trial registration: Clinicaltrials.gov, NCT02502656

Prognostic impact of R1 resection margin in synchronous and simultaneous colorectal liver metastasis resection: a retrospective cohort study

BackgroundA margin ≥ 1 mm is considered a standard resection margin for colorectal liver metastasis (CRLM). However, microscopic incomplete resection (R1) is not rare since aggressive surgical resection has been attempted in multiple and bilobar CRLM. This study aimed to investigate the prognostic impact of resection margins and perioperative chemotherapy in patients with CRLM.MethodsA total of 368 of 371 patients who underwent simultaneous colorectal and liver resection for synchronous CRLM between 2006 and June 2017, excluding three R2 resections, were included in this study. R1 resection was defined as either abutting tumor on the resection line or involved margin in the pathological report. The patients were divided into R0 (n = 304) and R1 (n = 64) groups. The clinicopathological characteristics, overall survival, and intrahepatic recurrence-free survival were compared between the two groups using propensity score matching.ResultsThe R1 group had more patients with ≥ 4 liver lesions (27.3 vs. 50.0%, P < 0.001), higher mean tumor burden score (4.4 vs. 5.8%, P = 0.003), and more bilobar disease (38.8 vs. 67.2%, P < 0.001) than the R0 group. Both R0 and R1 groups showed similar long-term outcomes in the total cohort (OS, P = 0.149; RFS, P = 0.414) and after matching (OS, P = 0.097, RFS: P = 0.924). However, the marginal recurrence rate was higher in the R1 group than in the R0 group (26.6 vs. 16.1%, P = 0.048). Furthermore, the resection margin did not have a significant impact on OS and RFS, regardless of preoperative chemotherapy. Poorly differentiated, N-positive stage colorectal cancer, liver lesion number ≥ 4, and size ≥ 5 cm were poor prognostic factors, and adjuvant chemotherapy had a positive impact on survival.ConclusionsThe R1 group was associated with aggressive tumor characteristics; however, no effect on the OS and intrahepatic RFS with or without preoperative chemotherapy was observed in this study. Tumor biological characteristics, rather than resection margin status, determine long-term prognosis. Therefore, aggressive surgical resection should be considered in patients with CRLM expected to undergo R1 resection in this multidisciplinary approach era.

Open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with oxaliplatin and 5-fluorouracil/folinic acid followed by curative surgical resection in patients with hepatic oligometastatic adenocarcinoma of the pancreas (HOLIPANC).

TPS4193 Background: As of today, the recommendation for patients with adenocarcinoma of the pancreas and hepatic metastases is systemic chemotherapy alone regardless of the number and location of metastases. In the past, case reports have repeatedly reported survival data of patients who received metastatic and primary tumor resection outside the guidelines. However, there are currently no controlled clinical data from prospective studies that have evaluated the effectiveness of systemic chemotherapy in combination with tumor and metastasis resection in the context of hepatic oligometastasis in pancreatic cancer. Methods: In this single arm, phase-2 trial, survival data from patients receiving neoadjuvant chemotherapy followed by R0/R1 resection will be compared to historic data from patients with oligometastatic adenocarcinoma of the pancreas. Inclusion criteria are patients with a maximum of 5 liver metastases and histology proven PDAC. The combination of liposomal irinotecan (nal-IRI), oxaliplatin (OX) and 5-fluouracil (5-FU)/folinic acid (FA) (Nal-IRIFOX) was chosen as neoadjuvant chemotherapy since recent data suggested superior efficacy and less toxicity compared to mFOLFIRINOX. The primary endpoint is overall survival (OS) after R0/R1 resection. Secondary efficacy endpoints are R0/R1 resection rate and progression-free survival (PFS). Secondary safety endpoints are type, frequency and severity of adverse events with severity according to NCI CTCAE version 5.0 and perioperative morbidity and mortality. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy in cycles of 14 days for a duration of 16 weeks in total. In patients with progressive disease during or after the first 4 cycles, neoadjuvant chemotherapy will be permanently discontinued. Patients with tumor response or stable disease after the first 4 cycles according to RECIST v1.1 but a non-resectable primary tumor will receive 4 more cycles. Patients with tumor response or stable disease and a resectable primary tumor after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumor and hepatic metastases, if feasible. In total 150 patients will be enrolled for this trial with an aim of 55 patients receiving a complete macroscopic synchronous tumor and metastatic resection. The study is currently ongoing on 11 high-volume centers for pancreatic surgery within Germany. This is the first clinical study to prospectively evaluate the value of multimodality therapy concepts in oligometastatic pancreatic cancer. Clinical trial information: NCT04617457 .

P-216 Surgical safety and oncological outcomes of laparoscopic liver resection for colorectal cancer liver metastasis in the Ukrainian state center

P-216 Surgical safety and oncological outcomes of laparoscopic liver resection for colorectal cancer liver metastasis in the Ukrainian state center

Resection of primary colon cancer with and without resection of liver metastases: Propensity-score matched analysis.

e15580 Background: Studies show that attempts to treat liver metastases during or before primary colonic cancer resection may improve survival. We aimed to compare overall survival of patients with colon cancer and liver metastases who underwent primary tumor resection with/without resection of liver metastases. Methods: This retrospective cohort study included patients with stage IV colon adenocarcinoma and isolated liver metastases who underwent surgical resection, using data from the National Cancer Database between 2015-2019. Patients with metastases to other organs or who did not have primary tumor resection were excluded. The cohort was divided into Colectomy-only (resection of primary colonic cancer only) and Colectomy-plus (resection of primary tumor and liver metastases) groups. After comparing, significant baseline and treatment confounders were identified and groups were matched using the nearest neighbor, 1:1 propensity-score method. Primary outcome was overall survival; secondary endpoints were short-term mortality and 30-day unplanned readmission. Results: 6780 patients who underwent primary tumor only resection and 4082 who underwent primary tumor and liver metastases resection were included. Patients in the Colectomy-only group were significantly older (63.73±13.59 vs 59.56±13.32 years;p &lt; 0.001), more often male (56% vs 53.5%;p = 0.01), had more comorbidities (Charlson score 3: 4.4% vs 3.3%;p = 0.001) and right-sided colonic cancer (45.7% vs 43.2%;p = 0.002), shorter time before surgery (10 vs 30 days;p &lt; 0.001), and more laparoscopic surgery (40.4% vs 35%;p &lt; 0.001). Colectomy-only group patients had less chemotherapy (48.6% vs 50.7%, p = 0.04) and immunotherapy (34.1% vs 40.6%, p &lt; 0.001) whereas Colectomy-plus group patients had more neoadjuvant systemic therapy (18.8% vs 10.2%;p &lt; 0.001). Median overall survival of the Colectomy-plus group was significantly longer than Colectomy-only group (45.1 vs 24.4 months; p &lt; 0.001). After matching for significant confounders, 2038 patients were included in each group. There were no significant differences between the two groups in 30-day (3.8% vs 3.1%;p = 0.3) and 90-day mortality (7.7% vs 6.6%;p = 0.2). Colectomy-plus group patients had significantly higher 30-day unplanned readmissions (7.2% vs 5.3%, p = 0.02) and significantly longer median overall survival (41.5 vs 28.4 months, p &lt; 0.001). On Cox-regression analysis, resection of liver metastases and primary colonic tumor was associated with 33% mortality reduction (HR: 0.678, 95%CI: 0.618-0.745, p &lt; 0.001). Conclusions: Resection of colonic cancer liver metastasis with the primary tumor is associated with significant survival benefit and may prolong survival by approximately 12 months, versus primary tumor resection alone. Synchronous resection of the primary tumor and liver metastases should be considered as it appears to offer survival benefit.

The clinicopathological spectrum and treatment outcomes in metastatic colorectal cancer in the KwaZulu-Natal province of South Africa.

In high-income countries (HICs) 17-20% of colorectal cancer (CRC) patients have metastatic CRC (mCRC) at the time of diagnosis, of which 10-25% are or become resectable, and a further 4-11% of patients will develop metachronous metastases. The study aimed to establish the prevalence and pattern of metastatic CRC to document treatment outcomes in KwaZulu-Natal (KZN), and to compare results to international norms. The study population comprised patients with mCRC presenting between 2000 and 2019. Demographics, primary tumour site, spectrum of metastatic disease and resection rate were assessed. MCRC occurred in 33% of the CRC patient population. Eight hundred and thirty-six patients had metastatic disease, comprising Africans (325, 38.8%), Indians (312, 37.3%), Coloureds (37, 4.4%) and Whites (161, 19.2%). Six hundred and fifty-four patients (79%) had synchronous metastases and 182 patients had metachronous metastases (21%). Single organ metastases occurred in 596 patients (71.2%) (M1A) and multiple organ metastasis occurred in 240 patients (28.7%) (M1B). Metastases occurred in the liver (613), lung (240) and peritoneum (85). Fifty-two patients (6.2%) underwent resection of their metastases. The prevalence of stage IV CRC in our setting is at the upper limit of international norms. mCRC occurred in 33%, with similar proportions in all races. Resection rate for metastases is low.

Nomogram predicting early recurrence defined by the minimum P value approach for colorectal liver metastasis patients receiving colorectal cancer resection with simultaneous liver metastasis resection: development and validation.

Simultaneous resections have been increasingly performed for colorectal liver metastasis patients. However, studies explored risk stratification for these patients are scarce. Among which, a clear definition of early recurrence remains controversial and models for predicting early recurrence in these patients are lacking. Colorectal liver metastasis patients who developed recurrence followed by simultaneous resection were enrolled. Early recurrence was determined by the minimum P value method, and patients were divided into an early recurrence group and late recurrence group. Standard clinical data were collected from each patient including demographics features, preoperative laboratory tests and postoperative regular follow-up results. All the data were accessed by clinicians and recorded accordingly. The nomogram for early recurrence was constructed in the training cohort and validated externally in the test cohort. The optimal value of early recurrence by the minimum P value method was 13 months. A total of 323 patients were included in the training cohort, of which 241 (74.6%) experienced early recurrence. Seventy-one patients were included in the test cohort, of which 49 (69.0%) experienced early recurrence. Significantly worse post-recurrence survival (median 27.0 vs. 52.8 months, P=0.00083) and overall survival (median 33.8 vs. 70.9 months, P<0.0001) were observed in patients with early recurrence in the training cohort. Positive lymph node metastases (P=0.003), tumour burden scores ≥4.09 (P=0.001), preoperative neutrophil-to-lymphocyte ratios ≥1.44 (P=0.006), preoperative blood urea nitrogen levels ≥3.55 µmol/L (P=0.017) and postoperative complications (P=0.042) were independently associated with early recurrence, and all these predictors were included in the nomogram. The nomogram for predicting early recurrence had a receiver operating characteristic curve of 0.720 in the training cohort and a receiver operating characteristic curve of 0.740 in the test cohort. The Hosmer-Lemeshow test and calibration curves showed acceptable model calibration in the training set (P=0.7612) and in the test set (P=0.8671). The decision curve analysis results for the training cohort and test cohort also indicated that the nomogram showed good clinical applicability. Our findings provide clinicians with new insights into accurate risk stratification for colorectal liver metastasis patients receiving simultaneous resection and contributing to the management of patients.

A case report of sigmoid colon cancer with the inferior mesenteric artery directly originating from the superior mesenteric artery

BackgroundThere are few reports describing the unusual origin of the inferior mesenteric artery (IMA). We report a rare case of advanced sigmoid colon cancer with the IMA arising from the superior mesenteric artery.Case presentationA 59-year-old man with diarrhea and abdominal distention was diagnosed with advanced sigmoid colon cancer. Colonoscopy revealed a semi-circumferential cancer lesion in the sigmoid colon. Enhanced CT scan and CT angiography showed that the IMA directly originated from the superior mesenteric artery at the level of the second lumbar vertebra. PET-CT suggested metastases in the para-intestinal lymph nodes and the liver, but not in the central lymph nodes along the IMA. Preoperative diagnosis was sigmoid colon cancer cT4aN2aM1a cStage IVA(UICC, 8th edition). We performed laparoscopic complete resection as the radical treatment of the primary region prior to resection of the liver metastases. Intraoperative findings showed that the IMA was running parallel to the abdominal aorta; meanwhile, the colonic autonomic nerve was supplied from the lumbar splanchnic nerve at the caudal side of the duodenum. Central lymph nodes around the colonic autonomic nerve were dissected en bloc with the regional lymph nodes. Pathological radical resection including the regional lymph nodes metastasis was achieved. Two months later, complete resection of the liver metastasis was performed. After the adjuvant chemotherapy, no recurrence was observed 1.5 years after the liver resection was performed.ConclusionsPreoperative confirmation of the anatomy helped us to safely complete radical surgery in a patient with unusual bifurcation of the IMA.

In Situ Sprayed Nanovaccine Suppressing Exosomal PD-L1 by Golgi Apparatus Disorganization for Postsurgical Melanoma Immunotherapy.

The anti-PD-L1 immunotherapy has shown promise in treating cancer. However, certain patients with metastatic cancer have low response and high relapse rates. A main reason is systemic immunosuppression caused by exosomal PD-L1, which can circulate in the body and inhibit T cell functions. Here, we show that Golgi apparatus-Pd-l1-/- exosome hybrid membrane coated nanoparticles (GENPs) can significantly reduce the secretion of PD-L1. The GENPs can accumulate in tumors through homotypic targeting and effectively deliver retinoic acid, inducing disorganization of the Golgi apparatus and a sequence of intracellular events including alteration of endoplasmic reticulum (ER)-to-Golgi trafficking and subsequent ER stress, which finally disrupts the PD-L1 production and the release of exosomes. Furthermore, GENPs could mimic exosomes to access draining lymph nodes. The membrane antigen of PD-l1-/- exosome on GENPs can activate T cells through a vaccine-like effect, strongly promoting systemic immune responses. By combining GENPs with anti-PD-L1 treatment in the sprayable in situ hydrogel, we have successfully realized a low recurrence rate and substantially extended survival periods in mice models with incomplete metastatic melanoma resection.

Laparoscopic and Open Liver Resections for Colorectal Cancer Liver Metastasis in the Ukrainian State Center.

Background Minimally invasive liver resections for metastatic colorectal cancer have been increasingly performed all over the world with promising results. We planned the current studyto review our experience on this matter and compare short- and long-term outcomes of laparoscopicliver resection (LLR) and open liver resection(OLR) in patients with colorectal cancer liver metastasis (CRLM). Materials and methods This is a single-center retrospective analysis of patients with CRLM who underwent laparoscopic (n=86) and open (n=96) surgical treatment for metastatic liver lesions between March 2016 and November 2022. Tumor characteristics, intra- and postoperative results, overall survival (OS), and disease-free survival (DFS)were analyzed and compared. Results LLR was associated with significantly shorter surgery duration (180 minutes versus 295 minutes, p=0.03). There was no significant difference in blood loss between the two groups (100 mL versus 350 mL, p=0.061). Additionally, the laparoscopic approach was associated with significantly shorter hospital stays (6 days versus 9 days, p=0.004). The rate of major complications (Clavien-Dindo classification ≥ 3) was lower in the LLR group (5.8% versus 16.6%, p=0.037). There was no mortality in the LLR group, and in the OLR group, one lethal case was induced by mesenteric thrombosis on the fifth postoperative day. We did not find a statistically significant difference in the OS rate between the two groups at one, three, and five years: 97.3%, 74.7%, and 43.4%, respectively,in the OLR group and 95.1%, 70.3%, and 49.5%,respectively,in the LLR group (p=0.53). DFS at one, three, and five years were 88.7%, 52.3%, and 25.5%,respectively, in the LLR group and 71.9%, 53.1%, and 19.3%, respectively, in the OLR group(p=0.66). Conclusions This study showed that laparoscopic liver surgery is a safe and effective method of CRLM treatment in our center. LLR was associated with a decrease in major morbidity, shorter surgery duration, and reduced postoperative hospital stay. Minimally invasive liver resections showed similar oncological outcomes to the open approach in terms of overall and disease-free survival.

Pre-operative exercise therapy suppresses colorectal liver metastases by triggering anti-tumor trained immunity of Kupffer cells

Abstract Hepatic recurrence after surgical resection of colorectal liver metastasis is the major cause of treatment failure. Pre-operative exercise therapy (PEx) has been shown to improve outcomes from major abdominal surgeries. We demonstrate that PEx significantly attenuates liver ischemia/reperfusion (I/R) injury by inducing an anti-inflammatory phenotype in Kupffer cells (KCs). However, the mechanisms by which PEx prevents surgery-induced hepatic recurrence remain unclear. Results: Four weeks of treadmill running significantly reduces I/R-induced hepatic metastatic tumor growth in mice compared to sedentary controls. Depletion of KCs substantially decreases I/R-induced tumor progression, indicating a pro-tumor role of KCs. Our scRNA-seq data reveal that PEx causes dramatic transcriptomic changes in KCs. A clear induction of trained immunity with noticeably higher levels of anti-tumor cytokines IFN-γ and TNF-α is observed in PEx-KCs. With scATAC-seq, we find that PEx triggers the chromatin accessibilities profile changes in KCs, which is associated with the metabolic reprogramming of itaconate/IRG1 pathway. Furthermore, PEx significantly changes the transcriptomic profile of polymorphonuclear myeloid-derived suppressive cells (PMN-MDSCs) in the tumor microenvironment (TME) and decreases them from forming neutrophil extracellular traps (NETs), which promote tumor progression. We identify the cell-cell interaction between KCs and PMN-MDSCs in the TME is significantly enriched after PEx, suggesting that PEx may facilitate KCs to modulate PMN-MDSCs. In summary, PEx ameliorates surgical stress-induced pro-tumorigenic inflammatory responses and sustains an anti-tumor immune microenvironment in the liver. Supported by grants from NIH (R01GM137203 for Hai Huang, R01CA214865 for Allan Tsung)

Intracranial and Extracranial Progression and Their Correlation With Overall Survival After Stereotactic Radiosurgery in a Multi-institutional Cohort With Brain Metastases

Clinical trials for metastatic malignant neoplasms are increasingly being extended to patients with brain metastases. Despite the preeminence of progression-free survival (PFS) as a primary oncologic end point, the correlation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survival (OS) is poorly understood for patients with brain metastases following stereotactic radiosurgery (SRS). To determine the correlation of ICP and ECP with OS among patients with brain metastases completing an initial SRS course. This multi-institutional retrospective cohort study was conducted from January 1, 2015, to December 31, 2020. We included patients who completed an initial course of SRS for brain metastases during the study period, including receipt of single and/or multifraction SRS, prior whole-brain radiotherapy, and brain metastasis resection. Data analysis was performed on November 15, 2022. Non-OS end points included intracranial PFS, extracranial PFS, PFS, time to ICP, time to ECP, and any time to progression. Progression events were radiologically defined, incorporating multidisciplinary clinical consensus. The primary outcome was correlation of surrogate end points to OS. Clinical end points were estimated from time of SRS completion via the Kaplan-Meier method, while end-point correlation to OS was measured using normal scores rank correlation with the iterative multiple imputation approach. This study included 1383 patients, with a mean age of 63.1 years (range, 20.9-92.8 years) and a median follow-up of 8.72 months (IQR, 3.25-19.68 months). The majority of participants were White (1032 [75%]), and more than half (758 [55%]) were women. Common primary tumor sites included the lung (757 [55%]), breast (203 [15%]), and skin (melanoma; 100 [7%]). Intracranial progression was observed in 698 patients (50%), preceding 492 of 1000 observed deaths (49%). Extracranial progression was observed in 800 patients (58%), preceding 627 of 1000 observed deaths (63%). Irrespective of deaths, 482 patients (35%) experienced both ICP and ECP, 534 (39%) experienced ICP (216 [16%]) or ECP (318 [23%]), and 367 (27%) experienced neither. The median OS was 9.93 months (95% CI, 9.08-11.05 months). Intracranial PFS had the highest correlation with OS (ρ = 0.84 [95% CI, 0.82-0.85]; median, 4.39 months [95% CI, 4.02-4.92 months]). Time to ICP had the lowest correlation with OS (ρ = 0.42 [95% CI, 0.34-0.50]) and the longest median time to event (median, 8.76 months [95% CI, 7.70-9.48 months]). Across specific primary tumor types, correlations of intracranial PFS and extracranial PFS with OS were consistently high despite corresponding differences in median outcome durations. The results of this cohort study of patients with brain metastases completing SRS suggest that intracranial PFS, extracranial PFS, and PFS had the highest correlations with OS and time to ICP had the lowest correlation with OS. These data may inform future patient inclusion and end-point selection for clinical trials.