Preoperative cachexia

Mason MC, et al. Preoperative cancer cachexia and short-term outcomes following surgery. J Surg Res. 2016 Oct; 205(2):398-406.

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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).

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Extended-duration thromboprophylaxis after CRS/HIPEC

Khan S, et al. Incidence, Risk Factors, and Prevention Strategies for Venous Thromboembolism after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2019 Jul;26(7):2276-2284.

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“A policy change was made in February 2010 to discharge all patients post-CRS/HIPEC with 14 days of additional pharmacothromboprophylaxis, which consisted of low-molecular-weight heparin in 327 of 447 (73%) cases (Supplemental Figure). The 60-day VTE rate decreased from 10.2 to 4.9% after this policy was instituted (p = 0.10, Fig. 2).”

“This policy is in accordance with established guidelines indicating the need for a total of 4 weeks of pharmacothromboprophylaxis in high-risk patients after abdominal or pelvic surgery for cancer. [2,21] Given that patients have an average length of stay of nearly 2 weeks, discharging them on 14 days of pharmacothromboprophylaxis fulfills this duration.”

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Stoma versus stent as a bridge to surgery for obstructive colon cancer

Veld JV, et al. Changes in Management of Left-Sided Obstructive Colon Cancer: National Practice and Guideline Implementation. J Natl Compr Canc Netw. 2019 Dec;17(12):1512-1520.

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Results: A total of 2,587 patients were included (2,013 ER, 345 DS, and 229 SEMS). A trend was observed in reversal of ER (decrease from 86.2% to 69.6%) and SEMS (increase from 1.3% to 7.8%) after 2014, with an ongoing increase in DS (from 5.2% in 2009 to 22.7% in 2016). DS after 2014 was associated with more laparoscopic resections (66.0% vs 35.5%; P<.001) and more 2-stage procedures (41.5% vs 28.6%; P=.01) with fewer permanent stomas (14.7% vs 29.5%; P=.005). Overall, more laparoscopic resections (25.4% vs 13.2%; P<.001) and shorter total hospital stays (14 vs 15 days; P<.001) were observed after 2014. However, similar rates of primary anastomosis (48.7% vs 48.6%; P=.961), 90-day complications (40.4% vs 37.9%; P=.254), and 90-day mortality (6.5% vs 7.0%; P=.635) were observed.

CONCLUSIONS: Guideline revision resulted in a notable change from ER to BTS for LSOCC. This was accompanied by an increased rate of laparoscopic resections, more 2-stage procedures with a decreased permanent stoma rate in patients receiving DS as BTS, and a shorter total hospital stay. However, overall 90-day complication and mortality rates remained relatively high.

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Consensus guidelines for the management of intraductal papillary mucinous neoplasms of the pancreas

This week’s discussion included information about the utility of the Fukuoka criteria.


Srinivasan N, et al. Systematic review of the clinical utility and validity of the Sendai and Fukuoka Consensus Guidelines for the management of intraductal papillary mucinous neoplasms of the pancreas.HPB (Oxford). 2018 Jun;20(6):497-504.

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RESULTS: Ten studies evaluating the FCG, 8 evaluating the SCG and 4 evaluating both guidelines were included. In 14 studies evaluating the FCG, out of a total of 2498 neoplasms, 849 were malignant and 1649 were benign neoplasms. Pooled analysis showed that 751 of 1801 (42%) FCG+ve neoplasms were malignant and 599 neoplasms of 697 (86%) FCG-ve neoplasms were benign. PPV of the high risk and worrisome risk groups were 465/986 (47%) and 239/520 (46%) respectively. In 12 studies evaluating the SCG, 1234 neoplasms were analyzed of which 388 (31%) were malignant and 846 (69%) were benign. Pooled analysis demonstrated that 265 of 802 (33%) SCG+ve neoplasms were malignant and 238 of 266 SCG-ve (90%) neoplasms were benign.

CONCLUSION: The FCG had a higher positive predictive value (PPV) compared to the SCG. However, the negative predictive value (NPV) of the FCG was slightly lower than that of the SCG. Malignant and even invasive IPMN may be missed according to both guidelines.

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Signet-ring cell carcinoma: a look at the rare colorectal cancer

A discussion this week included signet ring cell carcinoma.


Reference: Nitsche U, et al. Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Annals of Surgery. 2013 Nov;258(5):775-782; discussion 782-783. doi:10.1097/SLA.0b013e3182a69f7e

Additional Reading: Korphaisarn K, et al. Signet ring cell colorectal cancer: genomic insights into a rare subpopulation of colorectal adenocarcinoma. British Journal of Cancer. 2019 Sep;121(6):505-510. doi:10.1038/s41416-019-0548-9

Summary: In a study analyzing clinical, histopathological, and survival data of 3479 patients undergoing surgery for primary colorectal cancer between 1982 and 2012, Nitsche et al (2013) compared the characteristics of classical adenocarcinomas (AC) to the less common mucinous adenocarcinomas (MAC) and to the rare signet-ring cell carcinomas (SC).

SC

Approximately 10% of all colorectal cancers are MAC, and about 1% are SC. Because of their relatively rare occurrence, in particular, the evaluation of the clinical impact of SC is difficult. However, compared with AC, both MAC and SC have been shown to be associated with young age, advanced tumor stage, accumulation in female patients, and distinct molecular patterns, such as microsatellite instability and activating mutations of the BRAF gene. Although ambiguous, recent data and meta-analyses suggest that the
histological subtype MAC may be associated with worse outcome compared with AC. Poor prognosis of SC is more evident, mainly due to high rates of synchronous and metachronous distant organ metastasis associated with this histological subtype.

In describing SC, the authors state: “SC have been described as being positive for intestinal trefoil factor and MUC2, 2 peptides that are usually produced only by goblet cells. Thus, SC could arise from different cells of origin than AC. Although they can be localized in the colorectum, SC may be genetically more related to signet-ring cell cancers of other organs (eg, gastric cancer) than to AC or MAC of the colorectum. The
absence of E-cadherin/β-catenin and amplification of Bcl-2 are features typically shared with signet-ring cell cancer of the stomach but not with classical colorectal adenocarcinomas” (p.781).

The authors conclude that patients with MAC and SC could profit from closer follow-up or even intensified adjuvant therapy because of their high rates of local and distant recurrence. The biological behavior of SC differs in specific, and these patients require special awareness, despite the relatively rare prevalence.

D1 vs D2 resection for gastric cancer

One discussion this week included a trial out of Denmark comparing D1 and D2 lymph-node dissection for gastric cancer.

Reference: Bonenkamp JJ, et al. Extended lymph-node dissection for gastric cancer. NEJM. 1999 Mar 25;340(12):908-914.

Summary: Curative resection is the treatment of choice for gastric cancer, but it is unclear whether this operation should include an extended (D2) lymph-node dissection or a limited (D1) dissection. The authors conducted a randomized trial in 80 Dutch hospitals in which they compared D1 with D2 lymph-node dissection for gastric cancer in terms of morbidity, postoperative mortality, long-term survival, and cumulative risk of relapse after surgery.

Between August 1989 and July 1993, 996 patients were enrolled. Of these, 711 underwent randomly assigned treatment (D1 = 380, D2 = 331) and 285 received palliative treatment.

General findings:

  • Complications: 43% in D2, 25% in D1
  • Postoperative deaths: 10% in D2, 4% in D1
  • Length of stay: 16 median days in D2, 14 days in D1
  • 5-year survival rates: 47% in D2, 45% in D1

 

d1 v d2

One of the arguments for D2 dissection is its ability to reduce rates of local recurrence, thereby increasing the quality of life. The distressing finding of local recurrence, usually in a terminal phase of the disease, often leads to second operations to restore gastrointestinal continuity. In this trial, there was a tendency toward a reduced cumulative risk of relapse after D2 dissection, but the rate of relapse remained high and the difference from D1 dissection was not significant. A subgroup analysis indicated a significant or marginally significant difference for patients with disease in UICC stages II and IIIA, but this difference was attributable largely to stage migration.

The MAGIC Trial: Does perioperative ECF improve outcomes for gastric cancer patients?

One discussion this week included the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial. [Current Controlled Trials number: ISRCTN93793971.]

Reference: Cunningham D, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. NEJM. 2006 Jul 6;355(1):11-20.

Summary: A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. The MAGIC Trial assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.

METHODS: We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative  chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival.

CONCLUSIONS: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.

MAGIC

(p.16)

Additional Reading: Cunningham D, et al. Perio-operative chemoterhapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncology. 2017 Mar;18(3):357-370.  doi: 10.1016/S1470-2045(17)30043-8.

[ClinicalTrials.gov, number NCT00450203.]

The timing and accuracy of SLNB for nodal management after NAC

One discussion this week included nodal management after neoadjuvant chemotherapy (NAC).


Reference: Pilewskie M and Morrow M. Axillary nodal management following neoadjuvant chemotherapy. JAMA Oncology. 2017 Apr 1;3(4):549-555.

Summary: The increasing use of NAC has raised questions about the optimal approach to the axilla, including accuracy and timing of sentinel lymph node biopsy (SLNB) in patients who are clinically node negative (cN0) at presentation, use of NAC to avoid axillary lymph node dissection (ALND) in patients presenting with node-positive disease, and the relative importance of pre-and post-NAC stage in predicting the risk of locoregional recurrence (LRR).

The decrease in nodal metastases in cN0 patients undergoing post-NAC axillary staging and the increasing rates of pCR in the breast in patients treated with current chemotherapy regimens led to the study of SLNB among patients presenting with cN+ disease. Table 3 (below) summarizes data from three prospective, multi-institutional trials assessing the accuracy of SLNB after NAC among node-positive patients.

SLNB

The authors conclude: NAC reduces the need for ALND, and SLNB is an accurate
method of determining nodal status post NAC. The demonstration that SLNB accurately stages the axilla after NAC regardless of the presenting nodal stage (cN0, cN1) provides an important rationale for the use of NAC for axillary downstaging in patients who are candidates for breast-conserving surgery at presentation or who desire mastectomy. SLN identification rates and FNRs in those who are cN0 are similar to those seen with initial SLN surgery, and nodal recurrence after a negative SLNB is uncommon.

 

Additional Reading: Boughey JC, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013 Oct 9;310(14):1455-1461. doi:10.1001/jama.2013.278932.

Graft reconstruction in pancreaticoduodenectomy: outcomes and survival

One discussion this week included use of prosthetic graft reconstruction …


Reference: Chu CK, et al. Prosthetic graft reconstruction after portal vein resection in pancreaticoduodenectomy: a multicenter analysis. Journal of the American College of Surgeons. 2010 Sep;211(3):316-324. doi: 10.1016/j.jamcollsurg.2010.04.005

Summary: Use of prosthetic grafts for reconstruction after portal vein (PV) resection during pancreaticoduodenectomy is controversial. This paper (by Emory authors) review 33 patients who underwent pancreaticoduodenectomy (PD) with vein resection and reconstruction using PTFE grafts between 1994 and 2009. Patient, operative, and outcomes variables were studied. Graft patency and survival were assessed using the Kaplan-Meier technique.

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Is TNT a viable treatment strategy for rectal cancer?

One discussion this week included total neoadjuvant therapy (TNT) for rectal cancer.

Reference: Cercek A, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncology. 2018 Jun 14;4(6):e180071. doi:10.1001/jamaoncol.2018.0071.

Summary: Treatment of locally advanced rectal (LARC) cancer involves chemoradiation, surgery, and chemotherapy. The concept of total neoadjuvant therapy (TNT), in which chemoradiation and chemotherapy are administered prior to surgery, has been developed to optimize delivery of effective systemic therapy aimed at micrometastases.

OBJECTIVE: To compare the traditional approach of preoperative chemoradiation (chemoRT) followed by postoperative adjuvantchemotherapy with the more recent TNT approach for LARC.

METHODS: A retrospective cohort analysis using Memorial Sloan Kettering Cancer Center (MSK) records from 2009 to 2015 was carried out. A total of 811 patients who presented with LARC (T3/4 or node-positive) were identified; 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT). Of the 628 patients, 373 (59%) were men, 255 (41%) were women, and the mean age was 56.7 years.

RESULTS: Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose than those in the chemoRT with plannned adjuvant chemotherapy cohort. The complete response (CR) rate, including both pathologic CR (pCR) in those who underwent surgery and sustained clinical CR (cCR) for at least 12 months posttreatment in those who did not undergo surgery, was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. TNT(Cerek et al, 2018)

CONCLUSIONS: Total neoadjuvant therapy was associated with improved delivery of systemic therapy and increased response to treatment, and it provides a promising platform for nonoperative watch-and-wait protocols. Long-term follow-up is necessary to determine if early systemic chemotherapy improves overall outcome

The authors conclude their findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer.