Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Impact of "critical lesions" on outcomes following cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract. METHODS: Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS). RESULTS: Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p < 0.01), EBL higher (769 ml vs 405 ml, p < 0.01), transfusions higher (1.9 vs 0.7 Units, p < 0.001) and PCI higher (15.5 vs 9.5, p < 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p < 0.037) and 73% vs 87% (p < 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site. CONCLUSIONS: Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.

Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications. PATIENTS AND METHODS: Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44 °C, and mean perfusate temperature was 42 °C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2-10 mmHg, n = 28), target IAP group (10-20 mmHg, n = 71), and high IAP group (20-34 mmHg, n = 16) as well as with CBT as a continuous variable. RESULTS: 115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p = 0.035). CONCLUSIONS: IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

Serum CEACAM1 Elevation Correlates with Melanoma Progression and Failure to Respond to Adoptive Cell Transfer Immunotherapy.

Malignant melanoma is a devastating disease whose incidences are continuously rising. The recently approved antimelanoma therapies carry new hope for metastatic patients for the first time in decades. However, the clinical management of melanoma is severely hampered by the absence of effective screening tools. The expression of the CEACAM1 adhesion molecule on melanoma cells is a strong predictor of poor prognosis. Interestingly, a melanoma-secreted form of CEACAM1 (sCEACAM1) has recently emerged as a potential tumor biomarker. Here we add novel evidences supporting the prognostic role of serum CEACAM1 by using a mice xenograft model of human melanoma and showing a correlation between serum CEACAM1 and tumor burden. Moreover, we demonstrate that serum CEACAM1 is elevated over time in progressive melanoma patients who fail to respond to immunotherapy as opposed to responders and stable disease patients, thus proving a correlation between sCEACAM1, response to treatment, and clinical deterioration.

Delayed breast cellulitis following breast conserving operation.

A complication of breast conservation, which has been increasingly reported in the literature, is 'delayed cellulitis' in the treated breast. This is to be distinguished from wound infection in the breast following lumpectomy. This study reports 16 cases diagnosed with delayed cellulitis following breast conserving surgery, unresponsive to antibiotic therapy. Diagnostic criteria included: pain, erythema and edema in the operated breast. Symptoms appeared up to 10 months after surgery and time to resolution was seven and a half months. No patients had positive cytology and bacteriology tests were negative. Thirteen patients were observed, and three patients were treated with antibiotics with no apparent immediate effect. The appearance of breast cellulitis after surgery poses a problematic diagnostic and management dilemma. It is important to distinguish between this entity and infection, or inflammatory carcinoma. The picture may be attributed to impairment or occlusion of the lymphatic circulation in the breast. This seems to be a newly defined complication with an incidence of 3-5%.

Positive margins of breast biopsy: is reexcision always necessary?

BACKGROUND AND OBJECTIVES: Breast-conserving surgery requires excision of all gross tumor and subsequent radiation therapy. It is generally accepted that the presence of microscopically positive margins requires reexcision. The goal of this study was to identify characteristics that distinguish breast biopsy specimens with positive margins that when reexcised are free from residual tumor. This population of patients may benefit from breast irradiation only, without the need for another surgical procedure. METHODS: One hundred and fifteen of 395 cancer-proven biopsies had positive surgical margins and were treated with reexcision or mastectomy. Sixty-seven of these were negative for residual tumor and 48 were positive for residual tumor. Evaluation for tumor type, tumor size, grade, presence of vascular invasion, volume of the biopsy specimen, true positivity and the number of positive margins, multifocality of the tumor, and type of anesthesia was done by univariate and multivariate analysis. RESULTS: Univariate and multivariate analysis revealed that factors associated with a positive reexcision included margin status, method of detection, histologic appearance, and type of anesthesia used. CONCLUSION: These results suggest that small, clinically detectable unifocal tumors could be treated without the need for a further excision. Eradication of microscopic residual tumor could be done by irradiation only, sparing the patient an additional surgical procedure.

Revision hip arthroplasty in patients with a history of previous malignancy.

BACKGROUND AND OBJECTIVES: The potential association between implants and malignancy has been discussed in the literature, but never as a cause of loosening of joint arthroplasty. METHODS: The records of all patients who underwent revision arthroplasty at our institution between 1992 and 1995 were reviewed. RESULTS: Among 93 patients who underwent revision hip arthroplasties, 11 (11.8%) had a history of previous malignancy. At surgery, in 2 of these patients, metastasis was found to be the cause of loosening in the affected hip. CONCLUSIONS: When revision hip arthroplasty is considered, patients with a history of malignancy require attenuated pre-, intra-, and postoperative workup. Management algorithm in such cases is proposed.

Sentinel lymph node involvement--a predictor for axillary node status with breast cancer--has the time come?

AIMS: Axillary node dissection for breast cancer is important for staging and its prognostic value. Sentinel nodes are defined as the first nodes into which the primary cancer drains. This study investigates whether identification, removal and pathological examination of these nodes indicates whether the completion of axillary lymphadenectomy is required. METHODS: Using a vital dye injected at the primary tumour site, we were able to identify sentinel nodes in 96 out of 98 women examined. RESULTS: An average number of 2.7 +/- 1.2 nodes per patient were identified as sentinel nodes. In 83% of cases there was a correlation between the involvement of the sentinel nodes and the rest of the axillary nodes. In 14% of patients the sentinel nodes were the only nodes involved with tumour. In three cases the sentinel nodes were negative, but other axillary nodes were tumour-positive. CONCLUSION: The major problem in routine application of this method to the decision to perform axillary lymph node dissection (ALND) is the time needed for pathological identification of lymph node involvement by tumor.

Aprotinin improves hemostasis after cardiopulmonary bypass better than single-donor platelet concentrate.

Platelet transfusion and aprotinin administration improve platelet function and clinical hemostasis after extracorporeal circulation. To compare two methods of improving postoperative hemostasis, we preoperatively randomized 40 patients undergoing various open heart procedures into two groups. Group A included 20 patients who, immediately after bypass, received single-donor plateletpheresis concentrates collected from ABO-compatible donors (Baxter Autopheresis-C System). They were compared with 20 patients who received high-dose aprotinin (6 x 10(6) KIU) before and during cardiopulmonary bypass (group B). Group A patients showed significantly higher platelet count after single-donor plateletpheresis concentrate transfusion (157 +/- 36 x 10(9)/L compared with 118 +/- 42 x 10(9)/L (p < 0.05). However, platelet aggregation on extracellular matrix was better in group B (3.4 +/- 0.7 versus 2.8 +/- 0.9; p < 0.05). Total 24-hour blood loss and exposure to homologous blood products were significantly less in group B (396 +/- 125 mL and 1.1 +/- 1.6 units compared with 617 +/- 233 mL and 5.4 +/- 3.4 units; p < 0.01). Despite higher platelet count in patients after single-donor plateletpheresis concentrates transfusion, hemostasis in patients receiving aprotinin is better due to improved platelet function.

Age-dependent experimental tumor dissemination of murine melanoma B16.

Female C57BL/6 Jena mice, 3-, 12-, and 18-month-old, were inoculated intravenously (i.v.) with syngeneic melanoma B16 cells. The number of experimental lung metastases, counted 21 days after tumor inoculation, was significantly higher in older hosts. Pretreatment of young adult mice with immunosuppressive dose of cyclophosphamide considerably increased the number of lung nodules. The number of lung metastases was reduced when young and old animals were pretreated or treated with Poly (I:C). Similar treatment of mice with two other immunomodulators (thymalin and diacetyl-splenopentin 5) was practically without effect on metastasis formation. It is suggested that the higher number of experimental metastases of melanoma B16 in aged mice is mediated by immuno-senescence.

Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors.

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired. NK cells from healthy subjects kept their activity in culture with or without IFN for more than six days whereas SLE NK cell activity declined to zero at day 3. So, the increased IFN level of many SLE patients and a possible prior IFN priming effect seemed unrelated to the insensitivity to exogenous IFN in vitro. Inhibition factor(s) of SLE serum suppressed NK cytotoxicity in the presence of IFN whereas IFN sensitivity of MO remained unaffected indicating the complex regulation by serum components of immune reactions.

Studies on the mechanism of macrophage cytotoxicity.

The interactions with tumor target cells of resident and BCG-activated murine peritoneal macrophages (M phi) as well as of BCG-activated M phi additionally stimulated by a lymphokine-like factor were investigated in order to get some insight into the cytolytic process mediated by activated M phi. The lymphokine-like factor enhancing the cytotoxicity of BCG-activated M phi (MCF) was isolated and partially purified from cell-free fluid of rat Zajdela ascites hepatoma. M phi cytotoxicity was determined by a modified 51Cr release assay. Scanning and transmission electron microscopic findings suggested a two-step mechanism of target cell lysis: a first step of specific attachment of processes of M phi on the target cell surface and a second step with transport of lysosome-like vesicles to the target cells obviously with liberation of these vesicles in the immediate vicinity of target cells resulting in a local accumulation of cytolytic substances. This interpretation was supported by findings after treatment of interacting effector and target cells with amphotericin B and bestatin which substances were modifying M phi cytotoxicity. MCF caused only an augmentation of M phi cytotoxicity without qualitative differences to the cytolytic action of merely BCG-activated M phi.

[Determination of the chemotaxis of peritoneal macrophages from mice by means of different test systems (author's transl)]. / Bestimmung der Chemotaxis von Peritonealmakrophagen der Maus mit verschiedenen Testsystemen.

The chemotactical response of mouse peritoneal macrophages was examined by means of three different methods: 1. A modified migration chamber technique 2. An agarose assay 3. A 51chromium labelling assay. Casein and the synthetical peptide N-formylmethionin leucine were applied as chemoattractants. The results show that the migration chamber technique is more sensitive and therefore more suitable to determine the chemotactical response of mouse peritoneal macrophages than the assay under agarose. An additional labeling of macrophages with 51chromium in the migration chamber technique is inefficient.