Organ Invasion Research Articles

Laparoscopic conversion to open surgery in radical nephrectomy and tumor thrombectomy: causal analysis, clinical characteristics, and treatment strategies

BackgroundWe aimed to explore the causal analysis, clinical characteristics and treatment strategies of laparoscopic conversion to open approach (LCTOA) in radical nephrectomy and tumor thrombectomy.MethodsWe included all patients with Mayo level I–III renal tumors with inferior vena cava (IVC) tumor thrombus who underwent laparoscopic radical nephrectomy and tumor thrombectomy as the first choice from May 2015 to July 2019.ResultsThere were 70 cases of renal tumor with IVC tumor thrombus treated with a laparoscopic approach as the first choice; 31 Mayo level I, 30 Mayo level II, and 9 Mayo level III. A completely laparoscopic approach was performed in 51 cases (72.9%), and 19 cases (27.1%) underwent active or passive LCTOA. The LCTOA group had higher median preoperative serum creatinine (110.0 μmol/L vs 92.0 μmol/L; P = 0.026), longer postoperative hospital stay (9 days vs 7 days; P = 0.008), longer median operation time (374 min vs 311 min; P = 0.017), higher median intraoperative hemorrhage volume (1300 vs 600 ml; P = 0.020), and higher proportion of male patients (94.7% vs 66.7%; P = 0.016) vs the completely laparoscopic group, respectively. Although preoperative serum creatinine and gender were risk factors in the univariate analysis, multivariate analysis revealed no independent risk factors for LCTOA. We divided the reasons for LCTOA into active conversion and passive conversion; 4 (21.1%) cases underwent active conversion, and 15 (78.9%) underwent passive conversion. Most of the patients undergoing passive conversion had multiple concurrent risk factors, among which perirenal adhesion (30.9%), organ invasion (16.4%), and IVC adhesion (25.5%) were the most common. Fourteen (73.7%) cases underwent renal treatment, and 5 (26.3%) cases underwent tumor thrombus treatment.ConclusionsThe LCTOA group had a higher median preoperative serum creatinine concentration, longer hospital stay, longer median operation time, and higher median intraoperative hemorrhage volume. However, none of the predictors in our study was an independent risk factor for LCTOA. Perirenal adhesion, organ invasion, and IVC adhesion were the most common causes of LCTOA. Considering the limitations of this study, studies with large sample sizes are required to validate our conclusions.

Clinicopathological characteristics and surgical outcomes of sarcomatoid hepatocellular carcinoma.

BACKGROUNDHepatocellular carcinoma (HCC) is the sixth most common type of cancer and the fourth leading cause of cancer-related death worldwide. Sarcomatoid HCC, which contains poorly differentiated carcinomatous and sarcomatous components, is a rare histological subtype of HCC that differs from conventional HCC. It is highly aggressive and has a poor prognosis. Its clinicopathological characteristics, surgical outcomes and underlying mechanisms of its highly aggressive nature have not been fully elucidated.AIMTo examine the clinicopathological characteristics and surgical outcomes of sarcomatoid HCC and explore the histogenesis of sarcomatoid HCC.METHODSIn total, 196 patients [41 sarcomatoid HCC and 155 high-grade (Edmondson-Steiner grade III or IV) HCC] who underwent surgical resection between 2007 and 2017 were retrospectively reviewed. The characteristics and surgical outcomes of sarcomatoid HCC were compared with those of patients with high-grade HCC. The histological composition of invasive and metastatic sarcomatoid HCCs was evaluated.RESULTSSarcomatoid HCC was more frequently diagnosed at an advanced stage with a larger tumor and higher rates of nonspecific symptom, adjacent organ invasion and lymph node metastasis than high-grade HCC (all P < 0.05). Compared with high-grade HCC patients, sarcomatoid HCC patients are less likely to have typical dynamic imaging features of HCC (44.4% vs 72.7%, P = 0.001) and elevated serum alpha-fetoprotein levels (> 20 ng/mL; 36.6% vs 78.7%, P < 0.001). The sarcomatoid group had a significantly shorter median recurrence-free survival (5.6 mo vs 16.4 mo, log-rank P < 0.0001) and overall survival (10.5 mo vs 48.1 mo, log-rank P < 0.0001) than the high-grade group. After controlling for confounding factors, the sarcomatoid subtype was identified as an independent predictor of poor prognosis. Pathological analyses indicated that invasive and metastatic lesions were mainly composed of carcinomatous components.CONCLUSIONSarcomatoid HCC was associated with a more advanced stage, atypical dynamic imaging, lower serum alpha-fetoprotein levels and a worse prognosis. The highly aggressive nature of sarcomatoid HCC is perhaps mediated by carcinomatous components.

Prognostic Factors and Survival in Resected T4 Non-small Cell Lung Cancer: Is There Any Difference in the T4 Subgroups?

The eighth edition of the TNM classification revised the subgroups of T4 non-small cell lung cancer (NSCLC). This study aimed to compare the T4-NSCLC subgroups that underwent surgical treatment in terms of mortality, morbidity, survival, and prognostic factors based on the new classification. Between 2000 and 2014, a total of 284 T4-NSCLC patients who underwent lung resection (mediastinal organ invasion, n = 114; ipsilateral different lobe tumors, n = 32; and tumors larger than 7 cm, n = 138) were included in the present study. Surgical mortality and morbidity were 5.6% (n = 16) and 23.9% (n = 68), respectively. The 5-year survival rates were 46% for ipsilateral different lobe tumors, 45.4% for tumours larger than 7 cm, and 36.6% for mediastinal organ invasion (28% for patients with heart/atrium invasion, 43.3% for carina invasion, 37.5% for large vessel invasion) (p = 0.223). Age above 65 (p = 0.002, HR = 1.781), pN2 versus pN0/1 (p < 0.0001, HR = 2.564), incomplete resection (p = 0.003, HR = 2.297), and pneumonectomy (p = 0.02, HR = 1.524) were identified as poor prognostic survival factors. According to multivariate analysis, mediastinal lymph node metastasis (p = 0.001) and incomplete resection (p = 0.0026) were the independent negative risk factors for survival. According to the results of our study, surgical treatment is a good option in T4-NSCLC patients who have no mediastinal lymph node metastasis and are completely resectable. There is no difference in terms of survival among the T4 subgroups. The eighth edition of the TNM classification has a better prognostic definition than the previous version.

Radical excision for retroperitoneal soft tissue sarcoma: A national propensity-matched outcomes analysis

BackgroundGiven the rarity of retroperitoneal soft tissue sarcoma, few studies have assessed if radical excision of retroperitoneal soft tissue sarcoma with adjacent organs improves survival outcomes. This propensity score–matched study aimed to evaluate the impact of radical excision versus resection of tumor alone. MethodsThe National Cancer Database 2004 to 2015 was used to assess short- and long-term outcomes of resection of tumor alone versus radical excision (tumor plus ≥1 adjacent organs) via 1:1 propensity-matched analyses. Subgroup analyses included low-grade, high-grade, liposarcoma, leiomyosarcoma, adjacent organ involvement alone, localized tumors alone, and high-volume hospitals (≥10 resections/y). Multivariable logistic regression models identified factors associated with radical excision. ResultsComparison of propensity-matched groups (N = 1,139/group) revealed no significant differences in 30-day mortality, 90-day mortality, or overall survival (for all, P > .580). For all subgroup analyses comparing resection of tumor alone with radical excision, including localized tumors without organ invasion (N = 208/group), there were no identified differences in short- or long-term survival. Although it yielded lower R2 resection rates (P = .007), radical excision was associated with greater mean length of stay (P < .001). ConclusionRadical excision was not associated with improved retroperitoneal soft tissue sarcoma survival irrespective of grade, histology, hospital volume, or adjacent organ involvement. Resection of ostensibly involved adjacent viscera may increase morbidity without survival benefit. These results inform ongoing discussion regarding histology-tailored, situation-specific extent of retroperitoneal soft tissue sarcoma resections.

Development of anti-human CADM1 monoclonal antibodies as a potential therapy for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a highly invasive and refractory T-cell malignancy, with poor prognosis. We previously identified that cell adhesion molecule 1 (CADM1) is overexpressed consistently in ATLL cells, and that CADM1 expression increases the adhesion capacity of ATLL cells to endothelial cells and promotes the organ invasion of ATLL cells in a xenograft mouse model. In this study, we first show that newly developed several anti-human CADM1 antibodies, which were complete human IgG antibodies generated by phage display method, specifically recognize CADM1 on ATLL cells. Although most of the CADM1 antibodies did not have a direct cytotoxic effect against CADM1-positive ATLL cells, clone 089-084 exhibited weak but significant antibody-dependent cell-mediated cytotoxic activity. Moreover, clone 103-189 effectively inhibits the interaction between endothelial cells and CADM1-positive ATLL cells. Furthermore, in mice bearing intra-splenic transplantation of EL4 mouse lymphoma cells expressing CADM1, the treatment of 103-189 significantly suppressed the organ invasion of CADM1-positive EL4 cells, resulting in improved survival time of mice. Therefore, since the anti-CADM1 antibody may be useful for the suppression of organ invasion in ATLL patients, combination use of the anti-CADM1 antibody with chemotherapy drugs could be beneficial for the efficient elimination of ATLL cells.

Large tumor size, lymphovascular invasion, and synchronous metastasis are associated with the recurrence of solid pseudopapillary neoplasms of the pancreas

BackgroundSolid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood. MethodsTo evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared. ResultsFifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P < 0.001), and synchronous metastasis (P < 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P < 0.01), and lymphovascular invasion (P < 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence. ConclusionLymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.

Differentiation of intra-abdominal desmoid tumor from peritoneal seeding based on CT and/or 18F-FDG PET-CT in patients with history of cancer surgery.

To investigate differential imaging features of intra-abdominal desmoid tumors and peritoneal seeding in patients with history of cancer surgery. Thirty-two patients who had a single pathologically proven intra-peritoneal lesion that developed after cancer surgery were enrolled between January 2000 and June 2019. There were 16 desmoid tumors and 16 peritoneal seeding lesions. Portal phase CT and/or 18F-FDG PET findings were analyzed by two radiologists in consensus for the following items: location, size, shape, margin, contour, homogeneity, necrosis, adjacent organ invasion, calcification, intra-lesional fat, peritoneal infiltration, mass effect, and degree of enhancement. Hounsfield units (HU) and maximum standardized uptake values (SUVmax) of the lesions were measured. Imaging findings were compared using the Chi square test, Fisher's exact test, and student t test. Desmoid tumors frequently showed well-defined margins (9/16) and smooth contours (12/16), whereas peritoneal seeding had ill-defined margins (13/16) and lobulated contours (11/16) (P = 0.028 and 0.013, respectively). Intra-lesional fat was found more frequently in desmoid tumors (7/16) than peritoneal seeding (1/16) (P = 0.014). Desmoid tumors showed iso-attenuation (13/16) compared to psoas muscle in portal phase, while peritoneal seeding depicted high attenuation (12/16) (P = 0.002). Mean HU was significantly lower in desmoid tumors (64.3) than peritoneal seeding lesions (95.1) (P = 0.001). However, the mean SUVmax of desmoid tumors (4.1) did not significantly differ from peritoneal seeding lesions (5.2) (P = 0.519). Several CT features including iso-attenuation in portal phase and presence of intra-lesional fat can be helpful in differentiating desmoid tumors from peritoneal seeding in patients with history of intra-abdominal cancer surgery.

Surgical Treatment of a Patient with Invasion of Multiple Organs Including the Common Carotid Artery by Papillary Thyroid Carcinoma: Surgical Management for Invasion of the Aerodigestive Tract

Background: Extrathyroidal invasion has the greatest negative prognostic impact among several adverse prognostic factors of differentiated thyroid carcinoma (DTC). Surgical treatment for locally advanced DTC is challenging. In particular, the presence of great vessel involvement makes it more challenging, with vessel rupture and infection being common occurrences, especially in patients with laryngotracheal or esophageal intraluminal invasion.1 Locoregional tumors presenting with great vessel and/or multiple organ invasion have been deemed to be unresectable. However, there has been little discussion regarding which types of locoregional tumor are unresectable. Regarding the surgical management of aerodigestive invasion, the 2015 American Thyroid Association management guidelines state that surgical decision making can be complex and must balance oncologic surgical completeness with preservation of the upper aerodigestive tract head neck function. However, surgical management of aerodigestive tract invasion remains controversial.2 Materials and Methods: A right thyroid tumor was unexpectedly detected in a 77-year-old man by computed tomography images. The man was found to have papillary thyroid carcinoma (PTC) by fine needle aspiration biopsy. He was referred for the surgical treatment of multiple organ invasion by PTC. Tumor encasement of about 180° of the right common carotid artery and aerodigestive tract invasion were suspected on pre-operative magnetic resonance imaging. We performed total thyroidectomy, including resection of multiple organ infiltration and right lateral neck dissection. Our surgical strategy for locally advanced DTC is implemented with curative surgical intent for all patients and functional preservation or reconstruction, if possible. Results: The thyroid tumor infiltrated the right common carotid artery, internal jugular vein, prevertebral fascia, pharyngoesophagus, laryngotrachea, and right recurrent laryngeal nerve (RLN). We performed subadventitial resection of the common carotid artery, partial prevertebral fascia resection, muscle layer resection of the pharyngoesophagus, framework resection of the larynx, window resection of the trachea from first to fourth ring, and resection and intralaryngeal reconstruction of the right RLN.3 After tumor resection, the right common carotid artery was covered using a deltopectoral flap and separated from the tracheacutaneous fistula. Pathology analysis confirmed well-differentiated PTC, which was classified as pT4bN1bM0. The tracheocutaneous fistula was closed 2 months after surgery. The patient underwent radioactive iodine (RAI) adjuvant therapy of 100 mCi, 6 months after surgery. RAI uptake was noticed in only the thyroid bed. Maximum phonation time was 10 seconds, 6 months after surgery. Conclusions: This video illustrates the technical details of surgical management for invasion of the aerodigestive tract. These surgical techniques are effective for improving surgical curability and functional preservation. No competing financial interests exist. Runtime of video: 9 mins 29 secs

CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms.

PurposeCD56 is a neural cell adhesion molecule that plays a role in the cohesiveness of neuroendocrine cells. The aim of this study was to explore the biological values of CD56 expression in pancreatic neuroendocrine neoplasms (PNENs) and its role in predicting PNENs grades.Patients and MethodsA total of 138 patients with histological-proven PNENs was included (66 G1, 46 G2 and 26 G3). The clinicopathological characteristics, including mitosis count, ki67 index, chromogranin A (CgA), synaptophysin (Syn) and CD56 expression, were evaluated. We assessed the diagnostic performance of markers in predicting PNEN G3 and the association between CD56 expression and risk of G3 or organs invasion.ResultsLack of CD56 immunoreaction (CD56-) was more common in PNEN G3 than G1/G2 (31% vs 0–2%, p < 0.01). The sizes of CD56- tumors were larger than CD56 positive tumors in PNEN G3 (p < 0.01). The odds ratio (OR) of CD56- expression was 13.6 [95% confidence interval (CI): 2.1–88.1] in predicting PNEN G3. The OR of CD56- expression was 6.5 (95% CI: 1.1–38.6) and 31.9 (95% CI: 1.09–938.3) in predicting organs invasion and neuroendocrine carcinoma in PNEN G3, respectively. Tumor size (area under the curve [AUC] = 0.77 and size+CD56- expression [AUC = 0.84]) had acceptable performance in predicating PNEN G3.ConclusionLack of CD56 immunoreaction may be a predictor and biological behavior marker for PNEN G3.

Adjuvant lenvatinib in combination with TACE for hepatocellular carcinoma patients with high risk of postoperative relapse (LANCE): Interim results from a muticenter prospective cohort study.

4580 Background: Surgical resection was the main treatment for hepatocellular carcinoma (HCC) in China. Multiple clinical studies had demonstrated that the overall survival (OS) of the surgical resection group was significantly better than the transcatheter arterial chemoembolization (TACE) or radiotherapy group even for HCC patients with BCLC stage B or C. There was no standard adjuvant therapy for HCC patients to decrease the post-operative tumor relapse. For HCC patients with high recurrence risk, TACE significantly reduced tumor recurrence, prolonged the disease free survival (DFS) and OS, and was recommended as the adjuvant therapy. However, its effect is not very satisfactory. The purpose of this study was to assess the efficacy and safety of lenvatinib in combination with TACE versus TACE alone as adjuvant therapy in HCC patients with high recurrence risk after resection. Methods: This is a muti-center prospective cohort study. The criteria of HCC patients with high postoperative recurrence risk included: accompanied with gross vascular or bile duct invasion (tumor thrombi in portal vein, hepatic vein or bile duct); or tumor rupture or invasion of adjacent organs; or grade 2 of microvascular invasion (MVI) (M2) along with the tumor number more than 3 or the maximum diameter of tumor larger than 8cm or tumor showed invasive growth with unclear boundaries and imcomplete capsules. The patients were divided into two groups, the lenvatinb (8mg qd for weights &lt; 60kg and 12mg qd for weights≥60kg) in combination with TACE (Len+TACE) group and the TACE group. Results: A total of 90 patients were enrolled into the study, while 45 patients in the Len+TACE group and 45 in TACE group. The media age was 52 years (range from 23 to 73 years). Most patients were males (82.2%) and 66 patients had HBV background (73.3%). There were no significant differences between the two groups in the baseline clinicopathological characteristics including gender, age, HBV background, liver cirrhosis, liver function, tumor characteristic and AFP level. The media DFS was 12.0 months (95% CI 8.0-NA) in the Len+ TACE group, which was longer than that of TACE group (8.0 months, 95% CI 6.0-12.0, P = 0.0359; HR 0.5, 95% CI 0.3-1.0). The most common grade 3 or 4 adverse events were hypertension (11.1%) and diarrhea (7.7%) in the Len+TACE group. Conclusions: Lenvatinib in combination with TACE was effective and safe as adjuvant therapy, which can prolong the DFS of HCC patients with high recurrence risk after resection. Clinical trial information: NCT03838796 .

Multivisceral Resection of Advanced Sigmoid Colon Cancer

Abstract Introduction: Colorectal cancer is one of the most common digestive malignancies, with a high mortality and morbidity rate, with nonspecific symptoms in the early stages and with a diagnosis in the advanced stage most often. In a significant percentage there are cases in which tumors with invasion in the border organs and multiorgan resections are required. In women, the invasion frequently occurs in the vagina, uterus and bladder. Case report: We report the case of a 52-year-old woman, who presented in the Department of Surgery with the following complaints: fecaluria, pneumaturia, constipation and moderate abdominal pain, with onset of 4 months, in wich the patient neglected her symptoms. Following the investigations, a large tumor formation of sigmoid colon was diagnosed, with invasion in the uterus and bladder, with which it communicates through a 16mm fistula. The result of the biopsy was of low / moderate grade adenocarcinoma differentiated G2. Cystoscopy revealed bladder trigone invasion without being able to identify ureteral orifices, biopsy and urine cytology was also positive for cancer. The surgery was performed by a multidisciplinary team and a multivisceral resection was performed. Conclusions: Multiorgan resections require trained, experienced teams, and oncological pathology raises special issues when it comes to radical visa. The management of invasive colonic tumors in the border organs must be established preoperatively, in agreement with the patient, because it involves problems related to the quality of life and the potential for survival.

S100A4 is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma.

Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis.

The Role of the Actin‐Binding Protein Cortactin in the Activation of T Cells: Implications for T‐Cell Acute Lymphoblastic Leukemia

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive neoplasm due to high rates of organ infiltration and relapse, which are major obstacles for curing the disease. Infiltration of T‐ALL cells requires extravasation, a migratory process highly dependent on actin cytoskeleton dynamics. Cortactin is an actin‐binding protein that regulates actin remodeling and thus cell migration. Recently, we showed that cortactin overexpression in B‐cell ALL was correlated with infiltration, steroid treatment failure and relapse. However, it is unknown whether cortactin is expressed in leukemic T cells and what role it plays in T‐ALL biology. We analyzed cortactin expression in murine and human normal T cells and T‐ALL cell lines, and cortactin functions using different in vitro and in vivo methods such as transendothelial migration and xenotransplantation assays. We observed that the human leukemic T cell lines Jurkat, CEM and Molt‐3, as well as the leukemic murine T cell line 6645/4 expressed the 80 kDa WT isoform of cortactin. Importantly, all cell lines had significantly higher levels of cortactin than normal resting CD3+ cells. In addition, leukemic T cells transmigrated, infiltrated and colonized bone marrow organoids significantly more than normal T cells. Of note, in vivo xenotransplantation assays revealed that infiltrated leukemic T cells diminished cortactin expression suggesting that cortactin is needed for initial organ invasion, but not for subsequent functions within the organ. As leukemic cells display hyperactive TCR signaling, we examined cortactin and HS1 levels after activation of T cells. To this end, we used α‐CD3 and α‐CD28 to stimulate resting normal CD3+ cells and leukemic T cells, and found that in CD3+, Jurkat and CEM cells, cortactin was up‐regulated during activation (~1000 fold‐over resting) in a time‐dependent manner, reaching a peak after full activation at 72 hours. Cortactin upregulation was also seen after phorbol 12‐myristate 13‐acetate and ionomycin stimulation in all cells. Importantly, levels of the hematopoietic homologue of cortactin, HS1, diminished as cortactin expression increased in CD3+ cells. Taken together, our results show that cortactin is overexpressed in leukemic T cells to endow them with enhanced migratory abilities. Cortactin is upregulated in both leukemic and normal T cells upon activation suggesting that cortactin might be an important protein for effector functions of activated T cells such as cytokine secretion.

ОПЫТ МУЛЬТИВИСЦЕРАЛЬНЫХ РЕЗЕКЦИЙ ПРИ МЕСТНОРАСПРОСТРАНЁННОМ И ПЕРВИЧНО-МНОЖЕСТВЕННОМ РАКЕ ПРЯМОЙ КИШКИ

Objective: Assessing short-term and long-term results of multivisceral resections (MVR) performed for rectal cancer (RC) with invasion into adjacent pelvic organs, as well as the effectiveness of bladder reconstruction with the formation of a urinary reservoir of «low» pressure. Methods: The work was based on the results of surgical treatment of 37 patients with locally advanced or primary multiple RC underwent MVR. Invasion of adjacent small organs was observed in 89.2%, primary multiple malignant tumors (PMMT) – in 10.8% of patients included in the study. Results: According to the preoperative examination of tumor infiltration of one adjacent organ was diagnosed in 20 (54.1%), two or more organs – in 17 (45.9%) observations; more often affected the bladder – in 18 (48.6%) cases. Volumes of performed operations: in 6 (16.2%) cases of complete pelvic organs evisceration, in 10 (27%) cases of MVR with rectal extirpation, in 21 (56.8%) cases of MVR with resection of the rectum and adjacent organs. More often in 27 (72.9%) patients, there was urinary tract resection, of which 11 (29.7%) patients underwent primary bladder repair with the formation of ortho- (n=3) or heterotopic (n=6) urinary reservoir of «low» pressure. Postoperative complications developed in 14 (37.8%) patients, what required re-surgery in 8 (21.6%) observed, of which urological complications occurred in 4 (10.8%) patients. Complications were not observed during the formation of the artificial bladder according to the presented method. Long-term results: RC – overall and disease-free 2-year survival – 78.1% and 65.6% respectively, PMMT – all patients are alive without signs of relapse, the timeline of observation is 24 months. Conclusions: The immediate results of MVR on locally advanced RC can be considered as satisfactory. The level of postoperative complications is primarily due to the prevalence of primary tumors. In case of urinary tract resection, primary plastic surgery is preferred. Long-term results allows to examine such operations as a method of choice in the treatment of RC with invasion in adjacent organs. Keywords: Rectal cancer, surgical treatment, multivisceral resection, bladder reconstruction, postoperative complications, disease-free survival.

Feasibility, safety and long-term efficacy of laparoscopic total gastrectomy combined with distal pancreaticosplenectomy for T4b gastric cancer

Objective: To explore the feasibility, safety and long-term efficacy of laparoscopic total gastrectomy combined with distal pancreaticosplenectomy for the treatment of T4b gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of consecutive patients with T4b gastric cancer invading pancreatic tail undergoing laparoscopic or open total gastrectomy combined with distal pancreaticosplenectomy from January 2010 to December 2014 were analyzed retrospectively. Enrollment criteria: (1) primary gastric cancer confirmed by pathology as T4b adenocarcinoma; (2) chest+abdominal+pelvic enhanced CT indicated cancer invading pancreatic tail without distant metastasis, and R0 resection was evaluated as feasible before operation; (3) physical status was ECOG score 0 to 2, and was tolerant to operation. Patients with peritoneal implant metastasis and tumor invasion of other organs during operation, or changes in surgical methods for other reasons were excluded. All the operations were performed by the same surgical team, which had the experiences of more than 100 cases of laparoscopic and 100 cases of open radical gastrectomy with D2 lymph node dissection. The choice of surgical procedure was discussed by the surgeon and the patient, and decided according to the patient's intension. Patients were divided into the laparoscopic group and open group according to the surgical method. Intraoperative and perioperative findings were compared between the two groups. The 3-year disease-free survival rate were analyzed with Kaplan-Meier survival curve and compared by using log-rank test. Results: A total of 37 consecutive patients were enrolled, including 21 in the laparoscopic group and 16 in the open group, and no one receiving laparoscopic procedure was converted to open surgery. The baseline data of two groups were comparable (all P>0.05). Compared with the open group, the laparoscopic group had significantly longer operation time [(264.0±35.1) minutes vs. (226.6±49.9) minutes, t=2.685, P=0.011], significantly less intraoperative blood loss [(65.7±37.4) ml vs. (182.2±94.6) ml, t=-4.658, P<0.001], significantly shorter time to postoperative flatus [(2.8±0.7) days vs. (4.1±0.7) days, t=-5.776, P<0.001] and significantly shorter postoperative hospital stay [(13.3±2.8) days vs. (16.6±4.3) days, t=-2.822, P=0.008]. Morbidity of postoperative complications, including anastomotic leakage, pancreatic fistula, abdominal abscess, intraperitoneal hemorrhage and duodenal stump leakage, in two groups was similar [19.0% (4/21) vs. 4/16, P=0.705]. There were no cases of anastomotic bleeding or stenosis. The 30-day postoperative mortality was 0 in the laparoscopic group and 1/16 in the open group, respectively (P=0.432). The 3-year disease-free survival rates were 38.1% and 37.5% in the laparoscopic and open group, respectively (P=0.751). Conclusion: Laparoscopic total gastrectomy combined with distal pancreaticosplenectomy performed by experienced surgeons for T4b gastric cancer is safe and effective.

Evaluation of 3-week-old layer chicks intratracheally challenged with Salmonella isolates from serogroup c1 (O:6,7) and Salmonella Enteritidis

ABSTRACTWith the exception to Salmonella enterica serotype Typhimurium and S. Enteritidis (serogroups B [O:4] and D [O:9], respectively), there have been very few studies conducted on the respiratory tract as route of infection in chickens with salmonellas from serogroup C1 (O:6,7). Therefore, the purpose of this present study was to determine the potential organ invasion by Salmonella enterica serotype Potsdam (SP), S. Mbandaka (SM), and S. Infantis (SI) from serogroup C1 (O:6,7) and compare their characteristics with those of S. Enteritidis (SE) on intratracheally (IT) challenged 3-week-old layer chicks. A total of 360 one-day-old White Leghorn layer chicks were acquired from a commercial hatchery and randomly assigned into four treatment groups (SP, SM, SI, and SE, respectively), consisting of three independent trials. Chicks were grown up to 21 days (3 weeks) and IT-challenged thereafter with 106 CFU of respective salmonella organisms per group (n = 30). Chicks (n = 5) were humanely sacrificed every 24 h for 6 days post-IT infection and organs such as lung, heart, liver, spleen, kidney and caecal content were cultured for salmonella. All treatment groups exhibited colonization of lungs and caecal contents at 1 d (P = 0.475) and 4 d (P = 0.696) post-IT infection, respectively. There was no isolation of SP, SM, and SI in heart, liver, spleen, and kidney. In contrast, SE was obtained from heart, liver, and spleen of IT-infected chicks. The findings of this study contribute to a better understanding of the importance of the respiratory route in salmonella infection in poultry.

Milk Fat Globule-EGF Factor 8 Contributes to Progression of Hepatocellular Carcinoma.

Milk fat globule-EGF factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates a wide spectrum of pathophysiological processes. MFG-E8 has been studied as a key regulator of cancer cell invasion, migration, and proliferation in different tissues and organs. However, potential roles of MFG-E8 in the growth and progression of liver cancer have not been investigated to date. Here, we analyzed 33 human hepatocellular carcinoma (HCC) samples and found that levels of MFG-E8 expression were significantly higher in HCC cells than in normal liver tissues. In addition, our in vitro gain-of-function study in three different HCC cell lines revealed that overexpression of MFG-E8 promoted the proliferation and migration of HCC cells, as determined by RT-qPCR, MTT assays, and wound healing analyses. Conversely, an MFG-E8 loss-of function study showed that proliferation capacity was significantly reduced by MFG-E8 knockdown in HCC cells. Additionally, MFG-E8 activity-neutralizing antibodies profoundly inhibited both migration and proliferation of HCC cells, attenuating their tumorigenic properties. These reductions in migration and proliferation were rescued by treatment of HCC cells with recombinant MFG-E8 protein. Furthermore, an in vivo HCC xenograft study showed that the number of proliferating HCC cells and tumor volume/weight were all significantly increased by MFG-E8 overexpression, compared to control mice. These results clearly show that MFG-E8 plays an important role in HCC progression and may provide a basis for future mechanistic studies and new strategies for the treatment of liver cancer.

Surgery for Gastric Cancer: State of the Art

Surgery remains the undisputed mainstay in the management of gastric cancer, and advances in chemotherapy and radiation have improved outcomes in patients with resectable disease. A multidisciplinary approach, with active coordination across specialties dealing with management of gastric cancers provides improved quality of care and outcomes. Radical gastrectomy involves complete removal of tumor with adequate margins and appropriate lymph node dissection. Spleen preserving D2 lymphadenectomy is the present standard of care for all resectable tumors except few early tumors (T1a lesions) where endoscopic or local resections are deemed suitable. Perioperative or adjuvant chemotherapy should be offered to all patients with resectable tumor, having advanced T stage or node-positive disease. In patients with advanced tumors with invasion of adjacent organs, multivisceral resections can be offered selectively in the presence of good performance status and response to chemotherapy, which can lead to improvement in overall survival. The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy needs to be evaluated in patients with limited peritoneal disease.

Pancreatic sarcomatoid carcinoma: CT, MRI, and 18F-FDG PET/CT features

To investigate computed tomography (CT), magnetic resonance imaging (MRI), and combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/CT features of pancreatic sarcomatoid carcinoma (PSC). The hospital database was searched retrospectively for the patients with PSC confirmed at histopathology after surgery. Ten patients who underwent unenhanced and enhanced CT (n=4), unenhanced and enhanced MRI (n=2), 18F-FDG PET/CT (n=2), and both enhanced CT and 18F-FDG PET/CT (n=2) were enrolled. Two patients underwent additional delayed PET/CT. The maximum standardised uptake value (SUVmax) was measured on PET/CT images. Eleven lesions were detected in 10 patients. Solid and cystic components (n=6), intratumoural haemorrhage (n=1), nodular calcification (n=2), main pancreatic duct dilatation resulted from lesion obstruction (n=5) or compression (n=3), cholangiectasis (n=5), vascular and peripheral organ invasion (n=5 and 6, respectively), hepatic and lymphatic metastases (n=4 and 2, respectively) were detected. All five lesions in four patients who underwent PET/CT showed intense FDG uptake on PET/CT with SUVmax (16, range 10.9-21.1). Increase of FDG uptake (SUVmax = 18.9, 20.1, and 27.3, respectively) was revealed on the delayed scan of three lesions in two patients. PSCs were more commonly ill-defined solid cystic masses, which caused pancreatic duct obstruction/compression without pancreatic parenchymal atrophy, and these masses on PET/CT showed high FDG uptake on both initial and delayed PET/CT.

Retroperitoneal Sarcomas: Prognostic Factors and Outcomes of a Series of Patients Treated at a Single Institution.

Retroperitoneal sarcomas (RPS) are rare heterogeneous tumors arising in the retroperitoneum with unique biological and behavioral patterns that are thought to be closely linked to histology. The aim of the study was to audit our results and analyze various clinico-pathological factors including surgical excision, histology, and their implications on the recurrences and survival outcomes in RPS. Retrospective analysis of patients treated at a tertiary referral center in India from March 2008 to July 2017 was performed. The clinico-pathological variables were analyzed for their association with tumor recurrence and survival with special emphasis on histological subtype. The primary outcome was overall survival (OS). One hundred consecutive patients operated for RPS were analyzed. Of these, 27 were operated for recurrent tumors. Liposarcomas (LPS) and leiomyosarcomas (LMS) constituted 50% (n = 50) and 30% (n = 30) of patients respectively. Complete tumor excision was achieved in 83%, with 43% patients undergoing adjacent organ resection. At a median follow-up of 25.3months, the median disease-free survival (DFS) and overall survival (OS) were 30months and 87.8months respectively. On multivariate analysis, tumor grade was the only factor to significantly affect survival (p = 0.001 for DFS and 0.005 for OS). There was no difference in survival outcomes between infiltrative and adhesive tumors with respect to adjacent organ invasion (p = 0.361 for OS). Tumor grade remains an important prognostic factor affecting disease-free and overall survival in retroperitoneal sarcomas irrespective of tumor size, site, and histology.