Pelvic Recurrence After Curative Resection for Rectal Adenocarcinoma: Impact of Surgery on Survival.

BACKGROUND/AIM: Rectal cancer (RC) represents 30% of colon cancers. Despite the progress achieved in integrated chemoradiotherapy and surgical multidisciplinary treatments, the rate of local recurrence (LR) is 3.7-13%. Multivisceral resections allow many patients with pelvic recurrence to be treated in a curative manner. The purpose of this work is to assess the impact of surgery for rectal cancer patients with pelvic recurrence. PATIENTS AND METHODS: In a retrospective study from 2013 to 2018, data was collected from patients who had undergone rectal resection for adenocarcinoma. We compared perioperative data, postoperative outcomes, oncological results, and survival rates. RESULTS: 106 rectal cancer patients (40-87 years old) requiring surgery were included. The local recurrence rate was 15% (15 patients). LR patients requiring intervention were nine (56%) who underwent sphincter sparing surgeries, and 6 (44%) who underwent surgeries with sphincter resection. There was no statistically significant difference (p=0.416) in the 5-year overall survival rate of patients without recurrence compared to those with pelvic recurrence. CONCLUSION: Curative surgery for local recurrence from rectal cancer is safe and feasible and should be considered in selected cases as it seems to provide acceptable surgical and oncological outcomes.

Prognostic features of gastro-entero-pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties.

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR] = 7.61, 95% confidence interval [CI] = 3.96-14.6, P < 0.0001 for RFS; HR = 3.28, 95% CI = 1.56-6.87, P = 0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR = 1.98, 95% CI = 1.25-3.13, P = 0.0036 for RFS and HR 2.59, 95% CI = 1.27-5.26, P = 0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.

Recurrent Leiomyosarcoma of the Small Bowel: A Case Series.

BACKGROUND/AIM: Leiomyosarcoma is an extremely rare, small bowel neoplasm (2% of all gastrointestinal tumours). Early diagnosis is challenging due to the slow growth of the cancer. The biological behaviour of this group of tumours is aggressive, and the first-line treatment is surgical resection. PATIENTS AND METHODS: This is a report of 4 cases of small bowel leiomyosarcoma that were treated in the last ten years at Hospital San Martino: one involving the jejunum and three involving the ileum (age range=69-86 years). Three patients underwent surgical resection and one was treated with chemotherapy. RESULTS: All patients who were eligible for surgery underwent radical resection with R0 margins. Mean overall survival was 33 months (range=8-84 months). CONCLUSION: Specific guidelines for small bowel leiomyosarcoma do not currently exist and these rare cases should be discussed in a multidisciplinary context. The first treatment approach is surgery, and in some cases, multivisceral resection may be needed to obtain free margins, even in recurrent cases.

Inferior vena cava resection without reconstruction for retroperitoneal malignancies.

Inferior vena cava (IVC) involvement in retroperitoneal malignancies is a rare occurrence and radical surgery with major vascular resection represents the only potential curative treatment. IVC replacement after resection is still controversial and only small series and few prospective data are available. We report a series of three patients affected by retroperitoneal masses involving IVC treated with vena cava resection without replacement. All patients were treated by a radical R0 surgical procedure associated with infrarenal IVC resection and no reconstruction. Based on preoperative radiologic imaging and intraoperative findings, one patient also underwent right nephrectomy, while another patient underwent left renal vein ligation without nephrectomy. Neither early nor late severe post-operative complications related to the absence of IVC outflow were observed. Resection without replacement of the infrarenal IVC results in acceptable morbidity, thus specific risks related to the use of prosthetic grafts can be avoided.

Different Features of Tumor-Associated NK Cells in Patients With Low-Grade or High-Grade Peritoneal Carcinomatosis.

Peritoneal carcinomatosis (PC) is a rare disease defined as diffused implantation of neoplastic cells in the peritoneal cavity. This clinical picture occurs during the evolution of peritoneal tumors, and it is the main cause of morbidity and mortality of patients affected by these pathologies, though cytoreductive surgery with heated intra-peritoneal chemotherapy (CRS/HIPEC) is yielding promising results. In the present study, we evaluated whether the tumor microenvironment of low-grade and high-grade PC could affect the phenotypic and functional features and thus the anti-tumor potential of NK cells. We show that while in the peritoneal fluid (PF) of low-grade PC most CD56dim NK cells show a relatively immature phenotype (NKG2A+KIR-CD57-CD16dim), in the PF of high-grade PC NK cells are, in large majority, mature (CD56dimKIR+CD57+CD16bright). Furthermore, in low-grade PC, PF-NK cells are characterized by a sharp down-regulation of some activating receptors, primarily NKp30 and DNAM-1, while, in high-grade PC, PF-NK cells display a higher expression of the PD-1 inhibitory checkpoint. The compromised phenotype observed in low-grade PC patients corresponds to a functional impairment. On the other hand, in the high-grade PC patients PF-NK cells show much more important defects that only partially reflect the compromised phenotype detected. These data suggest that the PC microenvironment may contribute to tumor escape from immune surveillance by inducing different NK cell impaired features leading to altered anti-tumor activity. Notably, after CRS/HIPEC treatment, the altered NK cell phenotype of a patient with a low-grade disease and favorable prognosis was reverted to a normal one. Our present data offer a clue for the development of new immunotherapeutic strategies capable of restoring the NK-mediated anti-tumor responses in association with the CRS/HIPEC treatment to increase the effectiveness of the current therapy.

Single-Port Versus Conventional Laparoscopic Cholecystectomy: Better Cosmesis at the Price of an Increased Incisional Hernia Rate?

Background: The incidence of trocar site hernia (TSH) in single-port laparoscopic cholecystectomy (SPC) is still a debated issue. Aim of this retrospective study was to compare the incidence of postoperative hernia and cosmetic results among patients undergoing SPC and multiport laparoscopic cholecystectomy (MPC) performed at a single institution. Methods: A series of 60 SPC and 60 MPC patients operated on between July 2016 and May 2018 were compared. Primary endpoint was to assess the incidence of TSH at long term. All the patients were admitted as outpatients for physical examination and scar measurement. Secondary endpoints were the cosmetic results assessed by a cosmesis score (CS) and the body image questionnaire (BIQ). Results: After a median 18-month follow-up (range: 6-29 months), a hernia in umbilical trocar site was detected in 4 (7.1%) SPC patients and 1 (2%) MPC patient, the difference not being statistically significant (P = .216). BIQ was almost equivalent in SPC and MPC groups (5.15 versus 5.27; P = .518), respectively. Statistically significant differences in favor of SPC were found in CS (22.3 versus 19.72; P = .001) and in total length of scars (1.2 cm versus 4 cm; P < .001). Conclusions: SPC technique has proved to be safe and effective in experienced hands. Superior cosmesis of SPC over MPC is confirmed, but close attention to fascial closure is a vital component of SPC, and surgeons performing single-site surgery need to be aware of this increased potential for hernia formation.

Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas.

INTRODUCTION: Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis. AREAS COVERED: The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials. EXPERT OPINION: Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted.

Investigational PI3K/AKT/mTOR inhibitors in development for endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is the most common neoplasm of the female genital tract in developed countries. Despite the progress in early detection and treatment, a significant number of cases of advanced ECs are still diagnosed. These patients have few treatment options and a poor prognosis. Our understanding of EC pathogenesis and progression has been enhanced by recent genomic studies. Among the relevant biological pathways, phosphatidylinositol 3-kinase/AKT (PIK3/AKT)-mammalian target of rapamycin (mTOR) signaling is frequently upregulated in this cancer. AREAS COVERED: This review covers investigational EC therapeutics acting on the PI3K/AKT/mTOR pathway. The authors review the results of clinical studies and highlight ongoing trials. EXPERT OPINION: Several new agents are under evaluation for treating patients with metastatic, recurrent, and persistent EC. Clinical trials investigating PI3K/AKT/mTOR inhibitors have yielded controversial results. In the near future, new studies with dual inhibitors or multi-pathways inhibitors as mono or combination therapies with conventional chemotherapy (CT) or other targeted drugs may provide more promising data. Moreover, the evaluation of new serum and histological biomarkers is an attractive strategy for patient selection.

Peritoneal carcinomatosis from ovarian paraganglioma: Report of a rare case and systematic review of the literature.

Paraganglioma is one of the rarest neoplasms involving the ovary, with only 10 previous reports. We present a case of peritoneal carcinomatosis from primary ovarian paraganglioma and a systematic review of the literature. Clinical information was retrieved from medical records, and a systematic review of the literature was performed according to meta-analysis of observational studies in epidemiology guidelines. A 33-year-old woman presented with a 12-month history of hypertension and weight loss. She was diagnosed with ovarian paraganglioma and was treated with extensive debulking surgery to no residual disease after three cycles of neoadjuvant chemotherapy. She recurred after 6 months and was started on somatostatin-analogue. Following further disease progression with bone metastasis (treated with palliative radiotherapy), a trial with Sunitinib was started. The patient died 30 months after initial diagnosis. Of the cases reported to date, only one had peritoneal metastasis at presentation but none of them had such an ominous prognosis. Ovarian paraganglioma is an extremely rare condition. We report the first case of primary malignant ovarian paraganglioma with an exceptionally aggressive behavior. Clinicopathological correlation with immunohistochemistry is essential to avoid misdiagnosis. A standard treatment is not recommended yet but cytoreductive surgery seems to be a favorable approach to prolong survival.

Giant Filiform Polyposis not Associated with Inflammatory Bowel Disease: A Case Report.

BACKGROUND: Filiform polyposis (FP) is an uncommon cause of non-neoplastic and non-syndromic polyposis. Several hypotheses concerning its pathogenesis have been published. FP is most frequently associated with a post-inflammatory reparative process; indeed, the most frequent association is with inflammatory bowel disease (IBD). FP is characterized by one to hundreds of uniform, slender, arborizing, vermiform projections of the large bowel mucosa and submucosa lined by normal or inflamed colonic mucosa. The most common sites for these polyps are the transverse and descending colon. CASE REPORT: In this report we present a case of giant FP associated with locally invasive adenocarcinoma of the right colon in a 73-year-old man with no past medical history of IBD. CONCLUSION: Few of these cases have been reported in the literature, and out of the approximately 20 of such case reports only one other was associated with colorectal adenocarcinoma.

Recurrent acute Budd-Chiari syndrome after right hepatectomy: US color-Doppler vascular pattern and left hepatic vein stenting for treatment.

After extended right hepatectomy remnant liver can be affected by outflow obstruction due to torsion of the inferior vena cava or kinking of the left hepatic vein. Remnant liver fixation is therefore suggested to avoid postoperative acute Budd-Chiari syndrome. Despite remnant liver reposition during surgery, a 76-years-old woman developed complete outflow obstruction. This clinical situation, due to left hepatic vein kinking, was suspected by US examination and confirmed by CT scan that showed a pathological intrahepatic vascular pattern. Patient required urgent relaparotomy and the liver was replaced in normal position. However, recurrence of outflow obstruction occurred and it was ultimately treated by inferior vena cava angiogram with left hepatic vein stenting.

Laparoscopic resection of hepatocellular carcinoma. Considerations on lesions in the posterosuperior segments of the liver.

AIM: The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR) of hepatocellular carcinoma (HCC) including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. MATERIAL OF STUDY: Between June 2005 and May 2009, we performed 22 LLR for HCC. The underlying cirrhosis was staged as Child A in 19 cases and Child B in 3. RESULTS: LLR included a non anatomic resection in 15 cases and an anatomic resection in 7. A conversion to laparotomy occurred in one (4.5%) patient for hemorrhage. Mortality and morbidity rates were 0% and 18.1% (4/20). Over a mean follow-up period of 29 months (range: 19-65 months), 11 (50%) patients presented recurrence, mainly at distance from the surgical site. DISCUSSION: A laparoscopic approach is more suitable when the lesion is located in the peripheral "laparoscopic" segments 2 to 6. Nevertheless, six resections were made in the posterosuperior segments. Although parenchymal-sparing resection is required by the presence of underlying liver disease, anatomic resection has always to be considered and pursued to reduce local recurrence. In our series the recurrence rate was similar to those reported for other laparoscopic studies and for open resection of HCC. CONCLUSIONS: LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncologic adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.

CEUS Retrograde Cystography Is Helpful in Percutaneous Drainage of Complex Posttransplant Lymphocele.

After monolateral dual kidney transplantation, a 69 years old male patient developed symptomatic lymphocele with mild hydroureteronephrosis, impaired renal function, and right inferior limb oedema. A percutaneous ultrasound-guided drainage of the fluid collection was planned, but the complex mutual relations between the collection and the renal hilus did not allow to identify a suitable route for a safe drainage insertion during conventional ultrasound examination. A retrograde cystography using echographic contrast agent was, therefore, performed, and it clarified the position of both ureters and the renal vessels, permitting an harmless ultrasound-guided percutaneous lymphocele drainage. In conclusion contrast-enhanced ultrasound retrograde cystography may be helpful in percutaneous drainage of complex posttransplant lymphocele.

Laparoscopic right posterior sectionectomy for hepatocellular carcinoma using a modified liver-hanging maneuver.

BACKGROUND: Posterosuperior liver segments are the most difficult locations for laparoscopy to access. This location is considered by most surgeons to be a poor indication for a laparoscopic liver resection due to the limited visualization and the difficulty of controlling bleeding. The liver-hanging maneuver (LHM) is a technique taking aim at reducing intraoperative blood loss through an open approach. METHODS: We report our early experience on adopting a modified liver-hanging technique to perform a totally laparoscopic right posterior sectionectomy to remove a 5-cm hepatocellular carcinoma located in Couinaud's segments 6 and 7. RESULTS: The procedure was completed laparoscopically with acceptable time of surgery and blood loss. A 3.5-cm tumor-free resection margin was achieved. The patient was discharged on postoperative Day 10 without complications. No evidence of recurrence was seen at the 12-month follow-up. CONCLUSIONS: Total laparoscopic posterior sectionectomy using a modified LHM is a possible operative procedure greatly facilitating surgical manipulation. This maneuver was successfully used to mobilize the liver, to guide the hepatic transection, and to prevent bleeding. The potential advantages of this procedure should be evaluated in a comparative study on a large number of patients.

Hepatic flow optimization in full right split liver transplantation.

Split liver transplantation for two adults offers a valuable opportunity to expand the donor pool for adult recipients. However, its application is mainly hampered by the physiological limits of these partial grafts. Small for size syndrome is a major concern during transplantation with partial graft and different techniques have been developed in living donor liver transplantation to prevent the graft dysfunction. Herein, we report the first application of synergic approaches to optimise the hepatic hemodynamic in a split liver graft for two adults. A Caucasian woman underwent liver transplantation for alcoholic cirrhosis (MELD 21) with a full right liver graft (S5-S8) without middle hepatic vein. Minor and accessory inferior hepatic veins were preserved by splitting the vena cava; V5 and V8 were anastomosed with a donor venous iliac patch. After implantation, a 16G catheter was advanced in the main portal trunk. Inflow modulation was achieved by splenic artery ligation. Intraportal infusion of PGE1 was started intraoperatively and discontinued after 5 d. Graft function was immediate with normalization of liver test after 7 d. Nineteen months after transplantation, liver function is normal and graft volume is 110% of the recipient standard liver volume. Optimisation of the venous outflow, inflow modulation and intraportal infusion of PGE1 may represent a valuable synergic strategy to prevent the graft dysfunction and it may increase the safety of split liver graft for two adults.

Early effects of portal flow modulation after extended liver resection in rat.

INTRODUCTION: The incidence of small-for-size-liver-syndrome after liver transplantation and extended liver resection may be reduced by portal flow modulation. However, many aspects of the small-for-size-liver-syndrome pathogenesis are still unclear. In this experimental study we evaluated the early effects of portal flow modulation after 80% hepatic resection in rats. MATERIALS AND METHODS: Rats were randomised in: sham operation (G1), conventional hepatic resection (G2), splenectomy and hepatic resection (G3), splenic transposition followed by hepatic resection after three weeks (G4). Six hours after operation, oxygen saturation of hepatic vein blood, glutathione, and standard liver markers were measured from hepatic venous blood. Glutathione measurement and histopatological examination were performed in the remnant liver. RESULTS: Total bilirubin and liver glutathione did not show differences between groups. Aspartate aminotransferase and alanine aminotransferase significantly increased in G2-G4 groups. Blood glutathione and oxygen saturation of hepatic vein blood were lower in G2 than in other groups. A gradient of micro-vesicular degeneration was more severe in G2 compared with G3 and G4. Apoptosis, hemorrhagic necrosis, mitochondrial damage and leucocyte adhesion were evident in G2. CONCLUSION: The portal flow modulation induced by splenectomy or splenic transposition was effective in limiting early damage after extended liver resection.

Reversed arterial flow in the paramedian segments of the liver after pancreaticoduodenectomy.

Variation of splanchnic arterial anatomy is frequent and may complicate pancreatic surgery, leading to life-threatening postoperative complications. We report a case of severe hepatic dysfunction after pancreaticoduodenectomy due to accidental section of the right hepatic artery. Bedside ultrasound examination showed a reversed arterial flow in the paramedian segments of the liver. Based on intraoperative and ultrasound findings, a retrograde arterial supply of the right liver from the left hepatic artery through spontaneous anastomosis between the arteries of segment 4 and the right paramedian segments was assumed and confirmed by postoperative CT examination.

Simultaneous laparoscopic anterior resection and left hepatic lobectomy for stage IV rectal cancer.

We report the case of a 68-year-old female patient affected by rectal cancer and a synchronous metastatic lesion measuring 8 cm in diameter in the left hepatic lobe. After a laparoscopic ultrasonography exploration of the liver to detect possible occult metastases, a simultaneous colorectal resection and a left hepatic lobectomy including a partial resection of segment IV were performed. Five ports were used for the entire procedure. The resected specimens were extracted through a Pfannenstiel incision. The procedure was completed laparoscopically. Total operative time was 455 minutes with negligible intraoperative blood loss. The postoperative hospital stay was 12 days. At 4-month follow-up, the patient recovered completely. A computed tomography scan performed at this time showed no signs of recurrent disease. This report confirms the feasibility of the laparoscopic approach to simultaneous hepatic and colorectal resections in stage IV rectal cancer. The known advantages of the miniinvasive approach could make such complex procedures more endurable.

Laparoscopic staging and radiofrequency of hepatocellular carcinoma in liver ci rrhosis. A "bridge" treatment to liver transplantation.

BACKGROUND/AIMS: Surgical resection and liver transplantation are the only curative treatments for hepatocellular carcinoma, although limited to early stage disease. Our objective was to assess a novel operative combination of laparoscopic ultrasound with laparoscopic radiofrequency ablation of small hepatocellular carcinoma in potential candidates to liver transplantation when radiological evaluation is equivocal. We also evaluated the feasibility and efficacy of laparoscopic radiofrequency ablation. METHODOLOGY: Over a 2-year period, a laparoscopic ultrasound exploration and a laparoscopic radiofrequency ablation was performed in 15 patients (mean age 57+/-5.4 years; male/female 13/2) with hepatocellular carcinoma in liver cirrhosis. RESULTS: LRFA procedure was completed in all patients and a thermoablation of 36 hepatocellular carcinoma nodules was achieved. Laparoscopic ultrasound identified 12 new malignant lesions (46.1%) undetected by preoperative imaging. Six patients were up-staged as a result of the procedure and 3 were precluded from liver transplantation listing. A complete tumor necrosis was observed in 32 thermoablated nodules (88.8%) via spiral computed tomography 1 month after treatment. Seven patients underwent liver transplantation after a 5.8-month mean interval, and pathological staging of the explants agreed with laparoscopic staging for number/size of hepatocellular carcinoma nodules in all cases. Residual tumor was found in 2/12 (16.6%) thermoablated nodules, in two different liver specimens. CONCLUSIONS: Laparoscopic ultrasound accurately staged hepatocellular carcinoma in advanced cirrhosis with minimal morbidity and it can be used in potential candidates to liver transplantation. Laparoscopic radiofrequency ablation of hepatocellular carcinoma proved to be a safe and effective technique, representing a valid "bridge" treatment to liver transplantation or an effective palliative option.