Radiomics of Intrahepatic Cholangiocarcinoma and Peritumoral Tissue Predicts Postoperative Survival: Development of a CT-Based Clinical-Radiomic Model.

BACKGROUND: For many tumors, radiomics provided a relevant prognostic contribution. This study tested whether the computed tomography (CT)-based textural features of intrahepatic cholangiocarcinoma (ICC) and peritumoral tissue improve the prediction of survival after resection compared with the standard clinical indices. METHODS: All consecutive patients affected by ICC who underwent hepatectomy at six high-volume centers (2009-2019) were considered for the study. The arterial and portal phases of CT performed fewer than 60 days before surgery were analyzed. A manual segmentation of the tumor was performed (Tumor-VOI). A 5-mm volume expansion then was applied to identify the peritumoral tissue (Margin-VOI). RESULTS: The study enrolled 215 patients. After a median follow-up period of 28 months, the overall survival (OS) rate was 57.0%, and the progression-free survival (PFS) rate was 34.9% at 3 years. The clinical predictive model of OS had a C-index of 0.681. The addition of radiomic features led to a progressive improvement of performances (C-index of 0.71, including the portal Tumor-VOI, C-index of 0.752 including the portal Tumor- and Margin-VOI, C-index of 0.764, including all VOIs of the portal and arterial phases). The latter model combined clinical variables (CA19-9 and tumor pattern), tumor indices (density, homogeneity), margin data (kurtosis, compacity, shape), and GLRLM indices. The model had performance equivalent to that of the postoperative clinical model including the pathology data (C-index of 0.765). The same results were observed for PFS. CONCLUSIONS: The radiomics of ICC and peritumoral tissue extracted from preoperative CT improves the prediction of survival. Both the portal and arterial phases should be considered. Radiomic and clinical data are complementary and achieve a preoperative estimation of prognosis equivalent to that achieved in the postoperative setting.

Radiomic Analysis of Intrahepatic Cholangiocarcinoma: Non-Invasive Prediction of Pathology Data: A Multicenter Study to Develop a Clinical-Radiomic Model.

Standard imaging cannot assess the pathology details of intrahepatic cholangiocarcinoma (ICC). We investigated whether CT-based radiomics may improve the prediction of tumor characteristics. All consecutive patients undergoing liver resection for ICC (2009-2019) in six high-volume centers were evaluated for inclusion. On the preoperative CT, we segmented the ICC (Tumor-VOI, i.e., volume-of-interest) and a 5-mm parenchyma rim around the tumor (Margin-VOI). We considered two types of pathology data: tumor grading (G) and microvascular invasion (MVI). The predictive models were internally validated. Overall, 244 patients were analyzed: 82 (34%) had G3 tumors and 139 (57%) had MVI. For G3 prediction, the clinical model had an AUC = 0.69 and an Accuracy = 0.68 at internal cross-validation. The addition of radiomic features extracted from the portal phase of CT improved the model performance (Clinical data+Tumor-VOI: AUC = 0.73/Accuracy = 0.72; +Tumor-/Margin-VOI: AUC = 0.77/Accuracy = 0.77). Also for MVI prediction, the addition of portal phase radiomics improved the model performance (Clinical data: AUC = 0.75/Accuracy = 0.70; +Tumor-VOI: AUC = 0.82/Accuracy = 0.73; +Tumor-/Margin-VOI: AUC = 0.82/Accuracy = 0.75). The permutation tests confirmed that a combined clinical-radiomic model outperforms a purely clinical one (p < 0.05). The addition of the textural features extracted from the arterial phase had no impact. In conclusion, the radiomic features of the tumor and peritumoral tissue extracted from the portal phase of preoperative CT improve the prediction of ICC grading and MVI.

Percutaneous management of postoperative Bile leak after hepato-pancreato-biliary surgery: a multi-center experience.

BACKGROUND: Bile leak (BL) after hepato-pancreato-biliary (HPB) surgery is associated with significant morbidity and mortality. Aim of this study was to evaluate effectiveness and safety of percutaneous transhepatic approach (PTA) to drainage BL after HPB surgery. METHODS: Between 2006 and 2018, consecutive patients who were referred to interventional radiology units of three tertiary referral hospitals were retrospectively identified. Technical success and clinical success were analyzed and evaluated according to surgery type, BL-site and grade, catheter size and biochemical variables. Complications of PTA were reported. RESULTS: One-hundred-eighty-five patients underwent PTA for BL. Technical success was 100%. Clinical success was 78% with a median (range) resolution time of 21 (5-221) days. Increased clinical success was associated with patients who underwent hepaticresection (86%,p = 0,168) or cholecystectomy (86%,p = 0,112) while low success rate was associated to liver-transplantation (56%,p < 0,001). BL-site,grade, catheter size and AST/ALT levels were not associated with clinical success. ALT/AST high levels were correlated to short time resolution (17 vs 25 days, p = 0,037 and 16 vs 25 day, p = 0,011, respectively) Complications of PTA were documented in 21 (11%) patients. CONCLUSION: This study based on a large cohort of patients demonstrated that PTA is a valid and safe approach in BL treatment after HPB surgery.

Simultaneous colorectal and parenchymal-sparing liver resection for advanced colorectal carcinoma with synchronous liver metastases: Between conventional and mini-invasive approaches.

The optimal timing of surgery in case of synchronous presentation of colorectal cancer and liver metastases is still under debate. Staged approach, with initial colorectal resection followed by liver resection (LR), or even the reverse, liver-first approach in specific situations, is traditionally preferred. Simultaneous resections, however, represent an appealing strategy, because may have perioperative risks comparable to staged resections in appropriately selected patients, while avoiding a second surgical procedure. In patients with larger or multiple synchronous presentation of colorectal cancer and liver metastases, simultaneous major hepatectomies may determine worse perioperative outcomes, so that parenchymal-sparing LR should represent the most appropriate option whenever feasible. Mini-invasive colorectal surgery has experienced rapid spread in the last decades, while laparoscopic LR has progressed much slower, and is usually reserved for limited tumours in favourable locations. Moreover, mini-invasive parenchymal-sparing LR is more complex, especially for larger or multiple tumours in difficult locations. It remains to be established if simultaneous resections are presently feasible with mini-invasive approaches or if we need further technological advances and surgical expertise, at least for more complex procedures. This review aims to critically analyze the current status and future perspectives of simultaneous resections, and the present role of the available mini-invasive techniques.

Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature.

BACKGROUND: The therapeutic approach of metastatic renal cell carcinoma (RCC) represents a real challenge for clinicians, because of the variable clinical course; the recent availability of numerous targeted therapies that have significantly improved overall oncological results, but still with a low percentage of complete responses; and the increasing role of metastasectomy (MSX) as an effective strategy to achieve a durable cure, or at least defer initiation of systemic therapies, in selected patients and in the context of multimodality treatment strategies. CASE SUMMARY: We report here the case of a 40-year-old man who was referred to our unit in November 2004 with lung and mediastinal lymph nodes metastases identified during periodic surveillance 6 years after a radical nephrectomy for RCC; he underwent MSX of multiple lung nodules and mediastinal lymphadenectomy, with subsequent systemic therapy with Fluorouracil, Interferon-alpha and Interleukin 2. The subsequent clinical course was characterized by multiple sequential abdominal and thoracic recurrences, successfully treated with multiple systemic treatments, repeated local treatments, including two pancreatic resections, conservative resection and ablation of multiple bilobar liver metastases, resection and stereotactic body radiotherapy of multiple lung metastases. He is alive without evidence of recurrence 20 years after initial nephrectomy and sequential treatment of recurrences in multiple sites, including resection of more than 38 metastases, and 5 years after his last MSX. CONCLUSION: This case highlights that effective multimodality therapeutic strategies, including multiple systemic treatments and iterative aggressive surgical resection, can be safely performed with long-term survival in selected patients with multiple metachronous sequential metastases from RCC.

Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases.

Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.

Centrally located small unifocal hepatocellular carcinoma between minor conservative liver resection and major hepatectomy. Case reports.

Hepatocellular carcinoma (HCC) is one of the leading cancer in the world, susceptible to potentially curative liver resection (LR) in selected cases. Centrally located HCC (CL-HCC) are sited in central liver segments and may require complex LR because of their relationship to major vascular and biliary structures and deep parenchymal location. Even though extended segment-oriented resections are recommended for oncological reasons, more conservative LR may be indicated in patients with cirrhosis to preserve an adequate function of the future remnant liver (FRL). To extend the indication to LR and to increase the safety of the surgical procedure, preoperative portal vein embolization (PVE) or sequential transarterial embolization/chemoembolization (TAE/TACE) and PVE have been widely used, to induce atrophy of the embolized segments involved by the tumor and compensatory hypertrophy of the FLR. The most appropriate surgical strategy for small uninodular CL-HCC remains controversial, and should be decided according to the features of the tumor at preoperative imaging, the relationship with major intrahepatic vessels and the expected function of the FRL. We report here two cases of elderly cirrhotic patients with unifocal small CL-HCC, where the surgical strategy was decided according to the kind of relationship of the tumor with the hepatic hilum at preoperative imaging. In the first case there was no clear evidence of neoplastic infiltration of the hilar vessels, so that a minor conservative LR was preferred. In the second patient the tumor was suspected to infiltrate the right portal vein, and a major LR was performed after sequential TACE/PVE. KEY WORDS: Centrally located, Future remnant liver, Hepatocellular carcinoma, Liver cirrhosis, Liver resection, Portal vein embolization, Transarterial chemoembolization.

Evolving role of FDG-PET/CT in prognostic evaluation of resectable gastric cancer.

Gastric cancer (GC) remains a leading cause of cancer death worldwide. Radical gastrectomy is the only potentially curative treatment, and perioperative adjuvant therapies may improve the prognosis after curative resection. Prognosis largely depends on the tumour stage and histology, but the host systemic inflammatory response (SIR) to GC may contribute as well, as has been determined for other malignancies. In GC patients, the potential utility of positron emission tomography/computed tomography (PET/CT) with the imaging radiopharmaceutical 18F-fluorodeoxyglucose (FDG) is still debated, due to its lower sensitivity in diagnosing and staging GC compared to other imaging modalities. There is, however, growing evidence that FDG uptake in the primary tumour and regional lymph nodes may be efficient for predicting prognosis of resected patients and for monitoring tumour response to perioperative treatments, having prognostic value in that it can change therapeutic strategies. Moreover, FDG uptake in bone marrow seems to be significantly associated with SIR to GC and to represent an efficient prognostic factor after curative surgery. In conclusion, PET/CT technology is efficient in GC patients, since it is useful to integrate other imaging modalities in staging tumours and may have prognostic value that can change therapeutic strategies. With ongoing improvements, PET/CT imaging may gain further importance in the management of GC patients.

Successful surgical resection of solitary plasmacytoma of the liver mimicking hepatocellular carcinoma. A case report.

Solitary extramedullary plasmacitomas (SEMP) of the liver are very rare. We report the case of an elderly woman with a huge symptomatic SEMP of the liver mimicking hepatocellular carcinoma (HCC). The patient was a 89-year-old woman who presented with severe abdominal pain and a huge solid mass in the right hypochondrium. The laboratory data on admission revealed normal liver function tests. A multiphasic computed tomography (CT) showed a huge solid mass of the left hemiliver, hypoattenuating on noncontrast images, dishomogeneously hyperenhancing in the late arterial phase, with washout in the portal venous and equilibrium phases. A 18F-FDG positron emission tomography (18F-FDG PET)-CT scan documented a marked FDG uptake within the lesion, without evidence of extrahepatic metastases. We considered the clinical and radiologic findings consistent with the diagnosis of high-grade HCC with areas of intratumoral necrosis preluding to possible tumour rupture. Surgical resection was ultimately considered feasible with a reasonable risk and the patient underwent left hepatectomy with diaphragmatic resection. Pathological examination exhibited an extramedullary plasmacytoma. At immunohistochemical analysis neoplastic cells were positive for CD45, CD38, IRF4, HTPD52, kappa-chain, but negative for lambda- chain; Mib-1 proliferation index was 50%. Subsequent clinical evaluation excluded any sign of multiple myeloma, so that a diagnosis of truly localized SEMP of the liver was finally established. To our knowledge, this is the first case of a solitary extramedullary plasmacitoma of the liver undergoing successful radical liver resection. The patient is alive and well 5 years after surgery without evidence of local recurrence and of systemic disease. KEY WORDS: Extramedullary plasmacytoma, Hepatocellular carcinoma, Liver, Liver resection, Multiple myeloma.

Multifocal intraductal papillary mucinous neoplasm of the pancreas from mild dysplasia to invasive carcinoma A case report.

UNLABELLED: Intraductal papillary mucinous neoplasm (IPMN) is defined as an intraductal mucin-producing neoplasm of the pancreatic ducts. IPMNs may be multifocal, have malignant potential and exhibit a broad histological spectrum ranging from adenoma to invasive carcinoma. The "hyperplasia-dysplasia-carcinoma sequence" in the evolution of IPMNs is considered very similar to the "adenoma-carcinoma sequence" of colorectal tumours. Patients with multifocal IPMN are potential candidates to total pancreatectomy, which still carries significant perioperative risks, especially in the elderly. In selected cases a reasonable alternative to total pancreatectomy is represented by the resection of the dominant tumour leaving deliberately in place the smaller, low-risk tumours. In this context, intraoperative ultrasonography (IOUS) can be useful to define the extent of IPMNs and to plan the surgical strategy. We report the case of a 84-year-old female with multiple IPMNs showing different stages of neoplastic progression up to invasive carcinoma. The patient underwent IOUS-guided distal splenopancreatectomy, while the small multiple branchduct type IPMNs of the head of the pancreas were considered at very low risk of neoplastic progression and were deliberately left in place. The patient is alive without recurrence 96 months after surgery and without evidence of progression of the branch-duct type IPMNs of the head of the pancreas. IOUS-guided pancreatectomy should be considered in selected elderly patients affected by multifocal IPMN evolved to invasive carcinoma without evidence of distant metastases. KEY WORDS: Intraductal papillary mucinous neoplasm, Intraoperative ultrasonography, Pancreatectomy.

One stage curative resection of double intestinal neuroendocrine tumors with thirty-two bilobar liver metastases. A case report.

Neuroendocrine tumours (NETs) of the midgut are often multifocal and have a noticeable attitude to metastasize to locoregional lymph nodes and liver. Surgery is the only curative treatment for metastatic NETs of the midgut, even though only a minority of patients are candidates to radical surgical resection. The optimal timing for surgical resection in case of synchronous presentation of primary intestinal neoplasms and resectable LM is still controversial, especially when LM are multiple and/or involve multiple liver segments. Even though a staged approach with initial intestinal resection followed by liver resection is still preferred, recent studies have shown favourable results for simultaneous procedures, which have the striking advantage of avoiding a second laparotomy, with morbidity and mortality rates comparable to staged resections. We report here the case of a patient with double midgut well-differentiated NET and thirty-two synchronous bilobar LM who received successful simultaneous curative right hemicolectomy and radical but conservative liver resection and radiofrequency thermal ablation with the guidance of intraoperative ultrasonography. He is alive without evidence of recurrence 48 months after surgery.

Intermittent clamping of the hepatic pedicle in simultaneous ultrasonography-guided liver resection and colorectal resection with intestinal anastomosis: is it safe?

PURPOSE: In patients with colorectal cancer (CRC) and synchronous colorectal liver metastases (CRLM) potentially candidates to combined liver (LR) and colorectal resection (CRR), the extent of LR and the need of hepatic pedicle clamping (HPC) in selected cases are considered risk factors for the outcome of the intestinal anastomosis. This study aimed to determine whether intermittent HPC is predictive of anastomotic leakage (AL) and has an adverse effect on the clinical outcome in patients undergoing combined restorative CRR and LR. METHODS: One hundred six LR have been performed for CRLM in our unit from July 2005. Patients who received CRR with anastomosis and simultaneous intraoperative ultrasonography (IOUS)-guided LR/ablation for resectable CRLM were included in this study. CRR was performed first. Intermittent HPC was decided at the discretion of the liver surgeon. The perioperative outcome was evaluated according to occurrence of AL and overall postoperative morbidity and mortality. RESULTS: Thirty-eight patients underwent simultaneous IOUS-guided LR/ablation and CRR with intestinal anastomosis; 19 underwent intermittent HPC (group ICHPY) while 19 did not (group ICHPN); the mean ± SD (range) duration of clamping in group ICHPY was 58.6 ± 32.2 (10.0-125.0) min. Postoperative results were similar between groups. One asymptomatic AL occurred in group ICHPY (5.2 %). Major postoperative complications were none in group ICHPY and one (5.2 %) in group ICHPN, respectively. One patient in group ICHPY died postoperatively (5.2 %). CONCLUSIONS: This study suggests that intermittent HPC during LR is not predictive of AL and has no adverse effect on the overall clinical outcome in patients undergoing combined restorative colorectal surgery and hepatectomy for advanced CRC.

[Synchronous adenocarcinoma of the sigmoid colon and multifocal intraductal papillary mucinous neoplasm of the pancreas in an elderly patient]. / Adenocarcinoma del colon e neoplasia papillare intraduttale mucinosa multifocale sincrona del pancreas in un paziente anziano: caso clinico e revisione della letteratura.

Intraductal papillary mucinous neoplasms are a well-recognized pathologic entity of the pancreas that is being reported with increasing frequency. These tumours carry a relatively favourable prognosis and are frequently associated with extrapancreatic malignancies. The combination of advanced age and co-existence of two neoplasms challenges the planning of the best treatment option. A 78-year-old man presented with rectal bleeding which led to the diagnosis of a stenosing adenocarcinoma of the sigmoid colon. No metastatic lesions were present but a 30 mm intraductal papillary mucinous neoplasm with mural nodules was detected in the uncinate process of the pancreas. Small diffused dilations of the side branches were present in the body and tail of the gland. A two-stage procedure was planned: an R0 sigmoid resection was undertaken first with an uneventful postoperative course. Forty-five days later a pancreaticoduodenectomy was performed and the postoperative course was again uneventful apart from delayed gastric emptying. Histology showed a combined-type intraductal papillary mucinous neoplasm with foci of non-invasive carcinoma. The patient is still alive without evidence of cancer recurrence 33 month after the pancreatico-duodenectomy. The co-existence of a potentially malignant pancreatic tumour with an extra-pancreatic overt malignancy in elderly patients poses difficulties in the attempt to cure the patient with minimal morbidity. In the present case we considered a staged surgical procedure with the aim of reducing the perioperative risk, since the excision of the pancreatic neoplasm required a pancreaticoduodenectomy in an elderly patient.

[Echo-guided spleen-preserving resection of the pancreas tail for pancreatic intraductal papillary mucinous neoplasms]. / Resezione della coda del pancreas "spleen preserving" ecoguidata per neoplasia intraduttale mucinosa (IPMN) del pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a distinct entity with malignant potential, which may recur after surgical excision. Limited pancreatectomies have been recently proposed for non-invasive tumours. We report our technique of intraoperative US-guided resection of non-invasive IPMNs located in the tail of the pancreas with spleen and splenic vessel preservation. Following adequate exposure of the distal pancreas, a thorough ultrasonographic examination of the parenchyma is accomplished to define the features of the neoplasia, its relationship with the main pancreatic duct and splenic vessels and to mark the transection line with electrocautery. Dissection begins at the inferior edge of the pancreatic tail and proceeds in a lateral to medial direction up to the transection line. The main pancreatic duct is identified and sutured, the parenchyma is then closed and the suture line is reinforced with a fibrinogen/thrombin-coated collagen patch. Patient 1 was a 63-year-old male who underwent intraoperative US-guided resection of the pancreatic tail for an IPMN of the pancreatic tail measuring 28 mm with moderate dysplasia at histology, and was discharged 9 days after surgery. Patient 2 was a 60-year-old male who underwent intraoperative US-guided resection of the pancreatic tail for an IPMN of the pancreatic tail measuring 30 mm with carcinoma in situ at histology, and was discharged 9 days after surgery. Limited distal pancreatic resection with spleen and splenic vessel preservation is an adequate surgical technique for non-invasive IPMN of the tail of the pancreas. Intraoperative ultrasonography is crucial in planning "radical but conservative" pancreatic resection.

[Hepatocellular carcinoma with neoplastic thrombosis of the common hepatic duct]. / Carcinoma epatocellulare con trombosi neoplastica del dotto epatico comune: caso clinico e revisione della letteratura.

Biliary tract involvement in patients with hepatocellular carcinoma usually occurs in advanced stages and is due to tumour compression or infiltration. In a few cases, however, a tumour thrombus may grow into the biliary ducts (bile duct thrombosis). Identification of this condition is important because surgical treatment may be beneficial in selected cases. A 69-year-old man came from another hospital after repeated sessions of radiofrequency thermoablation and alcoholisation of 3 nodules of hepatocellular carcinoma. At admission to our unit, the nodule in S5-S8 was still viable and a neoplastic thrombus had invaded the right and common bile ducts. S5-S8 sub-segmentectomy, S6 wedge resection and removal of the tumour thrombus were performed. Seventeen months later the tumour thrombus recurred in the hepatic ducts without evidence of intrahepatic recurrence and was again removed. Eight months later a large metastatic lymph node appeared at the hepatic hilum, without evidence of liver recurrence or distant metastases, and the patient underwent lymphadenectomy. Eighteen months after the last procedure the patient is alive without recurrence. The appearance of bile duct thrombosis in the natural history of hepatocellular carcinoma does not necessarily entail an unfavourable prognosis. An early diagnosis is crucial to select the appropriate treatment. Biliary decompression with removal of tumour debris and blood clots and curative resection of the hepatocellular carcinoma can result in effective palliation and occasional long-term survival. Also in the presence of intrabiliary, hepatic or limited extrahepatic recurrence, surgical exeresis is the best therapeutic choice in selected cases.