Cornerstones and divergencies in the implementation and use of liver hypertrophy techniques: results from a nationwide survey for the set-up of the prospective registry.

BACKGROUND: The aim of this national survey on liver hypertrophy techniques was to track the trends of their use and implementation in Italy and to detect analogies and heterogeneities among centers. METHODS: In December 2022, Italian centers with liver resection activity were specifically contacted and asked to fill an online questionnaire composed of 6 sections including a total of 51 questions. RESULTS: 46 Italian centers filled the questionnaire. The proportion of major/total number of liver resections was 27% and the use of hypertrophy techniques was required in 6,2% of cases. The most frequent reason of drop out was disease progression in 58.5% of cases. Most frequently used techniques were PVE and ALPPS with an increasing use of hepatic venous deprivation (HVD). Heterogeneous answers were provided regarding the cutoff values to indicate the need for hypertrophy techniques. Criteria to allocate a patient to different hypertrophy techniques are not standardized. CONCLUSIONS: The use of hypertrophy techniques is deep-rooted in Italy, documenting the established value of their role in improving resectability rate. While an evolution of techniques is detectable, still significant heterogeneity is perceived in terms of cutoff values, indications and managing protocols.

Predictors of morbidity and mortality in patients submitted to cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for ovarian carcinomatosis: a multicenter study.

OBJECTIVES: The aim of this retrospective study is to assess the incidence of morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) and to evaluate their predictors, in patients with peritoneal metastasis of ovarian origin. METHODS: A retrospective multicenter study was carried out investigating results from eight Italian institutions. A total of 276 patients met inclusion criteria. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: Overall morbidity was 71.4%, and severe complications occurred in 23.9% of the sample; 60-day mortality was 4.3%. According to univariate logistic regression models, grade 3-4 morbidity was related to Peritoneal Cancer Index (PCI) (OR 1.06; 95% CI 1.02-1.09; p<0.001), number of intraoperative blood transfusions (OR 1.21; 95% CI 1.10-1.34; p<0.001), Completeness of Cytoreduction (CC) score (OR 1.68; 95% CI 1.16-2.44; p=0.006) and number of anastomoses (OR 1.32; 95% CI 1.00-1.73; p=0.046). However, at the multivariate logistic regression analysis, only the number of intraoperative blood transfusions (OR 1.17; 95% CI 1.5-1.30; p=0.004) and PCI (OR 1.04; 95% CI 1.01-1.08; p=0.010) resulted as key predictors of severe morbidity. Furthermore, using multivariate logistic regression model, ECOG score (OR 2.45; 95% CI 1.21-4.93; p=0.012) and the number of severe complications (OR 2.16; 95% CI 1.03-4.52; p=0.042) were recorded as predictors of exitus within 60 days. CONCLUSIONS: The combination of CRS and HIPEC for treating peritoneal metastasis of ovarian origin has acceptable morbidity and mortality and, therefore, it can be considered as an option in selected patients.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy used as treatment of colo-rectal carcinomatosis: a multicentric study.

The aim of this study is to assess the morbidity and mortality related to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colo-rectal carcinomatosis. A retrospective multi-institutional study from seven Italian Centers was performed. One hundred and seventy-two patients, submitted to cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) to treat carcinomatosis of colorectal origin, were recorded. Postoperative morbidity was evaluated in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Post-operative mortality was evaluated as patients' death within 60 days from surgical procedures. Predictors of morbidity were evaluated with univariate and multivariate analyses. Post-operative morbidity occurred in 83 patients (48.3%): grades 1-2 in 29 cases (16.9%), and grades 3-4 in 54 (31.4%). Mortality occurred in four cases (2.3%). Number of anastomoses (OR 1.45; 95% CI 1.05-2.00; p = 0.024), number of blood transfusions (OR 1.31; 95% CI 1.11-1.54; p = 0.001) and chemotherapy regimen [Oxaliplatin (OX): OR 2.87; 95% CI 1.22-6.75; p = 0.015] remained, in multivariate analysis, in a statistically significant correlation with overall morbidity. The only variable that was proven to have statistically significant correlation with 3-4 morbidity was the number of blood transfusions (OR 1.25; 95% CI 1.07-1.46; p = 0.005). Morbidity and mortality do not preclude the use of CRS plus HIPEC in the treatment of peritoneal carcinomatosis of colorectal origin.

Rectal perforation by inadvertent ingestion of a blister pack: A case report and review of literature.

The accidental ingestion of a foreign body (FB) is a relatively common condition. In the present study, we report a peculiar case of rectal perforation, the first to our knowledge, caused by the inadvertent ingestion of a blister pill pack. The aim of this report is to illustrate the difficulties of the case from a diagnostic and therapeutic viewpoint as well as its unusual presentation. A 75-year-old woman, mentally impaired, arrived at our emergency department in critical condition. The computed tomography scan revealed a substantial abdominopelvic peritoneal effusion and free perigastric air. The patient was therefore submitted to an urgent exploratory laparotomy; a 2-cm long, full-thickness lesion was identified in the anterior distal part of the intraperitoneal rectum. Hence, we performed a Hartmann's procedure. Because of her critical condition, the patient was eventually transferred to the Intensive Care Unit, where she died after 10 d, showing no surgical complication. The ingestion of FBs is usually treated with observation or endoscopic removal. Less than 1% of FBs are likely to cause an intestinal perforation. The intestinal perforation resulting from the unintentional ingestion of an FB is often a difficult challenge when it comes to treatment, due to its late diagnosis and the patients' deteriorated clinical condition.

Evaluation of cisplatin plasma levels in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Introduction Peritoneal surface malignancies have long been regarded as incurable, however, they can be treated with cytoreductive surgery in addition to hyperthermic intraperitoneal chemotherapy. This approach is associated with an increase in morbidity and mortality, unless hyperhydration is provided in a timely manner. Methods Cisplatin (CDDP) is the most widely used chemotherapeutic agent. Plasma levels of cisplatin (CDDP), a widely used chemotherapeutic agent, were measured before, during, and after the procedure. This was done in order to identify the window of highest risk as a function of drug concentrations, assuming a dose-dependent effect. Results Plasma levels of CDDP peak during perfusion. The concentration remains high until the 4th post-operative day and returns to pre-operative levels by the 7th post-operative day. Conclusions Our findings suggest that ensuring hyperhydration as well as infusing albumin and fresh frozen plasma may be of particular value for at least the first 4 days after the procedure.

Wernicke encephalopathy as rare complication of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis of gastric origin is a frequent event with poor survival. A new promising approach is the association of the Cytoreductive Surgery (CRS) with the Hyperthermic Intraperitoneal Chemotherapy (HIPEC), which yet is characterized by high morbidity and mortality. We report, to our knowledge, the first case of Wernicke Encephalopathy (WE) complicating CRS plus HIPEC. WE, caused by a deficiency of thiamine, is characterized by ataxia, ocular motor cranial neuropathies and changes in consciousness. METHODS: A patient affected by gastric cancer with peritoneal seeding, submitted to CRS plus HIPEC, in 4th post-operative day had manifested the appearance of flapping tremors, with positive manoeuvre of Mingazzini, impaired vision and mental confusion. The brain Magnetic Resonance Imaging (MRI) confirmed the clinical suspicion of WE. Even though the appropriate therapy was promptly applied, the patient died in 10th post-operative day. CONCLUSION: WE is an uncommon neurological disorder. Only 16% of these patients inadequately treated recover fully, with a mortality rate of 10-20%. We consider useful to report this case, because it is the first time that WE is correlated to CRS plus HIPEC.

Giant retroperitoneal liposarcoma: Case report and review of the literature.

AIM: Retroperitoneal soft-tissue sarcomas are relatively uncommon diseases, the most frequent histotype, ranging from 20% to 45% of all cases, is represented by liposarcoma, which is a hard-to treat condition for its local aggressiveness and clinical aspecificity. PRESENTATION OF CASE: We report a case of a 64-years-old woman who underwent surgical resection for a giant pleomorphic retroperitoneal liposarcoma. DISCUSSION: Currently chemotherapy for retroperitoneal soft-tissue sarcomas is no effective, and radiotherapy has limited efficacy due to the toxicity affecting adjacent intra-abdominal structures, showed validity only in case of high-grade malignancy by reducing local recurrence, but with no advantage in overall survival. Nowadays only, the complete surgical resection remains the most important predictor of local recurrence and overall survival. CONCLUSION: The removal of a retroperitoneal sarcoma of remarkable size is a challenge for the surgeon owing to the anatomical site, to the absence of an anatomically evident vascular-lymphatic peduncle and to the adhesions contracted with the contiguous organs and with the great vessels. Therefore, we believe that, particularly for large-size diseases associated to high-grade malignancy, a complete surgical resection with removal of the contiguous intra and retroperitoneal organs when infiltrated represents the only therapeutic option to obtain a negative margin and therefore an oncological radicality.

Short-term outcome of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: preliminary analysis of a multicentre study.

AIM: To assess the incidence of morbidity and mortality of Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy. PATIENTS AND METHODS: A retrospective multicentric study was performed. Six hundred and eighty-three patients were recorded. Predictors of morbidity and mortality were evaluated with univariate and multivariate analysis. RESULTS: In univariate analysis, older age, Eastern Cooperative Oncology Group score, a greater value of Peritoneal Cancer Index (PCI) and sub-optimal cytoreduction were correlated with higher mortality, while older age, presence of ascites, ovarian origin of carcinomatosis, closed technique, a greater value of PCI, longer operative time and sub-optimal cytoreduction were predictors of higher morbidity. In multivariate analysis, older age and a greater value of PCI were correlated with higher mortality; older age, ovarian origin of tumor, presence of ascites, closed technique and longer operative time were predictors of higher morbidity. CONCLUSION: Careful patient selection has to be performed to improve clinical outcomes.

Cytoreductive surgery plus bicavitary chemohyperthermia as treatment of pseudomixoma peritonei with pleural extension. A case report and review of the literature.

AIM: Intrathoracic extension in patients with pseudomixoma peritonei is a rare event, but spread of the tumour beyond the abdomen in to pleuropulmonary cavity has been reported. MATERIALS AND METHODS: We report a case of a 50-years-old woman with synchronous pleural manifestation of pseudomixoma peritonei by a mucinous ovarian cancer. During the abdominal cytoreductive surgery an extensive disease under the right hemidiaphragm was noted, requiring partial diaphragmatic resection. Once the pleural space was entered,mucinous neoplastic implants on the pleural surface was observed. The diaphragmatic defect was left open during the hyperthermic chemoperfusion to treat both the pleural and peritoneal surfaces. After a postoperative course uneventful she died after 6 months for a myocardial infarction, in presence of a left side pleural effusion with a positive cytology for high-grade malignant cells with a smear background contained wispy mucin. DISCUSSION: Despite the aggressive spread of the pseudomixoma peritonei within the peritoneal cavity, lymphatic and hematogenous metastasis are rare. However, extension of disease into pleuropolmonary cavity has been well described as pleural effusion or pleuropulmonary metastases. This is the first report in literature, to our knowledge, in which the thoracic extension is due to a mucinous ovarian cancer, and is the second case in which a simultaneous bicavitary hyperthermic chemoperfusion was done as a management option for thoracic extension of pseudomixoma peritonei. CONCLUSION: Due to the rarity of the thoracic involvement by pseudomixoma peritonei, its correct treatment is still unclear. Simultaneous cytoreductive surgery associated to intraoperative intraperitoneal and intrathoracic chemohyperthermia can be a potential therapeutic option for these patients.

The role of prophylactic hyperthermic intraperitoneal chemotherapy in the management of serosal involved gastric cancer.

BACKGROUND: Peritoneal carcinomatosis of gastric origin is associated with poor survival. The use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) did not significantly improve the survival of patients with this disease. A promising approach can be based on the use of HIPEC as prophylaxis of peritoneal dissemination. PATIENTS AND METHODS: From our database, we have sampled 12 patients with advanced gastric cancer. In all cases, a D2 total gastrectomy was performed, associated with splenectomy in four cases. All patients were submitted to HIPEC. RESULTS: Morbidity and mortality were 33.3% and 8.3%, respectively. The median survival was 24 months, with only one case (8.3%) of peritoneal recurrence. CONCLUSION: In light of our experience and supported by literature data, we can affirm that HIPEC has a potential role in the prevention of gastric carcinomatosis. Certainly further studies are required on a larger scale to validate this new but promising approach.

Doppler perfusion index and colorectal hepatic metastases: personal experience and review of the literature.

BACKGROUND/AIMS: To evaluate the role of the hepatic perfusion in the assessment of the colorectal cancer. METHODOLOGY: For this research 18 patients affected by colorectal cancer were enrolled. All the patients were submitted to the evaluation of the Doppler Perfusion Index (DPI) which represents the ratio of hepatic arterial to total liver blood flow. RESULTS: The correlation between the evaluation of the Doppler Perfusion Index and the occurrence of the liver metastases did not show false negative but has highlighted 6 false positive, achieved a good sensitivity and very low specificity. CONCLUSIONS: A review of the literature and the results obtained in our study suggest that DPI may be helpful in detection of hepatic metastases.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in elderly patients.

BACKGROUND: The treatment of peritoneal malignancies in elderly patients with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is an ongoing question due to the high associated surgical risk. PATIENTS AND METHODS: Thirty patients, 11 (36.7%) older than 65 years, were submitted to CRS plus HIPEC. Criteria of patient eligibility were: peritoneal carcinomatosis of different origin, T3-4 gastric cancer, ECOG performance status ≤2, no extra-abdominal extension and no evidence of bowel obstruction. The median follow-up was 21.5 months (range: 1-63). The purpose of this retrospective study, was to evaluate the feasibility of this approach in elderly patients, with special reference to postoperative morbidity, mortality and survival. RESULTS: We have recorded, in elderly patients, higher grade 3 and 4 morbidity and mortality, similar mean duration of cytoreductive surgery, of postoperative hospital stay, of median survival and of overall survival rates. CONCLUSION: Since there no statistical differences, in terms of morbidity and mortality, CRS with HIPEC may also be suitable for elderly patients.

Rationale and techniques of cytoreductive surgery and peritoneal chemohyperthermia.

The evolution of loco-regional treatments has occurred in the last two decades and has deeply changed the natural history of primitive and secondary peritoneal surface malignancies. Several phase II-III studies have proved the effectiveness of the combination of cytoreductive surgery with peritoneal chemohyperthermia. Cytoreductive surgery allows the reduction of the neoplastic mass and increases tumoral chemosensitivity. The development of chemohyperthermia finds its origins in the necessity to exceed the limits of intraperitoneal chemotherapy performed in normothermia. It permits a continuous high concentration gradient of chemotherapeutic drugs between the peritoneal cavity and the plasma compartment to and a more uniform distribution throughout the abdominal cavity compared to systemic administration.

Treatment for retained [corrected] common bile duct stones during laparoscopic cholecystectomy: the rendezvous technique.

OBJECTIVE: To determine the feasibility and efficacy of the laparoscopic intraoperative rendezvous technique for common bile duct stones (CBDS). DESIGN: Case series. SETTING: Verona University Hospital, Verona, Italy. PATIENTS: A total of 110 patients were enrolled in the study; 47 had biliary colic; 39, acute cholecystitis; 19, acute biliary pancreatitis; and 5, acute biliary pancreatitis with associated acute cholecystitis. INTERVENTIONS: In all patients, CBDS diagnosis was reached by intraoperative cholangiography. Intraoperative endoscopy with rendezvous performed during laparascopic cholecystectomy for confirmed CBDS; for such a procedure, a transcystic guide wire was positioned into the duodenum. Intraoperative endoscopy with rendezvous was performed for retrieved CBDS during a laparoscopic cholecystectomy. MAIN OUTCOME MEASURES: Laparoscopic rendezvous feasibility, morbidity, postprocedure pancreatitis, and mortality. RESULTS: The laparoscopic rendezvous proved to be feasible in 95.5% (105 of 110 patients). The rendezvous failed in 3 cases of successfully performed laparoscopic cholecystectomy, and a conversion of the laparoscopy was needed in 2 cases of successful rendezvous. Two major complications and 2 cases of bleeding were registered after sphincterotomy was successfully performed with rendezvous, and severe acute pancreatitis complicated a traditional sphincterotomy performed after a failed rendezvous. CONCLUSIONS: Rendezvous is a feasible option for treatment of CBDS; it allows one to perform only 1 stage of treatment, even in acute cases such as cholecystitis and pancreatitis. Positioning of the guide wire may allow reduced complications secondary to papilla cannulation but not those of the endoscopic sphincterotomy.

Peritoneal carcinomatosis of colorectal origin.

Peritoneal carcinomatosis is, after liver metastases, the second most frequent cause of death in colorectal cancer patients and at the present time, is commonly inserted and treated as a stage IV tumour. Because there is no published data that outlines the impact of new therapeutic regimens on survival of patients with peritoneal surface diffusion, the story of carcinomatosis can be rewritten in light of a new aggressive approach based on the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Also if these treatment perhaps allow to obtain better results than standard therapies, we suggest, that a large prospective randomised control trial is needed to compare long-term and progression-free survival under the best available systemic therapy with or without cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

[Prognostic significance of the Mandard TRG classification after induction therapy in carcinoma of the oesophagus and cardia]. / Significato prognostico della classificazione TRG di Mandard dopo terapia induttiva nel carcinoma di esofago e cardias.

Mandard's tumor regression grade (TRG) is widely used to evaluate the pathological response to induction therapy with concurrent chemoradiotherapy in cancer of the oesophagus or gastro-oesophageal junction. The aim of this study was to evaluate the prognostic significance and clinical applicability of TRG. From 2000 to 2007, 108 patients with squamous cell carcinoma of the oesophagus (57 cases) or Siewert type I and II adenocarcinoma of the cardia (51 cases) were treated with induction chemoradiotherapy followed by surgery in the 1st Division of General Surgery of the University of Verona. The treatment was identical for all patients and consisted of cisplatin, 5 FU and docetaxel together with 50 Gy of concurrent radiotherapy. The treatment-induced response was evaluated by TRG. Fifty-one, 24, 17, 9 and 7 patients were classified, respectively, as TRG1, 2, 3 4 and 5. Fifty-two patients died of the disease. Disease-related survival decreased with the increase in TRG class in node-negative patients (p < 0.001), while in N+ patients it was poor, irrespective of TRG class (p = 0.241). Mandard TRG is therefore useful for staging patients undergoing preoperative chemoradiotherapy, because it displays high prognostic significance. In our study, however, N was the main prognostic factor and for this reason it is mandatory to consider nodal status along with TRG. Moreover, among N negative patients, the prognosis of each different TRG class is statistically different and for this reason different TRG classes cannot be grouped together.

Significance of super-extended (D3) lymphadenectomy in gastric cancer surgery.

BACKGROUND: The extension of lymphadenectomy is a matter of debate in gastric cancer surgery. The purpose of the present study was to analyse our experience on D3 lymphadenectomy in the treatment of gastric cancer with special reference to post-operative morbidity and mortality, incidence of para-aortic nodal metastases and long-term prognosis. METHODS: The results of 201 patients who underwent potentially curative gastrectomy with D3 lymphadenectomy for non-metastatic gastric adenocarcinoma at the First Department of General Surgery, University of Verona, from January 1988 to December 2004, were analysed statistically. The analysis did not include gastric stump and linitis plastica type tumors. RESULTS: Twenty-six out of the 201 patients (12.9%) showed para-aortic nodal metastases. Para-aortic node involvement was significantly higher in upper third tumors (29.1%) with respect to middle (6.1%) and lower third (7.5%) (P<0.001). Sixty-two patients (30.8%) developed post-operative complications with pulmonary affections (7%), pancreatic fistulas (4.5%) and abdominal abscesses (4.5%) as the most frequently observed complaints. In-hospital mortality was 1.5%. Overall 5-year survival rate for R0-patients was 53.6%. Considering survival in relation to nodal involvement, interestingly, patients with non-regional lymph node metastases (M1a) showed a slightly better prognosis with respect to pN3 patients (3-year survival: 13.9% and 19.4% for pN3 and M1a classes, respectively). CONCLUSIONS: D3 lymphadenectomy should be considered in curative surgery for advanced gastric cancer, especially for upper third tumors, with an acceptable morbidity and no increase in mortality. Further studies with a larger number of patients are required to confirm its prognostic value.

[Gastrointestinal stromal tumour: our experience]. / I tumori stromali gastrointestinali (GIST): nostra esperienza.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. These tumours originate in Cajal interstitial cells and the majority are located in the stomach and small intestine. They frequently develop in males aged 50-60 years. The symptoms of GIST are non-specific and depend on the size and location of the lesion. Imaging difficulties impede an early diagnosis; sometimes these tumours represent an unexpected intraoperative finding or an emergency abdominal picture. GISTs are classified as tumours with low- and high-risk of malignancy, depending on tumour size and mitotic count. Tumour site and acute onset are also significant parameters for prognostic purposes. Fifteen patients with GIST - gastric in 7 cases, ileal in 6, jejunal in 1 and colonic in 1 - were treated surgically and, in 9 cases, with adjuvant therapy (chemotherapy in 4 patients and imatinib mesylate in 5). The mean follow-up was 38 months. No postoperative mortality was recorded, and the morbidity was 13.3%. Histological examinations documented 6 benign tumours and 9 malignancies. Two patients, one with gastric and one with colonic GIST, were lost to follow-up. One patient, with two synchronous gastric neoplasms (GIST + adenocarcinoma) died after 16 months, while the other 5 patients with gastric GIST are still alive; two patients with ileal GIST, treated with chemotherapy, died after 15 and 18 months, respectively. The mean survival of patients treated with imatinib mesylate was 36 months. Surgical management and the use of imatinib constitute the therapeutic gold standard for GIST. The use of imatinib mesylate is recommended today in the treatment of advanced GIST, especially in cases with liver and peritoneal metastases.

Rare localizations of echinococcosis: personal experience.

BACKGROUND: The rare localizations of hydatidosis represent an interesting topic, especially with reference to epidemiological and diagnostic problems. Hydatid disease, common in Mediterranean countries, still remains endemic in some regions of Italy. METHODS: In the period April 1983-October 2003 73 patients with hydatid disease were observed. RESULTS: Seven patients (9.5%) presented a primary rare localization (thyroid, kidney, sacrospinal muscle, peritoneum and spleen). The main peculiarity of primary rare hydatidosis localizations concerns diffusion of the infecting embryo; the most reliable hypothesis is that liver and lung can be bypassed through precapillary anastomosis between pre- and post-parenchymal circulation. The new imaging techniques allow a correct topographic evaluation and so a radical surgical treatment. The chemotherapy, complementary to surgery, produced degenerative modifications of parasite in 75.8% of the present cases and reduction of recurrence from 23.3% to 6.7%. At follow up of 1-5 years no patients had recurrence. CONCLUSION: It is important to be aware, especially in countries where echinococcosis is endemic, that it is possible to find an echinococcosis cyst in a rare localization.