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BACKGROUND: Functional pelvic disorders in patients undergoing conservative surgical approach for rectal cancer are considered a major public health issue and represent one third of cost of colorectal cancer. We investigated the hypothesis that lymphadenectomy, involves the pelvic floor results in a localized hides or silent pelvic lymphedema characterized by symptoms without signs. PATIENTS AND METHODS: We examined 13 colo-rectal cancer patients: five intra-peritoneal adenocarcinoma: 1 sigmoid and 4 upper third rectal cancer (1 male and 3 female) and 9 extra-peritoneal adenocarcinoma: 3 middle and 5 lower third rectal cancer (4 male and 5 female) using 1.5-T magnetic resonance, one week before and twelve months after discharged from hospital. RESULTS: Lymphedema was discovered on post-operative magnetic resonance imaging of all 9 patients with extra-pertitoneal cancer, whereas preoperative magnetic resonance imaging as well as a post-operative examination of 4 intra-peritoneal adenocarcinoma, revealed no evidence of lymphedema. Unlike the common clinical skin signs that typify all other sites of lymphedema, pelvic lymphedema is hides or silent, with no skin changes or any single symptom manifested. Magnetic resonance imaging showed that pelvic illness alone is accompanied by lymphedema related exclusively to venous congestion, and accumulation of liquid in adipose tissue or lipedema. CONCLUSIONS: Alteration of the pelvic lymphatic network during pelvic surgery can lead to lymphedema and, pelvic floor disease. Patients should be routinely examined for the possibility of developing this post-surgical syndrome and further studies are needed to establish diagnosis and to evaluate treatment preferences. [ABSTRACT FROM AUTHOR]

We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5-66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs ( miR-378e , miR-1233 , miR-99b-5p , miR-1260b , miR-448 , -miR-1252-5p , miR-324-3p , miR-1233-3p ) showed a statistically significant negative association with PFS. When we considered PFS < 6 months, miR-378e , miR-99b-5p , miR-877-5p , miR-1297 , miR-455-5p , and miR-4536-5p were statistically associated with a poor outcome. In the multivariate analysis, the first three miRNAs confirmed a significant and independent impact on PFS. The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27 Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.

We retrospectively investigated in women treated with fulvestrant for HR+/HER2 negative advanced breast cancer clinical, pathological and molecular features associated with long-term benefit from treatment defined as being progression-free at 18 months. Specifically, we analyzed on formalin-fixed paraffin-embedded tumor samples ESR1 and PI3KCA mutations and miRNAs profiles. 59 patients were evaluable (median age of 67 years, range 32-92). 18-month PFS rate was 27%; the lack of visceral metastases significantly predicted the likelihood of being progression-free at 18 months, while PI3KCA mutations, found in 36% of patients, were not associated with 18-month PFS. As of miRNAs, miR-549a, miR-644a, miR-16-5p were negatively while let-7c-5p was positively associated with 18-month PFS. In addition, miR-520d-3p and miR-548g-3p values were significantly lower while miR-603, miR-181a-5p and miR-199a-miR-199b-3p values were significantly higher in patients achieving 18-month PFS. In silico analysis of targets modulated by these two latter groups of miRNAs show that in patients achieving 18-month PFS the Hippo and Wnt signaling pathways were predicted to be upregulated while endocrine resistance was potentially repressed by miR-603, miR-181a-5p and miR-199a-miR-199b-3p. Our results provide additional clues on the molecular mechanisms involved in fulvestrant activity and resistance. Underlying pathways should be further elucidated and confirmed in larger cohorts., (© 2022. The Author(s).)

Introduction: Anti-Müllerian hormone (AMH) is the most reliable biomarker of ovarian reserve; however, its role in predicting ovarian recovery after chemotherapy is unclear. Administration of a GnRH analog (GnRHa) during chemotherapy significantly reduces the ovarian failure rate and increases the pregnancy rate. The available data on the behavior of AMH during concurrent administration of chemotherapy and GnRHa are inconsistent. We investigated whether concurrent administration of triptorelin and adjuvant chemotherapy might reduce the expected drop of AMH., Methods: Eligible patients were premenopausal women aged <40 years, with a diagnosis of early breast cancer, and candidates to 4-8 cycles of adjuvant chemotherapy. Triptorelin (3.75 mg i.m.) was started before chemotherapy and administered every 4 weeks thereafter. The principal endpoint was the proportion of patients with an AMH percent change ≤50% between 12 months after chemotherapy and basal levels. The secondary endpoint was the proportion of patients achieving postchemotherapy AMH levels above the threshold of 0.2 ng/mL., Results: Fifty patients were enrolled, 31 of whom had blood samples available at baseline and 1 year after the end of chemotherapy. AMH decreased to nearly undetectable levels after chemotherapy and recovered after 12 months, but they did not exceed 1 tenth of the pretreatment levels. As for the secondary endpoint, 15 of the 31 patients recovered AMH levels above the threshold., Conclusions: This study did not reach its principal endpoint; however, the rate of 48% of patients who recovered AMH above threshold levels favorably compared with those in studies without concurrent GnRHa, supporting a better recovery of AMH with triptorelin., Competing Interests: R.T.: participation on the advisory board of and recipient of speaker fees from MSD, Pfizer, Lilly, and the Istituto Gentili. A.M.: advisory boards of Roche, Novartis, Pfizer, Lilly, Macrogenics, and Eisai. A.S.: participation on the advisory board of and recipient of speaker fees from Sandoz, Servier, EISAI, Roche, Novartis, Gilead, Pfizer, and BMS., (Copyright © 2021 by S. Karger AG, Basel.)

Aim: Aim of the study was to report the experience of a single center in the surgical treatment of anastomotic leak after colorectal resection for cancer, focusing on its incidence, diagnosis and management, with particular attention to surgical options., Methods: Demograhic and clinical data from 1284 consecutive patients operated on for colorectal cancer during a period of 11 years, were prospectively collected and inserted into an electronic database. For the purpose of the study, only patients in whom an anastomosis was performed were considered. Therefore, 128 patients (9.9%) were excluded and 1156 represent the study population. All complications occurring after surgery were systematically recorded. The incidence of colorectal anastomotic leak (CAL), its management and outcome was analyzed., Results: An ileo-colic anastomosis was performed in 426 cases (36.8%), ileo-rectal in 29 (2.5%), colo-colic in 409 (35.4), colo-rectal with partial mesorectal excision in 211 (18.3%) and lower colorectal or coloanal anastomosis with total mesorectal excision and temporary loop ileostomy in 81 (7%). Colorectal anastomotic leak occurred in 78/1156 patients (6.7%), accounting for 19% of overall complications. Thirty-six out of 78 patients (46.2%) were successfully treated conservatively, whereas 42 (53.8%) underwent re-operation. Nine out of 78 patients (11.5%) with CAL died owing to an uncontrolled sepsis. All had undergone previous re-intervention, with a post-operative mortality rate of 21.4% (9 out of 42)., Conclusion: Mortality rate in patients undergoing re-operation for colorectal anastomotic leakeage is still high, and accounts for up to 40% of the deaths after colorectal resection for cancer. In the light of these data, strategic clinical decisions are mandatory to optimize the selection of patients who need an early and fast surgical approach. What does this paper add to the literature? Systematic and prospective data recording is an essential tool to assess the quality of healthcare and to plan quality improvement programs. Every effort should be done to reach an early diagnosis of CAL, possibly in a pre-clinical phase in which non clinical methods could be used to predict it.

On December 23 of 1978, during first Italian recession since the end of World War II, Parliament voted for Law 833 that gives birth to the Italian National Public Health Services (SSN) as the new and alternative model of health care system. It was the beginning of the match of Italian health care with the world class level of the public health care. Each crisis requires solidarity and actions. Maintaining levels of health and other social expenditures is critical to protect life and livelihood and to boost productivity. The purpose of the present study is to establish an alternative point of view to demonstrate that Gross Domestic Product, is a function of health care expenditure. The chronology of the events was created by using the laws published on "Gazzetta Ufficiale" (GU). In order to analyze the corporate effectiveness and efficiency, we have divided the SSN into its three main components, namely resources (input), services (output) and performances (outcome). Health services have certainly been pioneers and are still today standard-bearers of a challenge which has borne its fruits. According to the "Organization for Economic Co-operation and Development", SSN ranks second in the world classification of the return on the health care services in 2000. The World Health Organization has published in 2005 the same result: SSN ranks second in the world for ability and quality of the health care in relationship to the resources invested The continuous reforms of health care system introduced stability to the Italian system more than others countries. Success of SSN function rooted in the ability of system to adapt assuring mechanism of positive feed-back correction. In the future SSN, will required new set of reforms, such as redefinition of structures and mechanisms of governance, strategic plans, clinical administrations.

Evaluation of tumor response is a vital element in clinical oncology research, particularly in the development of new drugs. Tumor response also plays a significant role in treatment decisions made by clinicians in practice. The underlying concept of tumor response, however, was developed as a result of limited understanding of tumor biology coupled with restricted availability of both effective treatments and imaging modalities. In recent years, impressive advances have been made in the treatment of cancer. Groundbreaking advances in our understanding of the molecular biology of tumor growth and proliferation have been made. New biologic agents have been approved for the treatment of several malignancies and, in many cases, biomarkers have been identified that can help predict those patients who will benefit. Pre-operative chemotherapy is now established for a number of tumor types. Modern imaging technologies allowing functional characterization of tumors have been introduced into clinical practice. In this new therapeutic landscape, the existing concept of tumor response risks becoming an anachronism, and revision of the criteria used to define tumor response is warranted. In this paper, we critically review the limitations of the classic criteria for tumor response assessment, and briefly discuss the potential role of alternative methodologies in providing a new, functional definition of tumor response.

Unresponsiveness to erythropoiesis-stimulating agents is a major limitation to the treatment of chemotherapy-related anemia. This is often related to a disregulation of iron metabolism leading to functional iron deficiency. However, the use of iron supplementation during treatment with erythropoiesis-stimulating agents has not been as rigorously pursued in anemic patients with cancer as it has in chronic kidney disease. In this article, we review and discuss the role of iron supplementation in the setting of chemotherapy-related anemia in view of recently published clinical trials addressing this issue., (2008 S. Karger AG, Basel.)

A 54 year-old man, without any remarkable medical history, was examined for recurrent episodes of colicky abdominal pain, over a period of nine months, with positive faecal occult blood test. Three months earlier he had undergone an extensive evaluation for a single episode of melaena, including upper gastrointestinal endoscopy, colonoscopy to the caecum, enteroscopy and an abdominal ultrasound scan, that were negative. He was then submitted to the video capsule endoscopy (Given Imaging Ltd, Yoqneam, Israel) that revealed a polypoid white-yellowish lesion in the mid portion of the jejunum. The patient was admitted to our Department of Surgery in January 2005. During the operation, performed by laparoscopic video-assisted approach, the lesion, measuring 1.5x2 cm, was found at about 100 cm from the ligament of Treitz and was successfully excised. At histology, the final diagnosis was submucosal lymphangioma. The lymphangioma is a benign neoplastic lesion of the lymphatic system that usually is present in infancy and is found, in the majority of the patients, in the subcutaneous tissue outside the abdomen. The intrabdominal site accounts for less than 1% of the cases, and often occurs in the mesentery of the small bowel. Finding the lesion in the submucosa of the jejunum in an adult is very rare. The case here reported seems unusual to the Authors and worthy of publication because of the chronic, ambiguous clinical symptomatology, the occult digestive blood loss, and all the diagnostic examinations resulting negative, except for the video-capsule endoscopy. Moreover, the choice of the laparoscopic video-assisted technique, confirming the expected site of the lesion, with a ''minimal'' small bowel resection, made the postoperative course of the patient very short and uneventful. He is well and free of disease one year after the intervention. From a brief review of surgical literature, the case reported is the second one detected by the video capsule endoscopy and the fifth operated on by laparoscopy.

Aim: The incidence of anastomotic fistula after colorectal surgery did not significantly change in the literature during the last years, despite the advances in the treatment with the use of surgical staplers. Taking into account this and other considerations, the authors present their recent experience in the surgical treatment of colorectal carcinoma, referring in particular to anastomotic fistula, related postoperative mortality and results of consequent reoperations., Methods: From January 1, 2002 to December 31, 2005, 448 patients affected with colorectal cancer were operated on at the Surgical Department of Valduce Hospital in Como, and in 373 cases an anastomosis was performed, subdivided as follows: 144 ileocolic (38.6%), 10 ileorectal (2.7%), 219 colocolic or colorectal (58.7%)., Results: Twenty-five out of 373 anastomotic leaks developed (6.7%). In 9 cases (36%), the fistulas spontaneously closed with conservative treatment, while in 16 (64%) reoperation was necessary. With reference to the anatomical site, the leak occurred in 9 out of 144 patients submitted to right hemicolectomy (6.3%), in 14 out of 219 patients after left hemicolectomy or anterior resection of the rectum (6.4%) and in 2 out of 10 patients (20%) after total colectomy. The following is a detailed report of the therapeutic choices adopted by the authors. Four out of 16 reoperated patients (25%) died postoperatively from infective complications related to the fistula, while the total postoperative mortality was 2.2% (10/448). Therefore, anastomotic dehiscence was responsible for 40% of all postoperative deaths., Conclusions: Among all the different operative choices, the authors give their preference to the direct suture of the fistula and loop ileostomy, which they consider the best available choice. The subsequent operation of ileostomy closure is easier for the surgeon to perform and for the patient to withstand than colostomy closure, particularly after Hartmann's operation.

Cavernous hemangioma is the most common benign tumour of the liver and is found quite commonly during abdominal ultrasonography performed for other diseases. It is often asymptomatic and undergoes enlargement in fewer than 10% of cases. Spontaneous rupture of a giant hepatic hemangioma (diameter > 4 cm) with hemoperitoneum occurs very rarely. Only 32 cases have been reported in a recent review of the medical literature, with an operative mortality of more than 35%. We describe a new case of a giant subcapsular hemangioma localised in hepatic segments II and III in an 84-year-old woman, which ruptured spontaneously into the abdominal cavity and presented with hemoperitoneum and hypovolaemic shock. The hemangioma was diagnosed preoperatively by spiral CAT and treated successfully with emergency hepatic bisegmentectomy.

Aim: Restoration of colorectal continuity is the second step of the procedure originally described by H. Hartmann for the treatment of sigmoid colon cancers. It is a safe, but complex procedure, that needs a meticulous surgical technique and is associated with a significant morbidity in as many as 40% of cases. For this reason, many patients are not submitted to reversal of the colostomy., Methods: The authors report their experience: 32 patients underwent colostomy closure after Hartmann's procedure during the last 8 years., Results: The mortality rate was nil, but post-operative complications occurred in 12 patients (37.5%), namely: wound infection (11 patients) and anastomotic leak (2 patients)., Conclusion: In light of this, it could be wiser to perform, in the patients affected with benign pathology, and in those affected with limited malignant pathology (T3), resection of the diseased segment of colon and primary anastomosis with temporary ileostomy, reserving Hartmann's procedure to patients unsuitable to one step treatment because of their poor general and local conditions.

The occurrence of an angiosarcoma of the residual breast after conservative surgery and adjuvant radiotherapy for early mammary carcinoma is a very rare event. In western countries only 57 cases have been published in the literature (5 in Italy) since the first described case in 1987. Radiotherapy seems to be the most important etiological factor in the development of the neoplasm. Diagnosis is often delayed, owing to the "benign" aspect of the lesion. The only effective treatment is residual mastectomy, because chemotherapy is ineffective. The prognosis is often dismal, because of the aggressive behaviour of the lesion in most cases. The case of a patient with a multicentric secondary angiosarcoma of the breast recently operated on is described.

Background: The surgical approach to periampullary cancers represents one of the major components of digestive tract surgery. Personal experience in the treatment of 21 patients affected with periampullary neoplasms, operated on between January 1994 and July 1996 is reported., Methods: Ten duodenopancreatectomies (DP) have been carried out (DP), 2 total pancreatectomies (TP). The remaining patients underwent palliative surgery: the resecability index was 57%. Primary cancer site included head of the pancreas in 10 cases, ampulla of Vater in 1 case and duodenum in 1 case. DP and TP have been performed using the pylorus-preserving technique, proposed by Traverso-Longmire., Results: No operative mortality was reported; the morbidity rate was 25%. Nasogastric tube has been left in place for a mean time of 8 days (range 6-12). The mean postoperative period was 20 days (range 11-54). Five patients subsequently died for progressive disease: 4 during the first year (mean survival time 9 months), 1 during the second year (survival time 17 months). The follow-up of the remaining patients ranges between 6 and 30 months. Endoscopy, performed at 3-6-12 months, revealed no anastomotic recurrences, but 1 benign jejunal ulcer., Conclusions: According to personal experience the Traverso-Longmire technique is an effective procedure to improve the quality of life of these patients having a so poor expectancy of survival.

Hemangiopericytoma is a rare and solitary solid tumor originating from pericytes, which are contractile pericapillary cells, first identified and described by Zimmermann in 1923. This neoplasm occurs most commonly in the lower extremities and retroperitoneum. The Authors describe the case of a patient affected with a giant retroperitoneal hemangiopericytoma. Echographic and computed tomographic scans have been fundamental in defining location and size of the neoplasm as well as its relations to the surrounding structures. However a definitive diagnosis was possible only by histologic examination, supported by the proper immunohistochemical stains. The Authors emphasize the difficulty to reliably predict the biological behaviour of these tumors and therefore the necessity of a follow-up of the patients for at least five years, even in the case of a histologically "benign" hemangiopericytoma.

The cystic lymphangioma of the liver is an extremely rare benign tumor that usually belongs to a systemic lymphangiomatosis. A case of an adult woman presenting a cystic lymphangioma as single hepatic lesion with no other viscera affected is described. Ultrasonography and computed tomography did not allow a differential diagnosis of the lesion from the more common hydatid cyst. Definitive diagnosis and treatment were reached only by exploratory laparotomy.

The effect of Chloroethylthiamin (CET), a structural analog of thiamin, on thiamin pyrophosphokinase (TPKase) activity of the supernatant of rat isolated enterocytes was compared with that on thiamin intestinal transport by rat everted jejunal sacs. Thiamin- thiazol-2(14C) was used as a substrate both for TPKase activity and for thiamin serosal transport and uptake. CET strongly inhibited TPKase activity of isolated enterocytes: at molar concentrations 10 or 100 times higher than labeled thiamin, the inhibition was 57 and 100% respectively. The inhibition was of the competitive type, with a Ki = 15 microM. At a molar concentration 10 times higher than labeled thiamin, CET lowered the thiamin serosal transport by 60%, and the sac wall content of free and phosphorylated thiamin by 54 and 42% respectively. At the 1:10 thiamin: CET molar ratio, the extent of the reductions of TPKase activity (57%) and of phosphorylated thiamin content of intestinal sac walls (42%) were of the same order. This indicates a relationship between the two events. Moreover, since TPKase activity inhibition alone resulted in the lowering of labeled thiamin serosal transport, thiamin phosphorylation and transport are probably two strictly related processes.

In order to estimate wave propagation "in vitro", aortic compliance has been studied by means of rings and stripes from 6 adult male Wistar rats. Lengthening and shortening maneuvres have been performed; the pulse transmission rate was evaluated by calculating the elastic modulus during the maneuvres. A Norepinephrine infusion has been done. Results obtained show that transmission rate is higher in shortening than in lengthening phases. Norepinephrine did not significantly affect the values. The rate values were not greatly different whether "in vitro" or "in vivo". By increasing specimen stress, the rate too was increased, but the amount was lower than "in vivo" values. Hence it was assumable that rate variations "in vivo", should be partially influenced by elastic modulus, and a vegetative intervention should be implied.

Pulse wave transmission rate has been measured "in vivo" in 6 male anaesthetized Wistar rats, by means of cannulae, inserted both in carotid and femoral arteries. The measure has been done by calculating the time delay of several corresponding levels in the two pressure pulses: at the foot, during the ascending phase, at the peak. Three different intervention have been carried out: Ach, NA, blood transfusion. The transmission rate outcame higher at the pulse foot than at the peak, in control animals and in Ach and blood transfusion interventions. The NA intervention inverted this behaviour, where the increase in transmission rate did not correspond to the rate of pressure growing. The possible influences of a vegetative component on arterial viscoelastic behaviour are discussed.