A Rare Case of Negative Serum Calcitonin in Metastatic Medullary Thyroid Carcinoma: Diagnosis, Treatment, and Follow-Up Strategy.

BACKGROUND Medullary thyroid carcinoma is a rare tumor and represents less than 5% of all thyroid cancers. Tumor size and the presence of possible metastases are strictly related to serum calcitonin level, which also suggests prognosis. A serum calcitonin level above the normal range is highly suspicious for medullary cancer. This tumor has no characteristic patterns on ultrasound and fine-needle aspiration, so serum calcitonin level is the only significant element for diagnosis. The literature contains 47 cases of serum calcitonin-negative medullary thyroid cancer with heterogeneous behavior, ranging from non-aggressive to aggressive form. CASE REPORT We report a rare case of a young man with negative serum calcitonin but with lateral cervical node metastases from medullary thyroid carcinoma. At the beginning, diagnosis was not achieved due to normal range of serum calcitonin and a negative thyroid ultrasonography for large nodules. Nevertheless, in another medical center he underwent a neck biopsy of the lateral cervical mass. The histologic findings showed metastases of medullary thyroid cancer. Therefore, a total thyroidectomy plus cervical lymphadenectomy was performed. During the follow-up, due to unusefulness of serum markers, and as CEA levels were negative pre- and post-operatively, an ¹8F-DOPA PET scan was performed. In 3 years of follow-up, there is still no evidence of disease relapse. CONCLUSIONS Our case shows how a normal serum level of calcitonin cannot exclude medullary thyroid cancer. Early diagnosis is crucial because it influences appropriate surgical therapy and patient outcome. The current lack of an optimal strategy for the diagnosis and postoperative follow-up for patients with negative serum calcitonin tumor presents a diagnostic challenge for physicians.

Short-term outcomes after laparoscopic right hemicolectomy for colon cancer: intracorporeal versus extracorporeal anastomosis.

BACKGROUND: The aim of this study was to compare the short-term outcomes of laparoscopic right hemicolectomy between intracorporeal (IA) and extracorporeal (EA) anastomosis techniques. METHODS: A retrospective chart review of 77 consecutive patients who underwent laparoscopic right hemicolectomy from January 2016 to June 2018 was performed. The intracorporeal group included 36 patients and the extracorporeal group 41 patients. RESULTS: Patient demographics and disease-related characteristics were similar. Mean operative time was 152±38.3 minutes in IA vs. 148±34.8 minutes in EA (P=0.664). IA was not associated with less overall postoperative complications and decreased rate of surgical site infections. There was no statistically significant difference in the incidence of postoperative leak, length of stay, mortality in both groups. There was no perioperative difference in median number of lymph node harvested. There was statistically significant difference in the length of larger incision (50 [50-70] mm in IA vs. 80 [70-100] mm in EA; P<0.001), length of the specimen (323±52.7 mm in IA vs. 295±64.7 mm in EA; P<0.05), free tumor margin (113.6±47.4 in IA vs. 75.6±37.4 mm in EA; P<0.001). There was a statistically significant difference in IA in the less postoperative use of analgesics (P<0.032) and return of bowel function (P<0.021). CONCLUSIONS: IA seems feasible and safe; it does not significantly affect the length of surgery, and it guarantees maintenance of radical oncological standards. Furthermore, IA significantly improves cosmesis and patient comfort postoperatively, reducing the rates of emesis, which leads to higher rates of early regular diet tolerance. Therefore, laparoscopic right hemicolectomy with intracorporeal anastomosis is associated with improved short-term outcomes.

Intracorporeal versus Extracorporeal Anastomosis for Laparoscopic Right Hemicolectomy: Short-Term Outcomes.

Laparoscopic right hemicolectomy represents an effective therapeutic approach for right colon cancer (RCC). The primary aim of this study was to evaluate bowel function recovery, length of hospital stay, operative time, and the number of general and anastomosis-related postoperative complications from intracorporeal anastomosis (ICA) vs. extracorporeal anastomosis (ECA); the secondary outcome was the number of lymph nodes retrieved. This observational study was conducted on 108 patients who underwent right hemicolectomy for RCC; after surgical resection, 64 patients underwent ICA and 44 underwent ECA. The operative time was slightly longer in the ICA group than in the ECA group, even though the difference was not significant (199.31 ± 48.90 min vs. 183.64 ± 35.80 min; p = 0.109). The length of hospital stay (7.53 ± 1.91 days vs. 8.77 ± 3.66 days; p = 0.036) and bowel function recovery (2.21 ± 1.01 days vs. 3.45 ± 1.82 days; p < 0.0001) were significantly lower in the ICA group. There were no significant differences in postoperative complications (12% in ICA group vs. 9% in ECA group), wound infection (6% in ICA group vs. 7% in ECA group), or anastomotic leakage (6% in ICA group vs. 9% in ECA group). We did not observe a significant difference between the two groups in the number of lymph nodes collected (19.46 ± 7.06 in ICA group vs. 22.68 ± 8.79 in ECA group; p = 0.086). ICA following laparoscopic right hemicolectomy, compared to ECA, could lead to a significant improvement in bowel function recovery and a reduction in the length of hospital stay in RCC patients.

Effects of infections on the pathogenesis of cancer.

Several studies have shown an inverse relationship between acute infections and cancer development. On the other hand, there is a growing evidence that chronic infections may contribute significantly to the carcinogenesis. Factors responsible for increased susceptibility to infections may include modifications of normal defence mechanisms or impairment of host immunity due to altered immune function, genetic polymorphisms, ageing and malnourishment. Studies have demonstrated that children exposed to febrile infectious diseases show a subsequent reduced risk for ovarian cancer, melanoma and many other cancers, while common acute infections in adults are associated with reduced risks for melanoma, glioma, meningioma and multiple cancers. Chronic inflammation associated with certain infectious diseases has been suggested as a cause for the development of tumours. Mechanisms of carcinogenesis due to infections include cell proliferation and DNA replication by mitogen-activated protein kinase pathway, production of toxins that affect the cell cycle and lead to abnormal cell growth and inhibition of apoptosis. This review was aimed to summarize the available evidence on acute infections as a means of cancer prevention and on the role of chronic infections in the development and progression of cancer.

Multidisciplinary management of elderly patients with rectal cancer: recommendations from the SICG (Italian Society of Geriatric Surgery), SIFIPAC (Italian Society of Surgical Pathophysiology), SICE (Italian Society of Endoscopic Surgery and new technologies), and the WSES (World Society of Emergency Surgery) International Consensus Project.

BACKGROUND AND AIMS: Although rectal cancer is predominantly a disease of older patients, current guidelines do not incorporate optimal treatment recommendations for the elderly and address only partially the associated specific challenges encountered in this population. This results in a wide variation and disparity in delivering a standard of care to this subset of patients. As the burden of rectal cancer in the elderly population continues to increase, it is crucial to assess whether current recommendations on treatment strategies for the general population can be adopted for the older adults, with the same beneficial oncological and functional outcomes. This multidisciplinary experts' consensus aims to refine current rectal cancer-specific guidelines for the elderly population in order to help to maximize rectal cancer therapeutic strategies while minimizing adverse impacts on functional outcomes and quality of life for these patients. METHODS: The discussion among the steering group of clinical experts and methodologists from the societies' expert panel involved clinicians practicing in general surgery, colorectal surgery, surgical oncology, geriatric oncology, geriatrics, gastroenterologists, radiologists, oncologists, radiation oncologists, and endoscopists. Research topics and questions were formulated, revised, and unanimously approved by all experts in two subsequent modified Delphi rounds in December 2020-January 2021. The steering committee was divided into nine teams following the main research field of members. Each conducted their literature search and drafted statements and recommendations on their research question. Literature search has been updated up to 2020 and statements and recommendations have been developed according to the GRADE methodology. A modified Delphi methodology was implemented to reach agreement among the experts on all statements and recommendations. CONCLUSIONS: The 2021 SICG-SIFIPAC-SICE-WSES consensus for the multidisciplinary management of elderly patients with rectal cancer aims to provide updated evidence-based statements and recommendations on each of the following topics: epidemiology, pre-intervention strategies, diagnosis and staging, neoadjuvant chemoradiation, surgery, watch and wait strategy, adjuvant chemotherapy, synchronous liver metastases, and emergency presentation of rectal cancer.

Familial adenomatous polyposis and changes in the gut microbiota: New insights into colorectal cancer carcinogenesis.

Patients with familial adenomatous polyposis (FAP), an autosomal dominant hereditary colorectal cancer syndrome, have a lifetime risk of developing cancer of nearly 100%. Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer. Some gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, Clostridium difficile, Peptostreptococcus, and enterotoxigenic Bacteroides fragilis, could be implicated in colorectal carcinogenesis through different mechanisms, including the maintenance of a chronic inflammatory state, production of bioactive tumorigenic metabolites, and DNA damage. Studies using the adenomatous polyposis coliMin/+ mouse model, which resembles FAP in most respects, have shown that specific changes in the intestinal microbial community could influence a multistep progression, the intestinal "adenoma-carcinoma sequence", which involves mucosal barrier injury, low-grade inflammation, activation of the Wnt pathway. Therefore, modulation of gut microbiota might represent a novel therapeutic target for patients with FAP. Administration of probiotics, prebiotics, antibiotics, and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP. The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.

Oral and Parenteral vs. Parenteral Antibiotic Prophylaxis for Patients Undergoing Laparoscopic Colorectal Resection: An Intervention Review with Meta-Analysis.

This study aims to systematically assess the efficacy of parenteral and oral antibiotic prophylaxis compared to parenteral-only prophylaxis for the prevention of surgical site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer resection. Published and unpublished randomized clinical trials comparing the use of oral and parenteral prophylactic antibiotics vs. parenteral-only antibiotics in patients undergoing laparoscopic colorectal surgery were collected searching electronic databases (MEDLINE, CENTRAL, EMBASE, SCIENCE CITATION INDEX EXPANDED) without limits of date, language, or any other search filter. The outcomes included SSIs and other infectious and noninfectious postoperative complications. Risk of bias was assessed using the Cochrane revised tool for assessing risk of bias in randomized trials (RoB 2). A total of six studies involving 2252 patients were finally included, with 1126 cases in the oral and parenteral group and 1126 cases in the parenteral-only group. Meta-analysis results showed a statistically significant reduction of SSIs (OR 0.54, 95% CI 0.40 to 0.72; p < 0.0001) and anastomotic leakage (OR 0.55, 95% CI 0.33 to 0.91; p = 0.02) in the group of patients receiving oral antibiotics in addition to intravenous (IV) antibiotics compared to IV alone. Our meta-analysis shows that a combination of oral antibiotics and intravenous antibiotics significantly lowers the incidence of SSI compared with intravenous antibiotics alone.

Gut Microbiota and Colorectal Cancer Development: A Closer Look to the Adenoma-Carcinoma Sequence.

There is wide evidence that CRC could be prevented by regular physical activity, keeping a healthy body weight, and following a healthy and balanced diet. Many sporadic CRCs develop via the traditional adenoma-carcinoma pathway, starting as premalignant lesions represented by conventional, tubular or tubulovillous adenomas. The gut bacteria play a crucial role in regulating the host metabolism and also contribute to preserve intestinal barrier function and an effective immune response against pathogen colonization. The microbiota composition is different among people, and is conditioned by many environmental factors, such as diet, chemical exposure, and the use of antibiotic or other medication. The gut microbiota could be directly involved in the development of colorectal adenomas and the subsequent progression to CRC. Specific gut bacteria, such as Fusobacterium nucleatum, Escherichia coli, and enterotoxigenic Bacteroides fragilis, could be involved in colorectal carcinogenesis. Potential mechanisms of CRC progression may include DNA damage, promotion of chronic inflammation, and release of bioactive carcinogenic metabolites. The aim of this review was to summarize the current knowledge on the role of the gut microbiota in the development of CRC, and discuss major mechanisms of microbiota-related progression of the adenoma-carcinoma sequence.

The Liquid Biopsy in the Management of Colorectal Cancer: An Overview.

Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A "liquid biopsy" is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer.

Acute abdominal pain in older adults: a clinical and diagnostic challenge.

INTRODUCTION: Abdominal pain (AP) is one of the most frequent clinical condition observed in elderly patients. The differential diagnosis is wide and definitive diagnosis is often difficult due to delayed symptoms, altered laboratory parameters, pre-existing medical disorders, abuse of drugs and in absence of an accurate medical history. EVIDENCE ACQUISITION: A systematic literature review was carried out through PubMed database for studies published in the last ten years. The following search string was used: {("geriatric"[Title] OR "older"[Title] OR "aged"[Title] OR "elderly"[Title]) AND ((("abdomen"[Title] AND "acute"[Title]) OR "acute abdomen"[Title] OR ("acute"[Title] AND "abdomen"[Title])) OR ("abdominal"[Title] AND "pain"[title]) OR "abdominal pain"[Title])}. Full articles and abstracts were included. Case reports, commentaries, editorials and letters were excluded from the analysis. EVIDENCE SYNTHESIS: As the age of people presenting AP advances, both rates of surgical procedures and mortality rate increase. CONCLUSIONS: A systematic approach based on the organization of differential diagnoses into categories, may provide a helpful framework by the combined use of history-taking, physical examination, and results of diagnostic studies. In elderly patients admitted to the emergency department, a crucial role is played by a prompt use of radiological investigations in order to discriminate between older subjects admitted to the emergency department with abdominal pain and pathological cases requiring immediate surgical treatment.

Gender Differences and Quality of Life in Parkinson's Disease.

Parkinson's disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson's disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson's disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson's disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson's disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson's disease symptoms and health-related quality of life.

Diagnosis and treatment of hypothyroidism in old people : A new old challenge.

PURPOSE: To review the diagnosis and the treatment of both subclinical and overt hypothyroidism in old people, which could represent a challenge for the clinicians. METHODS: Narrative literature review. An extensive literature search was performed using the databases of Scopus, Medline through PubMed, and Google Scholar from January 1975 to May 2019. The search terms were "hypothyroidism," "older adults," "elderly," and "myxedema." RESULTS: Hypothyroidism is more common among older subjects in comparison to the younger counterparts. The hypothalamic-pituitary-thyroid axis and its hormones undergo significant changes due to the physiological aging process. For a correct diagnosis of hypothyroidism in old people clinicians must take such age-related changes into account. CONCLUSIONS: The administration of replacement therapy in older adults should consider frailty, polypharmacy and a high risk to develop overtreatment symptoms. On the other hand, older patients with untreated or undertreated hypothyroidism may develop a state of myxedema coma.

Effects of vildagliptin, a DPP-4 inhibitor, in elderly diabetic patients with mild cognitive impairment.

INTRODUCTION: There is an unclear association between type 2 diabetes and mild cognitive impairment in the elderly. Both diseases are more prevalent in the older adults compared to the younger counterpart. Some anti-diabetic drugs seem to influence positively the evolution of mild cognitive impairment. This retrospective study investigated the effect of vildagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4), on the cognitive functioning of elderly diabetic patients with mild cognitive impairment (MCI) documented at mini mental state examination (MMSE). METHODS: We included 60 diabetic elderly people which were divided in 2 groups: Group A, 30 patients with HbA1c (glycated hemoglobin) ≤7.5% and treated with metformin, and Group B, 30 patients with HbA1c >7.5%, and treated with metformin plus vildagliptin. We collected data on MMSE, fasting plasma glucose (FPG) and HbA1c at baseline and after 180 ±â€¯10 days from the beginning of treatment. RESULTS: The two groups exhibited significantly different values in FPG (P < 0.05) and HbA1c (P < 0.01) at baseline, and in MMSE score (P < 0.001) after treatment. The intragroup comparison showed a significant (P < 0.05) reduction in MMSE score in group A, and in HbA1c (P = 0.01) in group B. CONCLUSION: Vildagliptin in addition to metformin resulted in the maintenance of MMSE score, showing a protecting role on cognitive functioning compared to the metformin only group.

Hypothyroidism as a Predictor of Surgical Outcomes in the Elderly.

There is a high prevalence of hypothyroidism in the elderly population, mainly among women. The most important cause is autoimmune thyroiditis, but also iodine deficiency, radioiodine ablation, and surgery may be responsible for hypothyroidism in elderly hospitalized patients. Thyroid-related symptoms are sometimes comparable to physiological manifestations of the aging process, and hypothyroidism may be related with many symptoms which can be present in critical patients, such as cognitive impairment, cardiovascular, gastrointestinal, and hematological alterations, and eventually myxedema coma which is a severe and life-threatening condition in older adults. Adequate thyroid hormone levels are required to achieve optimal outcomes from any kind of surgical intervention. However, only few randomized clinical trials investigated the association between non-thyroidal illness (or low-T3 syndrome), and adverse surgical outcomes, so far. The goal of this review is to discuss the role of thyroid function as a predictor of surgical outcomes in the elderly.

Surgical approach and geriatric evaluation for elderly patients with colorectal cancer.

This review aims to define the most appropriate surgical approach and geriatric evaluation for elderly patients with colorectal cancer (CRC). Surgery represents the main treatment for CRC, but elderly cancer patients still represent a challenge for the surgeon due to frequent comorbidities such as cardiovascular and pulmonary diseases, which increase operative risk as well as the risk of postoperative morbidity and mortality. Cancer patients with comorbidities show lower survival rates and quality of life, together with higher healthcare costs. There is also evidence that patients with comorbidities sometimes receive modified treatment, compromising optimal care. To optimize treatment, the approach to elderly cancer patients needs a multidisciplinary team to assess preoperative conditions, prevent post-surgical complications and improve outcome, especially for frail patients. Laparoscopic surgery for CRC shows a number of advantages compared to conventional surgery such as less postoperative pain, rapid return to prior activities and a decrease in costs. Recent studies confirm that laparoscopic procedures could be performed safely on both older and younger patients with no difference compared with open surgery as regards morbidity or length of hospital stay.

Olive Oil Effects on Colorectal Cancer.

Colorectal cancer is the fourth cause of cancer-related death worldwide. A Mediterranean diet showed protective action against colorectal cancer due to the intake of different substances. Olive oil is a fundamental component of the Mediterranean diet. Olive oil is rich in high-value health compounds (such as monounsaturated free fatty acids, squalene, phytosterols, and phenols). Phenolic compounds exert favourable effects on free radicals, inflammation, gut microbiota, and carcinogenesis. The interaction between gut microbiota and olive oil consumption could modulate colonic microbial composition or activity, with a possible role in cancer prevention. Gut microbiota is able to degrade some substances found in olive oil, producing active metabolites with chemopreventive action. Further clinical research is needed to clarify the beneficial effects of olive oil and its components. A better knowledge of the compounds found in olive oil could lead to the development of nutritional supplements or chemotherapeutic agents with a potential in the prevention and treatment of colorectal cancer.

Biomarkers in colorectal cancer: Current clinical utility and future perspectives.

Colorectal cancer (CRC) is a major cause of cancer death worldwide. CRC has poor prognosis and there is a crucial need for new diagnostic and prognostic biomarkers to avoid CRC-related deaths. CRC can be considered a sporadic disease in most cases (75%-80%), but it has been suggested that crosstalk between gene mutations (i.e., mutations of BRAF, KRAS, and p53 as well as microsatellite instability) and epigenetic alterations (i.e., DNA methylation of CpG island promoter regions) could play a pivotal role in cancer development. A number of studies have focused on molecular testing to guide targeted and conventional treatments for patients with CRC, sometimes with contrasting results. Some of the most useful innovations in the management of CRC include the possibility to detect the absence of KRAS, BRAF, NRAS and PIK3CA gene mutations with the subsequent choice to administer targeted adjuvant therapy with anti-epidermal growth factor receptor antibodies. Moreover, CRC patients can benefit from tests for microsatellite instability and for the detection of loss of heterozygosity of chromosome 18q that can be helpful in guiding therapeutic decisions as regards the administration of 5-FU. The aim of this review was to summarize the most recent evidence on the possible use of genetic or epigenetic biomarkers for diagnosis, prognosis and response to therapy in CRC patients.

Silybin supplementation during HCV therapy with pegylated interferon-α plus ribavirin reduces depression and anxiety and increases work ability.

BACKGROUND: Hepatitis C virus infection and interferon treatment are often associated with anxiety, depressive symptoms and poor health-related quality of life. To evaluate the Silybin-vitamin E-phospholipids complex effect on work ability and whether health related factors (anxiety and depression) were associated with work ability in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b (Peg-IFN) and Ribavirin (RBV). METHODS: Thirty-one patients (Group A) with chronic hepatitis and other 31 subjects in Group B were recruited in a randomized, prospective, placebo controlled, double blind clinical trial. Group A received 1.5 mg/kg per week of Peg-IFN plus RBV and placebo, while Group B received the same dosage of Peg-IFN plus RBV plus association of Silybin 94 mg + vitamin E 30 mg + phospholipids 194 mg in pills for 12 months. All subjects underwent to laboratory exams and questionnaires to evaluate depression (Beck Depression Inventory - BDI), anxiety (State-trait anxiety inventory - STAI) and work ability (Work ability Index - WAI). RESULTS: The comparison between group A and group B showed significant differences after 6 months in ALT (P < 0.001), and viremia (P < 0.05), after 12 months in ALT (P < 0.001), and AST (P < 0.001), at follow up in AST (P < 0.05), and ALT (P < 0.001). Significant difference were observed after 1 month in WAI (p < 0.001) and BDI (P < 0.05), after 6 months in WAI (P < 0.05) and STAI (P < 0.05), after 12 months and at follow up in WAI, STAI and BDI (p < 0.01). CONCLUSIONS: The supplementation with Silybin-vitamin E -phospholipids complex increased work ability and reduced depression and anxiety in patients treated with Peg-IFN and RBV. TRIAL REGISTRATION: NCT01957319 , First received: September 25, 2013. Last updated: September 30, 2013 (retrospectively registered).

Role of surgery for colorectal cancer in the elderly.

The prevalence of subjects with colorectal cancer is expected to grow in the next future decades and surgery represents the most successful treatment modality for these patients. Anyway, currently elderly subjects undergo less elective surgical procedures than younger patients mainly due to the high rates of postoperative morbidity and mortality. Some authors suggest extensive surgery, including multistage procedures, as carried out in younger patients while others promote less aggressive surgery. In older patients, laparoscopic-assisted colectomy showed a number of advantages compared to conventional open surgery that include lower stress, higher rate of independency after surgery, quicker return to prior activities and a decrease in costs. The recent advances in chemotherapy and the introduction of new surgical procedures such as the endoluminal stenting, suggest the need for a revisitation of surgical practice patterns and the role of palliative surgery, mainly for patients with advanced disease. In this article, we discuss the current role of surgery for elderly patients with colorectal cancer.