Tumor-infiltrating lymphocytes, PD-L1, and MMR-deficiency combined characterization may identify subgroups of rectal cancer patients who would benefit from immunotherapy.

INTRODUCTION: Mismatch repair deficiency, immunological fertility, and PD-L1 expression status are key histopathological and molecular features defining tumor responsiveness to immunotherapy and, eventually, prognosis. These were investigated in a series of locally advanced rectal cancer patients treated with postoperative chemotherapy and radiotherapy. MATERIALS AND METHODS: Tumor-infiltrating lymphocyte (TIL) density was assessed in hematoxylin-eosin tissue sections. PD-L1 expression and the expression of MMR proteins (MLH1, PSM2, MSH2, and MSH6) were assessed with immunohistochemistry. Their association with histopathological variables (node involvement and tumor budding) and prognosis was assessed. RESULTS: The TIL-density was significantly higher in the invading tumor front and was inversely related to tumor budding and directly with better overall survival (OS) and distant metastasis-free survival (DMFS) (p = 0.02 and 0.02, respectively). Cancer cell PD-L1 expression was related to high TIL-density (p < 0.01) but not to prognosis, although its overexpression defined a trend for poorer OS in patients with high TIL-density. High PD-L1 expression by stroma infiltrating immune cells was linked with better OS and DMFS (p = 0.007 and 0.001, respectively. MMR deficiency was recorded in 26.2 % of cases, and this was linked with higher TIL-density, but not with prognosis. CONCLUSIONS: Dense intratumoral lymphocytic infiltration relates to a better prognosis in rectal cancer, although it is also linked with PD-L1 expression that may adversely modulate the anti-tumor effects of TILs. This latter subgroup of patients (high TIL-density/high cancer cell PD-L1 expression) could be an additional target for anti-PD-1/PD-L1 immunotherapy, along with the established subgroup of MMR deficient patients.

The role of prophylactic parathyroidectomy during thyroidectomy for MTC in patients with MEN2A syndrome.

AIM: To define the role of prophylactic parathyroidectomy in the surgical treatment of medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type IIa (MEN2A) syndrome through a literature review.

Postoperative hypofractionated-accelerated radiotherapy (HypoAR) for locally advanced rectal cancer.

BACKGROUND: despite the advances in preoperative hypofractionated-accelerated radiotherapy for patients with locally advanced rectal cancer, postoperative radiotherapy delivered with standard fractionation (46-50 Gy in 5 weeks) remains a standard adjuvant schedule. The role of hypofractionated-accelerated radiotherapy in a postoperative setting remains largely unexplored. METHODS: eighty-eight patients with rectal cancer infiltrating the rectal wall and/or having metastasis to the perirectal lymph nodes were treated with surgery followed by adjuvant chemotherapy and, subsequently, with hypofractionated-accelerated radiotherapy. Ten fractions of 3.4 Gy were delivered to the pelvis for 10 consecutive fractions, within 12 days. The follow-up of patients alive at the time of analysis ranges from 12-120 months (median 48). RESULTS: mild abdominal discomfort and diarrhoea were frequent, but medical medication was demanded in 14/88 (15.9%) of patients. The incidence of late toxicities was low; 4/88 (3.5%) patients complained for intermittent intestinal urgency. Locoregional recurrence occurred in 8/88 patients (9%). The 5-year locoregional relapse-free survival was achieved in 89.7% of patients, and this dropped to 84% in node-positive patients (P = 0.45). The 5-year disease-specific overall survival was 72.4%. Nodal involvement showed a trend to negatively affect prognosis (5-year overall survival 68.2 vs. 79.6%; P = 0.23). CONCLUSION: postoperative hypofractionated-accelerated radiotherapy has minimal early and late toxicity. The locoregional control and disease-specific survival rates are similar to the expected from conventional postoperative chemoradiotherapy. The 2.5-fold decrease of radiotherapy treatment time, reduction of waiting lists and the lower overall cost of radiotherapy are additional benefits associated with hypofractionated-accelerated radiotherapy.

A Case of Symptomatic Gallbladder Agenesis with Chronic Abdominal Symptoms.

The anatomical area of the extrahepatic bile ducts exhibits plethora of anatomic variants. The detailed study and comprehension of anatomic variations of extrahepatic bile ducts is a prerequisite in order to avoid the intraoperative biliary or tract damages, but they are also necessary for the targeted treatment of any complications. Gallbladder agenesis is a rare congenital anomaly of the biliary tree with an estimated incidence of 0.007-0.027% in surgical series which is much lower compared to the incidence of other gallbladder anomalies. It may be asymptomatic, but sometimes is associated with symptoms such as upper quadrant abdominal pain, which may be mistaken for cholecystitis and can lead the patient to the operating room. We present a case of a 30-year-old male patient without any significant past medical history presented with a 2-year history of upper abdominal complaints, dyspepsia, epigastric abdominal pain and weight loss, normal laboratory workup and unclear radiological signs which led him to exploratory laparoscopy due to the patient's chronic symptoms, in order to exclude the presence of another underlying pathologic process. In addition to our case presentation, a relative  review of literature was conducted. As a conclusion, examinations, such as transabdominal ultrasonography, may be misleading and MCRP should be the principal method of investigation to establish a presumptive diagnosis. However, in cases with a strong suspicion for a different underlying pathology, further investigation with exploratory laparoscopy may be warranted.

Sister Mary Joseph's nodule: the tip of an iceberg.

Sister Mary Joseph's nodule is a rare palpable umbilical cutaneous lesion as a result of an advanced intra-abdominal and/or pelvic malignancy. It may be the initial clinical manifestation of an underlying malignancy, originating mainly from the gastro-digestive or genito-urinary tract. We present here a rare case of a 67-year-old woman with a Sister Mary Joseph's nodule. On surgical exploration, a left ovarian mass with anterior abdominal wall metastasis, ascites and extensive intra-abdominal metastatic lesions were observed. Our case report shows the importance of a careful physical examination as an invaluable diagnostic tool in modern medicine. High index of suspicion and awareness of this clinical sign may lead to the detection of the primary source, to its diagnosis and more appropriate treatment options in order to achieve the best survival possibility. KEY WORDS: Ovarian cancer, Sister Mary Joseph's nodule, Umbilical metastasis.